On the issue of recurrent thrombosis in cancer patients

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Aim: to identify the key pathogenic factors and triggers associated with recurrent venous thromboembolic events (VTE) in gynaecological oncology patients. Materials and Methods. There was conducted a retrospective cohort study with three groups of gynaecological oncology patients: 155 women with a history of thrombosis episodes (Group I), 66 patients with recurrent thrombosis and stage III–IV ovarian cancer (Group II), and 72 patients with tumours of the female genital organs who had previously contracted SARS-CoV-2 infection (Group III). All patients underwent comprehensive assessments for congenital thrombophilia (FV Leiden, prothrombin G20210A, MTHFR C677T, PAI-1 and platelet glycoproteins), acquired thrombophilia (anti-β2-GP1 antibodies, anti-annexin V antibodies, and anti-prothrombin antibodies), and markers of endothelial dysfunction – von Willebrand factor (vWF) and metalloprotease ADAMTS-13, and thromboinflammatory syndrome (D-dimer). Statistical analysis was performed using non-parametric tests at a significance level set at p < 0.05. Results. Recurrent VTE in gynaecological oncology patients was found to develop upon high prevalence of congenital and acquired thrombophilia, vWF/ADAMTS-13 axis disorders, and activation of the thromboinflammatory syndrome. In group I, genetic thrombophilia was detected in 145 patients (93.6 %), with multigenic variants occurring in 113 patients (72.9 %); antiphospholipid antibodies (aPL) circulation was found in 87 patients (55.8 %). In group II, genetic thrombophilia was detected in 44 (66.7 %) women and aPL circulation in 31 (47.0 %); the median vWF level was 1513 IU/L (p < 0.05); D-dimer levels exceeded 1500 ng/ml in 48 patients (72.7 %) with median 2700 ng/ml. In group III, recurrent VTE were observed in 39 (54.2 %) patients. The median vWF level was 3450 IU/L and ADAMTS-13 level was reduced down to 220 IU/L (p < 0.01) compared to group I and group II. The D-dimer level exceeded 1500 ng/ml in 33 patients (84.6 %) with median 2900 ng/ml. Circulating aPL was detected in 28 patients (71.8 %) with relapses. COVID-19 convalescent patients had 70 % higher recurrence risk (relative risk (RR) = 1.7; 95 % confidential interval (CI) = 1.1–2.8; p < 0.05). Conclusion. Recurrent VTE in oncogynaecological patients has a multifactorial etiology, collectively accounted for by congenital and acquired thrombophilia, endothelial dysfunction, and thromboinflammatory syndrome, which may be profoundly exacerbated by previous SARS-CoV-2 infection. The data obtained emphasize a need for comprehensively assessing risk factors and applying an individualized approach to prevent VTE recurrence in this patient group.

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