MPN-388: Assessment of Prevalence and Risk Factors for Subclinical Splanchnic Thrombosis in Patients with Myelofibrosis

Abstract

Context Splanchnic thrombosis (ST) is a characteristic feature of MPN-associated prothrombotic state. Objective To determine the prevalence of subclinical ST in patients with myelofibrosis and assess disease-related and hereditary factors as potential risk predictors. Design Single-center, cross-sectional. Setting Clinic of Medical Oncology, University Hospital “Sveti Georgi” EAD, Plovdiv, Bulgaria. Patients or Other Participants Patients were considered eligible if diagnosed with myelofibrosis according to WHO 2016 criteria (incl. post-PV and post-ET), >18 years, no symptoms of overt ST, and no previous history of thrombosis. 21 subjects were recruited. Interventions Patients underwent CT scan angiography to detect the presence of vascular occlusion in the splanchnic circulation. Digital droplet PCR was performed to quantitate JAK2 mutant and wild-type allele burden in copies per nanogram DNA. Hereditary thrombophilia was analyzed for a panel of four genes: f.V(R506Q), f.II(20210G>A), PAI(4G/5G), and MTHFR(677C>T) by RT-PCR. Statistical analysis was performed in R v.4.0.4. All patients provided written informed consent. Main Outcome Measures Primary outcome was presence of thrombosis (arterial and/or venous) in the splanchnic circulation. Potential predictors were Jak2mut/ng DNA, WBC, HGB, PLT, spleen size, ruxolitinib therapy, and presence of hereditary thrombophilia. Results Baseline characteristics: mean age 67 ±10.51 years, 53% (11) females, 48% (10) with IPSS int-2/high, 57% (12) on ruxolitinib. FV(R506Q) and f.II(20210G>A) were detected in two patients each (9%), PAI(4G/4G) was detected in 10 patients, only one patient was wild-type homozygous, 3 patients were MTHFR(677TT), and 9 were heterozygous. ST was detected in 7 patients (33%). Jak2mut/ng DNA, WBC, HGB, PLT, spleen size, and ruxolitinib were not found to be significant predictors by logistic regression. 6 out of 7 patients with thrombosis were homozygous mutant [either PAI(4G/4G): 5 patients or MTHFR(677TT): 1 patient] and heterozygous for at least one of the other three genes. The presence of mutant homozygosity and heterozygous carrier state were significantly predictive of ST (Bhereditary = 3.497, 95%CI: 1.22–6.76, p=0.008). Conclusions Subclinical ST has a relatively high incidence in myelofibrosis. However, hereditary rather than disease-related factors emerge as risk factors. Further investigation of PAI(4G/5G) and MTHFR(677C>T) screening utility is warranted. This study was funded by Medical University-Plovdiv [grant SDPD-18/2019].