Heparin Induced Thrombocytopenia

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Contents 1 Etiology 2 Epidemiology 3 Pathology 4 Clinical-manifestations 5 Laboratory 6 Complications 7 Management 8 More General Terms 9 Additional Terms 10 References

Etiology

• immune-mediated

• reactivation is due to circulating IgG antibodies to heparin- platelet factor IV complex

• non- immune form

• direct weak activation of platelets by heparin

• may occur with therapeutic dose, prophylaxis or intravenous flushes
• low molecular weight heparin is significantly less likely to cause HIT than standard heparin

Epidemiology

• 1% at 7 days, 3% at 14 days in patients receiving unfractionated heparin
• often occurs in patients initially treated with heparin for antithrombotic prophylaxis for atrial fibrillation

Pathology

• immune-mediated

• life-threatening venous & arterial thrombotic complications
• in-vivo platelet activation
• generation of procoagulant platelet-derived micro- particles
• IgG antiheparin antibody that reacts with:

• circulating heparin
• platelet factor-4 ( PF4) (an alpha-granule protein)

• immune complex binds to circulating platelets & activates Fc receptors which promote intravascular platelet aggregation
• immune complex also bind vascular endothelial cells & induce endothelial cell expression of tissue factor
• venous thrombosis in > 80% of patients
• arterial thrombosis may also occur
• IgG antiheparin antibody declines to undetectable levels at about 2 months [2]

• non- immune form

• generally NOT associated with adverse clinial outcomes
• spontaneous resolves or resolves with heparin withdrawal

Clinical-manifestations

• immune form

• generally occurs from 5-15 days [1] (4-10 days [2]) after initiation of unfractionated heparin therapy
• make occur much earlier (< 10 hours) in patients previously exposed (within 100 days) to unfractionated heparin (re-activation)
• may occur AFTER hospital discharge
• thromboembolism ( DVT)

• non- immune form

• generally occurs within 1st 2 days of heparin administration

Laboratory

• complete blood count ( CBC)

• thrombocytopenia (or decrease in platelet count of > 50%)

• functional heparin-induced thrombocytopenia assay

• washed platelet aggregation or serotonin-release

• antigen assays based upon reactivity with PF4 complexed with heparin, Heparin- PF4 ELISA [1]

Complications

• thromboembolic event 5-10 days after starting heparin

Management

• discontinue heparin

• cessation of all forms of heparin therapy including removal of heparin-coated catheters

• stabilize patient with direct thrombin inhibitor prior to initiation of warfarin

• argatroban (avoid in hepatic insufficiency)
• lepirudin (avoid in renal insufficiency)

• dextran followed by warfarin has also been used; dextran has been used as a substitute for heparin to prevent large artery thrombosis
• low-molecular weight heparin has about 90% cross-reactivity
• promising agents

• danaparoid sodium
• anacrod (defibrinogenating snake venom)
• heparinoid

More General Terms

• thrombocytopenia

Additional Terms

• alpha granule
• chemokine (C-X-C motif) ligand 4 or platelet factor-4 (PF-4)
• danaparoid (Orgaran)
• heparin
• heparinoid
• low molecular weight (LMW) heparin

References

1. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15 American College of Physicians, Philadelphia 1998, 2006, 2009
2. Journal Watch 21(10):77, 2001 Wartentin TE et al Temporal aspects of heparin-induced thrombocytopenia. N Engl J Med 344:1286, 2001 PMID: [1]
3. Journal Watch 22(7):57, 2002 Rice L et al Delayed-onset heparin-induced thrombocytopenia. Ann Intern Med 136:210, 2002 PMID: [2]
4. National Guideline Clearinghouse Treatment and prevention of heparin-induced thrombocytopenia. American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). ngc-guideline: [3]

heparin-induced thrombocytopenia (HIT)