Risk of Venous Thrombosis in Antithrombin Deficiency: A Systematic Review and Bayesian Meta-analysis

Abstract

Antithrombin deficiency is a strong risk factor for venous thromboembolism (VTE), but the absolute risk of the first and recurrent VTE is unclear. The objective of this paper is to establish the absolute risks of the first and recurrent VTE and mortality in individuals with antithrombin deficiency. The databases Embase, Medline Ovid, Web of Science, the Cochrane Library, and Google Scholar were systematically searched for case-control and cohort studies. Bayesian random-effects meta-analysis was used to calculate odds ratios (ORs), absolute risks, and probabilities of ORs being above thresholds. Thirty-five publications were included in the systematic review and meta-analysis. Based on 19 studies, OR estimates for the first VTE showed a strongly increased risk for antithrombin deficient individuals, OR 14.0; 95% credible interval (CrI), 5.5 to 29.0. Based on 10 studies, meta-analysis showed that the annual VTE risk was significantly higher in antithrombin-deficient than in non-antithrombin-deficient individuals: 1.2% (95% CrI, 0.8-1.7) versus 0.07% (95% CrI, 0.01-0.14). In prospective studies, the annual VTE risk in antithrombin deficient individuals was as high as 2.3%; 95% CrI, 0.2-6.5%. Data on antithrombin deficiency subtypes are very limited for reliable risk-differentiation. The OR for recurrent VTE based on 10 studies was 2.1; 95% CrI, 0.2 to 4.0. The annual recurrence risk without long-term anticoagulant therapy based on 4 studies was 8.8% (95% CrI, 4.6-14.1) for antithrombin-deficient and 4.3% (95% CrI, 1.5-7.9) for non-antithrombin-deficient VTE patients. The probability of the recurrence risk being higher in antithrombin-deficient patients was 95%. The authors conclude that antithrombin deficient individuals have a high annual VTE risk, and a high annual recurrence risk. Antithrombin deficient patients with VTE require long-term anticoagulant therapy.

Heart Disease and Stroke Statistics—2023 Update: A Report From the American Heart Association

“…Antithrombin deficiency is a rare variant that is associated with greatly increased risk of incident VTE (OR, 14.0 [95% CI, 5.5–29.0]). 48 A bayesian meta-analysis found that for childbearing females with this variant, VTE risk was 7% in the antepartum period and 11% postpartum. 49…”

Prevention of Venous Thromboembolism in 2020 and Beyond

“…One special case which deserves consideration is the presence of antithrombin deficiency, which is a potent inherited risk factor for VTE (OR: 14.0; 95% CI 5.5 to 29.0) and increases the absolute risk of a first VTE to >1% per year [65]. The risk of recurrent VTE for these patients is substantial, and antithrombin deficient patients should be continued on long-term anticoagulation after a first episode of VTE.…”

Pulmonary Thromboembolism in Immune Thrombocytopenia: A Report of Five Cases and a Review of the Literature

“…For example, Esmon et al 20 found that the increase in CRP resulted in a decrease in AT, while the decrease in AT reduced anticoagulant activity, one of the reasons for the hypercoagulable state leading to DVT. 21 In immune diseases, inflammatory stimulants such as CRP and tumor necrosis factor can promote clotting, leading to elevated clotting factor levels and DVT formation. 22 , 23 In general, multiple factors and mechanisms combine in the development of PTE in ITP patients.…”