Heparin-Induced Thrombocytopenia

 

Heparin’s mechanism of action: binds to antithrombin, enhancing its ability to inhibit factor Xa and thrombin

1. Inactivation of thrombin requires the binding of AT and thrombin simultaneously by heparin
2. Low molecular weight heparins have fewer saccharide units which are long enough to bind AT and thrombin, and thus their activity is primarily directed against factor Xa

 

 

Type I HIT - "Fake HIT" (not immune mediated), due to direct effect of heparin, fairly common, usually get mild drop in plts (but > 100k) within 2 days, and platelet count then recovers. (10-20% prevalence)

 

Type II HIT - "True HIT"

• Frequency: 1-3% (can occur with exposure to as little as 250U heparin from flush)
• Risk factors: UFH (10x that of LMWH), surgical patients, female
• Pathophysiology:
  • Antibodies develop against complex of heparin and platelet factor 4
  • Fc region of antibody is bound by platelets → further activation and release of PF4
  • Platelets aggregate → thrombocytopenia and release of thrombogenic microparticles from platelet
• Clinically, see drop in plts by < 50% on days 5-10, unless patient was recently exposed to heparin in prior months, in which case circulating Abs can still exist and cause HIT much earlier (within 1 day).
• Thrombosis is more of a problem than bleeding (despite thrombocytopenia)
• Can also get necrotic skin lesions, similar to warfarin-induced skin necrosis

  

Diagnosis: HIT is a clinical diagnosis!!  But labs can certainly help.

• HIT Antibody - ELISA test, used as screening test as it is highly sensitive (97%), not as specific (<80%).  The greater the titer or optical density, the more suggestive of HIT it is.
• HIPA (Heparin induced platelet aggregation assay) - more labor intensive, is highly specific (>90%) but not as sensitive as HIT Ab.  This is what we use at Stanford. 
• Serotonin Release Assay - gold stanford, both sensitive and specific.  This is a send-out test.

 

"The 4T's" - Scoring system that has been prospectively validated at two centers.  See attached article, but basically it assigns points for clinical characteristics (Thrombocytopenia, Timing, Thrombosis, and oTher causes for thrombocytopenia), and if low probability you really shouldn't even be checking for HIT Abs.

  

Management:

• Stop heparin-containing compounds
• Anticoagulation with direct thrombin inhibitor
• Lepirudin: renally cleared, and carries risk of anaphylaxis after exposure from antibodies which form against it
• Argatroban: hepatic clearance
• Bivalirudin: short acting (cleaved by thrombin once bound), partial renal clearance
• Anticoagulation should be continued at least until platelets recover to stable value, and preferably for 2-3 months, If you have thrombosis, duration of anticoagulation is standard 3-6 months.
• Can bridge to warfarin once platelets rise to >150K, overlap for 5 days once INR at goal

 

Prognosis: antibodies to heparin-PF4 typically disappear within 3 months, and at this point, if heparin is absolutely necessary (e.g. CABG), can potentially re-challenge

 

  
** If you make the diagnosis of HIT you must anticoagulate them, EVEN IF THERE IS NO EVIDENCE OF THROMBOSIS AT THE TIME.  In that case, the duration is a little controversial, but at a minimal until the platelet count returns to normal, and some suggest for up to 3 months.  The risk of thrombosis with HIT is ~50% at 1 month.

 

 

(Christopher Woo MD, 4/14/11)

(Chanu Rhee MD, 9/17/10)