Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by the persistent positivity of antiphospholipid antibodies (aPLA) together with thrombosis or obstetrical complications. Despite their recognized predominant role, aPLA are not sufficient to induce the development of thrombosis and a second hit has been proposed to be necessary. The mainstay of treatment of APS is anticoagulant therapy. However, its optimal intensity in different presentations of the disease remains undefined. Moreover, decision on which patients with aPLA would benefit from an antithrombotic prophylaxis and its optimal intensity are challenging because of the lack of stratification tools for the risk of thrombosis. Finally, decision on the optimal type of anticoagulant drug is also complex because the central pathway responsible for the development of thrombosis is so far unknown and should be carried out on an individual basis after a careful evaluation of the clinical and laboratory features of the patient. This review addresses the epidemiology, physiopathology, diagnosis and management of thrombosis and obstetrical complications in APS, with a special focus on the role of direct oral anticoagulants.

High plasma levels of factor VIII (FVIII) and von Willebrand factor (VWF) have been indicated as independent risk factors for venous thromboembolism. However, the genetic factors responsible for their increase remain poorly known. In a large Italian family with high FVIII/VWF levels and thrombotic episodes, whole exome sequencing (WES) was performed on 12 family members to identify variants/genes involved in FVIII/VWF increase. Twenty variants spread over a 8300 Kb region on chromosome 5 were identified in 12 genes, including the low frequency rs13158382, located upstream of the MIR143/145 genes, which might affect miR-143/145 transcription or processing. The expression of miR-143/145 and VWF mRNA were evaluated in the peripheral blood mononuclear cells of six family members. Members with the variant (n = 3) showed lower levels of both miRNAs and higher levels of VWF mRNA compared to members without the variant (n = 3). An analysis of genetic and expression data from a larger cohort of individuals from the 1000 Genomes and GEUVADIS project confirmed a statistically significant reduction (p-value = 0.023) in miR-143 in heterozygous (n = 35) compared to homozygous wild-type individuals (n = 386). This family-based study identified a new genetic variant potentially involved in VWF increase by affecting miR-143/145 expression.