Antiphospholipid syndrome (APS) is frequently associated with thrombocytopenia, in most cases mild and in the absence of major bleedings. In some patients with a confirmed APS diagnosis, secondary immune thrombocytopenia (ITP) may lead to severe thrombocytopenia with consequent major bleeding. At the same time, the presence of antiphospholipid antibodies (aPL) in patients with a diagnosis of primary ITP has been reported in several studies, although with some specific characteristics especially related to the variety of antigenic targets. Even though it does not enter the APS defining criteria, thrombocytopenia should be regarded as a warning sign of a “high risk” APS and thus thoroughly evaluated. The presence of aPL in patients with ITP should be assessed as well to stratify the risk of paradoxical thrombosis. In detail, besides the high hemorrhagic risk in secondary thrombocytopenia, patients with a co-diagnosis of APS or only antibodies are also at risk of arterial and venous thrombosis. In this narrative review, we discuss the correlation between APS and ITP, the mechanisms behind the above-reported entities, in order to support clinicians to define the most appropriate treatment strategy in these patients, especially when anticoagulant or antiplatelet agents may be needed.

C. difficile enterocolitis (CDAC) is the most common hospital infection, burdened by an increased incidence of coagulation-related complications such as deep vein thrombosis (DVT) and disseminated intravascular coagulation (DIC) as well as a significant sepsis-related mortality. In this review, we analyzed the available data concerning the correlation between coagulation complications related to C. difficile infection (CDI) and inflammasome activation, in particular the pyrin-dependent one. The little but solid available preclinical and clinical evidence shows that inflammasome activation increases the risk of venous thromboembolism (VTE). As proof of this, it has been observed that in vitro inhibition of the molecules (e.g., tissue factor) mainly involved in coagulation activation could block the process. In vivo studies show that it could be possible to reduce the incidence of complications associated with C. difficile infection (CDI) and mortality due to a state of hypercoagulability. A personalized therapeutic approach to reduce the inflammatory activity and prevent thromboembolic complications could be preliminarily defined to reduce mortality.

Rituximab is employed in the treatment of B-cell non-Hodgkin lymphomas (NHL) and autoimmune disorders of hematological interest (ADHI), such as autoimmune hemolytic anemia (AIHA), acquired hemophilia A (AHA), and immune thrombocytopenia (ITP). Rituximab induces profound B-cell depletion, reducing the titer of immunoglobulins and autoreactive antibodies, but secondary hypogammaglobulinemia increases risk of infections. We performed a retrospective, multicentric study across seven Italian centers to compare two cohorts of patients with either indolent NHL or ADHI treated with rituximab between March 2014 and March 2024. We evaluated the incidence and characteristics of infections and common antimicrobial prophylaxis adopted according to local clinical practice, in the absence of shared guidelines for ADHI. We included 285 patients (52% female; median age 55 years). The ADHI cohort comprised 187 patients (65%; 97 ITP, 78 AIHA, 12 AHA), while the control group included 98 i-NHL patients (34%). We documented 65 infectious events occurring in 65/285 patients (22.8%). Infection-related mortality occurred in 9 patients (4%). When stratified, the cumulative 180-day incidence of infections was 9.4% (IC95% 8.8%-10%) for NHL patients and 13.7% for ADHI (IC95% 12.2%-14.2%). Multivariate analysis identified prophylaxis (OR 2.62, p = 0.014) and post-treatment hypogammaglobulinemia (OR 2.73 p = 0.004) as risk factors. The risk of infection in patients with ADHI is high and comparable to that observed in NHL. Therefore, close monitoring of IgG levels is strongly advised, and mortality can be contained through rigorous antimicrobial stewardship.

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia caused by both immune-mediated platelet destruction and impaired platelet production in the bone mar-row, in the absence of any other identifiable cause of low platelets count. ITP in adult patients is a disease that frequently relapses and/or becomes refractory to multiple treatments during its course, with only a small minority of adult patients attaining a sustained complete remission off-therapy. Treatment of refrac-tory ITP can be challenging, due to the unlikeliness of attaining complete response over time. On the other hand, isolated thrombocytopenia may be due to a misdiagnosed clonal myeloid disorder, such as myelodys-plastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML), thus mimicking ITP. We here per-form a narrative review on the association between ITP and MDS/CMML and the possibility of overlap and misdiagnosis between these conditions, while we report also the case a patient treated for a severe re-fractory thrombocytopenia which bone marrow examination led to suspect an overlap of MDS and ITP. Our clinical case describes ITP which is refractory to glucocorticoids, high-dose immunoglobulins, Rituxi-mab, splenectomy, thrombopoietin receptor agonists and Fostamatinib, that ultimately attained a short-lived response to a hypometylating agent that was initiated due to bone marrow examination that aroused the suspect of MDS.

Background. Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder caused by neutralizing anti-FVIII antibodies. Its recognition may be delayed when acute limb swelling mimics venous thrombosis, exposing patients to potentially harmful anticoagulation. We report a case of AHA associated with systemic lupus erythematosus, initially misinterpreted as upper-limb thrombosis and later complicated by catheter-related femoral thrombosis.Case Report. A 62-year-old Caucasian man with recently diagnosed systemic lupus erythematosus presented to another emergency department with progressive swelling of the left arm. Suspected deep vein thrombosis led to low-molecular-weight heparin administration before transfer. Initial tests showed severe anemia (Hb 7.8 g/dL), isolated prolonged aPTT (85 s), and normal INR. At our center, CT angiography documented a large left arm/axillary/pectoral hematoma (6 x 5.3 x 11.7 cm) with active arterial contrast extravasation. The coagulation work-up showed FVIII:C 0.2%, normal VWF antigen/activity, and a mixing test consistent with an inhibitor and an anti-FVIII inhibitor titre of 25.92 BU/mL, confirming AHA. Antiphospholipid antibodies, viral serology, and tumor markers were negative. Haemostasis was achieved with activated prothrombin complex concentrate, escalated from 3000 IU to 4000 IU three times daily because of limb progression and then reduced after clinical and hemoglobin stabilization. Emergency embolization of the bleeding site was also performed. Inhibitor eradication included methylprednisolone 1 mg/kg/day, cyclophosphamide, and low-dose rituximab (100 mg weekly for four doses). During hospitalization, after femoral vascular access for embolization, the patient developed painful right leg swelling. Ultrasound and CT angiography showed right femoral deep vein thrombosis with femoral pseudoaneurysm (25 x 16 x 45 mm). Since full-dose anticoagulation was contraindicated by life-threatening bleeding, he received submaximal low-molecular-weight heparin, ultrasound-guided thrombin embolization of the pseudoaneurysm, and temporary inferior vena cava filter placement. At discharge, FVIII:C was still <10%, while inhibitor titre had decreased to 1.56 BU/mL. After rituximab completion and steroid tapering, FVIII:C increased to 79% with an undetectable inhibitor on March 27, 2026. Anticoagulation was switched to dabigatran, and the Cava filter was removed uneventfully on April 1, 2026.Conclusions. This case illustrates the diagnostic and therapeutic challenges of acquired hemophilia A, where delayed recognition may expose patients to inappropriate anticoagulation while subsequent invasive procedures may increase thrombotic risk. Early diagnosis and multidisciplinary management remain crucial to successfully navigate the bleeding–thrombosis balance