Greinacher A, Juhl D, Strobel U, Wessel A, Lubenow N, Selleng K, Eichler P, Warkentin T E
Institut für Immunologie und Transfusionsmedizin Ernst-Moritz-Arndt Universität Greifswald, Greifswald, Germany.
J Thromb Haemost. 2007 Aug;5(8):1666-73. doi: 10.1111/j.1538-7836.2007.02617.x. Epub 2007 May 7.
Platelet-activating antiplatelet factor 4/heparin (anti-PF4/heparin) antibodies are the major cause of heparin-induced thrombocytopenia (HIT). However, the relative utility of functional (platelet activation) vs. antigen [enzyme-immunoassay (EIA)] assays, and the significance of assay discrepancies remain unresolved.
Consecutive patient sera (n = 1650) referred for diagnostic HIT testing were screened prospectively by both the heparin-induced platelet activation (HIPA) test and anti-PF4/heparin EIA - including individual classes (IgG, IgA, IgM) - with clinical correlations studied. Platelet microparticle and annexin-V-binding properties of the sera were also investigated.
Only 205 (12.4%) sera tested positive in either the HIPA and/or EIA: 95 (46.3%) were positive in both, 109 (53.1%) were only EIA-positive, and, notably, only one serum was HIPA-positive/EIA-negative. Of 185 EIA-positive sera, only 17.6% had detectable IgM and/or IgA without detectable IgG. Among sera positive for EIA IgG, optical density values were higher when the sera were HIPA-positive (1.117 vs. 0.768; P < 0.0001), with widely overlapping values. Two HIPA-positive but EIA-IgG-negative sera became HIPA-negative following IgG depletion, suggesting platelet-activating antibodies against non-PF4-dependent antigens. Clinical correlations showed that HIPA-negative/EIA-positive patients did not develop thrombosis and had reasons other than HIT to explain thrombocytopenia. IgM/A antibodies did not increase microparticle penetration, but increased annexin-V binding.
The anti-PF4/heparin EIA has high ( approximately 99%) sensitivity for HIT. However, only about half of EIA-positive patients are likely to have HIT. Anti-PF4/heparin antibodies of IgM/A class and non-PF4-dependent antigens have only a minor role in HIT.
血小板活化抗血小板因子4/肝素（抗PF4/肝素）抗体是肝素诱导的血小板减少症（HIT）的主要病因。然而，功能性（血小板活化）检测与抗原[酶免疫测定（EIA）]检测的相对效用，以及检测结果不一致的意义仍未得到解决。
对连续送检进行HIT诊断检测的患者血清（n = 1650），前瞻性地采用肝素诱导的血小板活化（HIPA）试验和抗PF4/肝素EIA进行筛查，包括各个类别（IgG、IgA、IgM），并研究其临床相关性。还对血清的血小板微粒和膜联蛋白V结合特性进行了研究。
仅205份（12.4%）血清在HIPA和/或EIA检测中呈阳性：95份（46.3%）两者均为阳性，109份（53.1%）仅EIA呈阳性，值得注意的是，仅1份血清HIPA呈阳性/EIA呈阴性。在185份EIA呈阳性的血清中，只有17.6%检测到IgM和/或IgA而未检测到IgG。在EIA IgG呈阳性的血清中，当血清HIPA呈阳性时，光密度值更高（1.117对0.768；P < 0.0001），但数值有广泛重叠。两份HIPA呈阳性但EIA-IgG呈阴性的血清在IgG去除后变为HIPA阴性，提示存在针对非PF4依赖性抗原的血小板活化抗体。临床相关性表明，HIPA阴性/EIA阳性的患者未发生血栓形成，且有除HIT之外的其他原因可解释血小板减少。IgM/A抗体未增加微粒穿透，但增加了膜联蛋白V结合。
抗PF4/肝素EIA对HIT具有较高（约99%）的敏感性。然而，EIA呈阳性的患者中可能只有约一半患有HIT。IgM/A类抗PF4/肝素抗体和非PF4依赖性抗原在HIT中仅起次要作用。
