Heparin Induced Thrombocytopenia (HIT)

HEPARIN INDUCED THROMBOCYTOPENIA (HIT)

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

Cause:

• 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.

Types:

• 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.

MANAGEMENT:

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. 

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