Worrying features dGCS, chest pain, palpitations, abnormal ECG. Causes haemolysed samples (likely if several hours taken to reach lab), renal failure, K+-s paring diuretics (spironolactone, amiloride), ACEi, trauma, burns, excess K+, large blood t ransfusions, Addison \200\231s disease. Symptoms palpitations, dizziness, chest pain. Signs assess haemodynamic stability, irregular pulse, stigmata of renal failure. Investigat ions blds urgent repeat U+E; if K+<7mmol/l with no new ECG changes or the sample is reporte d as haemolysed then await the repeat sample, otherwise follow the treatment plan (b p384); if on digoxin, check levels since digoxin toxicity will worsen hyperkalaemia; ABG for acid osis if acute renal failure ECG initially peaked T waves, later broad QRS and fl at P waves , ultimately VF. Treatment Ca2+ gluconate protects the heart against iK+. Salbutamol and in sulin move K+ into cells to reduce plasma levels in the short term (1 \200\2232h) after whi ch a rebound increase may occur. Furosemide (with IV fl uids if necessary) or Calcium Reson ium (takes 24h, give with lactulose 30ml/6h PO) enhance K+ excretion. If refractory or ac idotic, dialysis may be neces- sary (b p373). Stop any causative or nephrotoxic medication. _OHFP.indb 385 _OHFP.indb 385 30/05/2014 16:18 30/05/2014 16:18 386 CHAPTER 12 Fluids and renal Hyponatraemia (Na+ <133mmol/l) Worrying features dGCS, irritable, seizures, iHR, dBP. Ask about diarrhea, vomiting, abdo pain, tiredness, urine frequency, quan- tity and color, thirst, constipation, SOB, cough, chest pain, weakness, head trauma; PMH heart, liver or ki dney problems; DH diuretics, opioids, antipsychotics, amiodarone, proton pump inhibitors, S SRIs, IV fl uids. Look for assess fl uid balance and volume status (b p380), basal creps, o edema (legs and sacrum), ascites, focal neurology, conscious level (if Na+ <120mmol/l the p atient may become irritable or confused, <110mmol/l there may be seizures or coma). Investi gations blds FBC, U+E, LFT, CRP, plasma osmolality; urine send paired sample for osmolality and Na+; assess underlying cause as follows: Hypovolaemic? p380 Yes No Urine Na+ >20mmol/l? Oedema? Yes No No Yes Hypovolaemia due to renal losses, eg diuretics, Addison \200\231s, salt-losing nephropathy Hypovolaemia due to non-renal losses eg diarrhea, vomiting, fistulae, burns, small bowel ob struction, heat exposure Consider excess 5% glucose or oral fluids, severe hypothyroidism, or SIADH (see box) Consider heart failure, renal failure and nephrotic syndrome, liver failure Fig. 12.2 Assessment of hyponatraemia. Spurious dNa+ (pseudohyponatraemia) can be caused by taking blood from an arm with IV fl uids running, a lipaemic sample (labs should detect th is) or osmotically active substances in the blood, eg in hyperglycaemia. Discuss with lab i f unsure. Syndrome of inappropriate ADH secretion (SIADH) In this condition, inappropriate hypothalam ic release of ADH leads to euvolaemic hyponatraemia. Beware of overcalling this diagnosis, which requires a careful workup: \200 Concentrated urine despite dilute plasma (ie urine osmolality > plasma): generally plasma osmolality <275mosm/kg and urine osmolality >500mosm/kg No recent diuretics \200 Clinical euvolaemia \200 Urine sodium >20mmol/l Causes include malignancy (lung, pancreas, lymphoma), lung infec- tions, CNS infections or vascular event s, drugs (eg SSRIs, tricyclics, carbamazepmine, antipsychotics) or idiopathic. Management r equires fl uid restriction (initially 1l/24h) ADH antagonists (eg demeclocy- cline 300mg /12h PO). Normal adrenal and thyroid function (check TSH and short Synacthen test). OHFP.indb 386 OHFP.indb 386 30/05/2014 16:18 30/05/2014 16:18 387 ELECTROLYTE IMBALANCE Treatment Although acute hyponatraemia (<48h duration) can be rapidly corrected, chronic hy ponatraemia (or where the timecourse is unclear) should be corrected slowly to prevent fl u id overload or osmotic demyelination. Aim for a rise of no more than 10mmol/l/24h. Get seni or help if seizures or coma (the rare situation where it may be necessary to raise Na+ rapi dly by 75mmol/l using hypertonic saline) or if Na+<120mmol/l. In all patients monitor fl ui d balance closely with cath- eter, regular obs and possibly CVP. Repeat U+E daily, or more frequently if neurological signs. Assess cause using Fig. 12.2 and treat accordingly. \200 Hypovolaemic replace lost fl uid with 0.9% saline according to degree of dehydration (b p 382); severe hypovolaemia should be corrected (b p478) and takes precedence over hyponatrae mia. Try to establish the cause of fl uid loss and treat accordingly. Stop diuretics \200 Normovolaemic or mild overload slow 0.9% saline IV eg 1l/8 \200\22310h, Na+ levels should rise over a few days. If urine osmolality >500mOsmol/kg consider SIADH (see box) Oedematous urine Na+ usually <10mmol/l, identify and treat the underlying cause (see relevant chapter). Causes of hyponatraemia covered elsewhere b p373 b p376 b p267 b p313 Heart failure Liver failure Renal failure Nephrotic syndrome Hypernatraemia (Na+ >146mmol/l) Worrying features dGCS, iHR, dBP. Causes fl uid loss (diarrhea, burns, fever, glycosuria eg DM, diabetes insip- idus) or inad equate intake (impaired thirst response in elderly or hypo- thalamic disease); more rarely excess Na+ (iatrogenic, Conn \200\231s syndrome). Symptoms anorexia, nausea, weakness, hype rrefl exia, confusion, dGCS. Signs assess fl uid balance, volume status (b p380), neurologi cal defi cit. Investigations blds plasma osmolality (likely to be raised); urine osmolality (>400mOsmol/kg if fl uid loss, <400mOsmol/kg if excess Na+, normal range 350 \200\2231000m Osmol/kg); consider CT head or MRI if suspect central cause. Treatment cells rapidly adapt to raised osmolality of extracellular fl uid by retention and production of intracellular osmolytes. This prevents osmotic fl uid losses from inside the cell, but if extracellular Na+ concentration rapidly corrected, osmotic forces will now dr ive fl uid into cells, causing lysis resulting in neurological damage and death. Hence aim for slow correction of Na+ (10mmol/l/24h at the very most). Treatment is guided by volume s tatus: \200 Hypovolaemic give 0.9% saline 1l/6h (prevents sudden Na+ shifts) until normovolaemic Normovolaemic encourage oral fl uids or 5% glucose 1l/6h. Monitor fl uid balance and plasma Na+; consider a urinary catheter. _OHFP.indb 387 _OHFP.indb 387 30/05/2014 16:18 30/05/2014 16:18 388 CHAPTER 12 Fluids and renal Hypocalcaemia (corrected Ca2+<2.2mmol/l) Although >99% calcium is stored in bones, and most of the remainder is intracellular, extracellular calcium is critical for neuromuscular and cardiac function. Albumin binds around 40% of extracellular calcium, so hypoalbuminaemia m ay give falsely low recordings of serum calcium; always check the \200\230corrected calciu m \200\231. Gut, renal, and bone calcium han- dling is critically regulated by vitamin D, w hich requires hydroxylation in functioning kidneys and liver to be active, and by PTH. Worrying features dGCS, chest pain, palpitations, dBP, abnormal ECG. Causes vitamin D defi ciency (elderly, Asians, Africans, chronic renal failure, intestinal malabsoprtion eg coeliac, Crohn \200\231s), hypoparathyroid, acute pancreatitis, alkalosis, dMg2+, alcoholism. Symptoms spasm of hands and feet (carpopedal), twitching muscles, tingling around the mouth , fatigue, depression, dry skin, coarse hair. Signs hyperrefl exia, tetany, Trousseau \200\231s (spasm of hand from infl ated BP cuff ) a nd Chvostek \200\231s (unilateral twitching of face from tapping facial nerve 2cm anterior to auditory meatus), dBP, bradycardia, arrhythmias. 3 \210\222, Mg2+, albumin, ALP, PTH, vi tamin Investigations blds U+E, Ca2+, PO4 D ECG prolonged QT, ST abnormalities, arrhythmias. Treatment treat arrhythmias according to b p248. If tetany is severe give 10ml 10% Ca2+ gl uconate IV over 10min. Always assess for and correct coexistent dMg2+. If Ca2+ defi cit is mild and the patient is asymptomatic, monitor. Prolonged dCa2+ will need vitamin D replacem ent and Ca2+ sup- plements, eg Calcichew-D3 Forte one tablet/24h PO. Complications arrhyt hmias, seizures, cataracts, bone fractures. Primary hypoparathyroidism dPTH, despite dCa2+ \200 Causes iatrogenic (neck surgery, irradiation), autoimmune, metal overload 3 \210\222 \200 Investigations dCa2+, dPTH, iPO4 \200 Treatment vitamin D, eg calciferol 1 \200 \2232.5mg/24h PO. Pseudohypoparathyroidism Genetic resistance to PTH, presents with dCa2+ b ut high PTH and dysmorphic features (short stature, strabismus, short 4/5th metacarpals, lo w IQ, obesity);1 treat as hypoparathyroid. Rickets/osteomalacia Rickets is the childhood equivalent of osteomalacia, both characterize d by vitamin D defi ciency or defect in metabolism. \200 Features dCa2+, dPO4 3 \210\222, iALP, decreased urine Ca2+, crush fractures, spontaneous fractures (eg of ribs), rickets rosary (prominent costochondral junctions), lon g bone bowing and Looser \200\231s zones (pseudofractures, perpendicular to cortex, common in femoral/ humeral necks) on X-ray Treatment depends on cause, but usually simply by intake of adequate diet (egg yolk, milk, some fortifi ed cereals); may require calciferol and Ca2+ supplements (eg Calcichew-D3 Fort e one tablet/24h PO). 1 Patients with the morphological appearance of pseudohypoparathyro idism but normal Ca2+ and PTH, are said to have Pseudopseudohypoparathyroidism. This is als o the longest real word in the Oxford English Dictionary. OHFP.indb 388 OHFP.indb 388 30/05/2014 16:18 30/05/2014 16:18 389 ELECTROLYTE IMBALANCE Hypercalcaemia (corrected Ca2+ >2.6mmol/l) yp ) Worrying features dGCS, chest pain, palpita tions, iHR, dBP, abnormal ECG. ( Causes primary/tertiary hyperparathyroidism, malignancy (myeloma, bone metastases, PTH-rela ted peptide secreting tumors), excess vitamin D supplements, sarcoidosis. Symptoms bones (b one pain fractures), stones (renal), moans (depres- sion), groans (abdo pain). Also vomit ing, constipation, weakness, tired- ness, thirst, polyuria, weight loss. Signs hypertension , arrhythmias, dehydrated (shock if severe), cachexia, bony tenderness secondary to a local lesion \200\223 especially along spine. 3 \210\222, ALP; send paired sample Investigation s blds FBC, U+E, Mg2+, Ca2+, PO4 for PTH (may have to be on ice \200\223 discuss with lab) ; consider ESR, serum and urine electrophoresis; ECG short QT, arrhythmias; CXR; bone scan. Treatment depends upon IV fl uids to correct any volume defi cit, then further fl uid rehy dration with coadministration of 40mg/12h PO or IV furosemide; consider catheterisation and CVP monitoring to assess fl uid balance; monitor U+E, Ca2+, and Mg2+ daily. IV bisphosphon ates (eg pamidronate 30mg in 300ml 0.9% saline over 3h) are useful in refractory hypercalca emia. Investigate and treat the cause. Complications renal failure, arrhythmias, osteopenia , renal stones, peptic ulcers, pancreatitis. Primary hyperparathyroidism iPTH from parathyr oid tumor \200 Investigations iPTH, iCa2+, iALP, dPO4 \200 Treatment correct iCa2+ then parathyroidectomy. Secondary hyperparathyroidism iPTH caused by dCa2+; treat the under- ly ing cause of dCa2+ (b p388). Tertiary hyperparathyroidism same presentation and treatment a s primary, but caused by a parathyroid adenoma due to prolonged secondary hyper parathyroid ism. Seen in end-stage renal failure. Myeloma Plasma-cell malignancy secreting monoclonal i mmunoglobu- lins. Presentations include asymptomatic hypercalcaemia, renal failure, bleedin g, infection or fracture. \200 Investigations iESR, iCa2+, normal ALP, often a degree of renal 3 \210\222 failure, monoclonal immunoglobulin band in urine or plasma (>30g/L, or >10% plasma cells on bone marrow biopsy else MGUS b p396) Treatment correct iCa2+ as above and with pamidronate IV; give adequate analgesia. Attempted cure requires bone marrow transplant. Lesions can be treated palliatively with radiotherapy or chemotherapy Complications infection, renal failure, hemorrhage. Paget \200\231s disease Excess bone rem odeling leads to structurally disorganized and weakened bone prone to fracture and deformit y. Typically found in axial bones of elderly. \200 Features iALP, Ca2+ normal (but may be raised if immobile), lytic lesions and coarse trabeculations on X-ray Treatment analgesia, bisphosphonates, surgery for fractures and nerve entrapment Complications fractures, osteoarthritis, osteosarcoma (rare), cranial nerve compression (eg new deafness), high output heart failure. p ( g ) g p Bone mets fi ve cancers commonly metastasise to bone \200\223 these can be remembered as \200\230BLT with Kosher Pickle \200\231 \200 Breast \200 Lung \200 Thyroid \200 Kidn ey \200 Prostate. _OHFP.indb 389 _OHFP.indb 389 30/05/2014 16:18 30/05/2014 16:18 This page intentionally left blank Chapter 13 Hematology 391 Anemia 392 Transfusion of blood products 398 Clotting emergencies 404 Bleeding 405 Anticoag ulation 406 _OHFP.indb 391 _OHFP.indb 391 30/05/2014 16:18 30/05/2014 16:18 392 CHAPTER 13 Hematology Anemia Reduced red blood cell (RBC) mass, usually conveniently approximated as reduced hemo globin concentration (eg 4 <130g/L, 5 <115g/L1). Causes easily divide into 3 basic mechanis ms (reduced RBC production, increased RBC des truction, RBC loss) with clues found in abnor malities of RBC size and shape.p Worrying features Hb<80g/L, SOB, iHR, dBP, dizziness, fainting, lethargy, palpitations, che st pain, dGCS/restlessness. Think about most likely hemorrhage, chronic blood loss (iron-defi - ciency anemia), anemia of chronic disease, renal failure other folate/ B12 defi ciency (coeliac disease, Crohn \200\231s disease, partial gastrectomy, pernicious anemia, elderly, alcoholism), haemoglobi nopathy (b p397), haemolysis, alcoholic liver disease, malignancy/lymphoma/myeloma, myelofi brosis, hypothyroidism dilutional pregnancy, fl uid resuscitation. Ask about any bleeding (eg epistaxis, haematemesis, haemoptysis, haematuria, menorrhagia, melaena, PR bleeding); e vidence of hypoper- fusion dizziness, SOB (exertional/at rest), chest pain, palpitations; c lues to etiology weight loss, change in bowel habit, abdominal cramps, PMH or FH haemoglobi nopathy; DH NSAIDs, trimethoprim, anticon- vulsants, atypical antipsychotics; SH alcohol, v egetarianism, dietary fads. Obs Resting tachycardia or postural BP drop suggest compromise. Look for pallor (conjunctiva, nail beds, tongue), glossitis, mouth ulcers, hepatomegaly, s plenomegaly, lymphadenopathy, jaundice; CVS bruits, signs of active bleeding, signs of hear t failure; PNS peripheral neurop- athy; CNS optic atrophy; PR melaena/blood. Investigations blds FBC (with MCV \200\223 Table 13.1), blood fi lm, iron, fer- ritin and TIBC, serum B1 2 and folate,2 reticulocyte count, direct antiglobulin test (see box), CRP, ESR, U+E, LFT, TFT, LDH, serum electrophoresis; ECG if CVS symptoms; CXR if suspicion of cancer and to hel p explain SOB; other urine Bence Jones protein, OGD, colonoscopy, bone marrow biopsy. See T able 13.2. Treatment Asymptomatic anemia \200 Look hard for a cause; exclude malignancy i n patients >40yr \200 Assess diet (B12: meat, eggs, milk; folate: leafy greens, legumes; iron: meat, legumes, greens) and consider oral supplements (eg vegans). Symptomatic anemia or Hb <80g/L Consider blood transfusion (b p398) and identify precipitat ing cause. Consider blood transfusion (b p398) and identify precipitating cause. Direct ant iglobulin test (Coombs test) This test forms part of any haemolysis screen. Animal antibodi es raised against human immunoglobulins cause RBC clumping in the presence of autoantibodie s already bound to the RBC surface. The indirect antiglobulin test screens the serum of a p otential transfusion recipient for antibodies against donor RBCs. 1 Note since 2013 UK NHS laboratories report Hb in g/L, not g/dl. 2 Always send before any transfusion, since transfusion may correct defi ciencies. OHFP.indb 392 OHFP.indb 392 30/05/2014 16:18 30/05/2014 16:18 393 anemia Table 13.1 Mean cell volume (MCV) in diff erent forms of anemia MCV <76 \202 MCV 77 \200\22395 \202 MCV >96 \202 Iron defi ciency Thalassaemia Haemoglobinopathies Haemolysis Renal failure Sideroblastic an emia Malignancy Anemia of chronic disease Anti-folate drugs (eg methotrexate) Pregnancy Hemorrhage B12/folate defi ciency Alcohol Liver disease Thyroid disease Myelodysplasia Bone marrow failure Table 13.2 Laboratory \201 ndings in diff erent forms of anemia Iron d d i TIBC i d d Ferritin d n or i i MCV d n n Iron defi ciency Chronic disease Haemolysis Abnormalities on the peripheral blood \201 lm (OHCM9 b p322) Irregularly shaped RBCs (liver disease) RBCs of various sizes (megaloblastic anemia/ thalas saemia) Nucleated precursor cells (myelofi brosis/leukemia) Spiculated RBCs seen in renal f ailure Nuclear remnants in RBCs (post-splenectomy) Acanthocytes Anisocytosis Blast cells Echinocytes Howell \200\223Jolly bodies Hypochromic Left shift Leukaemoid react ion Poikilocytes Reticulocytes Right shift Pale RBCs (iron-defi ciency anemia) Immature white cells (infection or marrow infi ltration ) Reactive leucocytosis (infection/burns/haemolysis) Variably shaped cells (iron or B12 defi ciency) Immature RBCs (hemorrhage/haemolysis) Hyper segmented neutrophils (megaloblastic anemia and liver disease) Clumping of RBCs (infection/ infl ammation) Fragmented RBCs (microangiopathic haemolytic anemia) Spherical RBCs (autoimm une or hereditary) RBCs with central staining and outer pallor (liver disease/haemoglobinop athy) Rouleaux Schistocytes Spherocytes Target cells _OHFP.indb 393 _OHFP.indb 393 30/05/2014 16:18 30/05/2014 16:18 394 CHAPTER 13 Hematology Anemia secondary to blood loss (b p478) Symptoms chest pain, palpitations; may be history o f peptic ulcer, recent surgery, trauma, epistaxis, haematemesis, melaena, or menorrhagia. S igns iHR, dBP, postural BP drop, iRR, dGCS/restlessness, shock, pallor, sweating, cold, cla mmy; look at the wound site if post-op; PR: melaena. See Table 13.3. Investigations blds in itially may be normal; Hb, MCV, U+E (iurea out of proportion to icreatinine in upper GI ble ed), LFT, clotting, G+S/ X-match; once stable recheck Hb, reticulocytes; OGD if suspect upp er GI source. Acute treatment (b p478) \200 Lay fl at, elevate legs if hypotensive; give O2 \200 IV access, take bloods, give rapid IV infusion (1l 0.9% saline STAT) \200 If bl eeding site is obvious, apply fi rm pressure and elevate \200 Contact your senior \200 \223 treat the cause (eg return to theater if bleeding from operation site). Table 13.3 Acute blood loss 3Measurement of hemoglobin does not accurately estimate the vol ume of blood loss in the \201 rst few hours after hemorrhage. Hb concentration may be normal initially, with red cells and plasma lost in equal proportio ns. With IV fl uids or normal haemodilution a fall in Hb becomes evident Acute Intermediate During IV fl uid resuscitation Hb and clotting factors are diluted, unmasking loss of RBCs. Even in the absence of IV therapy the body retains salt an d water in this circumstance, resulting in a natural haemodilution Homeostasis regulates th e volume of fl uid in the intravascular compartment and the Hb often rises as the \200\230 clear \200\231 fl uid (colloids/crystalloids) is eliminated. Without IV therapy Hb may rema in low until erythropoiesis generates more RBCs Late Anemia of chronic disease (OHCM9 b p320) Causes infection (eg TB, endocarditis), rheumatoid arthritis, malignancy, liver failure, most chronic diseases. Symptoms fatigue, SOBOE, leth argy; may have very few symptoms/signs. Investigations n MCV, dTIBC/serum iron, n/iferritin . Treatment treat the underlying disease; consider EPO in renal failure. Haemolytic anemia Causes acquired autoimmune, microangiopathic,1 mechanical heart valves, e xtracorporeal circuit, blood transfusion incompatibility, drugs, toxins, burns; hereditary haemoglobinopathy, G6PD defi ciency, red cell membrane disorder (eg spherocytosis). Signs m ild jaundice, murmurs, lymphadenopathy, hepatosplenomegaly. Investigations ibilirubin (unco njugated), reticulocyte count >85 \227109/l (or >2%), iLDH, dhaptoglobin, iurobilinogen. Tr eatment depends upon the cause. Often steroids, immunosuppression splenectomy if autoimmu ne, treat precipitating cause if acquired. 1 Microangiopathic haemolytic anemia refers to d estruction of red cells within capillaries. Schistocytes (fragmented red cells) are seen on a blood fi lm. Causes include disseminated intravascular coagulation (DIC, b p405), HELLP syndrome (b p505), thrombotic thrombo- cytopenic purpura (TTP), and haemolytic uraemic synd rome (HUS). OHFP.indb 394 OHFP.indb 394 30/05/2014 16:18 30/05/2014 16:18 395 anemia Iron-de \201 ciency anemia Iron found in most diets containing adequate meat, legumes or g reens. Causes GI loss (gastroduodenal ulcer, oesophageal varices, IBD, malignancy), menorrh agia, poor diet, malabsorption syndromes, intestinal helminthiasis. Symptoms abdominal pain , melaena or haematochezia, dysphagia, haem- optysis, haematemesis, diarrhea; menorrhagia, epistaxis. Signs pallor, koilonychia, glossitis, angular stomatitis; PR blood/melaena. Inve stigations blds fi lm (microcytic, hypochromic with anisocytosis and poikilocytosis), dseru m iron, dferritin, iTIBC; stool check for fecal occult blood; OGD colonoscopy; CT abdo if frail; video capsule endoscopy if suspect small bowel pathology. Treatment iron supplement s (ferrous sulfate 200mg/8h PO for 2wk, then 200mg/12h PO) \200\223 warn about side eff ec ts: change in bowel habit, black stools, nausea, epigastric pain. IV iron preparations avai lable for those unable to tolerate or absorb oral iron. Transfuse if anemia is severe enoug h to warrant (b p398), fi nd and treat the cause. Treatment with oral iron raises the Hb by 710g/L per week at best. g ( ) Folate/folic acid (vitamin B9) de \201 ciency Folate found in spinach/green vegetables, nu ts, liver, yeast. Body stores are small and depleted within weeks if dietary intake becomes inadequate. Causes malabsorption alcohol, coeliac disease, Crohn \200\231s disease, tropic al sprue; irequirement pregnancy, DM, lymphoma, malignancy; drugs anti- convulsants, trimet hoprim, methotrexate. Symptoms breathlessness, fatigue, headaches. Signs glossitis, other f eatures of anemia. Investigations blds B12, folate, iMCV, look for malabsorption (b p308). Treatment treat the cause; folic acid 5mg/24h PO for 4mth. For chronic haemolysis give long term, but exclude and treat any concurrent B12 y defi ciency as this may worsen B12 defi c iency neuropathy. y y y If planning pregnancy, folate should be taken 0.4mg/24h PO until 12/40 to reduce risk of fe tal neural tube defects. Vitamin B12 de \201 ciency Vitamin B12 found in liver, kidney, fi sh, chicken, dairy produ cts, eggs. Extensive total body stores and recycling from enterohepatic circulation means n utritional defi ciency may take several years to manifest in the absence of other GI pathol ogy: suspect pathology if dB12. Causes poor dietary intake, pernicious anemia, malabsorptio n (as for folate defi ciency), stomach/bowel resection, Crohn \200\231s disease. Symptoms s ensory neurological defi cit, autoimmune disorders (eg vitiligo, infectious mononucleosis, Addison \200\231s disease), dementia. Signs sore mouth (glossitis, angular cheilosis, mouth ulcers), neurological defects (peripheral neuropathy, optic atrophy), jaundice. Investigat ions blds B12, folate, iMCV, blood fi lm, intrinsic factor/gastric pari- etal cell antibodi es;1 imethylmalonic acid (MMA). Treatment dietary advice, hydroxocobalamin 1mg/72h IM for 2 wk, then 1mg/3mth IM as maintenance dose. 1 Gastric parietal cell antibodies sensitive (+ve in >90% with autoimmune gastritis, the end result of which is pernicious anemia), but not specifi c (+ve in 5 \200\22310% of healthy i ndividuals). Intrinsic factor antibodies are specifi c but less sensitive (+ve in 50 \200 \22370%). _OHFP.indb 395 _OHFP.indb 395 30/05/2014 16:18 30/05/2014 16:18 396 CHAPTER 13 Hematology Leukemia (OHCM9 b p346; see Table 13.4) Table 13.4 Epidemiology of common forms of leukemia Type Acute Patient 2 \200\2234yr >60yr Old>young, post-chemo 30% 5yr survival 60% 5yr survival 90% 5yr survival Prognosis Children 85% cure Elderly <20% cure Lymphoblastic (ALL) Myeloid (AML) Lymphocytic (CLL) >40yr, often male Myeloid (CML) Chronic Middle aged Symptoms recurrent/unusual infection, easy bruising, bleeding, joint pain, bone pain, malai se, weakness, abdo pain, weight loss, night sweats. Signs pallor, petechiae, bruises, bleed ing (check gums), lymphadenopathy, signs of infection, hepatosplenomegaly, focal neurology. Investigations blds FBC (anemia, iWCC, look at diff erential), blood fi lm, U+E, LFT, iLDH , iurate, clotting; bone marrow biopsy. Treatment acute antibiotics, blood and platelet tra nsfusions; chronic chemoradiotherapy, bone marrow transplant or observation. Complications infection, bleeding (DIC), hyperviscosity, cell lysis. Lymphoma (OHCM9 b p354; see Table 13 .5) Table 13.5 Basic epidemiology of lymphoma Type Hodgkin \200\231s Non-Hodgkin \200\231s Any age, especially the elderly Patient Young adults or elderly, often male Prognosis 60 \200\22390% 5yr survival 50% overall survival Symptoms enlarged non-tender lumps, fever, night sweats, infection, itching, tiredness, wei ght loss, malaise, weakness, occasionally pain with alcohol. Signs pale, lymphadenopathy, h epatosplenomegaly. Investigations blds FBC, blood fi lm, U+E, LFT, Ca2+, LDH, urate; CXR, C T/MRI chest/abdo/pelvis; biopsy lymph node (Reed \200\223Sternberg cell seen in Hodgkin \200\231s) and bone marrow. Treatment chemoradiotherapy, steroids, bone marrow transplant. Complications infection, bone marrow failure, SVC obstruction (b p283). Paraproteinaemia Se veral diseases can cause an excess of a single (clonal) immunoglobulin including myeloma (b p389). Elderly patients may get a monoclonal gammopathy of undetermined signifi cance (MGU S) distinguished from myeloma on the basis of paraprotein levels <30g/L, with <10% plasma c ells on bone marrow biopsy and no evi- dence of end-organ damage. MGUS will progress to mye loma in <2% patients/year. In Waldenstr m \200\231s macroglobulinameia, iIgM from a lympho plasmocytic lymphoma may lead to hyperviscosity. Myeloproliferative disease (OHCM9 b p360) Neoplastic diseases of myeloid progenitor cells with potential to transform to AML, includi ng CML, as well as: \200 Polycythaemia [rubra] vera (iHct; plethora, thrombosis) \200 E ssential thrombocytosis (iplatelets; thrombosis or bleeding) \200 Myelofi brosis (marrow fi brosis; marrow failure, splenomegaly). OHFP.indb 396 OHFP.indb 396 30/05/2014 16:18 30/05/2014 16:18 397 anemia Pancytopenia \200\223 dHb, dplts, and dWCC (OHCM9 b p358) Marrow failure aplastic anemia, malignancy, myelodysplasia, fi brosis. Other hypersplenism, SLE, infection (eg TB, AIDS), B 12/folate defi ciency. Investigations blds FBC, blood fi lm, B12, folate; bone marrow biops y. Treatment Address underlying cause; blood and platelet transfusions. Sickle-cell disease and trait1 (OHCM9 b p334) Point mutation in hemoglobin B-chain gene causes mutant Hb with tendency to polymerise under low oxygen tension. Resultant RBC deformities and increased en dothelial adherence lead to haemolysis, vaso-occlusive crises and microinfarcts. With heter ozygote frequencies as high as 30%, all patients with an African-Caribbean background must be screened by Hb electrophoresis before elective surgery. Homozygote haemolytic anemia, ir eticulocytes, ibilirubin; history of sickle cell crises; hyposplenism. Heterozygote (trait) normal Hb, usually healthy. Complications vaso-occlusive crises with severe pain in long b ones or acute abdomen; thromboses elsewhere may lead to splenic infarction, stroke, priapis m, or myocardial and renal microinfarcts; sickle chest syndrome with chest pain, tachypnoea and pulmonary infi ltrates is an emergency requiring ICU involvement; parvovirus B19 infec tion may lead to failure of erythropoiesis and aplastic anemia. Treatment supportive during crises, with opioid analgesia, vigorous IV hydration, warming, O2 broad-spectrum antibi otics; exchange transfusion in severe crises; hydroxyurea may reduce frequency and severity of crises. Hyposplenism (due to splenic infarction) results in greater susceptibility to i nfection: penicillin prophylaxis, pneumococcal vaccination (5yrly) and meningococcal vaccin ation (single dose) should be off ered, along with early identifi cation and treatment of i nfections. Thalassaemia1 (OHCM9 b p336) Genetic diseases of impaired production of diff ere nt Hb chains with wide variety in severity and named after the defective globin chain. Comm on in Mediterranean, Arabian, and Asian populations. b-thalassaemia major (homozygote) and a-thalassaemia cause severe anemia that requires transfusion (b p398). b-thalassaemia minor (heterozygote) causes a mild anemia (>90g/L, MCV<75fl ) that rarely requires treatment. Tr eatment repeated transfusions with chelation therapy to combat iron overload; splenectomy r educes transfusion requirements. Causes of lymphadenopathy Infection local infection, EBV, CMV, hepatitis, HIV, TB, syphilis , toxo- plasmosis, bartonella \200\230cat-scratch \200\231, fungal; malignancy lymphoma, l eukemia, metastases; autoimmune SLE, rheumatoid; other sar- coidosis, amyloidosis, drugs. 1 For information on the NHS Sickle Cell and Thalassaemia antenatal and neonatal screening programs, see (cid:27)sct.screening.nhs.uk _OHFP.indb 397 _OHFP.indb 397 30/05/2014 16:18 30/05/2014 16:18 398 CHAPTER 13 Hematology Transfusion of blood products The understanding of blood groups and safe blood transfusion underpinned the huge advances in medicine and surgery of the 20th century. However, blood p roducts carry risks which you must ensure do not outweigh benefi ts and consider alternativ es before prescribing any transfusion. When taking blood for blood bank samples it is essen tial to label the blood bottle at the bedside according to your hospital \200\231s transfus ion protocols (usually involving hand-labeling) and check details against the patient \200 \231s identifi cation wristband. Errors here are disastrous, but still happen.1 Group and s ave (G+S) blood is analyzed for ABO (Table 13.6) and Rh(D) grouping (see below) and for com mon red cell antibodies. Any further transfusion >72h after an initial transfusion will req uire a fresh G+S sample, since new antibodies may have formed. Crossmatch (X-match) blood i s analyzed as for G+S, then fully screened for any antibodies against a compatible stored b lood product. Ordering blood products for elective use depend upon the type of surgery plan ned or the severity of defi cit. Most hospitals issue guidance for juniors on pre-operative blood requests to prevent excess crossmatching resulting in waste. A G+S is suffi cient fo r most procedures since a subsequent X-match can usually be done within 45min. Ordering blo od products for emergency use is a daily occurrence in most hospitals. In extreme emergenci es blood can be issued without a full X-match (b p400), but this carries a greater risk of transfusion reactions. Ensure blood bottle and form are labeled fully and clearly, and indi cate the quantity and type of blood product(s) needed as well as where they are needed. Spe ak to the hematology technician and arrange a porter to collect and deliver the blood produ cts. 3If in doubt, ask. How many units to transfuse depends upon the clinical situation and following advice from a hematologist (where appropriate). In general, expect 1 unit to res ult in a Hb rise of approximately 10g/L in the absence of ongoing loss. Checking blood prod ucts before they are given to a patient requires two people, both of whom must be familiar with local transfusion protocols;2 this role will usually be taken by experienced nurses. C onfi rm and check the patient \200\231s name and DoB against their wristband and the compat ibility label on the blood product. Next check the name, DoB, hospital number and blood pro duct number, blood group and expiry date on each bag and the form; initial against each uni t on the prescription once checked. Table 13.6 ABO blood groups Blood group Serum antibodies UK frequency Comment O A B AB Anti-A, Anti-B Anti-B Anti-A None 44% 45% 8% 3% Universal donor Universal recipient 1 For those who fi nd transfusion protocols overly burdensome, the UK transfusion incident reports available at (cid:27)www.shotuk.org make sobering reading. 2 See (cid:27)transfusionguidelines.org.uk for UK national transfusion guidelines. OHFP.indb 398 OHFP.indb 398 30/05/2014 16:18 30/05/2014 16:18 399 TRANSFUSION OF BLOOD PRODUCTS Packed red cells Symptomatic/severe anemia or severe hemorrhage Indication Immunology Needs ABO and Rh(D) compatibility between donor and recipient Volume Donor Shelf life Cost Whole blood is seldom used and all blood is now leucocyte-depleted. 220 \200\223320ml Each unit from one donor 35d at 4 C; must be used within 4h once removed from fridge 7 130 per unit Platelets Symptomatic/severe thrombocytopenia, platelet dysfunction Indication Immunology Rh(D) compatibility more important than ABO, but not crucial1 Volume Donor Shelf life Cost For invasive procedures (eg LP or liver biopsy) transfuse to achieve a documented platelet count >50 x 109/l. Since transfused platelets have a short half-life, which may be further reduced in pathological thrombocytopenia, time the transfusion as clo se to the procedure as possible. 7300ml (adult dose is 300ml; one unit, 7300 x 109 platelets) Usually pooled from four donor s 5d at room temperature \200\223 must be kept agitated 7 210 per unit Fresh frozen plasma (FFP) Replacement of coagulation factor defi ciency (if no safe single factor concentrate availab le), multiple coagulation defi ciencies (associated with severe bleeding), disseminated int ravascular coagulation (DIC), massive blood transfusion Immunology Rh(D) compatibility more important than ABO, but not crucial1 7250ml; adult dose is 10 \200\22315ml/kg (usually thr ee to four units) Volume Each unit from one donor Donor 1 \200\2232yr at \200\22330 C; mu st be used within 4h once thawed Shelf life 7 30 per unit (7 120 per adult dose) Cost Indication Cryoprecipitate (cryo) Contains fi brinogen, von Willebrand \200\231s factor and factors VIII, XIII; used in DIC a nd massive transfusion Indication Immunology Rh(D) compatibility more important than ABO, but not crucial1 Volume Donor Shelf life Cost 250ml (adult dose 500ml; two units) Each (250ml) unit from fi ve donors 1 \200\2232yr at \200\22330 C; must be used within 4h once thawed 7 165 per unit (7 330 per adult dose) >50% adults will be chronically infected with Cytomegalovirus (CMV). New CMV infection in i mmunocompromised individuals (eg organ or bone marrow transplant, dialysis, HIV) can be fat al, hence products from CMV \210\222ve donors should specifi cally be requested for immuno suppressed patients who are known to be CMV \210\222ve. 1 Because of the presence of serum antibodies, compatibility is reversed for non-red cell b lood products so AB becomes the universal donor and O the universal recipient. Rh(D) status is unaff ected: Rh(D) \210\222ve recipients should receive Rh(D) \210\222ve blood produc ts if possible. _OHFP.indb 399 _OHFP.indb 399 30/05/2014 16:18 30/05/2014 16:18 400 CHAPTER 13 Hematology Red cell transfusion Indications To correct symptomatic or severe anemia; to replace blood loss in hemorrhage. Trigger factors for transfusion are described in the \200\230When to t rans fuse \200\231 section. Generally a unit of packed cells raises the Hb by 10g/L in an a dult. Contraindications absolute Patient refusal (eg Jehovah \200\231s Witness); relative P ernicious anemia/macrocytic anemia, CRF/fl uid overload. Prescribing Blood should be prescr ibed on the fl uid part of the drug chart (some hospitals may have dedicated transfusion ch arts). If the patient is hypovolaemic from hemorrhage then each unit of blood should be inf used quickly (STAT-30min), though for more elective transfusions each unit can be administe red at 3 \200\2234h. In elective transfusions it may be necessary to give furosemide 20 \200\22340mg STAT PO/IV with alternate units (starting with the second unit) to prevent fl uid overload in patients with LV dysfunction. See Figs 13.1 and 13.2. In acute hemorrhage i t may be necessary to obtain blood quickly. Table 13.7 illustrates options available in thi s situation: Table 13.7 Options for crossmatching of packed red cells O-negative Universal donor. Often stored in the ED, theaters or blood bank. Does not fi rst require a specimen from patient. ABO and Rh(D) status specifi c. Takes 715min Group-specifi c Full crossmatch ABO, Rh(D) status and antibody tested. Takes 745min Transfused blood must be given through a dedicated giving set with an in-line fi lter. A st andard IV cannula of any size may be used; for rapid infusion, larger-bore cannulas, eg 16G (gray) are needed. Blood should not be left unrefrigerated for more than 4h and cannot be returned to blood bank if it has been unrefrigerated for >30min. Monitoring of the patient should be undertaken regularly during transfusion, paying close attention to HR, BP, RR and temp. A small rise in temp and HR are common. See b p402 for transfusion reactions. Close monitoring requirements may strain nursing staffi ng levels and aff ect safety, hence only urgent transfusions should be performed out of hours. Date Route Fluid Additives Vol Rate Signature 01/09/14 IV Red cells Nil 1 unit 4h JFRivett 01/09/14 IV Red cells 20mg furosemide 1 unit 4h JFRivett Fig. 13.1 Example of an elective transfusion. Date Route Fluid Additives Vol Rate Signature 01/09/14 IV Red cells Nil 1 unit STAT HL Dixon 01/09/14 IV Red cells Nil 1 unit STAT HL Dixon 01/09/14 IV Red cells Nil 1 unit 30min HL Dixon Fig. 13.2 Example of an emergency transfusion. OHFP.indb 400 OHFP.indb 400 30/05/2014 16:18 30/05/2014 16:18 401 TRANSFUSION OF BLOOD PRODUCTS