Splanchnic vein thrombosis is a rare but potentially life-threatening manifestation of venous thromboembolism, with challenging implications both at the pathological and therapeutic level. It is frequently associated with liver cirrhosis, but it could also be provoked by myeloproliferative disorders, cancer of various gastroenterological origin, abdominal infections and thrombophilia. A portion of splanchnic vein thrombosis is still classified as idiopathic. Here, we review the mechanisms of splanchnic vein thrombosis, including new insights on the role of clonal hematopoiesis in idiopathic SVT pathogenesis, with important implications from the therapeutic standpoint.

Acute promyelocytic leukemia (APL) is a rare and aggressive form of acute myeloid leukemia (AML). Instead of cytotoxic chemotherapy, a combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) represents front-line therapy in low-risk patients. However, the therapeutic approach could be challenging in the case of a concomitant diagnosis of Brugada syndrome (BrS), a genetic disease characterized by an increased risk of arrhythmias and sudden cardiac death. Here, we present the case of a BrS patient who has been diagnosed with low-risk APL and treated with ATRA and ATO without observing arrhythmic events. In particular, we highlight the difficulties encountered by clinicians during the diagnostic work-up and the choice of the best treatment for these patients.

Background and Aims. Antiphospholipid syndrome (APS) is characterized by the presence of antiphospholipid antibodies (aPL) and is associated with an increased risk of thrombotic events and pregnancy morbidity. However, risk stratification in aPL-positive subjects, particularly in those without prior clinical manifestations, remains challenging. This study aimed to evaluate platelet phenotype and thrombogenicity as potentially valuable tools for the identification and thrombotic risk stratification of patients with aPL. Methods. Thirty-two patients (16 males, age: 50±17, n=11 on warfarin, n=8 on aspirin) with aPL positivity (n=17 APS, n=10 with thrombocytopenia) was compared with age- and sex-matched healthy controls (n=40). Platelet aggregation was assessed by light transmission aggregometry and expressed as percentage of maximal aggregation (%MA). Platelet activation markers (CD62P and PAC-1) were evaluated by flow cytometry as mean fluorescence intensity (MFI). Global hemostatic potential was assessed using thrombin generation assay (TGA) and total thrombus-formation analysis system (T-TAS), a microchip-based flow chamber evaluating platelet thrombus formation (PL chip) and whole-blood thrombogenicity (AR chip). Results. Platelets from patients showed: i) reduced aggregability to 5µmol/l ADP (57±6 vs 72±4, p=0.045), 4 mg/l collagen (46±6 vs 85±4, p<0.01), 5µmol/l epinephrine (35±6 vs 66±7, p=0.02), arachidonic acid (35±7 vs 69±5, p<0.001); ii) increased basal CD62 expression (14±2 vs 6±0.4, p<0.001) and reduced binding to PAC-1 in response to 5µmol/l ADP (65±4 vs 80±2, p=0.02) and 1µmol/l TRAP-6 (0.74 ±0.15 vs 1.3 ±0.25, p=0.05). Patients also showed altered TGA profiles characterized by prolonged lag time (tLAG: 9.6±0.7 vs 6.2±0.5 min, p=0.005.) and reduced thrombin production (PEAK:273±23 vs 3872 ±636 nm/l, p<0.03) more evident in patients with thetra positivity to aPL, and by altered T-TAS profiles: AUC-PL:186±34 vs 362±11(p<0.001) and AUC-AR: 944±138 vs 1362±25 (p=0.01). These alterations were found independently of anti- aggregant or anti-coagulant therapy. Strong correlations between T-TAS and TGA parameters were also found. Conclusions. APS and aPL-positive subjects exhibit significant alterations in platelet activation and coagulation profiles. Platelets show reduced aggregability, increased expression of the activation marker CD62, and reduced PAC-1 binding, likely reflecting a shift toward a procoagulant phenotype. The positive correlation between thrombin generation parameters and T-TAS suggests that these two assays capture, at least in part, the same pathophysiological axis: the overall capacity to generate thrombin and to support thrombus formation and stability. For this reason, T-TAS may be a valuable tool to identify different aPL profiles can underlie different prothrombotic states.

Factor VII (FVII) deficiency is a rare bleeding disorder that can be classified as congenital or acquired, and the majority of acquired cases are due to vitamin K deficiency or liver disease. Isolated acquired FVII deficiency is a rare occurrence and has been associated with inhibitors or auto-antibodies. Here, we describe a patient with polycythemia vera who developed systemic mastocytosis and FVII deficiency simultaneously. FVII deficiency was not caused by inhibitors and improved with antineoplastic treatment. Acquired FVII deficiency has been reported in cases of sepsis, possibly due to proteolytic degradation induced by the activation of monocytes or endothelial cells. Malignancies have been shown to cause a depletion in circulating FVII through the direct binding of cancer cells. This case report suggests a potential association between SM associated with a hematological neoplasm (SM-AHN) and acquired FVII deficiency. Further evaluations are recommended in patients with systemic mastocytosis to gain a better understanding of the relationship between pathological mast cells and clotting factor concentrations.