Overview

• Disorders of primary hemostasis
  • General: present with mucocutaneous, post-operative bleeding
  • vWD
  • Platelet disorders
    • Medication-induced: NSAID, valproate, B-lactam, SSRI
    • Systemic disease: hepatic, renal failure
  • ITP: antibody-mediated platelet destruction
• Disorders of secondary hemostasis
  • General: present with bleeding into soft-tissue, joints
  • Hemophilia A (VIII)
  • Hemophilia B (IX)
• Disorders of both primary and secondary hemostasis
  • DIC
  • Liver disease
  • Severe vWD
• Evaluation
  • PT: VII, vitamin K
  • PTT: VIII, IX, XI, XIII, vWD, heparin
  • Increased PT/PTT: XI, V, vitamin K, heparin, DIC
  • CBC: degree of anemia, platelet count, differential (hematopoetic disorders)
• Management
  • Thrombocytopenia
    • Prophylactic transfusion for avoidance of spontaneous hemorrhage for platelet count <10,000
    • Transfusion for active bleeding at platelet count <50,000
    • Dosing
      • Adults: one RDP increases platelet count by 7-10,000
      • Pediatrics: 5-10ml/kg
    • ITP
      • Transfuse platelets for active bleeding
      • High-dose steroids (prednisone 1mg/kg)
      • IVIG (1g/kg/d)
    • Uremia
      • Hemodialysis
      • DDAVP (0.3ug/kg IV)
    • vWD
      • DDAVP (0.3ug/kg IV)
      • Severe: VWF (Humate-P) 40-80IU/kg
      • Tranexamic acid
    • Hemophilia A
      • Minor: 20IU/kg
      • Major: 50IU/kg
    • Hemophilia B
      • Minor: 40IU/kg
      • Major: 100IU/kg

DIC/TTP/HUS

• Disseminated Intravascular Coagulation
  • Etiology: severe systemic illness/injury
    • Trauma, burn, crush
    • Sepsis
    • Malignancy
    • Obstetric complication: abruption, amniotic fluid embolism
    • Hemolytic anemia
  • Exam: petechiae/purpura, hemorrhage (puncture site, GI, GU, pulmonary)
  • Labs:
    • PT/PTT
    • Fibrinogen
    • CBC: schistocytes, thrombocytopenia
    • FDP/D-Dimer
  • Management
    • Treat underlying illness
    • Transfuse (PRBC, FFP for INR > 2, cryoprecipitate for fibrinogen < 100)
    • Heparin if apparent embolic events
    • Consult hematology
• TTP/HUS
  • Presentation
    • Thrombocytopenia
    • Altered mental status
    • Renal dysfunction
    • Fever
    • MAHA
  • TTP: more commonly associated with altered mental status
    • Etiology: drugs, pregnancy, infection (HIV)
    • Mechanism: ULvWF uncleaved by dysfunctional ADAMTS-13
  • HUS: more commonly associated with renal dysfunction
    • Mechanism: toxin from E. coli, Shigella
    • Timing: 1-2wks after diarrheal illness
  • Evaluation
    • CBC: anemia, schistocytes, thrombocytopenia
    • PT/PTT (normal)
    • BUN/Creatinine
    • LDH
  • Management
    • Platelets contraindicated except as stopgap measure in ICH (can worsen process)
    • Plasma exchange with FFP (replaces functional ADAMTS-13)
    • Steroids (prednisone 1mg/kg daily)
    • Hematology consultation

Complications of anti-thrombotic therapy

• Agents
  • Anti-platelet
    • TXA: Aspirin
    • ADP: clopidogrel, ticagrelor, prasugrel
    • GPIIb/IIIa: abciximab, eptifibatide, tirofiban
  • Anti-coagulants
    • Anti-thrombin: heparin, LMWH (enoxaparin, dalteparin)
    • Vitamin K antagonist: warfarn (anti-II, VII, IX, X)
    • Direct thrombin inhibitor: bivalirudin, argatroban, dabigatran
    • Xa inhibitor: rivaroxaban, apixaban
  • Fibrinolytics
    • Alteplase, tenectaplase
• Complications
  • HIT: platelet count decrease >50% at 5 days

Summary of Management

Agent	Reversal
Aspirin, clopidogrel	5-10U platelets DDAVP 0.3ug/kg
GPIIb/IIIa	Abciximab: 5-10U platelets Eptifibatide/tirofiban: none
Heparin	Protamine 1mg/100mg heparin in last 2-3 hours
LMWH	Enoxaparin: 1mg/1mg Dalteparin: 1mg/100U
Warfarin	See supratherapeutic INR algorithm
DTI	Dabigatran: Praxbind, hemodialysis, consider Factor VIIa
Xa	PCC
Fibrinolytics	10U cryoprecipitate, 2U FFP, consider platelets and aminocaproic acid (4-5g IV)