Mechanism of Heparin Induced Thrombocytopenia - USMLE Forums
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Old 05-19-2011
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Default Mechanism of Heparin Induced Thrombocytopenia

Pathogenesis of HIT:

Platelet Factor 4 is released from alpha granules of platelets when they are activated. PF4 normally binds to endogenous heparin and inactivates it to allow for clotting to occur. When exogenous heparin is administered to a patient, this PF4 binds to the heparin, and once this heparin-PF4 complex is made it binds to the surface of an activated platelet. Once bound to the surface of a platelet, the complex is recognized by the Fab region of the HIT antibody (IgG usually). The Fc portion of this bound antibody now activates other platelets, which triggers the release of alpha granules and even more PF4, creating a positive feedback look.

Thus more platelets are activated/consumed. Since more platelets are activated, clotting is favored but these platelets are also cleared more quickly from circulation so you get thrombocytopenia.

What about Delayed onset HIT, which occurs after withdrawal of Heparin?

This is thought to be mediated by HIT antibodies as well but the complex is made up of PF4 and a non-heparin GAG like chondroiton sulfate. Studies have shown that the antibody binding epitope of the HIT antibody is located on PF4 and that this site can be exposed when PF4 is bound to targets other than heparin.


Label normal RBC’s with Radiolabeled Serotonin. Add patient’s serum + heparin. Look for release of Serotonin (Positive result = HIT)


Most commonly DVT’s and PE


Lepirudin or Bivalirudin - These drugs directly inhibit thrombin and are used for anticoagulating patients with HIT. They are derivatives of Hirudin, which is a anticoagulant found in the saliva of leeches

Low Molecular Weight vs Unfractionated Heparin:
LMW Heparin is a smaller molecule and thus is less likely to cause complex formation (just based on size alone), thus is less likely to lead to HIT

Source: Summary of article from UptoDate. If you have access: e=1~150#H3

Last edited by apx85; 05-19-2011 at 10:35 AM.
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Hematology-, Pharmacology-, Physiology-

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