Department of Neurology, Centro Hospitalar Universitário de Lisboa Norte - Hospital de Santa Maria, Lisbon, Portugal (D.A.d.S., J.M.F.).
Faculdade de Medicina, Universidade de Lisboa, Portugal (D.A.d.S., J.M.F.).
Stroke. 2022 Jun;53(6):1892-1903. doi: 10.1161/STROKEAHA.121.036824. Epub 2022 Mar 4.
Cerebral venous thrombosis (CVT) has recently been reported as a common thrombotic manifestation in association with vaccine-induced thrombotic thrombocytopenia, a syndrome that mimics heparin-induced thrombocytopenia (HIT) and occurs after vaccination with adenovirus-based SARS-CoV-2 vaccines. We aimed to systematically review the incidence, clinical features, and prognosis of CVT occurring in patients with HIT.
The study protocol was registered with PROSPERO (CRD42021249652). MEDLINE, EMBASE and Cochrane CENTRAL were searched up to June 1, 2021 for HIT case series including >20 patients, or any report of HIT-related CVT. Demographic, neuroradiological, clinical, and mortality data were retrieved. Meta-analysis of proportions with random-effect modeling was used to derive rate of CVT in HIT and in-hospital mortality. Pooled estimates were compared with those for CVT without HIT and HIT without CVT, to determine differences in mortality.
From 19073 results, we selected 23 case series of HIT (n=1220) and 27 cases of HIT-related CVT (n=27, 71% female). CVT developed in 1.6% of 1220 patients with HIT (95% CI,1.0%-2.5%, =0%). Hemorrhagic brain lesions occurred in 81.8% of cases of HIT-related CVT and other concomitant thrombosis affecting other vascular territory was reported in 47.8% of cases. In-hospital mortality was 33.3%. HIT-related CVT carried a 29% absolute increase in mortality rate compared with historical CVT controls (33.3% versus 4.3%, <0.001) and a 17.4% excess mortality compared with HIT without CVT (33.3% versus 15.9%, =0.046).
CVT is a rare thrombotic manifestation in patients with HIT. HIT-related CVT has higher rates of intracerebral hemorrhage and a higher mortality risk, when compared with CVT in historical controls. The recently reported high frequency of CVT in patients with vaccine-induced thrombotic thrombocytopenia was not observed in HIT, suggesting that additional pathophysiological mechanisms besides anti-platelet factor-4 antibodies might be involved in vaccine-induced thrombotic thrombocytopenia-related CVT.
最近有报道称，疫苗诱导的血栓性血小板减少症与脑静脉血栓形成（CVT）有关，这种综合征类似于肝素诱导的血小板减少症（HIT），发生在基于腺病毒的 SARS-CoV-2 疫苗接种后。我们旨在系统地综述 HIT 患者发生 CVT 的发生率、临床特征和预后。
该研究方案已在 PROSPERO（CRD42021249652）上注册。截至 2021 年 6 月 1 日，我们在 MEDLINE、EMBASE 和 Cochrane CENTRAL 上检索了包含>20 例患者的 HIT 病例系列，或任何与 HIT 相关的 CVT 报告。检索了人口统计学、神经影像学、临床和死亡率数据。采用随机效应模型的比例荟萃分析得出 HIT 中 CVT 的发生率和住院死亡率。将汇总估计值与无 HIT 的 CVT 和无 CVT 的 HIT 进行比较，以确定死亡率的差异。
从 19073 个结果中，我们选择了 23 项 HIT 病例系列（n=1220）和 27 例 HIT 相关 CVT 病例（n=27，71%为女性）。HIT 患者中 CVT 的发生率为 1.6%（95%CI，1.0%-2.5%，=0%）。HIT 相关 CVT 中 81.8%的病例出现出血性脑损伤，47.8%的病例出现其他血管区域的同时性血栓形成。住院死亡率为 33.3%。与历史 CVT 对照组相比（33.3%对 4.3%，<0.001），HIT 相关 CVT 的死亡率绝对增加了 29%，与无 CVT 的 HIT 相比（33.3%对 15.9%，=0.046），死亡率也增加了 17.4%。
CVT 是 HIT 患者中一种罕见的血栓形成表现。与历史对照相比，HIT 相关 CVT 的颅内出血发生率更高，死亡率风险更高。最近报道的疫苗诱导的血栓性血小板减少症患者中 CVT 发生率较高，但在 HIT 中并未观察到，这表明除了抗血小板因子 4 抗体之外，可能还有其他病理生理学机制参与了疫苗诱导的血栓性血小板减少症相关 CVT。
