CXCL4-platelet factor 4, heparin-induced thrombocytopenia and cancer

https://doi.org/10.1016/S0049-3848(12)70026-9Get rights and content

Abstract

Platelet factor 4 (CXCL4-PF4) is a chemokine that binds to and neutralizes heparin and other negatively charged proteoglycans, but is also involved in angiogenesis and cancer development. In some patients exposed to heparin, antibodies are generated against the CXCL-PF4/heparin complex that may activate platelets and coagulation and lead to thrombocytopenia and arterial or venous thrombosis, a condition commonly named heparin induced thrombocytopenia (HIT). HIT has been investigated in numerous clinical settings, but there is limited data on the epidemiology and phenotype of HIT in cancer patients. The present review describes the role of CXCL4-PF4 in cancer, the immunobiology, clinical presentation and diagnosis of HIT, and the specific problems faced in cancer patients.

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      It is produced by megakaryocytes and stored in the platelet alpha-granules. When platelets are stimulated and activated, a large quantity of PF4 will be released into the peripheral blood [41–43] to bind to the negatively charged glycosaminoglycan (GAG) chains in the platelets [44] (Fig. 1a). Then, negatively charged heparin binds to the free positive charge PF4, resulting in the changes of the configuration of the tetramer PF4 [45].

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