Symptoms/signs 2 Occur 7 \200\22310d after blood transfusion. 2 Fever, anemia and jaundice. 2 haemoglobinuria. Management 2 Check DAT and repeat compatibility tests. 2 Transfuse patient with freshly cro ss-matched blood. 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 505 Hematological emergencies 505 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 506 Bacterial contamination of blood products Uncommon but potentially fatal adverse effect of blood transfusion (affects red cells and b lood products e.g. platelet concentrates). Implicated organisms include Gram \200\223ve ba cteria, including Pseudomonas, Yersinia and Flavobacterium. Features 2 Fever. 2 Skin flushing. 2 Rigors. 2 Abdominal pain. 2 DIC. 2 ARF. 2 Shock. 2 Car diac arrest. Management \200\224as per Immediate transfusion reaction 2 Stop transfusion. 2 Urgent resu scitation. 2 IV broad-spectrum antibiotics if bacterial contamination suspected. 506 Post-transfusion purpura Profound thrombocytopenia occurring 5 \200\22310d after blood or platelet transfusion. Usua lly due to high titre of anti-HPA-1a antibody in HPA-1a \200\223ve patient. Features 2 Rare. 2 Multiparous 3 most commonly (previous pregnancies or transfusions). 2 Ca used by platelet-specific alloantibodies (usually anti-HPA-1a). 2 Platelets 55 with associa ted bleeding/bruising \200\224may be severe and even life threatening. Management 2 IVIg if bleeding. 2 Plasma exchange worth considering. 2 If platelet transfusi on needed, use random donor platelets (no evi- dence that HPA-1a superior). 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 507 Hematological emergencies 507 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 508 Hypercalcaemia Clinical symptoms 2 General \200\224weakness, lassitude, weight loss. 2 Men tal changes \200\224impaired concentration, drowsiness, personality change and coma. 2 GIT \200\224anorexia, nausea, vomiting, abdominal pain (peptic ulceration and pancreatitis are rare complications). 2 Genitourinary \200\224polyuria, polydipsia. Clinical effects 2 Cardiovascular \200\2245 QT interval on ECG, cardiac arrhythmias and hypertension. 2 Renal \200\224dehydration, renal failure and renal calculi. Hematological causes 1. Myeloma. 2. High grade lymphoma. 3. Adult T-cell leukemia/lymphoma (ATLL). 4. Acute lymphoblastic leukemia. Hypercalcaemia occurs in other clinical situations including metastatic carcinoma of breast , prostate and lung. Theories for occurrence in hematological malignancy include increased bone resorption mediated by osteoclasts under the influence of locally or systemically rele ased cytokines such as PTH-related peptide, TGF, TNF-a, M-CSF, interleukins and prostagland ins. Increased intestinal absorption of calcium secondary to increased 1,25-hydroxycholecal ciferol. Normal range for plasma [Ca2+] 2.12 \200\2232.65mmol/L. 40% of plasma Ca2+ is bound to albu min. Most laboratories measure the total plasma Ca2+ although only unbound Ca2+ is physiolo gically active. For accurate mea- surement of plasma or serum Ca2+ blood sampling should be taken from an uncuffed arm, i.e. without the use of a tourniquet. 508 Correct for albumin corrected calcium = (Ca2+) + 0.02 [40 \200\223(Albumin)] corrected calcium = (Ca2+) \200 \223 0.02 [(Albumin) \200\22345] Albumin <40g/L Albumin >45g/L Management (cid:2) An emergency if Ca2+ >3.0mmol/L. 1. Rehydrate with normal saline 4 \200 \2236L/24h. 2. Beware fluid overload \200\224use loop diuretics and CVP monitoring if nec- essary. 3. Stop thiazide diuretics and consider regular loop diuretics. 4. Give bisphosphonates e.g . disodium pamidronate 60 \200\22390mg IV stat (see table). 5. Treat underlying malignancy. 6. Consider dialysis if complicating factors (CCF, advanced renal failure). 7. Other therapeutic options: \200\223 Calcitonin 200IU 8-hourly. 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 509 Hematological emergencies \200\223 Corticosteroids (e.g. prednisolone 60mg/d PO). \200\223 Mithromycin 25 g/kg IV 3 weekly. \200\223 Plicamycin. Treatment of hypercalcaemia with disodium pamidronate Serum Ca2+ (mmol/L) Up to 3.0 3.0 \200\2233.5 3.5 \200\2234.0 >4.0 Pamidronate (mg) 15-30 30-60 60-90 90 Infuse slowly (see BNF). Response often takes 3 \200\2235d. 509 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 510 Hyperviscosity Common hematological emergency. Defined as increase in whole blood viscosity as a result of an increase in either red cells, white cells or plasma components, usually Ig. Commonest situations arise as a result of 2 4 in red cell volume in polycythaemia rubra ver a. 2 High blast cell numbers in peripheral blood e.g. AML or ALL at presen- tation. 2 Presence of monoclonal Ig e.g. Waldenstr m \200\231s macroglobulinaemia (IgM). Clinical features \200\224polycythaemia (e.g. PRV) 2 Lethargy, itching, headaches, hyperte nsion, plethora, arterial throm- boses viz: MI, CVA and visual loss (central retinal artery occlusion). (cid:2) Emergency treatment Isovolaemic venesection. Remove 500mL blood volume from large b ore vein (antecubital usually) with simultanous replacement into another vein of 500mL 0.9% saline. Repeat daily until PCV <0.45. Clinical features \200\224high WBC (e.g. AML) 2 Dyspnoea and cough (pulmonary leucostasis) ; confusion, 5 conscious level, isolated cranial nerve palsies (cerebral leucostasis), visu al loss (retinal hemorrhage or CRVT). (cid:2) Emergency treatment 2 Unless machine leucapheresis can be obtained immediately, ven esect 500mL blood from large bore vein and replace isovolaemically with packed red cells if Hb <7.0g/dL \200\224otherwise replace with 0.9% saline to avoid increasing whole blood vis cosity. 2 Arrange leucapheresis on cell separator machine. Use white cell inter- face program to ap herese with replacement fluids depending on Hb as above. 2h is usually maximum tolerated. 510 2 Initiate tumor lysis prophylactic protocol (see p560) in preparation for chemotherapy. 2 Start chemotherapy as soon as criteria allow (high urine volume of pH>8 and allopurinol commenced). This is crucial as leucapheresis in this situation is only a holding maneuver while the patient is prepared for chemotherapy. 2 Continue leucapheresis daily until leucostasis symptoms resolved or until WBC <50 109/L. Hypergammaglobulinaemia (e.g. Waldenstr m \200\231s) Lethargy, headaches, memory loss, con fusion, vertigo, visual disturbances from cerebral vessel sludging \200\224rarely MI, CVA. (cid:2) Emergency treatment 2 Unless immediate access to plasma exchange machine available, vene- sect 500mL blood from large bore vein with isovolaemic replacement with 0.9% saline unless Hb <7.0g/dL when use packed red cells. 2 Arrange plasmapheresis on a cell separator machine using plasma exchange program (see p584). Replacement fluids on criteria as above. Aim for 1 \200\2231.5 blood volume exchange (usually 2.5 \200\2234.0L) 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 511 Hematological emergencies starting at lower end of range initially. Repeat daily until symptoms resolved. 2 Maintenance plasma exchanges at 3 \200\2236 weekly intervals may be suffi- cient treatmen t for some forms of Waldenstr m \200\231s macroglobuli- naemia. However, if hyperviscosity due to IgA myeloma or occasionally IgG myeloma, chemotherapy will need to be initiated. Note Diseases in which the abnormal Ig shows activity at lower temperature e.g. cold antibo dies associated with CHAD (see p118) require mainte- nance of plasmapheresis inlet and outl et venous lines and all infusional fluids at 37 C. Polyclonal 4 in Ig (e.g. some forms of cryoglobulinaemia) can also rarely cause hyperviscosity symptoms. Management is as above fo r monoclonal immunoglobulins. 511 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 512 Disseminated intravascular coagulation Pathological process characterized by generalized intravascular activation of the haemostat ic mechanism producing widespread fibrin formation, resultant activation of fibrinolysis, a nd consumption of platelets/coagula- tion factors (esp I, II, V). Usually the result of ser ious underlying disease but may itself become life threatening (through hemorrhage or throm - bosis). Mortality in severe DIC may exceed >80%. Hemorrhage usually the dominant feature and is the result of excessive fibrinolysis, depletion of coagulation factors and platelets and inhibition of fibrin polymerisation by FDPs. Wide range of disorders may precipitate D IC. Pathophysiology \200\224DIC may be initiated by 2 Exposure of blood to tissue factor (e.g. after trauma). 2 Endothelial cell damage (e.g. by endotoxin or cytokines). 2 Release of pr oteolytic enzymes into the blood (e.g. pancreas, snake venom). 2 Infusion or release of activated clotting factors (factor IX concentrate). 2 Massive thro mbosis. 2 Severe hypoxia and acidosis. Causes of DIC Tissue damage (release of tissue factor) e.g. trauma (esp brain or crush injury), thermal i njury (burns, hyperthermia, hypothermia), surgery, shock, asphyxia/hypoxia, ischaemia/infar ction, rhabdomyolysis, fat embolism. Complications of pregnancy (release of tissue factor) e.g. amniotic fluid embolism, abrupti o placentae, eclampsia and pre-eclampsia, retained dead fetus, uterine rupture, septic abor tion, hydatidiform mole. 512 Neoplasia (release of tissue factor, TNF, proteases) e.g. solid tumors, leukaemias (esp. ac ute promyelocytic). Infection (endotoxin release, endothelial cell damage) e.g. Gram \200\223ve bacteria (e.g. meningococcus), Gram +ve bacteria (e.g. pneumococcus), anaerobes, M tuberculosis, toxic sh ock syndrome, viruses (e.g. Lassa fever), protozoa (e.g. malaria), fungi (e.g. candidiasis) , Rocky Mountain spotted fever. Vascular disorders (abnormal endothelium, platelet activation) e.g. giant haemangioma (Kasa bach \200\223Merritt syndrome), vascular tumors, aortic aneurysm, vascular surgery, maligna nt surgery, cardiac bypass hypertension, pulmonary embolism, acute MI, stroke, subarachnoid hemorrhage. factor) Immunological anaphylaxis, acute haemolytic transfusion reaction, heparin-associate d thrombocytopenia, renal allograft rejection, acute vasculitis, drug reactions (quinine). (complement activation, release of tissue Proteolytic activation of coagulation factors e.g. pancreatitis, snake venom, insect bites. 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 513 Hematological emergencies Neonatal disorders e.g. infection, aspiration syndromes, small-for-dates infant, respirator y distress syndrome, purpura fulminans. Other disorders e.g. fulminant hepatic failure, cirrhosis, Reye \200\231s syndrome, acute f atty liver of pregnancy, ARDS, therapy with fibrinolytic agents, therapy with IX concentrat es, massive transfusion, acute intravascular haemolysis familial ATIII deficiency, homozygo us protein C or S deficiency. factor Clinical features Acute (uncompensated) DIC Rapid and extensive activation of coagulation, fibrinolysis or both, with depletion of procoagulant factors and inhibitors and signifi can t hemorrhage. Slow consumption of factors with normal or increased levels; often asymptomat ic or associated with thrombosis. Chronic (compensated) DIC Clinical features may be masked by those of the disorder which precipi- tated it and rarely is the cause of DIC obscure. DIC should be considered in the management of any seriously i ll patient. The specific features of DIC are: 2 Ecchymoses, petechiae, oozing from venepunc ture sites and post-op bleeding. 513 2 Renal dysfunction, ARDS, cerebral dysfunction and skin necrosis due to microthrombi. 2 MAHA. Laboratory features The following investigations are useful in establishing the diagnosis o f DIC though the extent to which any single test may be abnormal reflects the underlying ca use of DIC. 2 D-dimers \200\224more specific and convenient than FDP titre (performed on plasma sample). Significant 4 of D-dimers plus depletion of coagula- tion factors pla telets is necessary for diagnosis of DIC. 2 PT \200\224less sensitive, usually 4 in moderately severe DIC but may be normal in chronic DIC. 2 APTR \200\224less useful. May be normal or even <normal, particularly in chronic DIC. 2 Fibrinogen \200\2245 or falling fibrinogen levels are characteristic of many causes of DI C in the presence of D-dimers. Greatest falls are seen with tissue factor release. 2 Platelet count \200\2245 or falling platelet counts are characteristic of acute DIC, most notably in association with infective causes. 2 Blood movie may show evidence of fragmentation (schistocytes) though the absence of this finding does not exclude the diagnosis of DIC. 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 514 2 Antithrombin levels are frequently 5 in DIC and degree of reduction in plasma antithrombin and plasminogen may reflect severity. 2 Factor assays rarely necessary or helpful. In severe DIC levels of most factors are reduc ed with the exception of FVIIIc and von Willebrand factor which may be increased due to rel ease from endothelial cell storage sites. Management of DIC 1. 2. Supportive therapy as required (e.g. volume replacement for shock). 3. Replacement therapy if bleeding: platelet transfusion if platelets <50 109/L, cryopr ecipitate to replace fibrinogen, and FFP to replace other factors (10 units cryoprecipitate for every 3 units FFP). Identify and, if possible, remove the precipitating cause. 4. Prophylactic platelet transfusion may be helpful if platelets <20 109/L. 5. Monitor r esponse with platelet count, PT, fibrinogen and D-dimers. 6. Heparin (IVI 5 \200\22310iu/kg /h) for DIC associated with APML, carcinoma, skin necrosis, purpura fulminans, microthrombo sis affecting skin, kidney, bowel and large vessel thrombosis. 7. ATIII concentrate in intractable shock or fulminant hepatic necrosis. 8. Protein C conce ntrate in acquired purpura fulminans or severe neonatal DIC. 514 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 515 Hematological emergencies 515 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 516 Overdosage of thrombolytic therapy 2 Large doses of any thrombolytic agent (streptokinase, urokinase, TPA) will cause primary fibrinolysis by proteolytic destruction of circulating fibrinogen and consumption of plasmi nogen and its major inhibitor (cid:2)2- antiplasmin. 2 Overdosage is associated with high risk of severe hemorrhage partic- ularly at recent ven epuncture sites or surgical wounds; intracranial hemorrhage occurs in 0.5 \200\2231% of pat ients treated with thrombolytic therapy. 2 Superficial bleeding at venepuncture site may be managed with local pressure and the infusion continued. 2 Bleeding at other sites or where pressure cannot be applied necessi- tates cessation of thrombolytic therapy (t 1 \201\2042 <30mins) and determination of the th rombin time (if used to monitor thrombolytic therapy) or fib- rinogen level. If strongly in dicated and bleeding minimal or stopped the infusion may be restarted at 50% the initial do se when the thrombin time has returned to the lower end of the therapeutic range (1.5 ba seline). Treatment of serious bleeding after thrombolytic therapy 2 Stop thrombolytic infusion immed iately. 2 Discontinue any simultanous heparin infusion and any antiplatelet agents. 2 Apply pressure to bleeding sites, ensure good venous access and com- mence volume expansion. 2 Check fibrinogen and APTR. 2 Transfuse 10 units cryoprecipitate. 2 Monitor fibrinogen, repeat cryoprecipitate to maintain fibrinogen >1.0g/L. 516 2 If still bleeding, transfuse 2 \200\2234 units FFP. 2 If bleeding time >9 mins, transfuse 10 units platelets. 2 If bleeding time <9 mins, commence tranexamic acid. 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 517 Hematological emergencies 517 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 518 Heparin overdosage The most serious complication of heparin overdosage is hemorrhage. The therapeutic range us ing the APTT is 1.5 \200\2232.5 average normal control. The plasma t1/2 following IV admi nistration is 1 \200\2232h. The t 1 \201\2042 after SC admin- istration is considerably lon ger. Management guidelines \200\224APTT > therapeutic range Without hemorrhage Continuous IV infusion stop infusion, if markedly elevated, recheck after 0.5 \200\2231h; restart at lower dose wh en APTT in therapeutic range Intermittent SC heparin reduce dose recheck 6h after administration With hemorrhage Continuous IV infusion stop infusion; if bleeding continues, administer protamine sulfate b y slow IV injection (1mg neutralizes 100iu heparin, max dose 40mg/injection) Intermittent SC heparin if protamine is required, administer 50% of calculated neutralizati on dose 1h after heparin administration and 25% after 2h 518 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 519 Hematological emergencies 519 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 520 Heparin-induced thrombocytopenia (HIT) Uncommon but sometimes life-threatening condition due to immune complex-mediated thrombocyt openia in patients treated with heparin. Early recognition reduces morbidity and mortality. Incidence Estimated incidence 1 \200\2233% of patients receiving heparin for \211 1week. O ccurs both with full dose regimens and \200\230minidose \200\231 regimens (5000IU bd) or l ow doses used for \200\230flushing \200\230 IV lines. Less common with low molecular weigh t heparin. Pathogenesis IgG antibodies formed in response to heparin therapy form immune com- plexes w ith heparin and PF4, bind to platelet Fc receptors, trigger aggre- gation and cause thrombo cytopenia. Thrombin activation causes vascular thrombosis and microthrombi cause microvascu lar occlusion. Clinical features 2 HIT causes a fall in the platelet count 8d (4 \200\22314d) after a pat ient \200\231s first exposure to heparin but may occur within 1 \200\2233d in a patient who has recently had prior exposure to heparin. 2 Platelet count generally falls to 60 109/L but may fall to <20 109/L. 2 Venous and arterial thromboses occur in up to 15%. 2 Bleeding is rare. 2 Microvascular occlusion may cause progressive gangrene extending proximally from the extremities and necessitating ampu tation. In patients with HITT (thrombocytopenia and thrombosis) limb amputa- tion is requir ed in 10% and mortality approaches 20%. 520 HIT should be suspected in any patient on heparin in whom the platelet count falls to <100 109/L or drops by \211 30 \200\22340% or develops a new thromboembolic event 5 \200\223 10d after ongoing heparin therapy. ii Heparin should be discontinued immediately and confir matory investigations undertaken. Diagnostic test ELISA using PF4 to detect antibodies to heparin-low molecular weight protei n complex; may miss 5 \200\22310% of cases with antibodies to other pro- teins and up to 50 % false positives after CABG. Management 2 Discontinue heparin (platelet count normally recovers in 2 \200\2235d). 2 Subs titute alternative anticoagulation where necessary and to prevent further thromboembolic events: 2 Recombinant hirudin \200\223 Thrombin inhibitor; anticoagulant effect lasts 40min. \200\223 Slow IV bolus fo llowed by IVI. \200\223 Dose determined by body weight and renal function (see product lit - erature). \200\223 Monitor 4h after IV bolus dose using APTT or ecarin clotting time (ECT); target r ange 1.5 \200\2232.5 mean normal APTT; reduce target to 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 521 Hematological emergencies 1.5 if concomitant warfarin therapy and discontinue hirudin when INR \211 2.0. \200\223 Adverse effects bleeding (esp. with warfarin), anemia, haematoma, fever and abnormal LFTs. 2 Argatroban \200\223 Thrombin inhibitor; t 1 \201\2042 45min. \200\223 Initiate IV infusion at dose of 2 g/kg/min. \200\223 Check APTT at 2h and adjust dose for APTT 1.5 \200\2233 baseli ne (max 100s). \200\223 5 dose by 75% if hepatic insufficiency. \200\223 Side effect \200\224bleeding. 2 Danaparoid \200\223 A heparinoid with low level cross-reactivity with HIT antibodies. \200\223 IV bo lus dose by weight (see product literature) followed by decre- mental infusion schedule and maintenance infusion. \200\223 Monitor by factor Xa inhibition assay 4h after dose (target range 0.5 \200\2230.8U/ml). \200\223 Prolonged t 1 \201\2042 of 25h. \200\223 Side effect \200\224bleeding. ii Low molecular weight heparins frequently cross-react with HIT anti- bodies and are not r ecommended. 521 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 522 Warfarin overdosage Hemorrhage is a potentially serious complication of anticoagulant therapy and may occur wit h an INR in the therapeutic range if there are local predisposing factors e.g. peptic ulcer ation or recent surgery, or if NSAIDs are given concurrently. Management guidelines INR Action >7.0 Without hemorrhage: stop warfarin & consider a single 5 \200\22310mg oral dose of vitamin K if high bleeding risk; review INR daily 4.5 \200\2237.0 Without hemorrhage: stop warfarin & review INR in 2d >4.5 With severe life-threatening hemorrhage: give factor IX concentrate (50U/kg) or FFP (1L for an adult), consider a single 2 \200\2235mg IV dose of vitamin K >4.5 With less severe hemorrhage: e.g. haematuria or epistaxis, withhold warfarin for \211 1d a nd consider a single 0.5 \200\2232mg IV dose of vitamin K 2.0 \200\2234.5 With hemorrhage: investigate the possibility of an underlying local cause; reduce warfarin dose if necessary; give FFP/factor IX concentrate only if hemorrhage is serious or life thr eatening Vitamin K administration to patients on warfarin therapy Effect of vitamin K is delayed sev eral hours even with IV administration. Doses >2 mg cause unpredictable and prolonged resis tance to oral anti- coagulants and should be avoided in most circumstances where prolonged warfarin therapy is necessary. Particular care must be taken in patients with prosthetic ca rdiac valves who may require heparin therapy for several weeks to achieve adequate anticoag ulation if a large dose of vitamin K has been administered. 522 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 523 Hematological emergencies 523 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 524 Massive blood transfusion Massive transfusion defined as replacement of >1 blood volume (5L) in less than 24h. Haemos tatic failure may result from dilution or consump- tion of coagulation factors and platelet s, DIC, systemic fibrinolysis or acquired platelet dysfunction. Pathophysiology 2 Dilution/consumption e.g. replacement of intravascular volume with fluids lacking coagulation factors or platelets e.g. packed red cells and crystalloids . 2 DIC may follow tissue damage, hypoxia, acidosis, sepsis or haemolytic transfusion reactio n. Causes coagulopathy due to consumption of platelets and coagulation factors, fibrinolysi s and circulating fibrin degradation products (see p512). 2 Systemic fibrinolysis particularly associated with liver disease; causes rapid lysis of thrombi at surgical sites and plasmin-induced fibrinogenol- ysis; may be ass essed by the euglobulin lysis time. 2 Platelet dysfunction may be due to circulating FDPs, exhausted platelets activated by intravascular trauma or effects of transfusion of stored platelets. Investigations 2 Baseline tests \200\223 Haematocrit. \200\223 Platelet count. \200\223 Fibrinogen. \200\223 PT. \200 \223 APTT ratio. \200\223 D-dimers. 524 2 Frequent reassessment of tests to monitor effect of, and need for, further replacement therapy. Management Haematocrit Platelet count Fibrinogen PT APTT ratio <0.30 <75 109/L <1.0g/L >1.5 control Transfuse red cells Transfuse platelets Transfuse cryoprecipitate Transfuse FFP Red cell transfusion 2 Full crossmatch takes 30 \200\22340 minutes. 2 Uncrossmatched group- specific blood can be available in 10 minutes. 2 Uncrossmatched group O Rh (D) \200\223ve blood may be transfused in the emergency situation until group-specific blood can be made a vailable; group O Rh (D) +ve red cells may be given to males and older women if necessary. Platelet transfusion 2 Usually available within 10 \200\22315 minutes. 2 Standard adult dos e (6 units equivalent) will raise platelet count by 60 109/L in absence of dilution or consumption. 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 525 Hematological emergencies 2 As platelets do not carry Rh antigens, type incompatible platelets may be administered when necessary; Rh immune globulin should be administered when a Rh \200 \223ve patient has received Rh +ve platelets. 2 6 units of platelets contain 300mL plasma. Fresh frozen plasma 2 Takes up to 30 minutes to thaw; dose required 10mL/kg. 2 Use immedia tely for optimum replacement of coagulation factors. 2 Each unit contains 200 \200\223280m L plasma and 0.7 \200\2231.0iu/mL activity of each coagulation factor 2 ABO group compatible FFP should be administered \200\224no crossmatch is required. 2 If large volumes infused, serum [Ca2+] should be monitored to exclude hypocalcaemia due to citrate toxicity. Cryoprecipitate 2 Precipitate formed when FFP is thawed at 4 C; resuspended in 10 \200\22315mL plasma and refrozen at \200\22318 C; takes up to 15 minutes to thaw and p ool. 2 No grouping required. 2 Contains 80 \200\223100IU FVIIIC, 100 \200\223250mg fibrinogen, 5 0 \200\22360mg fibronectin and 40 \200\22370% of the original von Willebrand factor. 2 Should be used immediately for optimum replacement of fibrinogen and factor VIIIC. 2 Infusion of 8 \200\22310 bags raises fibrinogen concentration by 0.6 \200\2231.0g/L in a 70kg patient. 525 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 526 Paraparesis/spinal collapse May be due to tumor in the cord, spinal dura or meninges or by exten- sion of a vertebral t umor into the spinal canal with compression of the cord or as a result of vertebral collaps e. Spinal cord compression from vertebral collapse in a hematological patient is most commonly due to myeloma (in up to 20% of patients) but may occur in a patient with Hodgkin \200\231 s disease (3 \200\2238%) or occasionally non- Hodgkin \200\231s lymphoma. Spinal cord invol vement by leukemia is most common in AML, less so in ALL and CGL and least common in CLL. Onset of paraplegia may be preceded for days or weeks by paraesthesia but in some patients the onset of paraplegia may follow initial symptoms by only a few hours. Symptoms suggestive of spinal cord compression require urgent assess- ment by CT or MRI and referral to a neurosurgical unit for assessment for surgical decompression. Where this is not possible early radiotherapy may provide symptomatic improvement. However, if treatment is delayed until paraparesis has developed, this often proves to be irreversible despite su rgery and/or radiotherapy. 526 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 527 Hematological emergencies 527 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 528 Leucostasis Term is applied both to organ damage due to \200\230sludging \200\231 of leucocytes in the capillaries of a patient with high circulating blast count and to the lodging and growth o f leukaemic blasts, usually in AML, in the vascular tree eroding the vessel wall and produc ing tumors and hemorrhage. Features 2 More common in AML and blast crisis of CML. 2 Leucostatic tumors are associated with an exponential increase in blasts in the peripheral blood and, prior to the development of effec- tive chemotherapy, h emorrhage from intracerebral tumors was not an uncommon cause of death. 2 Pulmonary or cerebral leucostasis are serious complications which may occur in patients who present with a blast count >50 109/L. 2 Leucocyte thrombi may cause plugging of pulmonary or cerebral capil- laries. Vascular rupture and tissue infiltration may occur. 2 Less common manifestations are priapism and vascular insufficiency. 2 Pulmonary leucostas is causes progressive dyspnoea of sudden onset associated with fever, tachypnoea, hypoxaemia, diffuse crepitations and a diffuse interstit ial infiltrate on CXR. 2 Pulmonary hemorrhage and haemoptysis may occur. More common with monocytic leukaemias and the microgranular variant of acute promyelocytic leukemia. Differentiation from bacterial or fungal pneu- monia may be difficult. 2 Cerebral leucostasis may cause a variety of neurological abnormalities. 2 Anemia may prot ect a patient with marked leucocytosis from the effects of increased whole blood viscosity. Transfusion of RBCs to correct anemia prior to chemotherapy may initiate leucostasis. 528 Management Urgent leucapheresis is required for a patient with marked leucostasis (>200 109/L) or in any patient in whom leucostasis is suspected. Chemotherapy may be commenced co ncomitantly to further reduce the leucocyte count but may be associated with a high inciden ce of pulmonary and CNS hemorrhage. 13-haem emergencies.qxd 10.12.2003 04.29 PM Page 529 Hematological emergencies 529 13-haem emergencies.qxd 10.12.2003 04.30 PM Page 530 Thrombotic thrombocytopenic purpura Definition Fulminant disease of unknown etiology characterized by increased platelet aggreg ation and occlusion of arterioles and capillaries of the microcirculation. Considerable ove rlap in pathophysiology and clinical fea- tures with HUS \200\224fundamental abnormality m ay be identical. Incidence: Rare, 1 in 500,000 per year. 3:9 = 2:1. HUS much commoner in chil- dren, TTP co mmoner in adults \200\224peak age incidence is 40 years, and 90% of cases <60 years old. Th ere is some case clustering. Clinical features 2 Classical description is of a pentad of features: 1. Microangiopathic h aemolytic anemia. 2. Severe thrombocytopenia. 3. Neurological involvement. 4. Renal impairm ent. 5. Fever. In practice, few patients have the full monty. 50 \200\22370% have renal abn or- malities (cf. nearly all with HUS) and they are less severe. Neurological involvement i s more prevalent in TTP than HUS. 40% of TTP patients have fever. 2 Haemolysis \200\224severe and intravascular causing jaundice. 2 Thrombocytopenia \200 \224severe, mucosal hemorrhage likely and intracranial hemorrhage may be fatal. 2 Neurological \200\224from mild depression and confusion7visual defects, coma and status epilepticus. 2 Renal \200\224haematuria, proteinuria, oliguria and 4 urea and creatinine. 530 HUS >TTP. 2 Fever \200\224very variable, weakness and nausea common. 2 Other disease features: seriou s venous thromboses at unusual sites (e.g. sagittal sinus \200\224microthrombi in the brain seen on MRI scan). Abdominal pain severe e nough to mimic an acute abdomen is some- times seen due to mesenteric ischaemia. Diarrhea i s common, partic- ularly bloody in HUS. Diagnosis and investigations 2 Made on the clinical features above \200\224exclude other d iseases e.g. cere- bral lupus, sepsis with DIC. 2 FBC shows severe anemia and thrombocytopenia. 2 Blood movie shows gross fragmentation of red cells, spherocytes and nucleated red cells with polychromasia. 2 Reticulocytes 44 (>15%). 2 LDH 44 (>1000iu/L). 2 Clotting screen including fibrinogen and FDPs usually normal (cf. DIC). 2 Serum haptoglobin low or absent. 2 Urinary haemosiderin + ve. 2 Unconjugated bilirubin 4. 2 DAT \200\223ve. 2 BM hypercellular. 13-haem emergencies.qxd 10.12.2003 04.30 PM Page 531 Hematological emergencies 2 U&E show increases (HUS > TTP). 2 Proteinuria and haematuria. 2 Renal biopsy shows microt hrombi. 2 Stool culture for E. coli 0157 +ve in most cases of HUS in children, less often in adult TTP. 2 MRI brain scan shows microthrombi and occasional intracranial haem- orrhage. 2 Lumbar puncture \200\223 do not proceed with LP unless scans clear and there is suspicion of infective meningitis. 2 Look for evidence of viral infection. Association of syndrome with HIV, SLE, cyclosporin usage and the 3rd trimester of pregnancy. Treatment is a hematological emergency \200\224seek expert help immediately 1. Unless antecubital venous access is excellent, insert a large bore central apheresis catheter (may need blood product support). 2. May need ITU level of care and ventilation. 3. Initiate plasmapheresis as soon as possib le. Exchange 1 \200\2231.5 plasma volume daily until clinical improvement. May need 3 \200 \2234L exchanges. Replacement fluid should be solely FFP. In the event of delayed access to cell separator facilities, start IV infu- sions of FFP making intravascular space with diu retics if necessary. Once response achieved, 5 frequency of exchanges gradually. If no resp onse obtained within one week, change FFP replacement to cryosupernatant (rationale: it lac ks high molecular weight multimers of von Willebrand factor postulated in endothelial damag e disease trig- gers). 531 4. Give RBC as necessary but reserve platelet transfusions for severe mucosal or intracrani al bleeding as reports suggest they may worsen the disease. 5. Cover for infection with IV broad spectrum antibiotics including teicoplanin if necessary to preserve the apheresis catheter. 6. Start anticonvulsants if fitting. 7. Most would start high dose steroids (prednisolone 2 mg/kg/d PO) with gastric protection although evidence is equivocal. 8. Aspirin/dipyridamole/heparin may be considered for non-responders. 9. Refractory patient s ( 10%) should be considered for IV vincristine. 10. Still refractory patients may achieve remission with splenectomy. 11. Response to treatment may be dramatic e.g. ventilated, com atose patient watching TV in the afternoon after plasma exchange in the morning! Prognosis 2 90% respond to plasma exchange with FFP replacement. 2 30% will relapse. Most respond again to further plasma exchange but leaves 15% who become chronic relapsers. 2 Role of prophylaxis for chronic relapsers unclear. Intermittent FFP infusions or continuo us low dose aspirin may help individual cases. 13-haem emergencies.qxd 10.12.2003 04.30 PM Page 532 Sickle crisis Management (cid:2) Early and effective treatment of crises essential (hospital). (cid:2) Re st patient and start IV fluids and O2 (patients often dehydrated through poor oral intake of fluid + excessive loss if fever). (cid:2) Start empirical antibiotic therapy (e.g. cephalosporin) if infection is sus- pected whilst culture results (blood, urine or sputum) are awaited. (cid:2) Analgesia usually required \200\224e.g. intravenous opiates (diamorphine/morphine) especially when patients are first admitted to hospital. Switch late r to oral medication after the initial crisis abates. (cid:2) Consider exchange blood trans fusion (if neurological symptoms, stroke or visceral damage). Aim to 5 HbS to <30%. (cid:2) Exchange transfusion if PaO2 <60mm on air ((cid:2)chest syndrome). (cid:2) a-adrene rgic stimulators for priapism. (cid:2) Seek advice of senior hematology staff. (cid:2) Cons ider regular blood transfusion if crises frequent or anemia is severe or patient has had CVA/abnormal brain scan. (cid:2) Top-up transfusion if Hb <4.5g/dL (hunt for cause). Transfusion and splenectomy may be lifesaving in children with splenic sequestration. 532 (cid:27) www.bcshguidelines.com/pdf/SICKLE.V4_0802.pdf 13-haem emergencies.qxd 10.12.2003 04.30 PM Page 533 Hematological emergencies 533 13-haem emergencies.qxd 10.12.2003 04.30 PM Page 534 This page intentionally left blank 534 14-supportive care.qxd 10.12.2003 04.32 PM Page 535 Supportive care 14 Quality of life 536 Pain management 538 Psychological support 540 14-supportive care.qxd 10.12.2003 04.32 PM Page 536 Quality of life In managing any disease problem a key objective is to improve the quality of a patient \200 \231s survival as well as its duration. Part of the clinical decision- making process takes into account quality of life (QoL) in judging the most appropriate treatment. Defining quality of life precisely is not easy; it has been described as a measure of the d ifference at a particular time point between the hopes and expectations of the individual a nd that individual \200\231s present experi- ences. QoL is multifaceted and can only be ass essed by the individual since it takes into account many aspects of that individual \200 \231s life and their current perception of what, for them, is good QoL in their specific ci rcumstances. A clear distinction exists between performance scores (e.g. Karnofsky or WHO) which record functional status and assess independence; these are assessed by the physician according to pre-set criteria. They have erro- neously been considered to be surrogate markers of QoL. Patient QoL as assessed by the treating physician has been shown to be unreliable in an onc ological setting. There is no single determinant of good QoL. A number of qualities which go to make up QoL a re capable of assessment; these include ability to carry on normal physical activities, abi lity to work, to engage in normal social activities, a sense of general well-being and a pe rception of health. Several validated instruments now exist to measure QoL; these mainly involve questionnaires completed by the patient. They are simple to com- plete and involve \200\230yes \200\231 or \200\230no \200\231 answers to specific questions, answers on a linear analog scale or the use of 4- or 7- point Likert scales. 536 Available QoL instruments include 2 Functional Living Index \200\223 Cancer (FLIC)1 2 Func tional Assessment of Cancer Therapy (FACT)2 2 European Organization for Research and Treatm ent in Cancer (EORTC) Quality of Life Questionnaire C-30 (QLQ C30)3 Data from validated QoL questionnaires are now accepted as a require- ment and a clinical e nd point in many major clinical trials, especially in malignancies, particularly those wher e survival differences are minimal between contrasting therapy approaches. Where survivals are minimally affected it is then essential to focus on treatments which will offer the bes t QoL. Schipper, H. et al. (1984) Measuring the quality of life of cancer patients: the Functional Living Index \200\223Cancer: development and validation. J Clin Oncol, 2, 472 \200\223483; Cella, D.F. et al. (1993) The Functional Assessment of Cancer Therapy scale: development a nd validation of the general measure. J Clin Oncol, 11, 570 \200\223579; Aaronson, N.K. et al. (1993) The European Organization for Research and Treatment of Cancer QLQ-C30: a qualit y-of-life instrument for use in international clinical trials in oncology. J Natl Cancer In st, 85, 365 \200\223376. 14-supportive care.qxd 10.12.2003 04.32 PM Page 537 Supportive care 537 14-supportive care.qxd 10.12.2003 04.32 PM Page 538 Pain management Pain is a clinical problem in diverse hematological disorders, notably in sickle cell disea se, hemophilia and myeloma. Acknowledgement of the need to manage pain effectively is an es sential part of successful patient care and management in clinical hematology. Pain may be local or generalized. More than one type of pain may be present and causes may be multifactorial. It is most important to listen to the patient and give him/her the chanc e to talk about their pain(s). Not only will this help determine an appropriate therapeutic strategy, the act of listening and allowing the patient to talk about their pains and asso ci- ated anxieties is part of the pain management process.