Migita Kiyoshi, Asano Tomoyuki, Sato Shuzo, Motokawa Satoru
Department of Rheumatology, Fukushima Medical University School of Medicine.
Clinical Research Center, NHO Nagasaki Medical Center.
Fukushima J Med Sci. 2018 Apr 17;64(1):1-8. doi: 10.5387/fms.2018-06. Epub 2018 Apr 7.
Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin. These pathogenic antibodies against PF4/heparin bind and activate cellular FcγRIIa on platelets to induce a hypercoagulable state culminating in thrombosis. Recent studies indicate several conditions, including joint surgery, induce spontaneous HIT, which can occur without exposure to heparin. To determine the real-world evidences concerning the incidences of venous thromboembolism (VTE) after total joint arthroplasty for rheumatic disease, we conducted a multicenter cohort study (J-PSVT) designed to document the VTE and seroconversion rates of anti-PF4/heparin antibody in 34 Japanese National hospital organization (NHO) hospitals. J-PSVT indicated that prophylaxis with fondaparinux, not enoxaparin, reduces the risk of deep vein thrombosis in patients undergoing arthroplasty. Multivariate analysis revealed that dynamic mechanical thromboprophylaxis (intermittent plantar device) was an independent risk factor for seroconversion of anti-PF4/heparin antibodies, which was also confirmed by propensity-score matching. Seroconversion rates of anti-PF4/heparin antibodies were significantly reduced in rheumatoid arthritis (RA) patients compared with osteoarthritis (OA) patients, which may link with the findings that IgG fractions isolated from RA patients not OA patients contained PF4. Our study indicated that a unique profile of anti-PF4/heparin antibodies is induced by arthroplasty for rheumatic diseases.
肝素诱导的血小板减少症（HIT）是肝素治疗的一种免疫并发症，由针对血小板因子4（PF4）与肝素复合物的抗体引起。这些针对PF4/肝素的致病性抗体结合并激活血小板上的细胞FcγRIIa，从而诱导高凝状态，最终导致血栓形成。近期研究表明，包括关节手术在内的几种情况可诱发自发性HIT，这种情况可在未接触肝素的情况下发生。为了确定关于风湿性疾病全关节置换术后静脉血栓栓塞（VTE）发生率的真实世界证据，我们开展了一项多中心队列研究（J-PSVT），旨在记录34家日本国立医院机构（NHO）医院中VTE的发生情况以及抗PF4/肝素抗体的血清转化情况。J-PSVT研究表明，使用磺达肝癸钠而非依诺肝素进行预防，可降低接受关节置换术患者发生深静脉血栓的风险。多变量分析显示，动态机械性血栓预防措施（间歇性足底装置）是抗PF4/肝素抗体血清转化的独立危险因素，倾向得分匹配也证实了这一点。与骨关节炎（OA）患者相比，类风湿关节炎（RA）患者中抗PF4/肝素抗体的血清转化率显著降低，这可能与从RA患者而非OA患者分离出的IgG组分中含有PF4这一发现有关。我们的研究表明，风湿性疾病关节置换术可诱导产生独特的抗PF4/肝素抗体谱。
