Hematology · Coagulation Disorders
The facts most likely to be tested
Heparin-induced thrombocytopenia (HIT) is caused by IgG antibodies against the heparin-platelet factor 4 (PF4) complex.
The classic clinical presentation is a greater than 50% drop in platelet count occurring 5 to 10 days after the initiation of heparin therapy.
HIT is a prothrombotic state characterized by paradoxical venous and arterial thrombosis rather than bleeding.
The 4Ts score (Thrombocytopenia, Timing, Thrombosis, oTher causes) is the primary clinical tool used to assess the pretest probability of HIT.
The serotonin release assay (SRA) is the gold standard confirmatory test for the diagnosis of HIT.
Immediate management requires the discontinuation of all heparin products and the initiation of a non-heparin anticoagulant such as argatroban or fondaparinux.
Warfarin must be avoided in the acute phase of HIT until the platelet count has recovered to at least 150,000/µL to prevent venous limb gangrene.
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A 62-year-old male is hospitalized for a deep vein thrombosis and is started on unfractionated heparin. On hospital day 7, his platelet count drops from 280,000/µL to 110,000/µL. Physical examination reveals a new, painful, erythematous, and swollen right lower extremity. A venous duplex ultrasound confirms a new extensive deep vein thrombosis in the right popliteal vein. The patient has no history of recent surgery or malignancy.
What is the most appropriate next step in management?
Discontinue heparin and initiate argatroban.
The patient exhibits a classic >50% platelet drop 5-10 days after heparin exposure with new thrombosis, meeting high-risk criteria for HIT; immediate cessation of heparin and transition to a non-heparin anticoagulant is required.
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Etiology / Epidemiology
Immune-mediated reaction to heparin-PF4 complex. Risk is highest with unfractionated heparin and surgical patients.
Clinical Manifestations
New thrombosis despite falling platelets. 4Ts score is the primary clinical assessment tool.
Diagnosis
Serotonin release assay (SRA) is the gold standard. Platelet count drop of >50% from baseline is diagnostic.
Treatment
Stop all heparin immediately. Start Argatroban or Bivalirudin. Do not use warfarin until platelets recover.
Prognosis
High risk of venous/arterial thrombosis. Mortality is 20-30% if untreated.
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Epidemiology & Etiology
HIT occurs in 1-3% of patients exposed to unfractionated heparin. It is an immune-mediated disorder, not a direct toxic effect. Exposure to low-molecular-weight heparin carries a lower, but non-zero, risk.
Pertinent Anatomy
The condition involves the systemic vasculature, specifically targeting the interaction between platelet factor 4 (PF4) and heparin. Thrombi can form in both the venous and arterial systems, leading to multi-organ involvement.
Pathophysiology
IgG antibodies form against the heparin-PF4 complex. These immune complexes bind to the FcγIIa receptors on platelets, causing massive activation and aggregation. This leads to a paradoxical state of prothrombotic consumption and thrombocytopenia.
Clinical Manifestations
The hallmark is a >50% drop in platelet count occurring 5-10 days after heparin initiation. Patients present with new venous limb gangrene or arterial thrombosis. Skin necrosis at injection sites is a classic warning sign.
Diagnosis
The 4Ts score (Thrombocytopenia, Timing, Thrombosis, oTher causes) guides pre-test probability. The Serotonin release assay (SRA) is the definitive functional test. ELISA for PF4-heparin antibodies is sensitive but less specific.
Treatment
Discontinue all heparin products immediately. Initiate non-heparin anticoagulation with Argatroban or Bivalirudin. Avoid warfarin initially due to the risk of venous limb gangrene caused by rapid protein C depletion.
Prognosis
Untreated HIT carries a high risk of thromboembolic complications. Patients require monitoring for new thrombosis and platelet recovery. Once platelets exceed 150,000/µL, warfarin may be cautiously introduced.
Differential Diagnosis
Pseudothrombocytopenia: EDTA-induced clumping in the collection tube
DIC: Associated with abnormal coagulation studies (PT/PTT/Fibrinogen)
TTP: Characterized by pentad including schistocytes and fever
Post-transfusion purpura: History of recent blood product exposure
Drug-induced thrombocytopenia: History of other offending agents like vancomycin