Heparin-Associated Antibody Syndrome - HIT

Heparin-Associated Antibody Syndrome - HIT

 

Heparin-associated antibody syndrome of heparin-induced thrombocytopenia (HIT) is defined by absolute thrombocytopenia or a 50% decrease in a patient’s baseline count.

Epidemiology

  • Prevalence – 1-5% occurrence in patients receiving unfractionated heparin
  • Age – uncommon in patients <18 years of age; higher risk in elderly patients
  • Sex – female predominance

Risk Factors

  • Age – adults
  • Medical-related event – surgical cases are more common than medical cases
  • Type of heparin
    • Porcine heparin (lower risk with porcine)
    • Unfractionated heparin (lower risk with low molecular weight heparin)

Pathophysiology

  • Involves platelet-activating heparin-dependent antibodies
  • Antibody is IgG and causes platelet activation with subsequent clot formation and platelet depletion – anti H-PF4 complex
  • Paradoxically increased risk for thrombosis

Clinical Presentation

  • Thrombocytopenia – 30% drop from baseline usually after 4-5 days of therapy
    • Thrombocytopenia during heparin therapy does not necessarily indicate HIT
  • Thrombosis
    • Venous – deep vein thrombosis (DVT), pulmonary embolism (PE), cerebral vein thrombosis
    • Arterial – distal sites, stroke, myocardial infarction (MI), mesenteric artery

Diagnosis

  • Indications for testing – thrombocytopenia in patient receiving heparin; venous or arterial thromboses in patient receiving heparin
  • Laboratory testing
    • Initial CBC with platelet count
    • Assess risk for HIT – score of 6-8 suggests >80% probability of positive antibodies on testing

The 4T’s Scoring System for HIT
4T’s 2 Points 1 Point 0 Points

Thrombocytopenia

Platelet count fall >50% and platelet nadir ≥20

Platelet count fall 30-50% or platelet nadir 10-19

Platelet count fall <30% or platelet nadir <10

Timing of platelet count fall

Clear onset between days 5-10 or platelet fall ≤1 day (prior heparin exposure within 30 days)

Consistent with days 5-10 fall but not clear (eg, missing platelet counts); onset after day 10; or fall ≤1 day (prior heparin exposure 30-100 days ago)

Platelet count fall <4 days without recent exposure

Thrombosis or other sequelae

New thrombosis (confirmed), skin necrosis, acute systemic reaction postintravenous unfractionated heparin (UFH) bolus

Progressive or recurrent thrombosis; non-necrotizing (erythematous) skin lesions, suspected thrombosis (not proven)

None

Other causes for thrombocytopenia

Not apparent

Possible

Definitive

Low probability = ≤3 points; intermediate = 4-5 points; high = 6-8 points
Stribling, W. Kyle; Slaughter, Thomas F.; Houle, Timothy T.; Sane, David C.; Beyond the Platelet Count: Heparin Antibodies as Independent Risk Predictors; American Heart Journal; June 2007; p. 904
  • Perform IgM and IgG platelet antibodies testing followed by serotonin testing if probability is not low
    • Negative test does not rule out heparin-induced thrombocytopenia

Differential Diagnosis

  • Antiphospholipid syndrome
  • Autoimmune thrombocytopenic purpura
  • Drug-induced thrombocytopenia caused by:
    • Diclofenac
    • Ibuprofen
    • Quinidine
    • Quinine
    • Trimethoprim-sulfa
  • Hemolytic uremic syndrome
  • Malignancy
  • Sepsis-induced thrombocytopenia and disseminated intravascular coagulation (DIC)
  • Systemic lupus erythematosus (SLE)
  • Vasculitis

Treatment

  • Remove heparin
  • Limit exposure to heparin
  • Directed therapies
    • Lepirudin, argatroban or danaparoid

See Also