A 43-year-old female patient was admitted with recurrent thrombosis for more than 2 years and thrombocytopenia for more than 1 year. Both arterial and venous thromboses developed especially at rare sites even during anticoagulation therapy such as cerebral venous sinus thrombosis. Antinuclear antibody, anti-ENA antibody and antiphospholipid antibody were all negative. Platelet count elevated to normal after high dose glucocorticoid and intravenous immunoglobulin (IVIG). Immune thrombocytopenia was suspected. When 4 grade thrombocytopenia recurred, intravenous heparin, rituximab 600 mg, IVIG and eltrombopag were administrated. After 3 weeks, thrombocytopenia did not improve, and new thrombosis developed instead. Screening of thrombophilia related genes revealed PROS1 gene heterozygous mutation and MTHFR TT genotype. Low amount of serum IgG κ monoclonal protein was detected. Heparin-induced thrombocytopenia was differentiated and excluded. Finally, serum negative antiphospholipid syndrome was considered the most likely diagnosis. Dexamethasone 20 mg/day × 4 days combined with sirolimus 2 mg/day was prescribed. The patient was discharged with low molecular weight heparin. At one month, her headache was greatly relieved. The platelet count raised to 20-30×109/L, and no new thrombosis or bleeding was reported.
患者女性，43岁。因反复血栓形成2年余，血小板（PLT）减低1年余就诊。患者临床表现为反复动静脉血栓形成、少见部位血栓及抗凝治疗中新发血栓，伴有进行性加重的血小板减少。外院及我院多次筛查抗核抗体、抗可溶性抗原抗体、抗磷脂抗体谱均为阴性。病程中糖皮质激素冲击及静脉免疫球蛋白（IVIG）曾使血小板升至正常，骨髓巨核细胞成熟障碍，支持免疫性血小板减低。入院后筛查易栓症的病因，同时予肝素静脉泵入抗凝，利妥昔单抗600 mg 1次；IVIG 20 g/d×3 d；口服艾曲波帕50 mg/d治疗。以上治疗3周后，血小板减少无明显改善，期间仍有新发血栓。后易栓症基因筛查回报PROS1基因杂合突变，MTHFR基因型为TT型，发现少量IgGκ型M蛋白，但仍不足以解释如此顽固的血栓倾向。在排除肿瘤、肝素诱导的血小板减少症等之后最终诊断血清阴性抗磷脂综合征可能性大。后续加用地塞米松20 mg/d×4 d，联合口服西罗莫司2 mg/d加强免疫抑制，抗凝方案过渡为低分子肝素后出院。1个月后电话随访，患者颅内静脉窦血栓所致的头痛症状好转，PLT升至（20~30）×109/L，无新发血栓及出血。.