Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, 30625 Hannover, Germany.
Department of Thrombosis and Hemostasis, Giessen University Hospital, Giessen, Germany, and Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, 35390 Giessen, Germany.
Viruses. 2022 Aug 1;14(8):1702. doi: 10.3390/v14081702.
Vaccine-induced thrombotic thrombocytopenia (VITT), or thrombosis with thrombocytopenia syndrome (TTS), is a rare but serious complication of adenovirus-based vaccines against severe respiratory syndrome coronavirus 2 (SARS-CoV-2). Observation of long-term outcomes is important to guide treatment of affected patients. This single-center consecutive cohort study included all patients diagnosed based on (1) vaccination 4 to 21 days before symptom onset, (2) signs or symptoms of venous or arterial thrombosis, (3) thrombocytopenia < 150/nL, (4) positive anti-platelet factor 4 (PF4) antibody, and (5) elevated D-Dimer > 4 times the upper limit of normal. Nine patients were enrolled. Acute management consisted of parenteral anticoagulants, corticosteroids, intravenous immunoglobulin (IVIG), and/or eculizumab. Eculizumab was successfully used in two patients with recurrent thromboembolic events after IVIG. Direct oral anticoagulants were given after hospital discharge. Median follow-up duration was 300 days (range 153 to 380). All patients survived the acute phase of the disease and were discharged from hospital. One patient died from long-term neurological sequelae of cerebral venous sinus thrombosis 335 days after diagnosis. Eight out of nine patients were alive at last follow-up, and seven had fully recovered. Anti-PF4 antibodies remained detectable for at least 12 weeks after diagnosis, and D-Dimer remained elevated in some patients despite oral anticoagulation. No recurrent thromboembolic events, other signs of VITT relapse, or bleeding complications occurred after discharge. In conclusion, VITT appears to be a highly prothrombotic condition. IVIG is not always successful, and eculizumab may be considered a rescue agent. Long-term management with direct oral anticoagulants appears to be safe and effective.
疫苗诱发的血栓性血小板减少症(VITT)或血栓性血小板减少综合征(TTS)是一种罕见但严重的严重呼吸综合征冠状病毒 2(SARS-CoV-2)腺病毒疫苗的并发症。观察长期结局对于指导受影响患者的治疗很重要。这项单中心连续队列研究纳入了所有根据以下标准诊断的患者:(1)在症状出现前 4 至 21 天接种疫苗,(2)存在静脉或动脉血栓形成的迹象或症状,(3)血小板计数<150/nL,(4)抗血小板因子 4(PF4)抗体阳性,和(5)D-二聚体升高至正常值的 4 倍以上。共纳入了 9 名患者。急性治疗包括静脉内给予抗凝剂、皮质类固醇、静脉注射免疫球蛋白(IVIG)和/或依库珠单抗。在 2 例患者中,IVIG 后复发血栓栓塞事件时成功使用了依库珠单抗。出院后给予直接口服抗凝剂。中位随访时间为 300 天(范围 153 至 380)。所有患者均存活过疾病的急性期并出院。1 例患者在诊断后 335 天死于脑静脉窦血栓形成的长期神经后遗症。9 名患者中,有 8 名在最后一次随访时存活,7 名已完全康复。抗 PF4 抗体在诊断后至少 12 周内仍可检测到,尽管进行了口服抗凝治疗,但一些患者的 D-二聚体仍升高。出院后未发生复发性血栓栓塞事件、VITT 复发的其他迹象或出血并发症。总之,VITT 似乎是一种高度促血栓形成的疾病。IVIG 并不总是有效,依库珠单抗可能被视为一种抢救药物。直接口服抗凝剂的长期治疗似乎是安全有效的。