Sharma Amit, Singh Kanwaljeet, Biswas Arijit, Ranjan Ravi, Kishor Kamal, Kumar Ravi, Pandey Hareram, Kamal Vineet Kumar, Saxena Renu
Department of Haematology, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India.
Institute of Naval Medicine (INHS) Asvini, Mumbai, 400005, India.
J Thromb Thrombolysis. 2017 Feb;43(2):217-223. doi: 10.1007/s11239-016-1469-6.
Resistance to APC (APCR) is a very important cause of thrombophilia and most frequently caused by the Leiden mutation. APCR is also seen in the absence of FV Leiden and associated with elevated levels of factor V (FV), factor VIII (FVIII) and antiphospholipid antibodies (APLAs). The aim of this prospective case control study was to find out the frequency and role of FV, FVIII and APLAs in the pathogenesis of APCR in FV Leiden negative deep vein thrombosis (DVT) patients in India. A total 30 APCR positive and FV Leiden negative patients with DVT and similar number of age and sex matched healthy controls were recruited. Significantly higher mean FVIII levels were observed in patients as compared to controls [patients: 132.3 ± 30.7 IU/ml, controls: 117.5 ± 17.7 IU/ml, p = 0.025]. A significant negative correlation was also observed between FVIII and APC ratio (Pearson correlation = 0.368, p = <0.001). Mean FV levels in patients [107.1 ± 13.1 IU/ml] and controls [102 ± 11.9 IU/ml] were not statistically significant (p = 0.119). Anti β2 glycoprotein I (Anti-β2-GPI, IgG) showed significant association with APCR phenotype (p = 0.050), unlike other factors such as protein C, protein S, lupus anticoagulant and anticardiolipin antibodies. The strong association of FVIII and anti-β2 GPI (IgG) antibodies with APCR phenotype is suggestive of incorporation of these factors in APCR positive DVT patients in the absence of FV Leiden mutation in India. However more studies in large sample size are required for setting up the proper investigation protocol in these patients.
对活化蛋白C的抵抗（APCR）是血栓形成倾向的一个非常重要的原因，最常见的是由莱顿突变引起。在没有FV莱顿突变的情况下也可见APCR，且与凝血因子V（FV）、凝血因子VIII（FVIII）和抗磷脂抗体（APLA）水平升高有关。这项前瞻性病例对照研究的目的是了解FV、FVIII和APLA在印度FV莱顿阴性的深静脉血栓形成（DVT）患者APCR发病机制中的频率和作用。共招募了30例APCR阳性且FV莱顿阴性的DVT患者以及数量相当、年龄和性别匹配的健康对照。与对照组相比，患者的平均FVIII水平显著更高[患者：132.3±30.7IU/ml，对照组：117.5±17.7IU/ml，p = 0.025]。FVIII与活化蛋白C比值之间也观察到显著的负相关（皮尔逊相关系数=0.368，p = <0.001）。患者[107.1±13.1IU/ml]和对照组[102±11.9IU/ml]的平均FV水平无统计学意义（p = 0.119）。抗β2糖蛋白I（抗β2-GPI，IgG）与APCR表型有显著关联（p = 0.050），这与蛋白C、蛋白S、狼疮抗凝物和抗心磷脂抗体等其他因素不同。FVIII和抗β2 GPI（IgG）抗体与APCR表型的强关联表明，在印度没有FV莱顿突变的APCR阳性DVT患者中，这些因素参与其中。然而，需要更多大样本研究来为这些患者制定合适的研究方案。
