Background Acquired von Willebrand factor (VWF) deficiency was described in Philadelphia‐negative myeloproliferative neoplasms, especially in essential thrombocythemia (ET). VWF phenotype in contemporary patients with polycythemia vera (PV) remains less explored. Objectives To characterize the VWF phenotype in PV and to compare VWF phenotype in PV with matched healthy subjects and ET patients. Patients/Methods We studied 48 PV patients, treated according to current recommendations (hematocrit ≤ 45%, on low‐dose aspirin prophylaxis); 48 healthy and 41 subjects with ET, all sex, age, and blood group matched. We measured VWF antigen, activity, multimeric pattern, ADAMTS‐13, and factor VIII (FVIII) antigen. Results In patients with PV, VWF antigen and activity were significantly higher than in healthy subjects (antigen: 119[96‐137] vs 93[79‐107] IU/dL; activity: 114[95‐128] vs 90[79‐107] IU/dL, respectively, medians and interquartile, P < 0.01), with normal multimeric distribution. ADAMTS‐13 levels were similar between patients with PV and healthy subjects. FVIII levels were higher in PV than in healthy subjects (141[119‐169] versus 98[88‐123] IU/dL, respectively, P < 0.01). By multivariable analysis, JAK2‐p.V617F allelic burden, erythrocyte count, and male sex significantly predicted VWF antigen and activity levels. As compared to patients with ET, patients with PV showed similar VWF antigen levels but approximately 40% higher activity (79[49‐104] vs 112[93‐125] IU/dL, respectively, P < 0.01). Conclusions Patients with PV show increased VWF and FVIII levels, predicted by JAK2‐p.V617F burden and erythrocyte count. At variance with ET, acquired VWF defect was not observed in PV. High VWF/FVIII levels may sustain the thrombotic diathesis of PV and may be investigated as biomarkers for risk stratification.

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by a hereditary or immune-mediated deficiency of the enzyme ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). TTPs are caused by the following pathophysiological mechanisms: (1) the presence of inhibitory autoantibodies against ADAMTS13; and (2) hereditary mutations of the ADAMTS13 gene, which is present on chromosome 9. In both syndromes, TTP results from a severe deficiency of ADAMTS13, which is responsible for the impaired proteolytic processing of high-molecular-weight von Willebrand factor (HMW-VWF) multimers, which avidly interact with platelets and subendothelial collagen and promote tissue and multiorgan ischemia. Although the acute presentation of the occurring symptoms in acquired and hereditary TTPs is similar (microangiopathic hemolytic anemia, thrombocytopenia, and variable ischemic end-organ injury), their intensity, incidence, and precipitating factors are different, although, in both forms, a severe ADAMTS13 deficiency characterizes their physiopathology. This review is aimed at exploring the possible factors responsible for the different clinical and pathological features occurring in hereditary and immune-mediated TTPs.

Direct oral anticoagulants (DOAC) and vitamin K antagonist drugs (VKA) are recommended for stroke prevention in atrial fibrillation and for treatment of venous thromboembolism. Undoubtedly, DOAC ha...

Liver cirrhosis is characterized by a delicate balance between thrombosis and bleeding. Parenchymal extinction due to microvascular thrombosis is involved in disease progression and anticoagulant therapy with low-molecular-weight heparin has been shown to reduce the frequency of hepatic decompensation [ 1]. Dysbiosis and bacterial translocation, which are hallmarks of liver cirrhosis, can influence the coagulation system through inflammation or by the activation of Toll-like receptors on endothelial cells and platelets [ 2]. However, little is known about the connections between the coagulation system, the occurrence of liver cirrhosis complications, and the gut microbiome.

Background/Objectives: Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by the formation of anti-ADAMTS13 antibodies. Caplacizumab is approved for the treatment of acute episodes of iTTP in conjunction with plasma exchange (PEX) and immunosuppression. Real-world data for the use of caplacizumab in Italy have been recently published by a limited number of centers located in the northern and middle regions of the country only. Methods: A total of 38 patients with iTTP were enrolled in the study in six Italian centers spread over the entire territory of the country. The patients’ data were registered in eCRF. Results: All patients achieved normalization of platelet count (median 2.0 days, IQR: 2–4), within a time significantly shorter than in the absence of caplacizumab, as previously reported in other studies. As to the secondary aims, patients treated with caplacizumab had a few exacerbations (4/38 (10.5%)) and relapses (2/38, 5.3%). No deaths or refractoriness were observed in these patients. The total length of hospitalization was 12 days (IQR: 9–18) and only one patient required 2 days of stay in the intensive care unit. Interestingly, when caplacizumab was initiated within the first 3 days, the plasma exchange (PEX) duration was 9 days (IQR: 8–10), which was significantly lower than those reported in previous studies conducted in the absence of caplacizumab. No severe adverse event was described in the caplacizumab-treated patients. Conclusions: Caplacizumab reduced exacerbations and refractoriness compared with previously reported standard-of-care regimens. When administered in association with PEX and immunosuppressive therapy, caplacizumab provided rapid normalization of platelet count, which was responsible for lower overall hospitalization time, ICU stay, lower exacerbations and relapses compared to previously reported outcomes of studies carried out without caplacizumab.

Extensive data support the safety of direct oral anticoagulants compared with vitamin K antagonists in patients with non‐valvular atrial fibrillation, leading to a significantly increase in the use of these compounds in clinical practice. However, there is no compelling evidence supporting the use of direct oral anticoagulant in individuals who are intubated or have a percutaneous endoscopic gastrostomy (PEG): patients with several co‐morbidities are underrepresented in clinical trials, so the best long‐term strategy for anticoagulation is difficult to ascertain. The aim of the present report was to evaluate the safety and efficacy of edoxaban administered via PEG in a patient with heart failure and a history of atrial fibrillation affected by amyotrophic lateral sclerosis (ALS). A 71‐year‐old man with atrial fibrillation, advanced ALS, type II diabetes mellitus, and hypertension presented to the emergency department with dyspnoea and tachycardia. Because vitamin K antagonist and rivaroxaban 15 mg were dropped because of difficult international normalized ratio control (time in therapeutic range <30%) and severe haematuria, respectively, edoxaban 30 mg (crushed pill) daily was administered based on the patient's weight of 58 kg. Mean edoxaban plasma concentration–time profiles were measured, as anti‐Xa activity, 2 h before and at 2, 6, and 22 h after drug administration and then compared with the pharmacokinetic profile of edoxaban 30 mg in healthy subjects. An additional testing of steady‐state peak plasma concentration of edoxaban after 10 days and a 30 day follow‐up were evaluated. The values of the pharmacokinetic parameters, analysed with a non‐compartmental analysis by PKSolver module, showed that C_max and AUC_0→t were only slightly higher than those observed in healthy subjects, while the half‐life and observed clearance were significantly longer and lower, respectively, than in normal subjects. Steady‐state peak plasma concentration of edoxaban was very similar to the levels reported in healthy subjects, and neither relevant bleeding nor thromboembolic event was reported at a 30 day follow‐up. These results support safe and effective anticoagulation with edoxaban 30 mg but suggest caution with the use of full dose of edoxaban (60 mg daily) in this kind of patients. We report, for the first time, a safe and effective anticoagulation based on the administration of edoxaban 30 mg daily through PEG in a patient with advanced ALS, acute respiratory, and heart failure, presenting with Takotsubo syndrome and atrial fibrillation.