November 28, 2023
Pavlina Chrysafi, MD; Kevin Barnum, MD, PhD; Genevieve Garhard, MD; Thita Chiasakul, MD; Arshit Narang; Megan McNichol; Nicolette Riva, MD, PhD; Walter Ageno, MD; Jeffrey Zwicker, MD; Rushad Patell, MBBS
Introduction:
Splanchnic vein thrombosis (SVT) is a common manifestation of myeloproliferative neoplasms (MPN). The optimal anticoagulation strategies in MPN-SVT remain unclear due to the challenge of balancing the concurrent prothrombotic state of MPN with the risk for SVT complications, such as gastrointestinal bleeding.
Methods:
We conducted a systematic review and meta-analysis to evaluate the safety and efficacy of anticoagulation in patients with MPN following SVT incidence. This study protocol was registered on PROSPERO (#CRD42023414120). On April 07, 2023, we comprehensively searched multiple databases from Cochrane Library, EMBASE, and PubMed/MEDLINE. Retrospective or prospective studies in English with at least ten adult patients with MPN-SVT were included. Study screening by title/abstract, full text, and data extraction were performed in duplicate. Primary outcomes included recurrence of venous thrombosis (SVT and non-SVT), arterial thrombosis, and major bleeding. The risk of bias was assessed with MINORS scale. Pooled risk ratio (RR) of recurrent thrombosis and major bleeding events with respective 95% confidence intervals (CI) were calculated using the Mantel-Haenszel method with random-effects model. Pooled rates of recurrent thrombosis and major bleeding events with respective 95% CI were calculated by DerSimonian and Laird method using random-effects model. Inter study heterogeneity was evaluated using the Cochran Q test and I 2 statistic.
Results:
Of a total of 4624 studies that were identified on the initial abstract screen, full texts were obtained and reviewed for 192 records. We included five retrospective and one prospective study that provided outcome rates for 387 patients with MPN treated with anticoagulation following SVT. All patients receiving anticoagulation in the six studies included in this analysis were treated with vitamin K antagonists (VKA). Of note, one additional study evaluating MPN-SVT with rivaroxaban was not included in the analysis because of short follow-up compared to the other six studies. Most studies were conducted in Europe (n=4), one was international, and one was done in the United Kingdom. The median follow-up was 3.2 years (follow-up was not reported in one study) and median age of patients at SVT diagnosis was 47.5 years old. JAK2V617F positivity was reported in 311/387 (80.3%). Regarding quality assessment and bias risk, four of the studies had moderate and two high risk of bias by the MINORS scale.
Pooled incidence rates showed that subsequent venous thrombosis was the most common complication while on anticoagulation (Pooled rate 9.6%; 95% CI 5.6 – 15.8; I 2=27%), followed by major bleeding (Pooled rate, 9%; 95% CI, 3.7 – 20.3; I 2=72%). Four of the six studies provided data comparing management with anticoagulation vs. no anticoagulation in 288 patients. The rates of venous (SVT and non-SVT) and arterial thrombosis following SVT were similar between the anticoagulation vs. no anticoagulation group (venous: RR 0.90; 95% CI, 0.412 – 1.966; I 2 = 0%, Figure 1 and arterial: RR, 1.01; 95% CI, 0.36 – 2.80; I 2=0%). Similarly, there was no significant difference in the risk of major bleeding between the two groups (RR, 0.52; 95% CI, 0.23- 1.14; I 2=0%). (Figure 2)
Conclusion:
Risk of recurrent thrombosis and bleeding in patients with MPN-SVT are considerable. Anticoagulation with VKA in MPN patients following SVT was not associated with a reduction in the risk of subsequent venous or arterial thrombosis or increased risk of major bleeding. Further studies with larger populations are warranted to elucidate the optimal medical management for MPN-SVT.