Plasma Coagulation Markers in Patients with Solid Tumors and Venous Thromboembolic Disease Receiving Oral Anticoagulation Therapy

Abstract

Purpose: To correlate the concentration of plasma coagulation markers at baseline and during follow-up in patients with solid tumors and venous thromboembolic disease with the risk of recurrence and death.Experimental Design: Patients (N ‫؍‬ 223) with first episode of venous thromboembolic disease received oral anticoagulation with warfarin for a target international normalized ratio of 2 to 3. Plasma coagulation markers were measured before instituting warfarin and at 3 monthly intervals, thereafter.Results: The median duration of oral anticoagulation was 6.7 months (range 2 weeks to 11 months). Major bleeding episodes occurred in 18 patients (8%), and minor hemorrhagic events occurred in 15 (6.7%) patients. Patients with advanced malignancy (P ‫؍‬ 0.032), history of surgery (P ‫؍‬ 0.057), and those with poor performance status (P ‫؍‬ 0.001) were more likely to encounter major bleeding episodes. Recurrence of venous thromboembolic disease was diagnosed in 31 patients (14%). At univariate analysis, advanced stage of cancer (P ‫؍‬ 0.03), performance status > 1 (P ‫؍‬ 0.001), treatment with chemotherapy (P ‫؍‬ 0.01), the presence of metastatic liver disease (P ‫؍‬ 0.03), higher D-dimer (P ‫؍‬ 0.001), and thrombin antithrombin complex levels (P ‫؍‬ 0.01) were features predictive of recurrent venous thromboembolic disease. At multivariate analysis, poor performance status (P ‫؍‬ 0.01) and D-dimer levels (P ‫؍‬ 0.001) were predictors of recurrent venous thromboembolic disease. Persistent activation of coagulation as indicated by an upward trend in D-dimer (P ‫؍‬ 0.001) and antithrombin (P ‫؍‬ 0.001) was observed in patients who developed recurrent thrombosis. Similar upward trends in D-dimer (P ‫؍‬ 0.001), antithrombin (P ‫؍‬ 0.001), and prothrombin fragment F1 ؉ 2 (P ‫؍‬ 0.001) was observed in the 76 patients who died during the study period and in the patients who received chemotherapy.Conclusions: Successful oral anticoagulation with warfarin in patients with cancer and venous thromboembolic disease is more likely to be achieved in patients with early stage tumors and good performance status. The persistence of activation of hemostasis as shown by plasma coagulation markers is a strong predictor of recurrence and poor outcome.

Risk of recurrent venous thromboembolism according to malignancy characteristics in patients with cancer-associated thrombosis: a systematic review of observational and intervention studies

“…No RCTs fulfilled our inclusion criteria. Four retrospective [15][16][17][18] and six prospective studies [8,11,[19][20][21][22] were selected with no discrepancies between the four reviewers with regard to study eligibility.…”

Venous thromboembolism and cancer: a systematic review

“…Other laboratory markers may also be associated with the risk of VTE, such as TF, C-reactive protein (CRP) [50], D-dimers [81,82] and P-selectin [83].…”

Pathogenesis, clinical and laboratory aspects of thrombosis in cancer

“…Of the markers used to detect hypercoagulability (plasma levels of F1 + 2, FPA and TAT), FPA was identified as the most sensitive [59]. The persistent activation of haemostasis is commonplace and may be interpreted also as a strong predictor of recurrence and poor outcome in patients with either solid tumors [60] or leukemic disorders [61] since intravascular activation of the coagulation system can already be observed in the majority of patients with acute leukemia at the time of diagnosis [62]. In a recent study by Dixit et al, decreased activities of proteins C and S were observed in nearly half of the patients with acute leukemia and there are no significant differences in the plasma levels of protein C, protein S, and antithrombin in patients with or without DIC [63].…”