Hematologic Emergency. Le Wang, MD, PhD Hematology & Oncology
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1 Hematologic Emergency Le Wang, MD, PhD Hematology & Oncology
2 Severe Thrombocytopenia (ITP)
3 Clinical: bleeding risk 0 no bleeding; 1 minimal bleeding after trauma; 2 spontaneous but selflimited bleeding; 3 spontaneous bleeding requiring special attention; 4 life threatening bleeding.
4 Diagnosis No golden standard: diagnosis of exclusion Essential: H & P, CBC and Peripheral Smear Exam Rule out 2 nd causes (infection, stress or drug induced, etc) HIV, HBV/HCV testing Bone marrow bx NOT needed Anti-platelet antibody testing NOT necessary or appropriate.
5 Emergent Management Corticosteroid: 1mg/kg, long course superior to shorter course. IVIG or anti-d if steroid are contraindicated (IVIG 1gm/kg/day x 2). Use IVIG + steroid when a rapid response is needed.
6 Heparin-induced thrombocytopenia
7 Mechanism of HIT
8
9 Memory B cells
10
11 Diagnosis: Pretest Probability, HIT Screening, HIT Confirmation
12 Pre-Test Probability: 4T Score
13 Platelet Count Nadirs: HIT vs D-ITP
14 Treatment Stop all heparin products Start Direct Thrombin Inhibitors (DTI) if 4T score > 4 No coumadin until platelet >150,000 No platelet transfusion Confirmation HIT test Duration for anticoagulation: 3 months if no thrombosis, 6 months if thrombosis.
15 DIC: Syndrome, NOT a disease Triggers Primary thrombin generation (pathologic) intravascular fibrin formation Secondary fibrinolysis bleeding Hemorrhage, thrombosis, multi-organ failure
16 Diagnosis: Clinical + Lab
17 Managing DIC DIE Treat the underlying cause Supportive: Hemodynamic and ventilatory support Treatment of bleeding: - Platelet transfusion: PLT <10,000 or 20,000 - FFP if plasma fibrinogen >100 mg/dl - Cryo if plasma fibrinogen <100 mg/dl - DO NOT USE antifibrinolytic agents Treatment of thrombosis: - Heparin
18 Medical Emergency Acute Promyelocytic Leukemia (APL) Coagulopathy DIC (medical emergency): - Tx: ATRA (all trans retinoic acid) ATRA Differention Syndrome: - Sx: fever, hypotension, dyspnea, edema, pulmonary hemorrhage - Tx: Glucocorticoid (Dex 10mg bid)
19 Purpura Fulminans Life-threatening emergency: acute widespread retiform purpura Cause: Meningococcal infection in the background of protein C deficiency Treatment: FFP/Protein C concentrate, treat underlying disease
20 Warfarin Skin Necrosis Causes: combined effect of protein C deficiency and Vit K antagonism. Sx: purpura and skin necrosis Tx: - Stop coumadin - Aggressively reverse coumadin (IV vit K) - Heparin - FFP/Protein C concentrate
21 TTP: Medical Emergency Hemolytic anemia Thrombocytopenia Neurologic Renal Fever Coomb-neg microagiopathic hemolysis
22 Diagnosis: clinical diagnosis ADMTS13 < 5% (NOT required for diagnosis)
23 ADAMT13
24 Types of TTP Idiopathic TTP (primary): IgG autoantibody directed against the vwf-cleaving metalloproteinase, leading to platelet-vwf aggregates under condition of high shear (arteriolar thrombosis). Familial recurrent TTP: gene mutation congenital deficiency of ADAMTS13 recurrent TTP. Drug-induced TTP (secondary): mitomycin, gemcitabine, cyclosporine, tacrolimus, ticlopidine Hemolytic-uremic syndrome: NOT caused by absence of ADAMTS13 (thus distinct pathogenesis)
25 Treatment Urgent Plasmaphresis!!! life-saving: daily 1 plasma vol exchange with cryo or FFP replacement No platelet transfusion
26 Acute Hemolytic Reaction ABO mismatches Sign/Sx: fever, hematuria, flank pain, nausea, vomiting, dyspnea, feeling of impending doom Mgt: - Hydration, urine output > 100cc/hr - Alkalinize urine (urine ph >7.5) - Diuresis - Increase renal blood flow (dopamine) - Watch for DIC (give platelet, FFP, etc)
27 Acute Anaphylactic Reaction (<1%) MOA: IgA-deficiency recipient Sx: Anxiety, uticaria, wheezing, progressing to cyanosis, seizures, shock, and possible cardiac arrest Mgt: - Stop transfusion, epinephrine, support - Extensively washed RBC for subsequent transfusion or IgA deficient blood
28 Transfusion Related Acute Lung Injury (TRALI) MOA: antibody in donor plasma against patient WBC Sx: occurs within 6hrs - Sudden hypoxia or increased FiO2 requirement, dyspnea. tachycardia, frothy sputum, characteristic CXR - No evidence of circulatory overload - No pre-existing or alternative etiology Mgt: - Stop transfusion, vent support,? Steroid - Test donor for anti-hla/neutrophil antibodies, inquire pregnancy history (forbid implicated donor ever donating blood again) - In the future, use only male plasma donors
29
30 Hyperviscosity Syndrome (HVS) Definition: increased blood viscosity, commonly from increased circulating serum Ig sludging and decreased perfusion of microvasculature clinical symptoms. Commonly associated with: - Waldenstrom (IgM), - Multiple myeloma (IgA, IgG3) - Polycythemia vera, - Leukostasis
31 HVS: Clinical Presentation Triad: mucosal bleeding, visual change, neurological symptoms. Heart failure, constitutional symptoms Ophthalmic exam: - Decreased visual acuity - Dilated retinal veins - Sausage-linked or boxcar segmentation of the retinal veins - Retinal hemorrhage Diagnosis: - elevated serum viscosity > 4 centipoises (CP, normal value <1.8) - work-up for underlying disease
32 HSV - Treatment Plasmapheresis: medical emergency! Plasma exchange: replacement with another fluid (albumin, FFP, etc) - Hyperviscosity: replace with albumin - TTP: replace with FFP
33 Leukostasis Definition: > 50 or 100 x 10 9 /L WBC Leukostasis: - medical emergency (one-week mortality = 20-40%) - Sx: fever, dyspnea, visual change, headache, etc confusion, coma Commonly seen in - AML: >100x10 9 /L, M4/M5. - ALL: rare - CML blast crisis - CLL: rare, may occur when WBC >400, 000
34 Treatment Leukapheresis: - Asymptomatic: hydroxyurea and/or chemo - Symptomatic: hydroxyurea plus leukopheresis, followed by chemothereapy Tumor lysis syndrome prevention
35 Tumor Lysis Syndrome (TLS) Definition: massive tumor cell lysis release of large amount of tumor cell contents into systemic circulation lethal metabolic derangement. Features of TLS: Hyperuricemia precipitate in renal tubules Hyperkalemia Hyperphosphatemia Hypocalcemia Metabolic acidosis and renal failure
36 TLS Risk Group High risk Burkitt lymphoma, DLBCL with bulky disease and LDH >2 ULN, ALL with WBC >100 x10 9 /L and/or LDH> 2 ULN, AML with WBC >100x10 9 /L Intermediate risk Small cell lung cancer, germ cell tumor, CLL treated with fludarabine, AML with WBC x10 9 /L Low risk Most solid tumor, MM, CML, HL, indolent NHL
37 TLS - Diagnosis Laboratory TLS: - two or more laboratory changes within seven days after cytotoxic therapy. Uric acid > 8mg/dl; K>6mEq/L, Phos >4.5mg/dl, Ca <7mg/dl. Clinical TLS: - laboratory TLS plus renal failure, cardiac arrhythmia, seizure or sudden death.
38 TLS - Prophylaxis Low risk for TLS Intermediate risk for TLS High risk for TLS Monitoring Hydration +/- Allopurinol Monitoring, q8hrs Hydration Allopurinol Monitoring, q6hrs Hydration Rasburicase
39 Thank You!
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