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LongRoom News › china
Loan apps exposed real-time location data on millions in China
CNET | 7/17/2019 | Alfred Ng
The exposed server was getting live updates from more than 100 loan-related apps, some of which were providing real-time location data. Millions of people in China who use loan apps to borrow money...
744 views princia 8:59 EST
Beijing builds a huge ship to 'safeguard' its largest outpost in disputed South China Sea
Mail Online | 7/16/2019 | MailOnline Reporter
China has built a massive supply ship to help it develop its largest outpost in disputed South China Sea. The vessel, with a displacement of 8,000 tonnes, will play a vital role in the safeguarding...
584 views moemajor 6:45 EST
FILE PHOTO: Vietnam's Prime Minister Nguyen Xuan Phuc (2nd L, front) and Deputy Prime Minister Truong Hoa Binh (2nd R, front) speaks with sailors of Coast Guard Force on field via video call during...
280 views taylorswift10 5:25 EST
'Expect Craziness' As China Readies Debut Of Nasdaq-Style Board
SHANGHAI (Reuters) – In a packed Shanghai classroom on a hot afternoon, nearly a hundred "mom-and-pop" investors were honing their trading skills ahead of the first opening bell for China's...
789 views PinkPuffFairy 3:20 EST
Google executive finally confirms that the tech giant is no longer working on a censored search engine for China
Business Insider | 7/17/2019 | Nick Bastone
Google finally said that it is killing the censored search engine it had been building for China, known internally as Project Dragonfly. "Yes, we have terminated that," Karan Bhatia, Google's VP of...
208 views ditranian 2:55 EST
Toyota, China's CATL In Partnership For New Energy Vehicle Batteries
TOKYO (Reuters) – Toyota Motor Corp said on Wednesday it had agreed to partner with China's Contemporary Amperex Technology Co Ltd (CATL) to supply and further develop batteries for new energy...
422 views eymira 2:38 EST
China's New Icebreaker Ship Ready For 'Polar Silk Road'
Chinese President Xi Jinping's Belt and Road Initiative to the Arctic was outlined last year in an official Arctic policy white paper that detailed China's push to build infrastructure and conduct...
439 views jolan 7/16/2019 11:29 PM EST
Google shut down Chinese censorship project but won't rule out working with China
Washington Examiner | 7/16/2019 | by Jerry Dunleavy
A top Google executive revealed today that the global tech firm had shut down its effort to build a search engine that would comply with the repressive censorship requirements of the Communist...
Google exec denies accusations company has been infiltrated by China
Karan Bhatia, a top executive for Google, repeatedly denied accusations Tuesday that Google has been infiltrated or comprised by the Chinese government while testifying in front of the Senate...
177 views echolea 7/16/2019 9:18 PM EST
PETER THIEL: "WOKE" GOOGLE EMPLOYEES PREFER COMMUNIST CHINA TO AMERICA
www.infowars.com | 7/16/2019 | Paul Joseph Watson
Billionaire investor Peter Thiel says one reason for Google aiding in the transfer of AI technology to the Chinese military in favor of America is that "woke" Google employees are anti-American and...
589 views red815 7/16/2019 7:55 PM EST
Billionaire Peter Thiel says 'woke' Google employees 'probably prefer Communist China to the US'
PayPal co-found Peter Thiel suggested that 'super left wing' Google employees are anti-American and prefer communist China to the US. The billionaire also said the tech giant is working with China...
528 views cyanbyte 7/16/2019 5:11 PM EST
If China takes strong measures to reduce its ozone pollution now, it could save hundreds of thousands of lives in the long run, according to a new study led by researchers at Columbia University's...
167 views kring 7/16/2019 4:15 PM EST
Bills Targeting China's Huawei Introduced In U.S. Congress
WASHINGTON (Reuters) – Members of the U.S. Senate and House of Representatives introduced bills on Tuesday to keep tight restrictions on Huawei Technologies Co Ltd, amid concern about President...
134 views max1 7/16/2019 12:34 PM EST
China startup deals shrink as fundraising for investors plummets
Chinese startups continue to weather tough times as private investors, caught in a cash crunch, are concentrating money into fewer deals. China's deal-making activity for startups in the six months...
256 views sally140353 7/16/2019 11:52 AM EST
China Thrilled by Prospect of Chinese Casting for Shang-Chi, 'Marvel's First Chinese Hero'
Variety | 7/16/2019 | Rebecca Davis
China's internet is thrilled by news that Marvel appears to be insisting on casting an ethnic Chinese actor as Shang-Chi in the master of kung fu's own spinoff film and has begun scouting out...
1.1K views PaMe 7/16/2019 4:21 AM EST
China Says Misleading To Suggest It Needs Trade Deal Due To Slowing Economy
BEIJING (Reuters) – China's Foreign Ministry said on Tuesday that it was misleading to suggest Beijing needed a trade deal with the United States because its economy was slowing, following a tweet by...
Peter Thiel: Google should be investigated by CIA, FBI over 'treasonous' China links
Fox Business | 7/15/2019 | Katherine Lam
Disruptive Tech Research chief analyst Lou Basenese argues Peter Thiel is raising "perfectly legitimate" concerns about China and Google. He also provided insight into Facebook's digital currency...
598 views Mkgirlz 7/16/2019 1:39 AM EST
China Arrests Canadian Citizen for Drug Offenses
Breitbart | 7/15/2019 | John Hayward
China's Foreign Ministry confirmed on Monday that another Canadian citizen has been arrested, this time on drug offenses. The Canadian foreign ministry, Global Affairs Canada, announced on Saturday...
577 views Mkgirlz 7/15/2019 11:41 PM EST
China Threatens Weapons, Rare Earth Sanctions on U.S. Companies Arming Taiwan
Breitbart | 7/15/2019 | Frances Martel
China's state-run Global Times newspaper published a story Sunday citing "experts" warning that the Communist Party could sanction American companies who sell weapons equipment to Taiwan.
308 views darktm22 7/15/2019 11:29 PM EST
China's First Half Fixed-Asset Investment Projects Rise 81% Year-On-Year To 472 Billion Yuan
BEIJING (Reuters) – China's fixed-asset investment project approval in the first six months increased 81% by value compared with a year earlier as Beijing ramped up infrastructure spending to help...
413 views emmymmile234567 7/15/2019 11:14 PM EST
"This Won't End Well" - Lies, Damned Lies, & China's Retail Sales Data
As far back as 2013, China's macro-economic data has been 'questionably' smoothed at best, and outright fake at worst. Whether it is trade data ("never been faker" than in 2016) or aggregate...
384 views iVchan 7/15/2019 8:12 PM EST
China Touts Trans-Cuban Railway as Belt and Road Expands in Latin America
China's Xinhua news agency published images Sunday of the debut of a new, Chinese-built railway connecting Havana to Santiago de Cuba, the largest cities on the east and west coasts of the island,...
168 views stefania 7/15/2019 5:44 PM EST
Peter Thiel Calls on CIA, FBI to Investigate Google's China Ties
Washington Free Beacon | 7/15/2019 | Paul Crookston
President Donald Trump's top supporter in Silicon Valley said Sunday the United States needs to investigate Google's "seemingly treasonous" work with the Chinese military.
307 views reantes 7/15/2019 2:41 PM EST
China's TikTok To Store Russian Users' Data Locally: Watchdog
MOSCOW (Reuters) – The Chinese video app TikTok will store Russian users' data locally to comply with Russian law, the communications watchdog Roskomnadzor said on Monday after a meeting with the...
261 views Traight 7/15/2019 1:46 PM EST
China GDP Growth Slumps As Trade War Bites
Sparta Report | 7/15/2019 | Doomberg
The pressure continues to build on China as GDP growth slows: China's economic growth slowed to 6.2% in the second quarter from a year earlier, the weakest in at least 27 years, as demand at home...
506 views itsdonaldk 7/15/2019 1:30 PM EST
China's Enlight Projects at Least 95% Fall in Net Profit in First Half of 2019
Beijing-based Enlight Media, one of China's most prominent production companies, said Monday it expects a steep decrease in net profits of up to 96% in the first half of the year compared to the...
335 views Mireille 7/15/2019 1:18 PM EST
Blain: There Are Two Kinds Of "China Watcher"
"If you play good cricket, a lot of bad things may remain hidden" What a Splendid Sports Sunday: Wimbledon, Grand Prix and the extraordinary finish to the Cricket World Cup.
382 views cobra662 7/15/2019 11:01 AM EST
China's Economic Growth Slows to Weakest Pace Since 1992
Breitbart | 7/15/2019 | John Carney
China's economic growth slowed by more than expected in the second quarter, official statistics showed Monday. The economy grew at a 6.2 percent annual rate in the April through June period, the...
313 views monna 7/15/2019 10:21 AM EST
China Box Office: 'The Lion King' Pounces as Ticket Sales Slump
Disney's "The Lion King" has pounced on the China market — a week ahead of its U.S. release — with a $53.8 million three-day debut that gave it pride of place at the Chinese weekend box office.
294 views melanie7 7/15/2019 6:21 AM EST
China Says Will Freeze Out U.S. Companies That Sell Taiwan Arms
BEIJING (Reuters) – China's government and Chinese companies will cut business ties with U.S. firms selling arms to Taiwan, China's Foreign Ministry said on Monday, declining to give details of the...
977 views monna 7/15/2019 5:16 AM EST
China Thanks 37 Countries, Including Islamic States, for Praising Its Uighur Policies
(CNSNews.com) – A three-week session of the U.N. Human Rights Council ended on a jarring note on Friday when it was revealed that more than three dozen countries had signed a letter supporting...
913 views gbabii05 7/15/2019 5:10 AM EST
Economic improvement in China's northeast rust belt is just skin deep as state firms continue to bleed
South China Morning Post | 7/15/2019 | Staff
Liaoning's industrial output grew just 6.7 per cent in the first five months of 2019, compared with a 10.5 per cent rise for the first quarter of last...
864 views smnth28 7/15/2019 5:09 AM EST
China's Didi Chuxing To Allow App Users To Access Rivals' Services
BEIJING (Reuters) – China's biggest ride-hailing company Didi Chuxing will allow users of its smartphone app to access services provided by apps of three domestic auto firms and others, in a push to...
638 views blockstyle 7/15/2019 4:48 AM EST
European Shares Edge Higher After Encouraging China Data
(Reuters) – European shares inched higher on Monday, tracking gains in Asian markets on encouraging factory output and retail sales data from China, which provided some respite from worries about...
285 views oxboy 7/15/2019 4:32 AM EST
SHANGHAI (Reuters) – China's Xiaomi Corp has taken a stake of roughly 6% in compatriot chip designer VeriSilicon Holdings Co Ltd, as the smartphone maker revamps its years-long pursuit of success in...
539 views spiderMonkey 7/15/2019 1:49 AM EST
Hellobike, survivor of China's bike-sharing craze, goes electric
Just two years ago, investors were heavily pouring money into China's dockless bike-sharing startups. Now that boom has busted with derelict bikes littering the streets of cities.
1.2K views Mireille 7/15/2019 12:40 AM EST
China Pig Herd Falls 25.8% In June, Sow Herd Down 26.7% – Agriculture Ministry
BEIJING (Reuters) – China's pig herd shrank 25.8% in June compared with the same month a year earlier, while the sow herd contracted 26.7%, the Ministry of Agriculture and Rural Affairs said on...
901 views Claw987 7/15/2019 12:00 AM EST
China Reports Slowest GDP Growth On Record, As Retail Sales, Industrial Output And Fixed Investment All Beat
Additionally, 2Q cumulative GDP rose 6.3% y/y, also matching the consensus estimate, and down from 6.4% in Q1. "We expect Beijing to ramp up stimulus measures in the second half despite more limited...
859 views chrismpotts 7/14/2019 11:22 PM EST
China's Q2 GDP grows at slowest pace in 27 years
MarketWatch | 7/14/2019 | MarketWatch
BEIJING--China's gross domestic product rose 6.2% in the second quarter from a year earlier, the slowest pace in at least 27 years, according to official data released on Monday.
797 views kshama-s 7/14/2019 11:15 PM EST
China's June Home Prices Rise 0.6% From May
BEIJING (Reuters) – China's new home prices grew 0.6% month-on-month in June, slowing from a 0.7% uptick in May, Reuters calculated from official National Bureau of Statistics (NBS) data on Monday.
614 views EGFZE 7/14/2019 10:25 PM EST
China Thanks 37 Countries – Including Islamic States – For Praising its Uighur Policies
At the U.N. Human Rights Council on Friday, China's ambassador thanked 37 countries for signing a letter supporting Beijing's policies in Xinjiang. According to Western governments and advocacy...
358 views shellshockked 7/14/2019 9:48 PM EST
Oil Prices Edge Down Ahead Of Expected Weak China Data
SINGAPORE (Reuters) – Oil prices edged down on Monday, dragged down by expectations that China, the world's largest crude oil importer, will post its slowest pace of economic growth in at least 27...
728 views Mandyixus 7/14/2019 9:32 PM EST
Asian Shares, Dollar Brace For China GDP
SYDNEY (Reuters) – Asian shares started the week on a softer note on Monday after posting their first weekly decline since early June, while the dollar was on the defensive ahead of key economic data...
1.3K views bungienet 7/14/2019 9:04 PM EST
China Increases Investment in Israeli Infrastructure Amid U.S. Concerns
Breitbart | 7/14/2019 | Deborah Danan
TEL AVIV – Prime Minister Benjamin Netanyahu is still deliberating what to do about regulating foreign investments in Israel amid concerns on the part of U.S. and Israeli security forces over the...
397 views KimmyPoo 7/14/2019 6:53 PM EST
Shanghai leads battle against China's rising mountain of trash
Nie Feng used to toss his rubbish outside his Shanghai flat without a thought while rushing to work, but saving China from a garbage crisis now requires him to consult a complex diagram each morning.
746 views Traight 7/14/2019 12:16 PM EST
China Drank The Most Beer In The World In 2018
China is apparently the best in the world when it comes to hammering beers. As one of my friends said yesterday about this news, it's "Red Dawn" all over again. If we let the Chinese overtake us in...
1.4K views Cocoa_Candy12 7/14/2019 11:50 AM EST
Report: U.S. Weighing Sanctions Against China for Buying Oil from Iran
Breitbart | 7/13/2019 | Edwin Mora
Some advisers within U.S. President Donald Trump's administration are allegedly urging secondary economic restrictions on Beijing for continuing to import Iranian oil despite American sanctions...
1.7K views ditranian 7/13/2019 8:20 PM EST
China's Fosun Group confirms Thomas Cook rescue bid
China's Fosun Group is considering nearly a billion dollar rescue of embattled British tour operator Thomas Cook, the Hong Kong-listed conglomerate confirmed Friday.
1.1K views TwiztedGurl 7/13/2019 2:29 PM EST
The systematic review and meta-analysis, funded by the National Institute for Health Research and published in the Journal of the American Heart Association, also found that Chinese children aged 3-6...
1.6K views blacky 7/13/2019 2:26 PM EST
Hong Kong Protesters March Near Border To Target Traders From China
HONG KONG (Reuters) – Thousands of Hong Kong people marched on Saturday to protest against mainland Chinese traders in a town near the border, tapping into anger behind huge demonstrations against an...
711 views MonkeyBubble 7/13/2019 7:05 AM EST
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Philadelphia – A federal judge issued a memo Wednesday saying the Trump administration cannot cut off grants to Philadelphia over the way the city deals with immigrants in the country illegally.
U.S. District Judge Michael Baylson issued the 93-page memo, saying the conditions placed on the city by the federal government in order to receive the funding are unconstitutional, "arbitrary and capricious." He also wrote that Philadelphia's policies are reasonable and appropriate.
Philadelphia has said as a so-called "sanctuary city," it will only turn over immigrants to Immigration and Customs Enforcement if they have a warrant signed by a judge. The city was fighting federal efforts to block grant funding as a result of the policy.
Several sanctuary cities have opted to limit cooperation with government enforcement of immigration law. The Justice Department has threatened to cut off millions of dollars in federal grants to cities if they don't meet certain criteria for cooperating with immigration officials. Philadelphia's attorneys had argued the move is unconstitutional and that it harms residents by withholding money earmarked to help buy kits to counteract opioid overdoses.
Attorney General Jeff Sessions has said that cities that don't help enforce immigration law are endangering public safety, especially when it comes to sharing information about immigrants who have been accused of crimes.


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Luned Whelan announced as TAC's New General Manager
Luned Whelan has begun work as General Manager of TAC (Teledwyr Annibynnol Cymru), the trade association for the Welsh independent television production sector.
Luned's role is to support TAC members in the independent TV production sector to protect the interests of those producers as a whole and to coordinate the investment of the companies in training. This will involve working with S4C, the BBC, Ofcom, Welsh Government and other bodies.
Iestyn Garlick, Chair of TAC, said: "TAC Council is delighted to welcome Luned Whelan to the post of General Manager. Luned worked in S4C for many years, and has been freelancing since 2010, during which time she has worked with a number of our independent production companies. Her experience in core elements of public broadcasting such as contracts, rights and communications will be beneficial to us, as will her creative experiences of scriptwriting and generating content, off- and online, for a variety of companies."
"Over the coming months, Luned will be busy producing an executive strategy based on the needs of the entire sector, and ensuring that the members' voice is heard at all levels in matters pertaining to the substantive developments to come over the next year in the broadcast sector in Wales."
For further information, contact Iestyn Garlick on 07974 184 764 / iestyn@antena.co.uk or Luned Whelan: 07388 377478 or 029 2245 0226 / l.whelan@tac-cymru.co.uk.

redpajama_set_name: RedPajamaCommonCrawl


East Africa Protectorate (also known as British East Africa) was an area in the African Great Lakes occupying roughly the same terrain as present-day Kenya from the Indian Ocean inland to Uganda and the Great Rift Valley. It was an administrative grouping of five separate British territories: Kenya, Uganda, the Sultanate of Zanzibar and British Somaliland.
Crowned bust of King George VI, left, wearing the Tudor Crown, English legend "George VI, King and Emperor of India" around.
Lion and mountains within 3/4 circle with fleur ends, date and denomination below.
Mintmark is positioned in soil under lion right above denomination.


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Chapter 436. Inherited Bleeding Disorders
Amy L. Dunn; Shannon L. Meeks; Thomas C. Abshire
Dunn AL, Meeks SL, Abshire TC. Dunn A.L., & Meeks S.L., & Abshire T.C. Dunn, Amy L., et al.Chapter 436. Inherited Bleeding Disorders. In: Rudolph CD, Rudolph AM, Lister GE, First LR, Gershon AA. Rudolph C.D., & Rudolph A.M., & Lister G.E., & First L.R., & Gershon A.A.(Eds.),Eds. Colin D. Rudolph, et al.eds. Rudolph's Pediatrics, 22e. McGraw Hill; 2011. Accessed February 01, 2023. https://accesspediatrics.mhmedical.com/content.aspx?bookid=455&sectionid=40310750
Dunn AL, Meeks SL, Abshire TC. Dunn A.L., & Meeks S.L., & Abshire T.C. Dunn, Amy L., et al. (2011). Chapter 436. inherited bleeding disorders. Rudolph CD, Rudolph AM, Lister GE, First LR, Gershon AA. Rudolph C.D., & Rudolph A.M., & Lister G.E., & First L.R., & Gershon A.A.(Eds.),Eds. Colin D. Rudolph, et al. Rudolph's Pediatrics, 22e. McGraw Hill. https://accesspediatrics.mhmedical.com/content.aspx?bookid=455&sectionid=40310750
Dunn AL, Meeks SL, Abshire TC. Dunn A.L., & Meeks S.L., & Abshire T.C. Dunn, Amy L., et al. "Chapter 436. Inherited Bleeding Disorders." Rudolph's Pediatrics, 22e Rudolph CD, Rudolph AM, Lister GE, First LR, Gershon AA. Rudolph C.D., & Rudolph A.M., & Lister G.E., & First L.R., & Gershon A.A.(Eds.),Eds. Colin D. Rudolph, et al. McGraw Hill, 2011, https://accesspediatrics.mhmedical.com/content.aspx?bookid=455&sectionid=40310750.
Inherited Bleeding Disorders: Introduction
The Hemophilias
Defects in the Tissue Factor (Extrinsic) Pathway
Defects in the Common Pathway
Dysfibrinoginemia and Afibrinoginemia
Factor XIII Deficiency
Defects in the Fibrinolytic Pathway
Inherited bleeding disorders are a heterogeneous group of conditions that lead to excessive hemorrhage. The disorders have distinct inheritance patterns, clinical bleeding symptoms, and laboratory abnormalities. Therefore, the history and physical examination are key to guiding appropriate laboratory testing and diagnosis.
Hemophilia A, or classical hemophilia, results from congenital deficiency or absence of circulating factor VIII (FVIII). It is an X-linked recessive disorder with an incidence of approximately 1:5000 male births.1 Hemophilia B is also known as Christmas disease after Stephen Christmas who was the first child described with the disorder.2 It results from a congenital deficiency or absence of factor IX (FIX). It is an X-linked recessive disorder with an incidence of approximately 1:25,000 male births.1 Hemophilia C is an autosomal recessive disorder resulting in decreased amounts of circulating factor XI. It affects 1 in 100,000 people.
Factor Structure and Function
Factor VIII is a plasma glycoproteinconsisting of 6 domains, A1-A2-B-A3-C1-C2 (eFig. 436.1) .3 The encoding gene is found on the long arm of the X chromosome (Xq28).The mature protein is a heterodimer with a light chain consisting of domains A3-C1-C2 and a heavy chain composed of the domains A1-A2-B. The majority of FVIII is thought to be synthesized in liver endothelial cells. Upon release into the circulation, it is immediately noncovalently linked to von Willebrand factor (vWF). This prevents enzymatic degradation of FVIII until it is needed during coagulation. As illustrated in eFigure 436.2, during coagulation tissue factor combines with FVIIa at the site of injury. This complex activates FX and FIX, leading to conversion of prothrombin to thrombin. The initial thrombin cleavage of the FVIII light chain causes FVIII to be released into the circulation and then activated to FVIIIa by further thrombin-mediated proteolysis. FVIIIa and FIXa then act as cofactors on a phospholipid surface (typically a platelet) during activation of factor X, V, and ultimately, thrombin (eFig. 436.2).4 Many molecular defects have been described in the pathology of hemophilia A. These include gross gene rearrangements of the DNA sequence, single gene rearrangements, deletions of some or all of the gene sequence, and DNA insertions. A continually updated list of mutations leading to hemophilia A can be found at http://europium.csc.mrc.ac.uk.
eFigure 436.1.
Domain structure of factor VIII. Factor VIII consists of 3 A domains, 1 B domain, and 2 C domains that are linked by an activation peptide (ap).
The coagulation cascade.
Factor IX is a vitamin K–dependent serine protease believed to be synthesized in the liver and released into the circulation in its inactive form. The gene is 33 kilobases long on the end of the X chromosome (Xq27).3 During coagulation, tissue factor and FVII activate FIX. Factor IXa in turn activates FVIII. Many mutations have been described in the FIX gene, including small and large deletions and additions, rearrangements, and missense mutations. A list of updated mutations can be found at the website http://www.kcl.ac.uk/ip/petergreen/haemBdatabase.html.
Patients with hemophilia A or B are unable to generate adequate thrombin due to lack of FVIII or IX and become dependant upon the tissue factor pathway. Circulating tissue factor pathway inhibitor efficiently downregulates the tissue factor-VIIa pathway as well as FXa, and as a result patients with hemophilia bleed. Thrombin-activatable fibrinolysis inhibitor production is also decreased in hemophilia, leading to more rapid dissolution of the fibrin clot.
FXI is a serine protease that participates in the contact pathway.5 It is synthesized in the liver and circulates in its inactive form as a homodimer. Each chain has a molecular weight of nearly 80,000 daltons. The gene encoding FXI is on chromosome 4q32-35. Its major role appears to be activation of FIX after having been activated itself by FXIIa. Bleeding in hemophilia C is likely related to inadequate FIX activation or lack of production of thrombin-activatable fibrinolysis inhibitor.6 FXI deficiency is more common in the Ashkenazi Jewish population but has also been reported in patients with Noonan syndrome. A list of mutations leading to hemophilia C is maintained at http://www.factorxi.com/.
Clinical Manifestations
The hallmark of hemophilia A– and B–related bleeding is delayed bleeding, along with joint and muscle hemorrhage. In comparison, patients with von Willebrand disease and hemophilia C more commonly manifest mucocutaneous bleeding. As hemophilia A and B are X-linked, the vast majority of affected patients are male. Females can be affected in cases of extreme X chromosome lyonization or gene abnormalities such as Turner syndrome. There is a particularly high rate of spontaneous mutation within the FVIII gene, and as a result approximately 30% of newly diagnosed patients will have a negative family history for hemophilia.
In general, the severity of bleeding in hemophilia A and B depends upon the percentage of circulating clotting factor activity. Patients with levels of greater than 5% to 40% are classified as having mild hemophilia, those with levels of 1% to 5% as moderate, and those with less than 1% activity as having severe disease. Commonly, patients with severe disease will suffer from spontaneous bleeding, and those with mild-moderate disease more typically bleed with trauma or surgery. In the newborn period, the most common symptoms are bleeding in the brain and at sites of blood withdrawal, immunizations, and circumcision. Therefore, infants born of known carrier mothers should not be circumcised until testing for FVIII or IX rules out hemophilia. Older children and adults may experience excessive bruising, hematomas, and intracranial, joint, muscle, and mouth bleeding. Carrier females can also experience menorrhagia, mouth bleeding, and surgical and trauma-related bleeding.
Patients with hemophilia C have a heterogeneous bleeding pattern that is not directly related to circulating levels.5 For example, some patients with levels above 50% bleed after surgery or trauma, whereas some with levels below 10% do not. In general, patients with less than 20% activity are considered to have severe disease. It is rare, however, for patients, even those with low levels, to suffer from spontaneous bleeding.
Laboratory Findings
An elevated active partial thromboplastin time and decreased plasma FVIII, IX, or XI activity assay confirm the diagnosis. Type 3 von Willebrand disease should be ruled out in female patients and if there is no family history of hemophilia. Patients with type 3 von Willebrand disease will have absent VWF multimers, along with low VWF antigen and ristocetin cofactor activity. Von Willebrand disease Normandy variant should also be considered in the setting of moderately low FVIII levels, poor response to recombinant FVIII therapy, or an autosomal inheritance pattern. In the Normandy variant, the abnormality is decreased FVIII binding to VWF. This leads to rapid proteolysis of FVIII despite adequate production. This can be evaluated with a FVIII-binding assay and mutation analysis.
The mainstay of hemophilia A and B care is intravenously delivered factor concentrates. Factor VIII and IX concentrates can be purified from plasma or recombinantly synthesized.7,8 The plasma-derived FVIII products contain varying amounts of vWF, depending upon the manufacturing process. eTables 436.1, 436.2, 436.3, 436.4 describe the currently available recombinant and plasma-derived FVIII and FIX concentrates along with their manufacturing steps. Due to a history of viral contamination of plasma pools, both types of products now undergo multiple viral and pathogen attenuation steps. Importantly, no infectious complications have been reported since these steps were incorporated into the manufacturing process. The possibility of contamination with new infectious agents such as prions, however, cannot be excluded with plasma-derived products.
eTable 436.1. Available Plasma-Derived Factor VIII Concentrates*
Pathogen Attenuation
Reconstituted Volume per vial
Low VWF Hemofil M® Pooled human plasma MoAbIA, IE, SD 10 mL
Monoclate-P® Pooled human plasma-NAT tested for HBV, HCV, HIV-1 MoAbIA, pasteurization 5–20 mL
High VWF Alphanate® Pooled human plasma IA, IE, SD 5–10 mL
Koate®-DVI Pooled human plasma SD, heat, gel permeation chromatography 5–10mL
Humate-P® Pooled human plasma–NAT tested for HBV, HCV, HIV-1 Cryoprecipitation, Al(OH)3 adsorption, glycine precipitation, NaCl precipitation, pasteurization 5–15 mL
VWF, von Willebrand factor; NAT, nucleic acid amplification technology; MoAbIA, monoclonal antibody immunoaffinity chromatography; IE, ion exchange; SD, solvent detergent; IU, international unit; Al (OH)3, aluminum hydroxide; NaCl, sodium chloride
*Additional information on the above products is available in the package insert.
eTable 436.2. Available Recombinant Factor VIII Concentrates*
Host Cell
Purification/Pathogen Attenuation
First Generation Recombinate® CHO MoAbIA, IE Albumin 10 mL
Second Generation HelixateFS/Kogenate FS® BHK MoAbIA, IE, SD, UF Sucrose 2.5–5mL
Refacto® CHO MoAbIA, IE, SD, nanofiltration Sucrose 4 mL
Third Generation Advate® CHO MoAbIA, IE, SD Trehalose 5 mL
BHK, baby hamster kidney; CHO, Chinese hamster ovary; MoAbIA, Monoclonal antibody immunoaffinity chromatography; IE, ion exchange; SD, solvent detergent; UF, ultrafiltration; IU, international unit
*Additional information on the above products is available in the package insert. Adapted with permission
eTable 436.3. Available Plasma-Derived Factor IX Products*
AlphaNine® SD
Pooled human plasma
DAEA chromatography, Dual affinity chromatography, NF, SD
Mononine®
Pooled human plasma, NAT tested for HCV, HBV, HIV-1
MoAbIA, UF, sodium thiocynate incubation
MoAbIA, monoclonal antibody immunoaffinity chromatography; IE, ion exchange; SD, solvent detergent; NF, nanofiltration; UF, ultrafiltration
*Additional information on these products may be obtained from the package insert.
eTable 436.4. Recombinant Factor IX Product*
BeneFIX® CHO MoAbIA, UF Sucrose, amino acids 5–10 mL
CHO, Chinese hamster ovary; MoAbIA, monoclonal antibody immunoaffinity chromatography; IE, ion exchange; UF, ultrafiltration
*Additional information on this product may be obtained from the package insert. Adapted with permission.
Factor infusions can be delivered either in response to bleeding episodes (demand therapy) or to prevent bleeding (prophylaxis). To prevent or minimize long-term sequelae, demand therapy should be given as soon as possible after a bleeding episode is recognized. Because the need for urgent treatment is so important, many patients affected by hemophilia are educated in home infusion techniques. In the emergency department or office setting, factor replacement therapy should never be delayed to perform imaging or laboratory studies. Demand therapy can be used to effectively treat bleeding episodes, but it is not effective in preventing the most common complication of hemophilia, which is blood-induced joint disease.9
In developed countries, prophylactic therapy delivered 1 to 4 times per week dosed to keep trough levels above 1% is considered the standard of care. If prophylactic infusions are started at a young age prior to the development of arthropathy, it is termed primary prophylaxis and is the only therapy proven to prevent the long-term complication of degenerative joint disease.10 While there is no universally accepted starting age, dose, or frequency of infusions for primary prophylaxis, it is common practice to begin prophylaxis prior to the onset of recurrent joint bleeding. This is because the risk of irreversible joint damage increases if the onset of prophylaxis is delayed.11Secondary prophylaxis refers to long-term factor replacement after a hemophilia complication has been experienced. This practice is commonly used after intracranial hemorrhage or once joint disease has become established. While secondary prophylaxis effectively reduces the frequency of bleeding episodes, it has not been shown to halt the progression of joint disease.12,13
The dose and frequency of factor delivery is calculated based upon the half-life of the product (typically 10 to 12 hours for FVIII and 20 to 24 hours for FIX), the intravascular volume of distribution (1 international unit [IU] of FVIII per kilogram raises the plasma concentration by about 2%, and 1 IU of FIX per kilogram raises the plasma concentration by about 1%), and the desired clotting factor activity. For example, to raise the factor level of a 30-kg child with severe hemophilia A to 100%, the dose should be 30 kg × 50 IU = 1500 IU. Forty percent activity is considered hemostatic in most cases; however, in the setting of surgery or life- or limb-threatening hemorrhage, higher levels are necessary. Ancillary measures such as compressive dressings, cautery, packing, and splinting should also be implemented when appropriate. Agents that affect platelet function should be avoided. Table 436-1 illustrates an approach to factor replacement therapy of commonly encountered bleeding events.14
Table 436-1. Suggested Approach to Treatment of Bleeding Episodes in Hemophilia
Bleed Site
Desired Factor Level
Length of Therapy
Central nervous system 100% 7–14 days then prophylaxis for ⩾ 6 months Continuous infusion factor
Antiepileptic prophylaxis
Surgical decompression
Persistent oral/mucosal 30–60% 3–7 days Antifibrinolytic therapy
Custom mouthpiece
Topical thrombin powder
Retropharyngeal 80–100% 7–14 days Continuous infusion factor
Antifibrinolytic therapy
Nose 30–60% 1–3 days Packing, cautery
Saline nose spray/gel
Nasal vasoconstrictor spray
Gastrointestinal 40–80% 3–7 days Antifibrinolytic therapy
Endoscopy with cautery
Persistent gross urinary 40–60% 1–3 days Vigorous hydration
Evaluation for stones/UTI
Avoid antifibrinolytic agents
Muscle 40–80% Every other day until pain free RICE
Iliopsoas 80–100% Until radiographic resolution Continuous infusion factor
Joint 40–80% 1–2 days RICE
Target joint 80% day 1 3–4 days RICE
40% day 2 & 4 Physical therapy
Desmopressin or DDAVP (1-deamino-8-d-argine vasopressin) is a synthetic form of the hormone vasopressin. DDAVP causes release of FVIII and vWF from storage sites along the endothelium and within platelet storage granules.15 Patients with mild or moderate hemophilia A can be tested with this product, and their response (rise in FVIII level) can be measured. If patients show a response by manifesting hemostatic levels of FVIII, this product is often sufficient to treat or prevent bleeding. FVIII storage pools become depleted after multiple doses, so this treatment is not adequate for lengthy therapy. Additionally, fluid intake must be monitored closely as severe hyponatremia may result.16In most cases, life- or limb-threatening bleeding episodes require exogenous factor replacement. Antifibrinolytic therapy to stabilize the fibrin clot is particularly useful in diminishing bleeding symptoms in locations with prominent fibrinolytic activity, such as the mouth, gastrointestinal tract, and uterus.
Therapy for patients with hemophilia C relies upon replacement of FXI with fresh-frozen plasma, the use of antifibrinolytic agents, and fibrin glue.5 Factor XI concentrates are available in Europe but thrombosis and disseminated intravascular coagulation has been reported with their use.17,18
Inhibitor Development
A common complication of hemophilia is development of inhibitory antibodies to the infused factor. These inhibitory antibodies occur in approximately 30% of patients with severe hemophilia A and to a lesser extent in mild and moderate disease.19 They are more likely to occur in the setting of a positive family history of inhibitors in association with large gene deletions such as introns 1 and 22 inversions and in patients who are not of European ancestry. It has also been suggested that factor exposure during times of "immunologic danger," such as surgery or infection, may increase the risk of inhibitor development.20,21 Continuous infusion of factor as opposed to bolus dosing has also been proposed as a risk factor.22 Young age at first exposure to concentrate does not appear to be a risk factor for inhibitor development, and early institution of routine prophylaxis seems to be somewhat protective.21 There is no clear evidence as to whether the rate of antibody formation is influenced by the type of product used. However, it has been suggested that plasma-derived products that contain von Willebrand factor (VWF) may be less immunogenic.23,24 These inhibitory antibodies are most commonly directed against the A2 or C2 domains. They often develop within the first 20 exposures to exogenous FVIII, but can occur at any age. They typically neutralize both endogenous and exogenous FVIII. The antibody titer is measured using a Bethesda assay and is expressed in Bethesda units (BU).25 One Bethesda unit is that level of antibody that lowers the plasma factor level by 50% in vitro when incubated for 2 hours at 37°C with normal plasma. These antibodies can develop in patients without hemophilia, leading to a condition known as acquired hemophilia. Low titer inhibitors less than 5 BU are often transient and of little clinical significance, whereas those 5 BU or greater can significantly impact patient care and quality of life. Immune tolerance therapy with repeated exposure to FVIII concentrate over a period of months to years may eradicate the antibody. Immune tolerance therapy has been accomplished using both high-dose (100–200 IU/kg/day) and low-dose (50 IU/kg/3 times per week) FVIII. Both recombinant and VWF containing plasma-derived products have been used successfully. Immunosuppressive agents such as cyclosporine and Rituximab have been used with some success. Bleeding in the setting of a high titer inhibitor often requires bypassing therapy with either high doses of recombinant FVIIa or a prothrombin complex concentrate. These agents can also be used in a prophylactic manner to reduce bleeding frequency in patients with inhibitors.26
Hemophilia B and C are rarely complicated by the development of inhibitory antibodies. While these antibodies occur in only approximately 3% of patients with severe hemophilia B, anaphylactoid reactions to exogenous FIX that in some cases are life-threatening have been reported prior to recognition of a positive antibody titer.27The rate of inhibitor development appears to be similar between plasma-derived and recombinant products. As with hemophilia A, the antibody titer is measured using a Bethesda assay and expressed in Bethesda units. Successful desensitization to FIX has been achieved in some patients, and immune tolerance therapy with repeated exposure to FIX concentrate may eradicate the antibody.28 Nephrotic syndrome, however, is a uniquely reported complication of immune tolerance therapy with FIX products and commonly does not occur until several months into therapy. Immunosuppressive agents such as cyclosporine and Rituximab have been used with some success. Bleeding in the setting of a high-titer inhibitor often requires bypassing therapy with recombinant FVIIa.
Hemophilic Arthropathy
Degenerative joint disease due to recurrent hemarthrosis is the single largest preventable cause of morbidity for patients with hemophilia A and B. Recurrent spontaneous or trauma-induced joint bleeding is often seen in children and adults with severe hemophilia. The impact of hemophilic arthropathy is wide-ranging. Many patients miss school or work and require assistive devices for ambulation or completion of activities of daily living.29 Although the pathogenesis of the resultant arthropathy is multifactorial, iron is the most likely trigger of the degenerative changes.
Hemophilic Synovitis
A normal synovial lining is thin, consisting of only 1 to 2 cell layers. After repeated bleeds, the synovium hypertrophies and becomes villous with intense neovascularization.30,31 Histologic examination shows iron deposits within the synovium and in subsynovial areas.32 Diffuse lymphocyte and macrophage infiltrates are observed, particularly in areas of iron deposition.31,32 The relative roles of angiogenesis, inflammatory cytokines, and proto-oncogene influence on the initiation and propagation of the synovial changes seen in hemophilic joint disease are not known. Clinically, however, joints with hypertrophic synovium are predisposed to recurrent bleeding and rapidly progressive joint damage. Decreased use of these abnormal joints leads to progressive muscular atrophy, stiffness, osteoporosis, and a self-perpetuating destruction of the joints.
Two scoring systems exist for evaluating plain radiographs of patients with hemophilia. The Arnold-Hilgartner score seen in eTable 436.5 was developed based upon the theory that blood-induced joint damage occurs in a progressive manner, from early soft tissue changes to later bony changes.33-39 The Pettersson scale in eTable 436.6 was developed with the assumption that these changes are additive in nature and can occur concomitantly.40 While neither scale has been validated in clinical trials, the Pettersson scale was adopted by the World Federation of Hemophilia, and current evidence suggests that the additive approach is likely to be more valid than the progressive approach.10 Unfortunately, physical findings are often subtle in the early stages of joint disease, and plain radiographs do not adequately evaluate soft tissue changes. Therefore, MRI may be required to demonstrate hemosiderin deposition and or hypertrophic synovium. To that end 2 MRI scoring systems were proposed. The Denver scale demonstrated in eTable 436.7 was a progressive scale whereas the European scale (eTable 436.8) relied on an additive approach.41,42 Subsequently, the scales have been merged into a compatible scale that is undergoing revision and validation.43 It remains to be seen if MRI can be used in a predictive manner.
eTable 436.5. Hemophilic Joint Radiographic Staging (Arnold-Hilgartner Scale)
Type of Change
Normal joint 0
No skeletal abnormalities, soft tissue swelling present I
Osteoporosis and overgrowth of epiphyses; no erosions; no narrowing of joint cartilage space II
Early subchondral bone cysts; squaring of the patella; widening of intercondylar notch of distal femur or humerus; cartilage space preserved III
Findings of stage III more advanced; joint space narrowed IV
Fibrous joint contracture; loss of joint cartilage space, marked enlargement of the epiphyses, and substantial disorganization of the joint V
eTable 436.6. Hemophilic Joint Radiographic Scale (Pettersson Scale)
Absent 0
Present 1
Enlarged Epiphysis
Irregular Subchondral Bone
Partly involved 1
Totally involved 2
Narrowing of Joint Space
Joint space > 1 mm 1
Joint space < 1 mm 2
Subchondral Cyst Formation
1 cyst 1
Erosions at Joint Margins
Incongruence of Joint Surfaces
Slight 1
Pronounced 2
Joint Deformity (angulation and or displacement between the articulating bony ends)
eTable 436.7. Hemophilia Joint MRI Staging (Denver Scale)
Effusion/Hemarthroses
moderate 2
Synovial Hypertrophy/Hemosiderin
Cyst/Erosion
one cyst or partial surface erosion 7
>one cyst or full surface erosion 8
Cartilage Loss
<50% 9
>50% 10
eTable 436.8. Hemophilia Joint MRI Score (European Scale)
Subchondral Cysts (part A)
Present in at least 1 bone
Present in at least 2 bones
More than 3 cysts in at least 1 bone
More than 3 cysts in at least 2 bones
Largest size more than 4 mm in at least 1 bone
Largest size more than 4 mm in at least 2 bones
Irregularity/Erosion of Subchondral Cortex (part A)
Involves more than half of joint surface in at least 1 bone
Involves more than half of joint surface in at least 2 bones
Chondral Destruction (part A)
Full-thickness defect in at least 1 bone
Full-thickness defect in at least 2 bones
Full-thickness defect involves more than one third of joint surface in at least 1 bone
Full-thickness defect involves more than one third of joint surface in at least 2 bones
Effusion/Hemarthrosis (e)
Hypertrophic Synovia (s)
Hemosiderin (h)
equivocal
The part A component has a maximum value of 16. The e, s, and h components are evaluated separately according to a 5-point scale (0–5). The maximum score is 16 (4:4:4).
Arthroscopic synovectomy has been used in children and adults with hemophilia to remove abnormal synovium and allow limited cartilage repair. The procedure is fairly expensive due to the need for aggressive factor replacement but has proved effective in reducing the frequency of joint hemorrhage.44-46 Loss or limitation of range of motion can complicate the procedure if aggressive physical therapy is not employed.46 Although bleeding rates are greatly reduced, articular changes can continue if significant cartilage damage was present at the time of the procedure.45 It remains to be seen if early synovectomy can prevent deterioration.
Radionuclide synovectomy/synoviorthesis has also been employed with good results to address recurrent bleeding in affected joints. In this procedure, a radioactive compound is injected into the joint and leads to subsequent synovial sclerosis. Multiple agents with different characteristics have been used with similar results.47,48 This procedure is less expensive than arthroscopic synovectomy but has the additional risk of radiation exposure. Two cases of leukemia have been reported in hemophilia patients who had this procedure, but causality is unclear49.
von Willebrand disease (vWD) was first described in 1926 by Erik von Willebrand in a group of patients with an autosomal inherited bleeding pattern. It is characterized by deficiency of vWF and is the most common inherited bleeding disorder, approaching an incidence of 0.1% to 1% in its most common manifestation (type 1 von Willebrand disease). Two major functions of the vWF protein are to mediate adhesion of platelets to sites of vascular injury via interaction with platelet glycoprotein Ib and to the subendothelial matrix (collagen). It also serves as a carrier protein for FVIII. vWF can only mediate platelet adhesion normally if it is assembled into large multimers. Accordingly, defects in vWF may cause bleeding by impairing both platelet adhesion and (more rarely) blood clotting. The clinical manifestations vary but usually comprise mucosal bleeding symptoms (bruising, nose bleeding, mouth/teeth-related bleeding, and menorrhagia) and bleeding immediately after invasive procedures or surgery. Von Willebrand disease is thought to be caused by an inherited mutation in the vWF gene located on chromosome 12p, but there may also be certain modifying factors and/or genes, especially in type 1 von Willebrand disease, that modulate its expression (eFig. 436.3). The disorder typically demonstrates an autosomal dominant inheritance pattern, although several subtypes are inherited in a recessive or doubly heterozygous fashion.50 The classification for von Willebrand disease (Fig. 436-1) includes 3 major categories: partial quantitative deficiency (type 1), qualitative deficiency (type 2), and total deficiency (type 3). Qualitative abnormalities (type 2) are further divided into four variants or subtypes (2A, 2B, 2M, and 2N).
Protein structure and its relation to von Willebrand disease variant subtype mutation location. Von Willebrand factor (VWF) contains specific domains that have been shown to have discrete functions, including (1) the interaction with factor VIII (D´ and D3), glycoprotein Ib (A1), collagen (a1 and A3), ADAMTS13 (A2), platelet glycoprotein IIb/IIIa (C1), and furin (D2-D´). The lower panel localizes hot spots for DNA mutations that cause VWF variants that tend to correlate with the functional domains. The variants include type 2A1 (2A variants that fail to multimerized properly), type 2N (decreased interaction with factor VIII), type 2B (increased binding to platelet glycoprotein Ib), type 2M (decreased binding to glycoprotein Ib but with normal VWF multimers), type 2A2 (2A variants caused by increased spontaneous proteolysis of VWF by ADAMTS13, a metalloprotease abnormal binding to collagen), and type 1C (type 1 von Willebrand disease variant with accelerated VWF clearance).
(Courtesy of RR Montgomery.)
Summary of von Willebrand disease (vWD) types, types 1, 3, 2A, 2B, 2M, 2N) and absence or defective platelet glycoprotein Ib receptor for vWF, platelet-type vWD (PT-vWF), or Bernard Soulier Syndrome (BSS). The lower portion illustrates the vWF multimers that are identified by sodium dodecylsulfate-agarose gel electrophoresis of vWF for each of these variants. BT, bleeding time; Conc, concentrate; LD-RIPA, ristocetin-induced platelet aggregation to low-dose ristocetin; N, normal; PFA, platelet function analyzer; Tx, treatment; vWF:Ag, von Willebrand factor antigen; vWF:RCo, vWF activity by ristocetin cofactor assay.
(Source: Courtesy of RR Montgomery.)
The clinical history is the most important criterion used in establishing a diagnosis of von Willebrand disease.51 Without a history of significant cutaneous or mucosal bleeding in the patient or a family history of bleeding, it is difficult to make a diagnosis. However, children as a group often have not been carefully questioned nor have they been hemostatically stressed; therefore, an underlying bleeding disorder might be missed. Laboratory studies are directed at documenting von Willebrand factor (vWF) deficiency or qualitative defects in vWF. Screening tests (prothrombin time, activated partial thromboplastin time, fibrinogen, thrombin time, and platelet function analyzer) are often normal, so specific testing for von Willebrand disease must be performed. The von Willebrand disease screening tests include von Willebrand factor antigen, ristocetin cofactor, FVIII activity, and vWF multimers tests. Abnormal values for von Willebrand factor antigen, ristocetin cofactor, and FVIII activity are usually less than 0.5 IU/dL (50%).52 There are a number of modulating factors that are associated with lower vWF levels, such as blood type O and hypothyroidism.53 Accordingly, for levels of 30% to 50%, caution must be exercised in rendering a diagnosis, particularly if the bleeding symptoms are minimal. Certain physiologic conditions such as pregnancy, the menstrual cycle, exercise and stress (blood drawing, bleeding, or acute infection) may elevate the vWF level. Conversely, if the patient has definite bleeding symptoms and levels are above 50%, these results may have been confounded by some of the previously described variables, and testing should be repeated in a carefully controlled setting.
Other causes of acquired low VWF levels include Wilms tumor, ventricular septal defects, valvular heart disease (eg, aortic stenosis), and hemangiomas. Also, if a patient has bleeding symptoms in the face of several normal VWF tests, one should consider other causes, such as FXI deficiency, congenital or acquired platelet function defect, collagen defect (eg, Ehlers Danlos syndrome), or plasminogen activator inhibitor 1 deficiency.
Type 1 von Willebrand Disease
Type 1 von Willebrand disease accounts for more than 75% to 80% of patients with von Willebrand disease and is caused by partial, quantitative vWF deficiency with proportional reduction in all the von Willebrand disease screening tests.54Unlike patients with type 2 disease, many patients with type 1 von Willebrand disease do not have a defined gene mutation. Neonates with type 1 disease rarely bleed, and establishment of the diagnosis is difficult due to high levels of vWF in the fetus and newborn. It is important to recognize a form of type 1 von Willebrand disease that has increased clearance (half-life < 1–2 hours) of the vWF (von Willebrand disease Vicenza).55 Usually, this type of von Willebrand disease is associated with a VWF less than 15 IU/dL at baseline and exaggerated VWF levels 15 to 30 minutes after desmopressin administration. Identification of von Willebrand disease Vicenza may mandate treatment with FVIII/VWF concentrates in the trauma or surgical setting.
A qualitative abnormality of the von Willebrand factor (vWF) protein with a disproportionate reduction of ristocetin cofactor compared to von Willebrand factor antigen is the hallmark of the type 2 von Willebrand disease defect, which accounts for 15% to 20% of patients with von Willebrand disease. Often, there is a defective vWF multimeric pattern. Most type 2 von Willebrand disease variants have known genetic mutations.56
Type 2a Von Willebrand Disease
On laboratory testing, a disproportionately low ristocetin cofactor relative to von Willebrand factor antigen reflects the decreased affinity of vWF for platelets due to an absence of large vWF multimers. Type 2A von Willebrand disease is transmitted as a dominant disorder. The loss of large and intermediate-sized vWF multimer forms is due to either impaired protein production or by proteolysis from the ADAMTS-13 metalloprotease. This type accounts for 10% to 12% of von Willebrand disease cases.
Type 2b Von Willebrand Disease
Type 2B von Willebrand disease occurs in 3% to 5% of von Willebrand disease subjects and is characterized by increased affinity of the abnormal vWF for the platelet glycoprotein Ib, followed by clearance of both the higher-molecular-weight multimers of vWF and platelets. The ristocetin cofactor is not as reduced as compared with von Willebrand factor antigen as seen in type 2A von Willebrand disease. The thrombocytopenia seen in type 2B disease may be intermittent and often is exacerbated by stress, infection, or pregnancy. Type 2B von Willebrand disease may initially be misdiagnosed as ITP or a more rare type of von Willebrand disease known as pseudo or platelet-type von Willebrand disease. In platelet-type von Willebrand disease, the defect is in the platelet (glycoprotein Ib receptor) and not in the vWF. The diagnosis of type 2B von Willebrand disease depends upon aggregation to low doses of ristocetin used in platelet aggregation testing.
Type 2m Von Willebrand Disease
von Willebrand disease type 2M occurs in 1% to 2% of the von Willebrand disease population and is due to decreased affinity to glycoprotein Ib, the opposite of type 2B von Willebrand disease. Laboratory results reveal a disproportionate decrease (approximately 50%) of ristocetin cofactor compared with von Willebrand factor antigen and a normal vWF multimer pattern.
Type 2n Von Willebrand Disease
Mutations that selectively inactivate the FVIII-binding site on vWF produce an autosomal recessive von Willebrand disease phenotype in which the platelet-dependent functions of vWF are preserved, but FVIII levels are low (< 10%). This defect occurs in 1% to 2% of the von Willebrand disease population and is known as type 2 Normandy. These patients may be misdiagnosed as having hemophilia A, although the inheritance pattern suggests an autosomal pattern. Test results typically show near-normal vWF levels and a prolonged activated partial thromboplastin time secondary to the low FVIII. Definitive diagnosis is made by demonstrating lack of effect of recombinant FVIII infusion, FVIII-binding studies, and/or molecular studies that confirm the type 2N mutation in the vWF gene.
This type of von Willebrand disease is characterized by the complete absence of vWF, with no functional activity and no antigenic protein. It is inherited as a recessive disorder. FVIII is in the moderate hemophilia range (3–5% FVIII activity). This type of von Willebrand disease is extremely rare and occurs in approximately one in 1 × 106 individuals.
Treatment of von Willebrand Disease
For minor bleeding (nose and mouth related), DDAVP and/or antifibrinolytic therapy are recommended.57 Administration of a concentrated intranasal formulation of desmopressin is often useful for home therapy of mild bleeding complications or for menorrhagia. For major bleeding or surgery, intravenous DDAVP or FVIII/vWF-containing concentrates are used. Repeated doses of DDAVP may result in tachyphylaxis; therefore, dosing is generally given every 24 to 48 hours as an inpatient and usually for only 3 days in the outpatient setting. Facial flushing is a common side effect. Blood pressure and serum sodium should be monitored, and patients should be fluid restricted to slightly below maintenance levels to avoid hyponatremia and possible seizures. This complication is most frequent in infants or in patients receiving excessive intravenous fluids.
Type 1 von Willebrand disease patients with an inadequate response to DDAVP, most patients with type 2 von Willebrand disease variants, and those with type 3 von Willebrand disease must be treated with virally inactivated FVIII/vWF-containing concentrates. Some patients with types 2A and 2M disease will have a favorable response to DDAVP, but the duration of response is often shorter than in patients with type 1 von Willebrand disease. In patients with type 2B von Willebrand disease, DDAVP releases the abnormal vWF from endothelial cells and may worsen the thrombocytopenia. Platelet-type von Willebrand disease should be treated with platelet concentrates. Transfusion with fresh-frozen plasma or cryoprecipitate should no longer be used because these products (particularly fresh-frozen plasma) do not contain enough vWF and cannot be virally inactivated (cryoprecipitate).
Factor VII is a 50-kDa, vitamin K–dependent serine protease that is produced in the liver and circulates in the blood at a concentration of 0.5 μg/mL. The half-life of FVII is very short at 3 to 4 hours. Deficiency is rare, with a prevalence of 1:500,000. The FVII gene is located on chromosome 13 (13q34) and is inherited in an autosomal recessive fashion. Homozygotes and compound heterozygotes often have levels less than 0.01 to 0.03 U/mL and can have a severe bleeding phenotype similar to classical hemophilia, whereas heterozygotes with levels around 0.5 U/ml are typically asymptomatic. In the majority of patients, FVII deficiency is associated with a mild bleeding phenotype characterized primarily by easy bruising, epistaxis, menorrhagia, gum bleeding, and bleeding with trauma or surgery. More severe phenotypes are at risk for bleeding like that seen in classical hemophilia, including hemarthrosis and intracranial hemorrhage. An acquired deficiency of FVII is more common than an inherited deficiency and can be seen in vitamin K deficiency, liver disease, and disseminated intravascular coagulation. FVII has the shortest half-life among the coagulation factors, thus FVII deficiency occurs earlier in the course of a disease process than other acquired factor deficiencies.58-61 Isolated prolongation of the prothrombin time is found in the initial workup in the patient with FVII deficiency and is confirmed with a low FVII activity level. Isolated FVII deficiency is differentiated from a combined deficiency of the vitamin K–dependent proteins by a normal activated partial thromboplastin time. First-line treatment for bleeding in FVII deficiency is recombinant FVIIa at a dose of 20 to 30 μg/kg.62 A single dose may be sufficient for mild to moderate bleeding or a minor surgical procedure. For most surgical procedures and severe bleeding, doses need to be given every 4 to 6 hours. Antifibrinolytic agents such as tranexamic acid and ε-aminocaproic acid may be beneficial for mucosal bleeding.
Prothrombin (factor II) is a 72-kDa, vitamin K–dependent glycoprotein with a plasma concentration of approximately 100 μg/mL. It is synthesized in the liver and is the inactive zymogen of thrombin, a serine protease. Homozygous prothrombin deficiency is exceedingly rare, occurring in approximately 1 in 1 million to 2 million people. The prothrombin gene is found on chromosome 11p11.2, and the deficiency is inherited in an autosomal recessive fashion. The half-life is approximately 3 days. Acquired prothrombin deficiency can occur in vitamin K deficiency, liver disease, warfarin therapy, and in the presence of inhibitors similar to those seen with the lupus anticoagulant.58-60
Factor V is a 330-kDa nonenzymatic cofactor that is synthesized in both hepatocytes and megakaryocytes, with 80% being secreted and 20% being stored in platelet α-granules. Homozygous FV deficiency is very rare, occurring at a rate of 1 in 1 million. The FV gene is found on chromosome 1q24.2, and the deficiency is inherited in an autosomal recessive fashion. The half-life is 36 hours.58,59,63
Factor X is a vitamin K–dependent glycoprotein that is synthesized in the liver as an inactive zymogen and circulates at a concentration of 8 to 10 μg/mL. Homozygous FX deficiency has a prevalence of 1 in 500,000. The gene is found on chromosome 13q34, and the deficiency is inherited in an autosomal recessive fashion. The half-life is 40 hours.58-60
Factors II, V, and X are essential parts of the common pathway of coagulation, and deficiencies in any of these factors can lead to prolongation of the prothrombin time and activated partial thromboplastin time. The finding of a prolonged prothrombin time and activated partial thromboplastin time that corrects when mixed with normal plasma suggests a factor deficiency, thus individual factor levels should then be evaluated. Most clinical laboratories use functional assays to test for factor levels. Antigen testing can be performed using an immunoassay and can be useful in separating type I and type II deficiency. Type I, or hypoproteinemia, occurs when there is a decreased level of normally functioning protein, characterized by a proportional decrease in protein antigen and activity. Type II, or dysproteinemia, occurs when there is a normal antigen level but a decreased level of activity.
Homozygous or compound heterozygous defects in the factor II, V, or X genes can lead to moderate to severe bleeding symptoms, with patients having FX deficiency more likely to manifest severe symptoms. Given the small number of cases reported in the literature, the genotype/phenotype correlation is difficult to ascertain, but In general, lower levels of protein are associated with more severe bleeding. Reported bleeding symptoms include easy bruising, mucosal bleeding, surgical bleeding, and trauma-related bleeding, whereas hemarthroses and intracranial hemorrhage are less common. Heterozygotes are typically asymptomatic; however, easy bruising, mucous membrane bleeding, and bleeding with surgery have been reported.58,59,63,64 Acute bleeding episodes in patients with these factor deficiencies can be treated with fresh-frozen plasmaat 15 to 20 mL/kg, which will usually raise the factor level by 25%. For surgical procedures or more severe bleeding episodes, a loading dose of 15 to 20 mL/kg of fresh-frozen plasma followed by 3 to 6 mL/kg every 12 to 24 hours is usually adequate for hemostasis. Bleeding symptoms as well as factor levels may be followed to guide replacement. For FII or X deficiency, another treatment option is a prothrombin complex concentrate at a dose of 20 to 30 IU/kg based on FIX units. Platelets can also be given for FV deficiency, potentially targeting FV to the site of bleeding. No pure factor II, V, or X concentrates are available. Antifibrinolytic therapies may be administered orally or intravenously to treat mucosal bleeding, with or without factor replacement. Hormonal therapy with estrogens and/or progesterones may help reduce menstrual blood loss in patients with menorrhagia. Prophylaxis with once-weekly home administration of prothrombin complex concentrates for factor II or X deficiency or FFP (fresh-frozen plasma) for factors II, V, or X deficiency has been reported for patients with severe disease.58-60
Combined deficiencies of the vitamin K–dependent proteins, factors II, VII, IX, and X, can occur when there is an abnormality in the gamma-glutamyl carboxylase gene or the vitamin K epoxide reductase complex. In the first months of life, prothrombin deficiency and FX deficiency must be differentiated from hemorrhagic disease of the newborn, in which all of the vitamin K–dependent factors are low. A combined deficiency of FV and VIII also occurs at a frequency of 1 in 1 million. This combined deficiency is due to a mutation in the LMAN1 gene found on chromosome 18, which encodes a transmembrane protein that resides in the endoplasmic reticulum and Golgi and acts as a chaperone in the intracellular transport of both factor V and factor VIII. Mutations in the MCFD2 gene and protein that acts as a cofactor for LMAN have also been described.
Fibrinogen is a 340-kDa glycoprotein that is primarily synthesized in the liver and has a plasma concentration of 200 to 400 mg/dL. Fibrinogen is also synthesized in megakaryocytes and stored in the α-granules of platelets. It has a half-life of 4 days and hemostatic level of approximately 50 mg/dL. It is made up of 2 copies each of 3 different chains (α, β, and γ), which are linked by disulfide bridges. When initiated by a hemostatic challenge, the coagulation cascade produces thrombin that then cleaves fibrinogen to fibrin, allowing polymerization and formation of a fibrin clot.This clot is further stabilized by FXIIIa that cross-links fibrin. Fibrinogen from the platelet α-granules serves as a bridge between glycoprotein IIb/IIIa receptors on the platelet surface during platelet aggregation. A different gene is responsible for the synthesis of each of the fibrinogen chains, α, β, and γ. Mutations in the fibrinogen genes may be inherited in an autosomal recessive or an autosomal dominant fashion. Homozygotes or compound heterozygotes for severe mutations have afibrinogenemia in which no fibrinogen is produced. Patients with hypofibrinogenemia have a decreased amount of a normal fibrinogen protein. Dysfibrinogenemia typically results from missense mutations inherited in an autosomal dominant fashion that alter the structure of the fibrinogen protein leading to different functional properties. The incidence of afibrinogenemia is approximately 1 in 1 million people. The incidence of dysfibrinogenemia is unknown.58,59,63,65 Patients with afibrinogenemia have an abnormal prothrombin time, activated partial thromboplastin time, and bleeding time due to fibrinogen's central role in clot formation. The thrombin time, which measures thrombin-induced conversion of fibrinogen to fibrin, is also prolonged. The prothrombin time and activated partial thromboplastin time are typically normal until fibrinogen levels are less than 100 mg/dL. Prolonged thrombin and reptilase clotting times are seen in dysfibrinogenemias, and immunoassays showing discrepant protein activity and antigen levels confirm the diagnosis. Fibrinogen is an acute phase reactant, and significant elevations may occur during periods of stress. Age, gender, race, smoking, obesity, and pregnancy are also known to alter fibrinogen levels. Hyperfibrinogenemia is a risk factor for stroke and coronary artery disease. Acquired causes of hypofibrinogenemia are liver disease, ascites, disseminated intravascular coagulation, and l-asparaginase therapy.
Clinical Features
Manifestations in patients with afibrinogenemia commonly include umbilical cord and mucosal bleeding, but joint and muscle bleeding, intracranial hemorrhage, and bleeding with surgery or trauma occur as well. Patients with hypofibrinogenemia typically have a less severe bleeding phenotype, with hemorrhage after surgery and mucocutaneous bleeding, including menorrhagia, being most common. Women with afibrinogenemia and hypofibrinogenemia have an increased risk of miscarriage. Splenic rupture has been reported in patients with afibrinogenemia.63,66 Patients with dysfibrinogenemia have a diverse clinical phenotype, ranging from asymptomatic to severe bleeding, delayed wound healing, and/or thrombosis, although there is some correlation between molecular defect and clinical phenotype. Clinical phenotypes include asymptomatic patients diagnosed because of family history or laboratory abnormalities, bleeding symptoms, thrombosis, and both bleeding and thrombosis. Patients may have hemorrhage after surgery or trauma. They also may have umbilical cord bleeding and intracranial hemorrhage, with these more severe symptoms being associated with lower functional fibrinogen levels. Delayed wound healing has also been reported.
No fibrinogen concentrates are currently available in the United States, although they are used in Europe. Cryoprecipitate, which contains more fibrinogen than fresh-frozen plasma with 200 to 250 mg per bag, is commonly used for treatment and prophylaxis. Typical dosing is 1 bag per 5 kg followed by 1 bag per 15 kg as needed to keep the fibrinogen level above 80 mg/dL. Rarely, fatal thrombosis has been associated with replacement therapy. For mucosal bleeding, treatment with an antifibrinolytic agent such as tranexamic acid or ε-aminocaproic acid is helpful. Antibody development to fibrinogen replacement therapy is rare, but anaphylaxis has been reported.
FXIII deficiency is an autosomal recessive disorder with a prevalence of approximately 1 in 2 million people. FXIII has a half-life of 10 days and levels of 2% to 3% are thought to be adequate for hemostasis. When activated, FXIII cross-links the fibrin clot, which is then resistant to fibrinolysis. Patients with FXIII deficiency can manifest moderate to severe bleeding symptoms. Most patients present early in life with severe or life-threatening bleeding. Bleeding from the umbilicus shortly after birth is seen in 80% of untreated patients, and 30% of patients have intracranial hemorrhage that can be spontaneous or follow minimal trauma.67 Excessive bruising, muscle bleeding, joint bleeding, menorrhagia, and bleeding following surgery or trauma also occur. Bleeding symptoms are often delayed. Recurrent miscarriage is seen unless treatment is given during pregnancy. There are also reports of delayed wound healing. The routine screening tests for hemostasis are all normal in FXIII deficiency, including the prothrombin time, partial thromboplastin time, bleeding time, and thrombin time. As a qualitative screening test, clot solubility is increased in the presence of 5 M urea, 2% acetic acid, or 1% monochloroacetic acid in patients with severe FXIII deficiency. Confirmatory testing with FXIII activity levels can be performed in specialized laboratories.58,59,63,68 Patients with FXIII deficiency can be treated with FXIII concentrates as well as fresh-frozen plasma and cryoprecipitate. Fibrogammin P (from CSL Behring Ltd.) is a plasma-derived FXIII heterotetramer concentrate that is approved in Europe and is available by investigational new drug application (IND) in the United States. A recombinant FXIII product is also in clinical trials.69 Given the high risk of severe or life-threatening bleeding, the long half-life, and the low levels of FXIII needed for hemostasis, patients with severe FXIII deficiency are ideal candidates for prophylaxis. Acquired deficiencies of FXIII can occur secondary to liver disease, leukemia, Henoch-Schönlein purpura, and a variety of autoimmune disorders.
In the fibrinolytic system, plasminogen is activated primarily by tissue plasminogen activator to plasmin, which in turns breaks down both fibrin and fibrinogen. The fibrinolytic system is regulated by plasminogen activator inhibitor-1, which inhibits the activation of plasminogen, and by α2-antiplasmin, which inhibits plasmin. Autosomally inherited deficiencies in plasminogen activator inhibitor 1 and α2-antiplasmin result in unopposed fibrinolysis by plasmin and lead to ineffective hemostasis and bleeding. Only a limited number of patients have been reported in the literature for each disorder. Bleeding symptoms in homozygotes range from moderate to severe and include soft tissue hematomas, mucocutaneous bleeding, hemarthroses, and bleeding following surgery or trauma. Heterozygotes are typically asymptomatic, but mild bleeding symptoms have been reported. All of the routine coagulation tests, including the prothrombin time, partial thromboplastin time, bleeding time, and thrombin time, are normal. When patients have an unexplained bleeding phenotype, both plasminogen activator inhibitor 1 and α2-antiplasmin levels may be checked. Treatment with anti-fibrinolytic agents prevents the binding of plasminogen to fibrin, thereby inhibiting fibrinolysis and stabilizing the fibrin clot. These products, such as tranexamic acid or ε-aminocaproic acid, may be given orally or intravenously to treat patients with bleeding symptoms or for prophylaxis prior to invasive procedures.70-72
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37.Hooiveld MJ, Roosendaal G, Vianen ME, van den Berg HM, Bijlsma JW, Lafeber FP. Immature articular cartilage is more susceptible to blood-induced damage than mature articular cartilage: an in vivo animal study. Arthritis Rheum. 2003;48(2):396-403.
38.Hooiveld M, Roosendaal G, Wenting M, van den Berg M, Bijlsma J, Lafeber F. Short-term exposure of cartilage to blood results in chondrocyte apoptosis. Am J Pathol. 2003;162(3):943-951.
39.Arnold WD, Hilgartner MW. Hemophilic arthropathy. Current concepts of pathogenesis and management. J Bone Joint Surg Am. 1977;59(3):287-305.
40.Pettersson H, Nilsson IM, Hedner U, Norehn K, Ahlberg A. Radiologic evaluation of prophylaxis in severe haemophilia. Acta Paediatr Scand. 1981;70(4):565-570.
41.Lundin B, Pettersson H, Ljung R. A new magnetic resonance imaging scoring method for assessment of haemophilic arthropathy. Haemophilia. 2004;10(4):383-389.
42.Kilcoyne RF, Nuss R. Radiological assessment of haemophilic arthropathy with emphasis on MRI findings. Haemophilia. 2003;(9 suppl 1):57-63, discussion 63-54.
43.Lundin B, Babyn P, Doria AS, et al. Compatible scales for progressive and additive MRI assessments of haemophilic arthropathy. Haemophilia. 2005;11(2):109-115.
44.Journeycake JM, Miller KL, Anderson AM, Buchanan GR, Finnegan M. Arthroscopic synovectomy in children and adolescents with hemophilia. J Pediatr Hematol Oncol. 2003;25(9):726-731.
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Introducing The Health Research Unit Zimbabwe
21 April 2022 London School of Hygiene & Tropical Medicine London School of Hygiene & Tropical Medicine https://lshtm.ac.uk/themes/custom/lshtm/images/lshtm-logo-black.png
The Zimbabwe LSHTM Research Partnership has officially changed its name to The Health Research Unit Zimbabwe (THRU ZIM). THRU ZIM are committed to improving health and wellbeing across the life-course through research that influences policy & practice. They achieve this by cultivating equitable partnerships and nurturing the next generation of global health leaders in Africa.
Professor Rashida Ferrand, THRU ZIM Director, introduces the unit and explains the reasons for the change.
The Health Research Unit Zimbabwe (THRU ZIM) – why rename from the Zimbabwe LSHTM Research Partnership?
After much deliberation, this change was made in responses to the concerns raised by both our staff and collaborators who wanted our unit to have a clear Zimbabwean identity and our name to reflect our collaboration, not only with the London School of Hygiene & Tropical Medicine (LSHTM), but with a large number of national and international institutions, and the previous name did not reflect this.
For those who aren't familiar with THRU ZIM, could you summarise what The Health Research Unit Zimbabwe does?
We are a unit embedded within the Biomedical Research and Training Institute (BRTI), a not-for-profit research institution registered in Zimbabwe. Our aim is to tackle public health problems of relevance to Zimbabwe and the region, through interdisciplinary observational and interventional research combined with advocacy and engagement with both policy makers and communities. Importantly, strengthening research capacity and training the next generation of global health leaders underpins all our work.
Your vision is "To deliver world-class Africa led research to improve health" – why is this important to you and your unit?
I firmly believe that research can effect step change but for this to happen we need to be embedded within health systems, ask relevant questions and engage with policy makers and communities. Health interventions need to be contextually-relevant and locally owned. For too long, however, the health research agenda and policy for Africa and much of the Global South has been driven by the Global North, and flow of knowledge has been from North to South - a legacy of colonialism. Our vision is to change this and to foster a different model of global health, whereby global health leaders from the South will work in equitable partnership - but not be dominated by - institutions in the global North, and that there will be bi-directional flow of knowledge and wisdom. I would like to stress that "Africa-led" research does not mean working in isolation - what we have achieved over the last decade would not have been possible without the investment – both financial, intellectual and more-of our partners.
Learn more about The Health Research Unit Zimbabwe.
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Una pila de mercurio (también llamada pila de óxido de mercurio, o celda de mercurio) es una batería electroquímica no recargable, una celda primaria.  Las baterías de mercurio utilizan una reacción entre el óxido de mercurio y electrodos de zinc en un electrolito alcalino.  La tensión durante la descarga se mantiene prácticamente constante a 1,35 voltios, y la capacidad es mucho mayor que una batería de carbono de zinc de tamaño similar. Desde el momento de II Guerra Mundial las baterías de mercurio se convirtieron en una fuente de alimentación popular para dispositivos electrónicos portátiles.

Las pilas de mercurio se utilizan en forma de las pilas de botón para relojes, audífonos y calculadoras, y en formas más grandes para otras aplicaciones.

Debido al contenido de mercurio,  y las preocupaciones ambientales resultantes, la venta de las pilas de mercurio está prohibida en muchos países para evitar el envenenamiento por mercurio.  Tanto ANSI y IEC han retirado las estándares para las baterías de mercurio.

Historia

El sistema de baterías de óxido de mercurio-zinc era conocido desde hace más de 100 años,  pero no se utilizó ampliamente hasta 1942, cuando Samuel Ruben desarrolló una célula de mercurio equilibrada que era útil para aplicaciones militares como detectores de metales, municiones y  walkie-talkies. El sistema de la batería tenía las ventajas de una larga vida estable (hasta 10 años) y una salida constante de voltaje. Después de la Segunda Guerra Mundial, el sistema de baterías fue ampliamente aplicado en dispositivos electrónicos pequeños, como marcapasos cardíacos y audífonos. Las baterías de óxido de mercurio se hicieron en una amplia gama de tamaños, desde células de botón en miniatura (usadas para audífonos y relojes de pulsera eléctricos), tipos cilíndricos (aparatos electrónicos portátiles), baterías rectangulares (radios transistores) y grandes embalajes multicelulares (aplicaciones industriales como radio control remoto para sistemas de grúa). En los Estados Unidos, las baterías de óxido de mercurio fueron fabricadas por compañías como  P. R. Mallory and Co Inc (ahora Duracell), Union Carbide Corporation (cuya antigua división de baterías se llama ahora Energizer Holdings), RCA Corporation y Burgess Battery Company.

Referencias

Baterías
Inventos de Estados Unidos del siglo XIX
Ciencia de 1884
Estados Unidos en 1884

redpajama_set_name: RedPajamaWikipedia


text:
State of student politics in Panjab University: Despite sweeping 2015 polls, SOI almost sinks into oblivion
Two years after sweeping the PU student polls, SOI has low-visibility on campus now, primarily due to change of regimes in Punjab.
punjab Updated: Aug 30, 2017 11:42 IST
Ifrah Mufti & Shub Karman Dhaliwal
Hindustan Times, Chnadigarh
(Representative Image)
With Shiromani Akali Dal out of power in Punjab, Students' Organisation of India (SOI) has almost sunk into oblivion on the Panjab University (PU) campus. Before the PU polls last year, SOI leaders used to come in cars with red-beacons atop, senior Akali functionaries as chaperones and gunmen on toes, thus branding them as VVIPs on campus.
Few SOI leaders, namely Vicky Midhukhera, Bheem Waraicha and Robin Brar, were even provided gunmen, allowing them to manoeuvre around the campus flaunting their status.
Punjab connection
Most of the senior SOI leaders hail from Malout, Abohar and Muktsar belt, the home turf of Badals. And ahead of council elections, they have held a string of meetings with SAD president Sukhbir Singh Badal, seeking support.
The leaders had travelled down to Faridkot lately to meet Badal and discuss the poll strategies for this year.
Bunty Romana, who continues to lead SOI, is confident to win the election this time as he claims to have done a lot for the campus students.
"I have observed that situation is really good, not in university only but in colleges too," Romana said.
"PU is dominated by students from Punjab and state of affairs in Punjab affects them. We have also observed that PU students are pro SOI, considering the fact that our leader Sukhbir Singh Badal is a youth icon and there is a lot of hope among the students to later join the party," he added.
'NSUI won't get any advantage this year'
On asking if the change of guards in Punjab will affect the elections this year, Romana said, "Had the government been doing well, it could have favoured the NSUI. But the way current government has failed to fulfil its electoral promises and lost its credibility, NSUI is not getting any advantage this time."
The organisation has seen a couple of senior leaders, including former SOI campus president Karan Randhawa, quitting the party.
Navi Khemkaran, who stood as election in-charge last year, has left and former SOI president University Institute of Engineering and Technology (UIET), Piyush Anand, has moved abroad, thus weakening their hold on the major departments of campus.
Dent in leadership
Randhawa has now joined the newly launched Indian Students' Association (ISA) while Navi is the current president of Panjab University Student Union (PUSU).
The duo were associated with SOI for the last four years and had openly stated that there was no freedom to express their views.
The organisation has brought fresh faces after facing defeat last year. SOI has introduced a 30-member team led by Iqbalpreet Singh Takhar, the last year's winning president of SD College.
"The main cadre which ensured my victory at SD is rigourous campaigning in departments," said Iqbal, who is campaigning at three-year law department.
'We fulfilled all our promises'
Vicky Midukhera, SOI state president, however said, "All of our promises were fulfilled when we were in the council. We were committed to the requirements of students and our former council president is still with us."
"However, the other student organisations on the campus believe that when SOI was in power, their claims to get the ₹10-crore grant had fallen flat," he added.
SAD had launched its youth wing in 2006.
However, SOI fought elections for the first time in 2014 and the party was re-launched after a senior Student Organisation of Panjab University (SOPU) leader joined it. In 2014, SOI lost the president's post by a margin of 58 votes.
When SOI tasted victory
In 2015, the SOI emerged as a winner. The victory margin for the post of president was 1,436 votes, the highest ever.
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Falmey est un village et une commune du Niger.

Références

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Village au Niger


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DevilFoehn News
June 18, 2018 DevilFoehn
Workspace Property Trust Completes $1.275 Billion Loan from JPMorgan Chase Bank, NA
HORSHAM, PA, June 18, 2018 /PRNewswire/– Workspace Property Trust ("WSPT®"), a real estate investment firm led by longtime successful industry veterans Thomas Rizk and Roger Thomas, announced today that it has closed on a $1.275 billionportfolio financing with JPMorgan Chase Bank, NA. The proceeds from this financing will be used to repay existing shorter-term debt, redeem preferred equity interests and for general corporate purposes. The facility was arranged and placed by JP Morgan Chase Bank, NAand closed in less than two months' time from the execution of a term sheet.
"Our ability to enter into this debt facility in both the amount and on the terms we did speaks volumes aboutthe value Workspace has generated in less than two years' time," said Thomas Rizk, WSPT Co-Founder and Chief Executive Officer. "The execution of this refinancing provides a tremendous validation of our strategic focus on suburban office and the strength of the platform that Workspace has created."
Since acquiring its portfolio from Liberty Property Trust, under two separate transactions in December 2015 and October 2016, WSPT has completed over 3 million square feet of leasing transactions; adding significant stability and value to the overall portfolio.
Roger Thomas, Co-Founder, President and Chief Operating Officer, commented, "From the beginning, Tom and I believed in the gravitational pull the suburbs would have on the growing numbers of millennials getting married, forming families and seeking lower costs of living, and better housing and schools, just as every generation before them. Employers are following this migration, resulting in higher rents and occupancy growth in our suburban office markets."
WSPT owns, leases and manages 147 properties and over 9.8 million square feet of premier office and light industrial space in top-rated suburbs in Philadelphia, Minneapolis, Tampa, Phoenix, and South Florida.
About Workspace Property Trust
Workspace Property Trust is a privately held, vertically integrated, full-service commercial real estate company specializing in the development, management, and operation of office and light industrial space. Workspace Property Trust is a partnership among Rizk Ventures, Safanad, Forum Partners, JMP Group, and EverWatch Capital.
Diana Bonner
dbonner@workspaceproperty.com
www.workspaceproperty.com
WORKSPACE PROPERTY TRUST © 2020 | ALL RIGHTS RESERVED