Excessive bleeding at surgery is a feared complication in patients with inherited platelet disorders. However, very few studies have evaluated the frequency of surgical bleeding in these hemorrhagic disorders. We performed a worldwide, multicentric, retrospective study to assess the bleeding complications of surgery, the preventive and therapeutic approaches adopted, and their efficacy in patients with inherited platelet disorders: the Surgery in Platelet disorders And Therapeutic Approach (SPATA) study. We rated the outcome of 829 surgical procedures carried out in 423 patients with well-defined forms of inherited platelet disorders: 238 inherited platelet function disorders and 185 inherited platelet number disorders. Frequency of surgical bleeding was high in patients with inherited platelet disorders (19.7%), with a significantly higher bleeding incidence in inherited platelet function disorders (24.8%) than in inherited platelet number disorders (13.4%). The frequency of bleeding varied according to the type of inherited platelet disorder, with biallelic Bernard Soulier syndrome having the highest occurrence (44.4%). Frequency of bleeding was predicted by a pre-operative World Health Organization bleeding score of 2 or higher. Some types of surgery were associated with a higher bleeding incidence, like cardiovascular and urological surgery. The use of pre-operative pro-hemostatic treatments was associated with a lower bleeding frequency in patients with inherited platelet function disorders but not in inherited platelet number disorders. Desmopressin, alone or with antifibrinolytic agents, was the preventive treatment associated with the lowest bleedings. Platelet transfusions were used more frequently in patients at higher bleeding risk. Surgical bleeding risk in inherited platelet disorders is substantial, especially in inherited platelet function disorders, and bleeding history, type of disorder, type of surgery and female sex are associated with higher bleeding frequency. Prophylactic pre-operative pro-hemostatic treatments appear to be required and are associated with a lower bleeding incidence.

Behçet disease (BD) is a rare multisystem, inflammatory disease of unknown etiology with vascular involvement and associated thrombogenicity. This review aims to describe the involvement of various mediators in endothelial cell damage and in the hypercoagulable state of BD. The scenario of the chronic inflammation present in BD shows an increased oxidative condition that contributes to endothelial cell damage and induces platelet, leukocyte, and endothelial cell activation through the release of proinflammatory cytokines and chemokines. These factors, together with the increased levels of homocysteine observed in BD patients, induce the endothelial cell expression of adhesion molecules (VCAM-1 and ICAM-1) and tissue factor; the release of cytokines, soluble CD40L (sCD40L), matrix metalloproteinase-9, and blood coagulation factor V; the inhibition of fibrinolysis; the disruption of nitric oxide metabolism; and the increase in platelet reactivity and lipid peroxidation. Endothelial cell dysfunction leads to a prothrombotic and antifibrinolytic phenotype in BD patients. Increased levels of homocysteine, fibrinogen, and plasminogen activator inhibitor type 1 seem to be involved in the procoagulant condition of this pathology that has been verified by end-point tests as well as by global coagulation tests.

The treatment goal for patients with immune thrombocytopaenia (ITP) is to raise platelet counts to levels that minimize or stop bleeding. Thrombopoietin receptor agonists (TPO-RAs) have been successfully and extensively employed as second-line therapy for ITP. However, TPO-RAs have a small but significant increase in the risk of thrombosis. The aim of this study was to elucidate the mechanisms involved in the pro-coagulant effect of TPO-RAs to take them into account when considering their use in ITP patients with concomitant diseases/conditions that might increase risk of suffering thrombotic events. Eighty-two patients with chronic primary ITP (40 untreated and 42 undergoing TPO-RA therapy) and 112 healthy individuals were recruited. The patients with ITP undergoing TPO-RA therapy presented a pro-coagulant profile due to the formation of a more fibrinolysis-resistant clot because of increased plasminogen activator inhibitor-1 (PAI-1) levels. Increase in platelet content of PAI-1 might be the result of the effect of TPO-RA during megakaryopoiesis, as suggested by experiments performed in MEG-01 cells. Moreover, patients under TPO-RA treatment presented an enhanced pro-coagulant activity associated with microparticles and an increased platelet apoptosis that causes a higher exposure of phosphatidylserine and, consequently, a larger surface for the binding of the prothrombinase complex.

Worldwide vaccination against SARS-CoV-2 has allowed the detection of hematologic autoimmune complications. Adverse events (AEs) of this nature had been previously observed in association with other vaccines. The underlying mechanisms are not totally understood, although mimicry between viral and self-antigens plays a relevant role. It is important to remark that, although the incidence of these AEs is extremely low, their evolution may lead to life-threatening scenarios if treatment is not readily initiated. Hematologic autoimmune AEs have been associated with both mRNA and adenoviral vector-based SARS-CoV-2 vaccines. The main reported entities are secondary immune thrombocytopenia, immune thrombotic thrombocytopenic purpura, autoimmune hemolytic anemia, Evans syndrome, and a newly described disorder, so-called vaccine-induced immune thrombotic thrombocytopenia (VITT). The hallmark of VITT is the presence of anti-platelet factor 4 autoantibodies able to trigger platelet activation. Patients with VITT present with thrombocytopenia and may develop thrombosis in unusual locations such as cerebral beds. The management of hematologic autoimmune AEs does not differ significantly from that of these disorders in a non-vaccine context, thus addressing autoantibody production and bleeding/thromboembolic risk. This means that clinicians must be aware of their distinctive signs in order to diagnose them and initiate treatment as soon as possible.