1. Copyright © 1999 American Medical Association. All rights reserved.
From: Anticoagulant-Induced Thrombosis
JAMA. 1999;282(4): doi: /jama
Figure Legend:
Platelet factor 4 (PF4), released from platelets on activation, formsan antigen complex with heparin or native endothelial cell–derived heparansulfate stimulating the formation of anti-heparin/PF4 IgG antibody (heparin-inducedthrombocytopenia [HIT]-IgG). The immune complex of HIT-IgG and its antigenbinds to the platelet Fc receptor and initiates coagulation by triggeringfurther platelet activation, aggregation, and platelet microparticle release.Experimental evidence suggests HIT-IgG also binds to heparan sulfate/PF4 complexeson endothelium enhancing the expression of tissue factor. The sum of these2 processes is intense thrombin generation. One of the naturally occurringinhibitors of coagulation, protein C (PC), is activated (+) by thrombin boundto thrombomodulin (TM) on endothelium. Activated protein C (aPC) and its cofactorprotein S (PS) down-regulate (−) thrombin generation by inhibiting activatedclotting factors V and VIII. This dampening effect on thrombin generationis diminished during treatment with warfarin, which impairs the synthesisof functional proteins C and S.
Date of download: 11/9/2017
Copyright © 1999 American Medical Association. All rights reserved.