DP059 | AN ITALIAN CARTOGRAPHY OF VEXAS-RELATED THROMBOSIS: A 218 PATIENT-YEARS ANALYSIS

While thrombotic events (TE) occur in up to 40% of VEXAS cases, a scarcity of data exists on its clinical-genomic associations or anti-coagulation strategies. To fill this gap in knowledge, we designed a two-step study aiming at elucidating prevalence, outcomes of TE in VEXAS and outline potential grounds for specific therapeutic strategies. First, we conducted a pilot-study to explore the prevalence of VEXAS in a general cohort of TE patients, taking advantage of the Thrombosis clinic (n=1086) of Rome Tor Vergata Hospital. By looking for VEXAS demographics and features, we selected 21 patients. None was positive for UBA1 mutations, suggesting that VEXAS should be suspected when specific manifestations are present, besides the mere occurrence of unexplained TE. Next, we leveraged our Italian VEXAS network to systematically investigate TE. We accrued 85 male patients, totaling 218 patient-years, with a median age of 70 years (IQR, 64-75). VEXAS co-occurred with MDS in 61% of cases, MGUS in 33%, and multiple myeloma in 1 case. Most patients presented with macrocytic anemia at diagnosis, with median hemoglobin of 9.9 g/dL (IQR, 8.4-11.4 g/dL) and MCV of 104 fL (IQR, 96-108). UBA1 genotype consisted of M41T in 43%, M41V in 33%, and M41L in 6% of cases while 18% carried other mutations. Overall, 53% of patients experienced TE, mostly affecting the venous system (78%). These were in majority of cases (62%) DVT, 10% PE, while 2 cases occurred in the splanchnic veins. About 18% of patients exhibited arterial thrombosis, mostly as cardiac events while in 1 case thrombosis involved the central retinal artery. With regards to timing of TE, this was synchronous with the VEXAS diagnosis in 67% of cases, antecedent in 7% while the others (26%) were identified subsequently. No baseline clinical nor molecular (UBA1 genotype) characteristic associated with TE. Notably, 10% of patients had concomitant thrombophilic conditions (3 heterozygous Factor V Leiden, 1 heterozygous Factor II G20210A, 5 anti-cardiolipin IgG/M antibodies). The therapeutic approach of TE consisted of DOACs in 47% of cases, LMWH in 26%, Fondaparinux in 17%, and VKAs in 7%. Longitudinal follow up revealed a complete resolution of TE in 76% of cases, while 14% had >1 TE with 4% occurring while on anti-coagulation. TE and thrombophilia are common in patients with VEXAS and are not associated with any baseline characteristics, prompting screening early at diagnosis for adequate management.