Approach
• Stabilize pt (ABCs, IV access/monitor) if necessary
• Differentiate cause of bleeding → PLT vs. coagulation abnlty
• Consult hematology for any pt w/ severe bleeding & known or suspected bleeding d/o
Findings
• Purpura
• Nonpalpable: TCP, PLT Dysfxn, DIC, TTP, cholesterol/fat emboli, scurvy, trauma
• Palpable: Vasculitis, HSP, PAN, RMSF, meningococcemia, bacterial endocarditis
Evaluation
• CBC w/ differential, Chem 7, coags; consider LFTs, peripheral blood smear, DIC panel (fibrinogen, D-dimer, LDH, haptoglobin)
THROMBOCYTOPENIA (TCP) AND PLATELET DYSFUNCTION
Approach
• Isolated TCP: ITP, immune, medications, infection
• TCP + abnl CBC/smear: DIC, HUS, TTP, aplastic anemia, malignancy
Definition
• By PLT count
• <150000: TCP
• >100000: No ↑ risk bleeding
• <50000: Risk of minor bleeding, increased bleeding in trauma
• <20000: Risk of spontaneous bleeding
• <10000: Risk of severe bleeding such as GIB, ICH
History
• PMH (EtOHism, HIV, malignancy, pregnant, meds), infection
Findings
• Splenomegaly, LAD, bleeding
Evaluation
• CBC w/ differential; consider the following:
• Hemolysis w/u: Reticulocyte count, LDH, haptoglobin, bilirubin, peripheral blood smear, coags, fibrinogen, D-dimer, direct Coombs
IMMUNE THROMBOCYTOPENIA (Blood 2010;115(2):168)
Approach
• This is a Dx of exclusion → w/u other etiologies beforehand (TTP/HUS, other immune-mediated dz, drugs, HIV, HCV)
• Consider myelodysplasia in pts >60 y/o
Definition
• Immune Ab-mediated destruction of PLTs (PLT count <100 × 109/L) subdivided into primary (no known cause) & secondary (to viruses, drugs, autoimmune dzs, vaccines)
History
• Gradual onset of petechiae, epistaxis, easy bruising, menorrhagia, hematuria, GIB, recent viral illness
Evaluation
• CBC w/ differential, peripheral blood smear, T + S, Ig levels, HIV/HCV, H. pylori, direct antiglobulin
Treatment
• Rarely indicated for PLTs >50 × 109/L unless increased risk for bleeding or surgery
• Consider hematology consult in adults: Often require tx 2/2 very low PLTs
• Steroids: Prednisone 0.5–2 mg/kg/d w/ taper → short-term utility; give methylprednisolone 1 g/d IV if active bleeding
• If active bleeding or unresponsive to steroids, Anti-Rh(D) Ig: 75 mcg/kg/d IV → for Rh(D)+ pts; IVIG: 1 g/kg/d IV × 1–2 d
• PLT transfusion for bleeding or very low PLTs → use w/ IVIG or Anti-Rh(D) Ig
• Children: Manage mild cases expectantly, treat if PLTs <20000 or active bleeding
• Steroids: Prednisone 4 mg/kg/d PO × 4 d
• Anti-Rh(D) Ig: 75 mcg/kg IV × 2 d
• IVIG: 0.8–1 g/kg IV × 1 dose
Disposition
• Home: If no active bleeding, PLTs >20000
• Admit: Any pt w/ PLTs <20000 &/or active bleeding
Pearls
• Though 50–75% pts respond to steroids, <20% have sustained remission after taper
• ∼50% ITP occurs in children
HEPARIN-INDUCED THROMBOCYTOPENIA (HIT) (Chest 2012;141(2 suppl):e495S)
Definition
• Either direct (type I) or Ab-mediated (type II) PLT activation → heparin stimulates formation of IgG → binds to PF4 & heparin on PLT surface → PLT-derived microparticles form & promote thrombin release → ↑ thrombosis
Diagnosis
• PLTs: <150000 or ↓ 30–50% from baseline
• Thrombosis in all vascular beds: eg. PE, DVT, limb ischemia, stroke, MI → up to 50% pts
• Increased heparin resistance
• HIT Ab (PF4-heparin ELISA): ↓ PPV (10–93%) & ↑ NPV (>95%), so send only if intermediate/high PreTP ± confirm w/ PLT aggregation test
History
• Low PLTs ± thrombosis, 5–10 d after starting heparin (rarely causes bleeding), more rapid onset less common but a/w more recent heparin exposure (<30 d)
Treatment (NEJM 2006;355:809)
• STOP heparin + any device/flush that contains heparin
• Consult hematology
• If on therapeutic heparin: Switch to alternative (argatroban, bivalirudin, lepirudin)
• Avoid PLT transfusions unless bleeding or high risk of bleeding
• Future use of heparin (NEJM 2001;344:1286): Risk may be low if negative for PF4 Ab >100 d after Dx
Disposition
• Admit
HEMOLYTIC-UREMIC SYNDROME (HUS) AND THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP) (J Intensive Care Med 2007;22(2):82; Br J Haematol 2012;158(3):323; NEJM 2006;354:1927)
Definition
• Systemic (TTP) or intrarenal (HUS) vascular occlusive d/o via PLT aggregation → MAHA (TCP/hemolysis), though their underlying cause is different
• A/w ADAMTS-13 deficiency → inability to cleave vWF → microthrombi
Differential
• Sepsis, DIC, HELLP
History
• HUS:
• HUS triad: MAHA, TCP, renal failure
• Children w/ bloody diarrhea → 2/2 enterohemorrhagic E. coli Shiga toxin
• TTP:
• TTP pentad (uncommon): MAHA, TCP, renal failure, AMS, fever
• Adults → often idiopathic or 2/2 drugs (ie, clopidogrel, chemotherapy, quinidine)
Evaluation
• CBC w/ differential, Chem 7, peripheral blood smear, coags, LFTs, LDH, haptoglobin, fibrinogen, D-dimer, UA
• Dx: MAHA + TCP (same for HUS or TTP)
• MAHA: Evidenced by schistocytes, ↑ LDH, ↑ indirect bilirubin, ↑ Cr (HUS > TTP), ↓ haptoglobin
Treatment
• Consult hematology, consider renal consult early
• TTP:
• Plasma exchange: All pts w/ TTP → ↑ survival @ 6 mo (NEJM 1991;325:393)
• FFP: If there is a delay to plasma exchange
• Steroids: Prednisone 1–2 mg/kg/d, methylprednisolone 1 g/d max 3 d (no well-designed studies evaluating efficacy)
• Low-dose aspirin when PLTs recover (anecdotal evidence), folate supplementation
• HUS: Mainly supportive ± dialysis
Disposition
• Admit
Pearls
• Do not give PLTs → ↑ microvascular thrombosis
• Mortality of TTP is up to 90% w/o tx (NEJM 2006;354:1927), while HUS often resolves w/o tx
VON WILLEBRAND’S DISEASE (vWD) (NEJM 2004;351:683; Haemophilia 2008;14(2):171)
Definition
• vWF defect/↓: A substrate for PLT aggregation/carrier of factor VIII
• Autosomal dominant or recessive, or acquired (eg, malignancy, meds)
History
• Can present like TCP &/or coagulopathy → role w/ PLTs & factor VIII
• Mucocutaneous bleeding & bleeding after surgery, menorrhagia, easy bruising, epistaxis, rarely hemarthrosis, hematoma (severe forms)
Evaluation
• CBC w/ differential (↓ PLTs), Chem 7, coags (↑ PTT), ↓ factor VIII, ↓ vWF: Ag, ↓ vWF activity
Treatment
• Desmopressin (DDAVP): Efficacy is variable, causes endothelial release of vWF
• vWF replacement: Via cryoprecipitate (requires up to 8–12 bags), plasma-derived vWF/factor VIII concentrate (Humate-P), or recombinant vWF, w/ antifibrinolytic amino acids (as adjunct)
Disposition
• Depends on pt’s presentation, severity of vWD, & location of bleeding
Pearl
• Most common inherited bleeding d/o
COAGULOPATHY
Approach
• Differentiate inherited vs. acquired, & tx underlying causes
Evaluation
• CBC, PT, PTT, LFTs, fibrinogen, factor inhibitors
DISSEMINATED INTRAVASCULAR COAGULATION (DIC) (Br J Haematol 2009;145(1):24)
Approach
• DIC is an acquired d/o → look for underlying cause (see below)
Definition
• Widespread activation of coagulation → fibrin → thrombosis of small/midsized vessels; if severe, ongoing coagulation → ↓ PLTs/coagulation proteins → bleeding
Evaluation
• Dx based on predisposing condition (above) + ↓ PLTs (usually <100), ↑ PT/PTT, ↑ D-dimer, ↓ fibrinogen, ↑ LDH, ↑ FDP, antithrombin, end-organ damage
Treatment
• Treat underlying disorder
• Heparin: Low dose (IV) if thromboembolism is predominant component (controversial)
• Antithrombin III may reduce mortality in pts w/ severe sepsis & DIC (↑ bleeding risk) (Blood Coagul Fibrinolysis 2006;17(7):521)
• Transfuse: PLTs, cryoprecipitate, FFP, prothrombin complex concentrate (if ↑ volume)
Disposition
• Admit to ICU
Pearl
• Can be difficult to differentiate from severe liver dz
HEMOPHILIA (NEJM 2001;344:1773)
Approach
• Differentiate type of hemophilia, severity, & prior tx for bleeding
• Contact hematology early for any suspicion of bleeding
Definition
• X-linked d/o caused by ↓ or inhibitor of factor VIII (hemophilia A), acquired hemophilia A, or factor IX (hemophilia B)
Findings
• Bleeding (GI, GU, mucosa), hematoma, hemarthroses, bruising
Evaluation
• ↑ PTT, nl PT, CBC
Treatment
• Consider intranasal desmopressin w/ tranexamic acid to control mild bleeding in mild hemophilia
• Factor (VIII or IX) concentrate–dosing based on extent of deficiency & severity/location of bleeding; refer to product-specific information guide or Haemophilia 2013 Jan;19(1):e1 for dosing instructions
• Consider factor VIIa or anti-inhibitor coagulant complex to reduce bleeding in pts w/ factor inhibitors