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 When to transfuse While consumption of blood products has remained pretty constant over the last few years, the size of the donor pool has shrunk, making blood and blood products mor e scarce. Up-to-date information on blood stocks in the UK can be viewed on the National Bl ood Service website.1 Why not transfuse? Besides the fact that blood products are expensive and have limited availability, they carry signifi cant risks (see Table 13.8). Transfusion triggers Hb values of 80g/L are often considered a trigger to thinking about transfusion. However, many patients are asymptomatic at these values and have suffi cient hemoglobin to provide tissue oxygena- tion. In an otherwise fi t patient (eg a young man who has undergon e repair of an open femoral fracture), transfusion is often not required for an Hb 80g/L, t hough a frail arteriopath may suff er with SOB or anginal symp- toms at an Hb of 90g/L and may benefi t from slow transfusion of 2 units. Interestingly, more conservative transfusion strategies have proven to be safe, and possibly advantageous, in acute GI bleed2 and ICU s tudies.3 If in doubt speak to your senior after assessing the patient for signs or symptoms relating to anemia hypovolaemia (b p380). Always ensure the cause for the anemia is know n, or appropriate inves- tigations including serum B12/folate/iron studies have been sent. This is easy enough to forget in the heat of the moment, but measurements made post-transfu sion will include a contribution from the donor and lead to missed defi ciencies. Table 13.8 Complications of blood and blood product transfusion Immunological Anaphylaxis U rticaria Alloimmunisation Incompatibility Haemolytic transfusion reactions Non-haemolytic t ransfusion reactions Transfusion-associated lung injury Non-immunological Transmission of infection: Bacteria (staph/strep) \200 Viruses (HIV, HCV, CMV etc) \200 Parasites (malaria etc) \200 Prion (vCJD) Fluid overload/heart failure Iron overload (repeated transfusions) 3Massive blood transfusion Replacement of one or more circulating volumes (usually >10units ) within a 24h period, or >50% circulating volume in 3h. Consider that platelets, clotting factors and fi brinogen will have been lost/ diluted and that these should also be transfus ed, as well as electrolytes and minerals. Speak to a hematologist who will advise appropria tely. Activate all hospitals should have a massive blood transfusion protocol, which you ca n activate by calling the hematology lab. They will issue blood products and advise upon ad ministration and further testing as appropriate. Ensure that steps are being taken to preve nt further blood loss and that senior members of the team have considered a transfusion cei ling if appropriate. 1 Available at (cid:27)www.blood.co.uk. More detailed guidelines issue d by the British Committee for Standards in Hematology make interesting reading for the enthusiast, available at (cid:27)w ww.bcshguidelines.com 2 Villanueva, C. et al. NEJM 2013 368:11 available free at (cid:27)www.nejm.org/doi/full/10 .1056/ NEJMoa1211801 3 H bert, P.C. et al. NEJM 1999 340:409 available free at (cid:27)www.nejm.org/doi/full/10 .1056/ NEJM199902113400601 _OHFP.indb 401 _OHFP.indb 401 30/05/2014 16:18 30/05/2014 16:18 402 CHAPTER 13 Hematology Transfusion reactions \200 These are potentially fatal, so must be managed urgently \200 ABO incompatibility is the most serious complication; reactions are seen within minutes of starting the transfusion Low-grade pyrexia is common during a transfusion, though a rapid rise in temp at the start is worrying. Signs itemp, iHR, dBP, cyanosis, dyspnoea, pain, rigors, urticaria, signs of heart failure. Investigations blds FBC, U+E, bilirubin, LDH, blood fi lm, direct anti- globulin test, clot ting, repeat G+S (check blood group), antibody screen, blood cultures (if pyrexia persists) ; urine free hemoglobin; CXR if signs of heart failure. Treatment \200 As outlined in Table 13.9 \200 Inform senior and hematologist early \200 Re-check labeling on blood products and return bags to laboratory. Table 13.9 3Acute transfusion reactions (OHCM9 b p343) Features Management \211 2 of: \200 Temp >40 C \200 Chest/abdo pain \200 iHR/dBP \200 Agitation \200 Flushing Likely haemolytic transfusion reaction (ABO incompatibility \200\223 potentially life-thre atening) Stop transfusion. Call senior help. 15l/min O2, 1l 0.9% saline STAT (via new givin g set), hydrocortisone 200mg STAT IV, chlorphenamine 10mg STAT IV. Monitor BP, urine output . Check ECG, U+E (iK+), clotting/fi brinogen Likely non-haemolytic transfusion reaction Slo w transfusion. Give paracetamol 1g/6h PO Monitor obs (HR, BP, temp) Call senior help if no improvement or worsening Likely anaphylaxis (b p470) Stop transfusion. Call senior help. 15 l/min O2, adrenaline (epinephrine) 0.5mg (1:1000) IM, 1l 0.9% saline STAT (via new giving s et), hydrocortisone 200mg STAT IV, chlorphenamine 10mg STAT IV Likely allergic reaction Obs erve closely to exclude anaphylaxis Slow transfusion. Inform senior. Monitor obs (HR, BP, t emp) Hydrocortisone 200mg STAT IV, chlorphenamine 10mg STAT IV Slow transfusion. 15l/min O2 and sit upright Consider furosemide 40mg STAT IV. Catheterise. See b p282 Call senior help if no improvement or worsening Temp <40 C \200 Shivering iHR/dBP \200 Bronchospasm \200 Cyanosis \200 Oedema Urticaria \200 itemp <40 C \200 iitch Fluid overload Following a blood transfusion It takes 76 \200\22312h after a transfusion for the concentra tion of the RBCs to settle; FBC measurement before this is likely to give an inaccurate val ue. OHFP.indb 402 OHFP.indb 402 30/05/2014 16:18 30/05/2014 16:18 403 TRANSFUSION OF BLOOD PRODUCTS The Jehovah \200\231s Witness and blood products Healthcare professionals must not be frigh tened to talk to any patient about sensitive matters if it may aff ect their care, and pati ents who are Jehovah \200\231s Witnesses are no diff erent. You might feel uncomfortable ta lking to a Jehovah \200\231s Witness about what they regard as acceptable practice, but the y will welcome the fact you are open and addressing an issue which is an important part of their religion. You are also likely to learn a great deal about their religion and about th e person inside. Most Jehovah \200\231s Witnesses carry an advanced directive stating their requests with regards to blood products. Acceptable treatments includes non-blood volume e xpanders (saline, Hartmann \200\231s, glucose, gelatins (Gelofusine ), starches (Voluven ), dex- trans), agents which control hemorrhage (recombinant factor VIIa (NovoSeven ), tra nexamic acid) and agents which stimulate red cell production (recombinant erythropoietin; c heck preparation is free from human albumin), IV iron. Unacceptable treatments are those wh ich involve the transfusion of donor whole blood, packed red cells, white cells, fresh froz en plasma and platelets. Pre-operative autologous (self-donated) blood is also not usually acceptable. Treatments which individuals may consider include blood salvage (intra- operati ve and post-operative), haemodilution, haemodialysis and cardiac bypass (pumps must be prim ed with non-blood fl uids). Some fractions of plasma or cellular components may be consider ed acceptable by some individuals (cryoprecipitate, albumin, immunoglobulins, clotting fact ors, and hemoglobin-based O2 carriers). Transplants including solid organ (heart, liver) as well as bone and tissue may also be accepted. For further information the Hospital Liaison Committee for Jehovah \200\231s Witnesses, has several centers all over the country run by Jehovah \200\231s Witnesses. Hospital switchboard will have contact details of your local representatives though there is also a 24h contact service for urgent advice for patients a nd Healthcare professionals (0208 906 2211); non-urgent enquiries can be sent via email to his@wtbts.org.uk. Pediatric patients, consent and Jehovah \200\231s Witnessess1 Children aged 16 or 17 can co nsent to any treatment. Parental agreement is not legally required, although in practice di scussion should involve parents. Children under the age of 16 may still consent to treatmen t, including transfusion, if they have suffi cient maturity, understanding and intelligence to enable them to under- stand what is being proposed (see Gillick competence, b p28). The law on refusal of treatment is more complex. Children under the age of 18 have no automati c right to refuse recommended treatment; parental agreement will over-ride any such a refus al. On rare occasions, parents may refuse life-saving treatment on behalf of a minor. In an immediately life- threatening situation where further delay may cause harm, treatment such as blood products may be given in the child \200\231s best interests, but the team should always involve consultant pediatricians and hospital ethicists where practical. If the requ irement is less immediate then the consultant will be able to seek further legal advice, wh ich might involve approaching the High Court for a specifi c Issue Order under Section 8 of The Children \200\231s Act 1989. 1 For an excellent review see Woolley, S. Arch Dis Child. 2005 90:715 available free online at (cid:27)www.ncbi.nlm.nih.gov/pmc/articles/PMC1720472 _OHFP.indb 403 _OHFP.indb 403 30/05/2014 16:18 30/05/2014 16:18 404 CHAPTER 13 Hematology Clotting emergencies iPT/INR (OHAM3 b p582) Most likely over-anticoagulation with warfarin (see Table 13.10), consider DIC (see b p405), and acute liver failure (see b p313). For oth er causes of iPT/INR see b p567. Table 13.10 Management of raised PT/INR Patient not bleeding Patient bleeding INR 5 \200\2238 \200 Withhold warfarin until INR <5 \200 Identify cause of iINR Medical emergency \200 Seek senior help urgently \200 Discuss with hematologist \200 Vitamin K 5mg STAT IV \200 Consider factors II, VII, IX INR 8 \200\22312 \200 Withhold warfarin until INR <5 \200 Vitamin K 2mg STAT PO/IV \200 Daily INR \200\223 consider admission \200 Identify cause of iINR and X \200 Beriplex /Octaplex \200 or FFP 15ml/kg STAT \200 Withhold warfarin unti l INR <5 \200 Identify cause of iINR INR >12 \200 Withhold warfarin until INR <5 \200 Vitamin K 5mg STAT PO/IV \200 Admit for daily INR \200 Identify cause of iINR iAPTT (OHAM3 b p582) Most likely over-anticoagulation with heparin (b p407), consider DIC ( see b p405). For other causes of iAPTT see b p567. OHFP.indb 404 OHFP.indb 404 30/05/2014 16:18 30/05/2014 16:18 405 BLEEDING Bleeding 3Disseminated intravascular coagulation (OHAM3 b p596) Pathological activation of the clotting cascade results in formation of microvascular thrombi and multiorgan failure. Consumption of fi brinogen, platelets, and clotting factors results in haemorrhagic complic ations. Signs bleeding + petechiae with signs of underlying precipitant (see box) Investiga tions blds dplatelets, iPT/INR, iAPTT, dfi brinogen, iiD-dimer. General treatment request u rgent senior help and discuss with haematolo- gist. Treat underlying cause (most commonly s epsis), supportive measures for BP, acidosis, hypoxaemia, and maintain normothermia. Blood transfusion to compensate for anemia (may exacerbate coagulopathy). Correction of coagulopa thy give FFP (15ml/kg, ie 3 \200\2234 units) if PT or APTT >1.5 x control. Platelets, cryop recipitate (rich in fi brinogen) or factor concentrates may be advised by hematologist. Com plications massive hemorrhage, end-organ failure, death (DIC is an independent predictor of mortality in trauma or sepsis). Common precipitants of DIC \200 Septicaemia (Gram \200\223ve > Gram +ve) \200 Dissemin ated malignancy \200 Incompatible blood transfusion reactions Obstetric emergencies \200 Liver failure \200 Severe trauma/burns. Thrombocytopenia Often an incidental fi nding, but patients may present with bleeding (gums , epistaxis) or easy bruising. Spontaneous bleeding tends not to occur until platelet count s <20 109/l, but if surgery or an invasive procedure is planned then aim for counts >50 109/l. Reduced production (eg aplastic anemia, leukemia), increased consumption (eg immu ne thrombocyto- penic purpura (ITP), haemolytic-uraemic syndrome), and drug-induced (eg ami odarone, carbamazepine) forms are all recognized. Treatment includes identifi cation and re versal of cause, with guidance by a hematologist. Avoid IM injections. Consider heparin-ind uced thrombocytopenia (HIT) if occurs 4 \200\22314d after commencing heparin (b p406). Blee ding disorders (OHCM9 b p338) Hemophilia A factor VIII defi ciency; X-linked recessive, but 30% of cases have no FH due to new mutation. Presents with bleeding in childhood, usually haemarthrosis. Investigations iAPTT and dfactor VIII. Treatment avoid NSAIDs and IM injecti ons. Seek senior help early, and ensure team speaks to hematologist on-call if patient is b leeding. Hemophilia B (Christmas disease) factor IX defi ciency; X-linked recessive. Clinic ally treat in the same fashion as hemophilia A. von Willebrand disease mild but common (1/1 000) autosomal dominantly inherited coagulopathy associated with defi ciency of von Willebr and factor (vWF). Presents with mucocutaneous bleeding and menorrhagia. Investigations iAPT T; PT and platelets normal; specialist specifi c assays. Treatment is not usually required. Discuss with hematologist on-call if problematic bleeding. _OHFP.indb 405 _OHFP.indb 405 30/05/2014 16:18 30/05/2014 16:18 406 CHAPTER 13 Hematology Anticoagulation Anticoagulant drugs are used to prevent thrombotic events in those at risk of thrombosis or to prevent clot propagation after a thrombotic event has occurred. Recent years have seen a number of new agents become avail- able. Generally parenteral routes are preferred in the acute setting, with oral dosing used for those who require longer term the rapy.1 Table 13.11 Anticoagulant treatment options Uses Notes VTE1TP2 ACS CVA3 Heparin (unfractionated) IV (cid:57) (cid:57) (cid:57) (cid:57) Also used in arterial thrombus; risk of HIT (see box); reverse by stopping with protamin e Lower risk of HIT (see box); preferred option in pregnancy; monitor anti- Factor Xa level s only in those at risk of bleeding; partial reversal with protamine Preferred option in AC S; monitoring not required; no specifi c reversal agent \200\223 discuss with hematology I n use since 1954; see b p407 Routine monitoring not required; no specifi c reversal agent \200\223 discuss with hematology Heparin (low molecular weight: LMWH) Fondaparinux SC (cid:57) (cid:57)4 (cid:57) SC (cid:57) (cid:57) (cid:57) (cid:57) PO (cid:57) Warfarin PO Dabigatran Apixaban PO Rivaroxaban PO (cid:57) (cid:57)6 (cid:57)6 (cid:57)6 (cid:57)5 (cid:57)5 (cid:57)5 1 VTE: Venous thromboembolism (PE/DVT treatment and prevention of recurrence). 2 TP: Thromb oprophylaxis \200\223 see below. 3 CVA: Prevention of stroke and systemic embolism in eg A F, mechanical heart valves. 4 Licensed for TP in medical patients and subset of surgical pa tients (GI + hip/leg orthopedics). 5 Licensed for TP only in hip/knee orthopedic surgical p atients. 6 Licensed in atrial \201 brillation in absence of mitral valve disease or repla cement and with \211 1 risk factor: eg previous CVA/TIA/PE/DVT, diabetes, CCF, HTN, age \211 75 years. All anticoagulants should be avoided in patients with active bleeding or at high risk of bl eeding. Seek specialist advice in patients with renal failure, liver failure and hemophilia . Unfractionated heparin This has a rapid onset of action, a short half-life (0.5 \200\2232.5 h, but longer in hypothermia) and is reversible with protamine (1mg protamine over 10min IV neutralizes 100 units unfractionated heparin within 15min). This makes it the best, if cu mbersome option for situations where eff ective but rapidly reversible anticoagulation is d esired (eg patients with metallic valves awaiting surgery or at risk of bleeding). Administ ration is by bolus followed by a con- tinuous infusion set at a rate determined according t o 6h measurements of the APTT \200\223 check your local policy. Heparin-induced thrombocytopenia (HIT)1 The development of procoagulant antibodies in those receiving heparin may lead to thrombocytopenia with thrombosis. Perform a baseline FBC and con- sider HIT in those with dplt >30% and/or new thrombosis within 4-14d of starting hepa rin. Discuss any suspected cases with hematology. 1 British Committee for Standards in Hema tology guidelines available free at (cid:27)onlinelibrary. wiley.com/doi/10.1111/bjh.12059/full 1 Exceptions to this include those with active cancer and a DVT or PE, in whom longer term therapy with LMWH is more eff ective than warfarin. OHFP.indb 406 OHFP.indb 406 30/05/2014 16:18 30/05/2014 16:18 407 ANTICOAGULATION Thromboprophylaxis1 In medical patients Consider if mobility signifi cantly reduced for \211 3 days, or ongoing reduced mobility and 1 or more risk factors of: age >60yr,2 active cancer, dehydration, obese, PMH or FH of DVT/PE, known throm- bophilia, on COCP/HRT, signif i cant active medical comorbidity. In surgical/trauma patients Consider if 1 or more of abo ve risk factors, or if 1 or more of: signifi cantly reduced mobility, total anesthetic time >90min, pelvic/lower limb surgery lasting >60min, signifi cantly reduced mobility, acute i nfl ammatory or intra-abdominal condition. Bleeding risk Balance benefi ts of thromboprophy laxis against bleeding risk, including any active bleeding, acquired or inherited bleeding disor- ders, concurrent use of anticoagulants (eg warfarin), LP/epidural/spinal anesthesia within the previous 4h or within the next 12h, acute stroke, thrombocytopenia, uncontrolled hypertension ( \211 230/120 mmHg). Treatment In addition to good hydration and early mobil ization, where bene- fi ts outweigh bleeding risk, off er pharmacological therapy. In most instances this will be with LMWH (eg enoxaparin 40mg/24h SC or 20mg/24h if eGFR <30ml/min). Alternatives include fondaparinux (inhibits activated factor Xa), rivaroxaban or apixaban (direct activated Xa inhibitors) and dab- igatran (thrombin inhibitor) \200\223 see Table 13.11. Compression stockings off er less eff ective prophylaxis for those in whom pharmacol ogical therapy is con- traindicated, but should be avoided in those with vascular disease o r stroke. Warfarin antagonizes the vitamin K-dependent synthesis of factors II, VII, IX, an d X. Warfarin slows clot formation, as measured by the INR. Counseling advise patients of t he risks and benefi ts of therapy and discuss the need for compliance with INR monitoring. Discuss the large number of drug interactions and the need to inform doctors of warfarin th erapy before starting any new medication (see Table 13.12). Loading should always be initia ted according to local guidelines, with close monitoring of INR and dose adjustment. Warfar in may be prothrombotic over the fi rst 36 \200\22348h, as levels of regulatory proteins C and S fall faster than clotting factors; hence, with the exception of very slow loading reg imens (<5mg/day), continue LMWH for at least 72h after starting warfarin and until INR ther apeutic. Target INR will generally be in the range 2 \200\2233. In those with prosthetic he art valves, or previous thromboembolism whilst on warfarin, higher targets (range 3 \200 \2234) may be required, despite increased bleeding risk. Treatment duration is lifelong for most indications (or until risks>benefi ts). In DVT/PE, treatment should be reviewed at 3m th, and early cessation considered where a clear, temporary provocative factor can be ident ifi ed. Stopping warfarin for a procedure may require no additional cover (low- risk indica tions eg AF) or cover with heparin (LMWH or unfractionated according to local policy). Meta llic mitral valves carry a much higher risk of thrombus formation than valves in the higher pressure aortic position. Discharging patients requires suitable anticoagulation service f ollow-up to be in place, with current dosing documented (eg UK \200\230yellow book \200 \231). Over-anticoagulation with warfarin see b p404 Table 13.12 Drugs interacting with war farin \200\223 consult Appendix 1 of BNF Drugs which iINR Drugs which dINR Alcohol, amiodarone, cimetidine, simvastatin, NSAIDs Carbamazepine, phenytoin, rifampicin, oestrogens 1 NICE guidelines available at (cid:27)guidance.nice.org.uk/CG92 2 Age >35yr if pregnant or up to 6 weeks post-partum. _OHFP.indb 407 _OHFP.indb 407 30/05/2014 16:18 30/05/2014 16:18 This page intentionally left blank Chapter 14 Skin and eyes 409 Rash emergency 410 Rash 411 Bacterial infections causing a rash 412 Viral infections causin g a rash 414 Fungal infections causing a rash 416 Infestations causing a rash 416 Chronic i nfl ammatory rashes 417 Other causes of rash 418 Skin lumps 420 Skin cancers 422 Breast lum ps 423 Leg ulcers 424 Acute red eye emergency 426 Sudden visual loss 429 Gradual visual los s 430 Other visual disturbances 431 _OHFP.indb 409 _OHFP.indb 409 30/05/2014 16:18 30/05/2014 16:18 410 CHAPTER 14 Skin and eyes Rash emergency 3Call for senior help early if patient unwell or deteriorating. \200 15l/m in O2 if short of breath, O2 sats <94% or unwell \200 Monitor pulse oximeter, BP, defi br illator ECG leads if unwell \200 Obtain a full set of observations including temp, BP, an d RR \200 Take history if possible/check notes/ask ward staff \200 Examine patient: ski n examination and condensed CVS, RS, abdo \200 Establish likely causes and rule out serio us causes \200 Look for the fi ndings listed in Table 14.1 which may aid diagnosis. Table 14.1 Features of serious causes of rash Finding Shock (iHR, dBP) Meningococcal septicaemia b p413 Allergic reaction/anaphylaxis b p 470 Necrotising fasciitis b p413 Allergic reaction/anaphylaxis b p470 Meningococcal septica emia b p413 Necrotising fasciitis b p413 Allergic reaction/anaphylaxis b p470 Allergic reac tion/anaphylaxis b p470 Erythema multiforme major b p418 Allergic reaction/anaphylaxis b p4 70 Erythema multiforme major b p418 Meningococcal septicaemia b p413 Life-threatening diagnoses to consider Wheeze/SOB Purpura Post-operative Following drug administration Mouth involvement OHFP.indb 410 OHFP.indb 410 30/05/2014 16:18 30/05/2014 16:18 411 RASH Rash Worrying features RR >30, sats <92%, wheeze, systolic <100mmHg, confusion, tachy/bradycardi a, rapidly changing or non-blanching rash. Think about life-threatening meningococcal septicaemia, necrotising fasciitis, toxic epider mal necrolysis, Stevens \200\223Johnson syndrome, urticaria (anaphylaxis), staphylococcal s calded skin syndrome; other acute cellu- litis, viral exanthem (eg chickenpox, measles), sh ingles, fungal infections, erythema nodosum, erythema multiforme, Henoch \200\223Sch nlein purpura, ecchymosis; chronic psoriasis, dermatitis (eg atopic, contact), vasculitis, eryth ema ab igne, bullous disease. Ask about speed of onset, distribution of rash, associated symptoms, exacerbating and relie ving factors, family history; PMH previous skin disease, joint/GI disease, immunosuppressio n, weight loss; DH allergies, vaccinations, antibiotics, previous drugs to treat skin disea se; SH occupation, exposure to irritants, pets, exposure to others with illness/skin diseas e. Obs temp, RR, BP, HR, O2 sats. Look at hands and nails for pitting, Janeway lesions or Osle r \200\231s nodes, splinter hemorrhages, and then examine aff ected area and rest of skin. Try to form a description of the lesions based upon size, shape, color, palpability, bliste rs and associated features (b p138). Also examine the scalp and mouth. Other examination as dictated by history. Investigations blds if suspect infection or systemic disease; FBC, CRP, ESR, U+E; blood cul tures. Further specialist investigations are listed in Table 14.2. Table 14.2 Investigating cutaneous infections Test Use Example Viral culture Autoantibodies Serology Fungal culture Allergy testing Culture Histology Immu nohistochemistry Cutaneous lymphoma Fungal culture Microscopy Bacterial culture Fungal fl u orescence Herpes simplex Systemic lupus erythematosus Streptococcal cellulitis Onychomycosis Nickel a llergy Mycobacteria/fungi Pemphigus Blister fl uid Blood test Nail clippings Patch testing Skin biopsy Skin scrapings Tinea Scabies Impetigo Scalp ringworm Skin swab Wood \200\231s light Treatment depends upon cause; see following topics. _OHFP.indb 411 _OHFP.indb 411 30/05/2014 16:18 30/05/2014 16:18 412 CHAPTER 14 Skin and eyes Bacterial infections causing a rash Impetigo Superfi cial epidermal infection typically seen around the faces of children. Symp toms weeping, spreading erythema, highly contagious Signs erythema with yellow crust and se rous discharge; occasionally blisters. Investigations skin swabs show Staphylococcus aureus in >90% of cases, but group A streptococci (S. pyogenes) can sometimes be found. Treatment of localized disease can be achieved with topical fusidic acid (Fucidin )/8h for 1wk. Mor e extensive impetigo may require oral anti biotics, eg fl ucloxacillin 500mg/6h PO (for sta phylococci) and phenoxymethylpeni- cillin 500mg/6h PO (for streptococci). Ensure close cont acts are examined and treated if necessary; encourage good hand hygiene and avoidance of sh aring towels. Erysipelas Epidermal streptococcal infection with involvement of cutaneous ly mphatics; results in tense, well-demarcated erythema and lymphadenopathy; typically seen on face or legs. Treatment as for cellulitis. Cellulitis Non-necrotising infection of the der mis. Symptoms hot, sometimes tender area of erythema, usually on leg or face; may be spread ing; history of trauma to skin (insect bite, cannula site). May be systemic eff ects: fever , anorexia, N+V, diarrhea. Signs blanching warm spreading erythema (outline area with marke r to observe response to treatment), mild oedema, break in the skin, serous discharge, ly mphadenopathy in draining nodes, itemp, iHR, iRR. Investigations blds iWCC and N \230, iCRP /ESR; blood cultures if pyrexial; D-dimer likely to be raised in infection so not useful in diff erentiating cel- lulitis from DVT; skin swabs not usually helpful, but check multisit e MRSA swab results; USS to exclude DVT (depending on Wells score b p450) or ruptured Bake r \200\231s cyst. Treatment \200\223 check local guidelines; likely organisms include S. a ureus (may be MRSA) or group A streptococci: \200 If patient is systemically well and has no other signifi cant comorbidities, oral antibiotics (fl ucloxacillin 1g/6h PO; if MRSA suspected or proven doxy cycline 200mg STAT then 100mg/24h PO) If signs of systemic upset (itemp, iHR, iRR) or coexisting disease (DM, IHD, PVD) admit for short-course IV antibiotics (fl ucloxacillin 1g/6h IV; if MRSA suspected or proven vancomy cin 1g/12h IV) \200 If profoundly unwell, request senior help immediately and consider 3necrotising fasciitis (b p413) Painful or restricted eye movement, proptosis or visual disturbance all suggest 3orbital cellulitis, an ophthalmology emergency. Erythematous cannula sites Cannulae should be resited every 72h to prevent local infection. If a cannula site is red and infl amed or pus is present, take a skin swab for C+S, remove cannula, and clean and dress the site. Give fl ucloxacillin 1g/6h PO or clarithromycin 500 mg/12h PO (if penicillin allergic) for 5d. OHFP.indb 412 OHFP.indb 412 30/05/2014 16:18 30/05/2014 16:18 413 BACTERIAL INFECTIONS CAUSING A RASH 3Necrotising fasciitis (OHAM3 b p473) Symptoms rapidly spreading painful erythema with feat ures of systemic sepsis, fever, sweating, N+V, diarrhea, anorexia, dGCS; may occur at break in skin or operation site but often no apparent skin trauma. Signs rapidly spreading blanc hing erythema (outline area with marker to observe rate of spreading), blisters, oedema, lymphadenopathy in draining nodes, sometimes crepitus over tissues, itemp, iHR, iRR, dBP. I nvestigations blds iWCC and N \230, iCRP/ESR; blood cultures and skin swabs/tissue aspirati on may identify infective organism(s) but do not withhold treatment to do these tests if pa tient is systemically unwell; X-ray may reveal gas in subcutaneous tissues of aff ected are a. Treatment \200\223 3this is a surgical emergency. \200 Seek senior help immediately ( the moment you suspect, not once you have watched the fasciitis evolve and confi rm your su spicions) Surgical debridement is the most important measure, consult senior surgeon without delay Likely to need a combination of IV benzylpenicillin, gentamicin, clindamycin, and metronidazole \200\223 seek urgent microbiology advice. Pathogens may be a mixture of aerobic and anaerobic organisms seen following abdominal surgery or in diabeti cs (type 1), a group A strepto- coccus (type 2) or clostridia (type 3 \200\223 gas gangren e). Outcome depends upon speed of identifi cation and initiation of treat- ment, as well as comorbidity and the site aff ected. Extensive tissue loss from surgery and necrosis is com mon; overall mortality is 725%. 3Meningococcal septicaemia (OHCM9 b p832) Symptoms include fever, joint and muscle ache, non-blanching (purpuric) rash, N+V, diarrhea, anorexia, malai se; meningitis frequently occurs, refl ected by headache, neck stiff ness and photophobia. Signs itemp, iHR, iRR, cap refi ll >2s, dBP, non-blanching petechial or purpuric rash; meni ngism/photophobia if meningitis also present (b p360). Investigations blds iWCC and N \230, iCRP/ESR, meningococcal PCR, deranged clotting if severe sepsis (DIC); blood cultures do n ot withhold antibiotics before taking these if patient is systemically unwell. Treatment \200\223 3this is a medical emergency \200 Airway, Breathing (give O2), Circulation (obta in IV access) \200 Seek help immediately \200\223 contact your seniors as soon as you su spect \200 If patient is in shock (systolic BP <100), involve ICU team urgently \200 0. 9% saline 1l STAT IV and goal-directed fl uid resuscitation (b p481) \200 Ceftriaxone 4g STAT IV if septicaemia is suspected \200 Inform public health consultant once patient is stable. Pathogen Neisseria meningitides, a Gram-negative diplococcus; since the introductio n of a vaccine for serogroup C, serogroup B accounts for the majority of infections seen in Europe and North America. Outcome depends upon speed of identifi cation and initiation of treatment. Mortality for meningococcal septicaemia is about 10% in the developed world. Com plications in survivors include neurological defi cits (eg cogni- tive impairment, deafness ), limb amputation, renal failure and adrenal failure (Waterhouse \200\223Friderichsen synd rome). _OHFP.indb 413 _OHFP.indb 413 30/05/2014 16:18 30/05/2014 16:18 414 CHAPTER 14 Skin and eyes Viral infections causing a rash Chickenpox (varicella zoster virus \200\223 VZV) (OHCM9 b p400) Symptoms begin with fever and malaise 14 \200\22321d after exposure to VZV. The typic al rash then develops: Flat lesions initially, evolving to itchy scabs. Older children and adults are at risk for the development of pneumonitis or encephalitis, manifesting as breat hlessness or altered mental function. Signs itemp, iHR, and presence of evolving rash; macu les, papules, vesicles, pustules, scabs, in centripetal distribution (spreading out from th e trunk). iRR and dO2 sats suggest respiratory involvement. Altered personality, dGCS, or a taxia suggests CNS involvement. Investigations not usually undertaken but vesicular \202 uid can be exam- ined under electron microscopy or sent for viral PCR; serology viral antib ody titres can be monitored but this is seldom necessary; CXR may show diff use consolidati on in varicella pneumonitis; CT brain to exclude other causes of neurology in presumed vari cella encephalitis. Treatment for simple cutaneous disease is symptomatic with antipyretics and topical antihistamines. Antiviral therapy is usually given to patients >16yr (aciclovi r 800mg/5h PO). In the immunocompromised or those with rare complications (pneumonitis, enc ephalitis) use aciclovir 10mg/kg/8h IV. Consider ICU admission for respiratory support in p neumonitis. Pregnancy Primary VZV infection during the 1st 20wk of pregnancy is associ- ate d with 1 \200\2232% risk of fetal anomalies and spontaneous abortion; infection within 5 da ys of delivery is also associated with a risk of neonatal VZV infec- tion. Women without a clear history of chickenpox should have viral specifi c IgG titres checked and if negative, should be off ered VZV vaccination before becoming pregnant. The vaccine cannot be used in pregnancy, when primary infection may require zoster immune globulin (ZIG) to prevent the onset of gy disease, and oral aciclovir if the disease develops \200\223 discuss with micr obiology. p Chickenpox very rarely occurs in the same individual twice. Shingles only occurs in patient s who have had chickenpox previously; the virus lies dormant in the dorsal root/cranial ner ve ganglia. Non-immune individuals can catch chickenpox from patients who have either chick enpox or shingles; the infectious period runs from 48h prior to onset of the rash until all lesions crust over.