Treatment of Splanchnic Vein Thrombosis with Anticoagulant Therapy in Patients with Cancer and Myeloproliferative Neoplasm
Creators: name: Zahrai, Amin
Publisher: name: Université d'Ottawa | University of Ottawa
Year: 2024
Subjects: Venous Thromboembolism
Splanchnic Circulation
Anticoagulants
Neoplasms
Myeloproliferative Diseases
Cancer-Associated Thrombosis

description: Venous thromboembolism (VTE) is a frequent complication in patients with cancer and myeloproliferative neoplasms (MPN). Approximately 4 to 20% of patients with cancer experience VTE at some disease stage and the overall thrombosis risk is as high as 20% in patients with MPN. VTE includes deep vein thrombosis (DVT) (e.g., lower extremities, splanchnic veins, etc.) and pulmonary embolisms (PE). Splanchnic vein thromboses (SVTs) are rare VTEs that include splenic, mesenteric, portal, and hepatic vein thromboses that occur in the veins that drain a major portion of the digestive system. Without treatment, SVTs can expand and may lead to complications such as mesenteric ischemia, Budd-Chiari syndrome, major bleeding, and mortality. There is high variability in the incidence, site, and type of SVTs reported in the medical literature. SVTs are frequently occurring in patients with cancer or MPN given their hypercoagulable state. Recommendations from clinical practice guidelines on the management of SVTs are derived from small observational studies or expert consensuses. While anticoagulant therapy is often recommended to treat SVTs in patients with cancer or MPN, type and dosing of anticoagulant along with their respective effectiveness and safety profiles remain unclear. To address these important knowledge gaps, we performed a systematic review of the literature using EMBASE, MEDLINE, and CENTRAL databases to identify studies comparing effects of anticoagulant therapy for the management of SVTs in patients with cancer or MPN. Anticoagulant therapy seems to increase the risk of clinically-relevant bleeding by 2-fold (incidence rate ratio (IRR): 2.22 (95% confidence intervals (CI): 1.02-4.86)) without decreasing the rate for recurrent VTE (IRR: 0.86 (95% CI: 0.29-2.55)) or all-cause mortality (IRR: 0.71 (95% CI: 0.34-1.48)) among patients with cancer. In patients with MPN and SVT, anticoagulant therapy decreased the risk of recurrent VTE (IRR: 0.49 (95% CI: 0.32- 0.74)) without increasing the risk of clinically-relevant bleeding (IRR: 0.53 (95% CI: 0.26-1.07)) or all-cause mortality (0.17 (95%CI: 0-8.40)). A survey of practice was then conducted to assess practice variation among Canadian VTE specialists. The online survey was distributed by three national hematology organizations (Thrombosis Canada, CanVECTOR, and Canadian Hematology Society). All respondents agreed that a parenteral low molecular weight heparins (LMWH) or direct oral anticoagulants (DOAC) were effective for the management of SVT in patients with cancer, while 89% reported that these anticoagulant regimens were not associated with heightened risk of clinically-relevant bleeding complications in patients with MPN. A total of 80% were interested in participating in a randomized controlled trial (RCT) comparing DOAC and LMWH in patients with SVT and cancer or MPN, while 56% were interested in participating in a placebo-controlled RCT of anticoagulation in patients with SVT and cancer or MPN. The responses on the minimal clinically important difference (MCID) to lower the rate of recurrent VTE required for a RCT comparing two different types of anticoagulants (e.g., DOAC vs. LMWH) were heterogenous but 50% of respondents reported that an increase of 1% in clinically-important bleeding would be reasonable to use a DOAC instead of LMWH and lead to change in clinical practice. Results of these investigations were then used to develop a protocol for a pilot RCT comparing DOACs to LMWH for the management of SVT in patients with cancer. The pilot trial will assess the feasibility of a non-inferiority RCT comparing therapeutic dose of DOAC to LMWH for 6 months in patients with acute, symptomatic objectively-diagnosed SVT and active cancer. The feasibility outcomes include rates of recruitment, retention, and adherence to study procedures.