Clinical bleeding manifestations are commonly encountered reasons for medical consultations in both general and specialized fields. A comprehensive medical history, encompassing personal and familial contexts, plays a pivotal role in predicting a bleeding disorder. Employing a bleeding clinical score constitutes the primary approach. While routine coagulation tests are useful, they are inadequate for definitively ruling out a potential hemostatic abnormality. If a strong suspicion of hemostasis dysfunction exists, a comprehensive array of biological assessments must be requested. This evaluation should encompass primary hemostasis, coagulation factors, and fibrinolysis. This combined clinical and biological strategy is instrumental in recognizing whether a coagulation disorder is acquired or hereditary, in elucidating its underlying cause, and in gauging its severity. The commonly encountered congenital causes comprise platelet functional disorders, von Willebrand disease, hemophilia A/B, and deficiencies in coagulation factors like Factor VII and Factor XI, as well as hyperfibrinolysis. Nonetheless, a notable subset of patients is unlikely to benefit from this diagnostic approach. This prompts us to an undetermined source of the bleeding tendency, necessitating cautious attention to its potential implications. For hemostatic interventions, it is crucial to exercise vigilance. Indeed, the aim of such procedures is to attain effective management or bleeding prevention, while sidestepping unnecessary treatments with inherent risks, such as allergies, immunization, infections, and even thrombotic complications.

Platelet factor 4 (PF4) is a positively charged molecule stored in the alpha granules of blood platelets and secreted during platelet activation, endothelial breach, or in the presence of microorganisms. PF4 binds to glycosaminoglycans on the endothelial surface and neutralizes their anticoagulant properties. Moreover, PF4 can combine with heparin, mainly unfractionated, in heparin-induced thrombocytopenia (HIT), with cartilage components or other negatively charged polyanions (so-called spontaneous HIT), and with some constituents of the SARS-CoV-2 adenovirus vaccine, resulting in post-vaccination thrombocytopenia. The common feature of these molecules is their negative charges which induce their binding to PF4 and a conformational change of the latter. This complex is recognized by anti-PF4 antibodies, which activate platelets and inflammatory cells via the Fc receptor, induce a pro-thrombotic state, and venous, arterial, or microcirculation thrombosis. The diagnosis of HIT is based on the detection of anti-PF4-heparin antibodies by immunoassay in cases of clinical suspicion and intermediate or high pre-test probability, estimated by different scores, the 4T score being the most common. Functional tests may also be performed. HIT management consists in stopping heparin and starting non-heparin anticoagulant therapy.

VEXAS (Vacuoles, Enzyme E1, X-linked, Autoinflammatory, Somatic) syndrome has been recently described as a late-onset inflammatory disease caused by a somatic mutation in UBA1 in myeloid cells. It mostly affects men over 40 years of age with inflammatory symptoms (recurrent fever, dermatitis), rheumatologic disorders (arthritis, chrondritis), or hematologic abnormalities for several years. The presence of vacuoles in bone marrow myeloid cells is a characteristic (yet non-specific) sign of the disease. VEXAS syndrome may be associated with hematologic diseases, such as myelodysplasia and multiple myeloma, as well as an increased risk of thromboembolic event. The mortality is about 25-35% at 5 years. The disease is usually steroid-resistant. Studies with JAK2 inhibitors have shown promising results and are currently ongoing. Allogeneic stem cell transplantation is currently the only curative option for young, otherwise healthy patients.