Heparin Induced Thrombocytopenia (HIT)



  • Definition: Heparin-induced thrombocytopenia is an antibody-mediated pro-thrombotic disorder.


  • Results due to Ig-G antibody formation to heparin-platelet factor-4 complexes.
  • Antibodies bind platelets & activate them.
  • Results in pro-thrombotic state, even in presence of thrombocytopenia.
  • Usually occurs 5-10 days after exposure to heparins.


  • 2 types –
  • Type I HIT
  • Type II HIT

Type I HIT:

  • Non-immune mediated reaction.
  • Decrease in platelets is b/w 10-30,000/ml.
    • Platelet drop is due to direct heparin effect on platelet activation.
  • Not of much clinical consequence.
  • Need not discontinue heparin.

Type II HIT:

  • Immune-mediated reaction.
  • Decrease in platelets by 50% or less than 150,000.
  • Heparin needs to be stopped.
  • Alternative anticoagulation needs to be started.


Treatment initiation criteria: 

  • Increased platelet count, after stopping heparin, in absence of other causes – Diagnostic criteria (even without confirmatory labs).

I) General management:

  • Stop all heparin forms, including LMW Heparins, heparin line flushes or use of heparin-coated catheters.
  • Contraindicated therapies:
  • During this time, certain therapies are contraindicated, including:
    • Platelet transfusions contraindicated.
    • LMWH contraindicated – Due to cross-reactivity.
    • Warfarin (Coumadin) contraindicated initially.

II) Drug therapy:

  • Divided into initial therapy & as continuation therapy.

1. Initial therapy:

  • Direct thrombin inhibitors:
    • Are mainstay therapy.
  • DOC – Lepirudin & Argatroban.
  • Lepirudin –
    • Safe in liver failure.
    • Lepirudin continued till platelet count reaches 1,00,000/µL.
    • Goal aPTT of 1.5-2.5x
    • Side effect – Bleeding (18%).
  • Argatroban
    • Interferes at thrombin active site.
    • Adjusted aPTT of 1.5-3x.
    • Safely administered in anuria (renal failure).
    • Not safe for hepatic failure cases, due to hepatic clearance.
  • Side effect – Bleeding (7%) & anaphylaxis.

2. Continuation therapy:

  • After lepirudin therapy (on direct thrombin inhibitors discontinuation), warfarin therapy started.
  • Reason:
    • Warfarin causes hypercoagulability, hence avoided as initial therapy.
    • Warfarin given for at least 30 days.

3. Other drugs indicated:

  • Xa inhibitors:
    • Drug Fondaparinux & Rivaroxaban
    • Fondaparinux  – Synthetic pentasaccharide.

III) Case-specific management methods:

1. For cases with HIT without thrombosis:

  • Continue anticoagulation, until at least normal platelet count.
  • Increased thrombosis risk for 2-4 weeks.
  • Coumadin for 1-3 month.

2. For cases of HIT with thrombosis:

  • Initiate Coumadin (Only after normal platelet count achieved).
  • Overlap for 5 days with thrombin inhibitor until INR therapeutic. 
  • Continue Coumadin for 3-6 months at INR 2-3.

3. For severe cases with persistent & worsening thrombosis despite HIT treatment.

  • IVIG usage.
  • Plasma exchange.
  • Aspirin, if life-threatening thrombosis.
  • Thrombolysis.
  • Thromboembolectomy.

4. Re-treatment with heparin in known HIT cases:

  • HIT antibodies (IgG or PF4 or heparin) persisting for 100 days/3 months.
  • Heparin is avoided.
  • On mandatory heparin need (As during cardiopulmonary bypass) –
    • Confirm absence of HIT antibodies.
    • Only limited & short-term usage recommended.

5. Preventive strategies:

  • Limit heparin duration (short term recommended).
  • Past HIT history listed as an allergy. 

Exam Important


  • Heparin-induced thrombocytopenia usually occurs 5-10 days after exposure to heparins.
  • Type-1 HIT is a non-immune mediated reaction, resulting in decreased platelet count up to 10-30,000/ml.
  • In type-1 HIT, there is not any need for discontinuation of heparin.
  • Type-2 HIT is an immune-mediated reaction, resulting in decreased platelet count up to 50%, or less than 150,000.
  • In type-2 HIT, heparin is discontinued & alternative anti-coagulant is started.
  • Platelet transfusions, LMWH administration & warfarin usage particularly at initial stages, are all contraindicated during HIT management.
  • Direct thrombin inhibitors are mainstay therapy for HIT management.
  • Drugs included in direct thrombin inhibitors are Lepirudin & Argatroban.
  • Lepirudin & Argatroban are DOC for treating HIT.
  • Lepirudin is safe in liver failure & used for indicated for HIT treatment even during hepatic conditions.
  • During HIT management, lepirudin continued till platelet count reaches 1,00,000/µL.
  • Main goal aimed for lepirudin usage is achieving aPTT levels of 1.5-2.5x.
  • Argatrobanused for HIT treatment nterferes at thrombin active site.
  • During HIT management, only after direct thrombin inhibitors discontinuation (lepirudin therapy)warfarin therapy is started.
  • Main reason “hypercoagulability”.
  • Xa inhibitors like Fondaparinux & Rivaroxaban are used for HIT management.
  • Heparin antibody used during management of HIT is “HIT antibodies”(IgG or PF4 or heparin).


Don’t Forget to Solve all the previous Year Question asked on HEPARIN INDUCED THROMBOCYTOPENIA (HIT)

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