Amiral J, Bridey F, Wolf M, Boyer-Neumann C, Fressinaud E, Vissac A M, Peynaud-Debayle E, Dreyfus M, Meyer D
Serbio Research Laboratory, Gennevilliers, France.
Thromb Haemost. 1995 Jan;73(1):21-8.
As heparin-PF4 (H-PF4) complexes are the target for antibodies associated to heparin-induced thrombocytopenia (HIT), an ELISA has been developed and optimised for testing antibodies binding to H-PF4. This test was consistently negative in 50 healthy subjects (A492 < 0.3) and 35 patients with other causes of thrombocytopenia (A492 < 0.5). In contrast, 43 out of 44 HIT patients showed antibodies to H-PF4 (A492 = 1.70 +/- 0.81) including 5 patients with a negative platelet aggregation test. In one patient with HIT, antibodies to H-PF4 were already present at day 7, whereas platelet counts dropped < or = 100 x 10(9)/l only at days 11-12. Surprisingly, among 41 patients under heparin for > 7 days, 5 showed antibodies to H-PF4, without HIT. These findings underline the major interest of this ELISA for the early diagnosis of HIT. We also showed that LMWH as well as other sulphated polysaccharides can bind to HIT antibodies in the presence of PF4 and that their reactivity is dependent on the molecular weight and the sulphation grade. The mechanism for HIT involves platelet PF4 receptors which bind the macromolecular H-PF4 complexes formed in the presence of a well defined heparin/PF4 ratio.
由于肝素-PF4（H-PF4）复合物是与肝素诱导的血小板减少症（HIT）相关抗体的靶标，因此已开发并优化了一种ELISA方法来检测与H-PF4结合的抗体。该检测在50名健康受试者（A492 < 0.3）和35名患有其他血小板减少症病因的患者（A492 < 0.5）中始终呈阴性。相比之下，44名HIT患者中有43名显示出针对H-PF4的抗体（A492 = 1.70 +/- 0.81），其中包括5名血小板聚集试验阴性的患者。在一名HIT患者中，第7天时就已存在针对H-PF4的抗体，而血小板计数仅在第11至12天时降至≤100×10⁹/L。令人惊讶的是，在41名接受肝素治疗超过7天的患者中，有5名显示出针对H-PF4的抗体，但无HIT。这些发现强调了该ELISA方法在HIT早期诊断中的重要意义。我们还表明，低分子肝素以及其他硫酸化多糖在存在PF4的情况下可与HIT抗体结合，并且它们的反应性取决于分子量和硫酸化程度。HIT的机制涉及血小板PF4受体，该受体可结合在明确的肝素/PF4比例存在下形成的大分子H-PF4复合物。
