Heparin with Platelet Factor

Heparin-induced thrombocytopenia (HIT), characterised by arterial thromboemboli and haemorrhage, occurs in about 2-3% of patients who receive standard heparin for a week or more (less in patients on LMW heparins). It is due to an autoantibody directed against heparin in association with platelet factor 4, causing platelet activation, and occurs most commonly with heparin derived from bovine lung. HIT should be suspected in any patient in whom the platelet count falls by 50% or more after starting heparin, and usually occurs 5 or more days after starting therapy (or sooner if the patient has previously been exposed to heparin). Up to 30% of patients may require amputation or may die. 

Stuckey JA, St Charles R, Edwards BF. A model of the platelet factor 4 complex with heparin. Proteins 1992 14 277-87. 

The second type of heparin-induced thrombocytopenia is severe and may be associated with a platelet count below 100,000/mm and thrombosis. ° ° The platelet count generally begins to decline 5 to 10 days after the start of heparin therapy (sooner in patients previously treated with heparin). Thrombocytopenia and thrombosis may develop with low-dose heparin, heparin-coated catheters, or even heparin flushes. Historically, the reaction was thought to be mediated by the formation of antibodies to the platelet-heparin complex. However, evidence suggests a complex interaction between heparin, platelet factor 4 (PF4), platelet membrane Fc receptors, and possibly heparin-like molecules on the surface of endothehal cells (Fig. 102-6). Circulating heparin reacts with PF4 to produce a... 

Heparin-induced thrombocytopenia (HIT). Most frequent antibody-mediated drug-induced thrombocytopenia. Occurs in 1-2% of patients treated with heparin intravenously for longer than four days. Mediated by antibodies to complexes formed between heparin and the endogenous platelet factor 4 (PF4). 

Some platelet release factors (e.g., serotonin and ADP from dense granules) enhance platelet aggregation on foreign surfaces, while the roles of others (platelet factor 4 with its heparin neutralizing activity (HNA) and P thromboglobulin from a granules) remain to be clarified. 

The importance of chemokines binding to endothelial surfaces was suggested soon after the family was identified by the demonstration that neutrophils migrated toward immobilized IL-8/CXCL8 by a mechanism called haptotaxis (Rot, 1993). Interestingly, the chemokine field actually started with the identification of a protein by heparin-sepharose affinity chromatography, platelet factor 4 (PF4)/CXCL4 (Deuel, Keim, Farmer, Heinrikson, 1977). 

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