There is accumulating evidence supporting an association between the thrombosis and thrombocytopenia syndrome (TTS) and adenovirus vector-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Yet TTS and TTS-associated cerebral venous sinus thrombosis (CVST) remain poorly characterized. We aim to systematically evaluate the proportion of CVST among TTS cases and assess its characteristics and outcomes.

We performed a systematic review and meta-analysis of clinical trials, cohorts, case series, and registry-based studies with the aim to assess (1) the pooled mortality rate of CVST, TTS-associated CVST, and TTS and (2) the pooled proportion of patients with CVST among patients with any thrombotic event and TTS. Secondary outcomes comprised clinical characteristics of patients with postvaccination thrombotic event. This meta-analysis is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology proposal.

Sixty-nine studies were included in the qualitative analysis comprising 370 patients with CVST out of 4,182 patients with any thrombotic event associated with SARS-CoV-2 vector-based vaccine administration. Twenty-three studies were included further in quantitative meta-analysis. Among TTS cases, the pooled proportion of CVST was 51% (95% confidence interval [CI] 36%–66%; I² = 61%). TTS was independently associated with a higher likelihood of CVST when compared to patients without TTS with thrombotic events after vaccination (odds ratio 13.8; 95% CI 2.0–97.3; I² = 78%). The pooled mortality rates of TTS and TTS-associated CVST were 28% (95% CI 21%–36%) and 38% (95% CI 27%–49%), respectively. Thrombotic complications developed within 2 weeks of exposure to vector-based SARS-CoV-2 vaccines (mean interval 10 days; 95% CI 8–12) and affected predominantly women (69%; 95% CI 60%–77%) under age 45, even in the absence of prothrombotic risk factors.

Approximately half of patients with TTS present with CVST; almost one-third of patients with TTS do not survive. Further research is required to identify independent predictors of TTS following adenovirus vector-based vaccination.

The prespecified study protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (CRD42021250709).

越来越多的证据支持血栓形成和血小板减少综合征 (TTS) 与针对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的基于腺病毒载体的疫苗之间存在关联。然而，TTS 和 TTS 相关的脑静脉窦血栓形成 (CVST) 的特征仍然很差。我们旨在系统地评估 CVST 在 TTS 病例中的比例，并评估其特征和结果。

我们对临床试验、队列、病例系列和基于注册的研究进行了系统回顾和荟萃分析，旨在评估 (1) CVST、TTS 相关 CVST 和 TTS 的汇总死亡率和 (2)合并任何血栓事件和 TTS 患者中 CVST 患者的比例。次要结局包括疫苗接种后血栓事件患者的临床特征。该荟萃分析是根据系统评价和荟萃分析指南的首选报告项目报告的，并根据流行病学观察性研究的荟萃分析提案编写。

定性分析纳入了 69 项研究，包括 4,182 名患有与基于 SARS-CoV-2 载体的疫苗接种相关的任何血栓事件的患者中的 370 名 CVST 患者。23 项研究被进一步纳入定量荟萃分析。在 TTS 病例中，CVST 的合并比例为 51%（95% 置信区间 [CI] 36%–66%；I ² = 61%）。与没有 TTS 的患者相比，疫苗接种后发生血栓事件的患者发生 CVST 的可能性更高（比值比 13.8；95% CI 2.0–97.3；I ²= 78%）。TTS 和 TTS 相关 CVST 的合并死亡率分别为 28% (95% CI 21%–36%) 和 38% (95% CI 27%–49%)。在接触基于载体的 SARS-CoV-2 疫苗后 2 周内出现血栓并发症（平均间隔 10 天；95% CI 8-12），主要影响年龄以下的女性（69%；95% CI 60%-77%） 45，即使在没有促血栓形成危险因素的情况下。

大约一半的 TTS 患者出现 CVST；几乎三分之一的 TTS 患者无法存活。需要进一步研究以确定基于腺病毒载体的疫苗接种后 TTS 的独立预测因子。

预先指定的研究方案已在正在进行的系统评价国际前瞻性登记册 PROSPERO (CRD42021250709) 中注册。