Safety and efficacy of combined dual antiplatelet therapy and factor VIII prophylaxis in patients with haemophilia A after acute coronary syndrome.

INTRODUCTION: The increased life expectancy of patients with haemophilia A (HA) has led to a growing prevalence of cardiovascular risk factors and events. There is still scarce evidence on the safety and appropriate duration of dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) in HA patients. AIM: We describe our experience on the clinical management of Italian HA patients after ACS. METHODS: Nine patients with congenital HA treated with DAPT after a revascularization procedure performed for ACS have been enrolled and followed at the Angelo Bianchi Bonomi Haemophilia and Thrombosis Center in Milan between 2005 and September 2022. The safety and efficacy of DAPT with or without FVIII prophylaxis were assessed. RESULTS: Ten ACS events occurred in the nine HA patients (four mild and five severe). All events were treated with percutaneous transluminal coronary angioplasty with deployment of 1 to 3 drug-eluting stents followed by DAPT for 1-12 months. All patients except one were treated with FVIII prophylaxis during DAPT aimed at achieving FVIII trough levels ≥20-30 IU/dL. DAPT was effective in all cases in preventing early ACS recurrence, with only a late recurrence. We observed two clinically relevant non-major bleeds (one in a patient without FVIII prophylaxis) and three minor bleeds. No venous thrombosis occurred. CONCLUSION: The long-term secondary antithrombotic prevention consisting of DAPT and FVIII prophylaxis achieving a trough level of 20-30 IU/dL can be effective and safe in HA patients.

Clinical and Laboratory Presentation and Underlying Mechanism in Patients with Low VWF.

BACKGROUND: Low von Willebrand factor (VWF) refers to subjects with plasma levels of 30 to 50 IU/dL. The mechanism of low VWF is poorly understood. We chose to determine the clinical presentation, laboratory phenotype, and underlying mechanisms of low VWF. MATERIAL AND METHODS: We included 250 patients characterized with low VWF. The International Society on Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH-BAT) was used to assess clinical symptoms. To determine the underlying mechanisms of low VWF, we used as markers the VWF propeptide (VWFpp) assay and FVIII:C/VWF:Ag ratio for VWF synthesis and the VWFpp/VWF:Ag ratio for VWF clearance. Results were compared with those of 120 healthy controls. Cases with abnormal screening tests were further evaluated for coagulation factor levels and platelet disorders. RESULTS: The median age of the cohort was 35 years (range 3-85), 21% were children (n = 53), 34% were adult males (n = 85), and 45% (n = 112) were adult females. According to the ISTH-BAT, abnormal bleeding was found in 35% of children, 47% of males, and 49% of females. No association was found between VWF activity levels and ISTH-BAT. Patients showed an overall decreased VWF synthesis/secretion and an enhanced VWF clearance was identified in 33% of them. In 89 patients (36%), there were other hemostasis-related defects, but there was no difference in the ISTH-BAT between the two groups. CONCLUSION: Our findings indicate that reduced VWF synthesis/secretion and enhanced VWF clearance are major mechanisms of low VWF levels. Patients with low VWF have significant bleeding manifestations. While other hemostasis defects occurred together with low VWF, this combination did not exacerbate clinical symptoms.

Plasma Exchange in a Patient with Immune Thrombocytopenia Associated with Antiphospholipid Syndrome Hospitalized for COVID-19.

Thrombocytopenia is a common feature of antiphospholipid syndrome (APS) and rarely requires treatment. Here we present the case of a 71-year-old man hospitalized for severe immune thrombocytopenia (ITP) secondary to APS and concomitant SARS-CoV-2 infection. The patient was successfully treated with systemic corticosteroids, intravenous immunoglobulins, and plasma exchange (PEX). Few data are published on the use of plasma exchange in the treatment of thrombocytopenia in non-catastrophic APS. In the setting of acute infection when immunosuppressive therapies might be contraindicated, plasma exchange may be considered an effective therapeutic option. SARS-CoV-2 infection may be a trigger for a relapse of immune thrombocytopenia.

Gender and age normalization and ventilation efficiency during exercise in heart failure with reduced ejection fraction.

AIMS: Ventilation vs. carbon dioxide production (VE/VCO2 ) is among the strongest cardiopulmonary exercise testing prognostic parameters in heart failure (HF). It is usually reported as an absolute value. The current definition of normal VE/VCO2 slope values is inadequate, since it was built from small groups of subjects with a particularly limited number of women and elderly. We aimed to define VE/VCO2 slope prediction formulas in a sizable population and to test whether the prognostic power of VE/VCO2 slope in HF was different if expressed as a percentage of the predicted value or as an absolute value. METHODS AND RESULTS: We calculated the linear regressions between age and VE/VCO2 slope in 1136 healthy subjects (68% male, age 44.9 ± 14.5, range 13-83 years). We then applied age-adjusted and sex-adjusted formulas to predict VE/VCO2 slope to HF patients included in the metabolic exercise test data combined with cardiac and kidney indexes score database, which counts 6112 patients (82% male, age 61.4 ± 12.8, left ventricular ejection fraction 33.2 ± 10.5%, peakVO2 14.8 ± 4.9, mL/min/kg, VE/VCO2 slope 32.7 ± 7.7) from 24 HF centres. Finally, we evaluated whether the use of absolute values vs. percentages of predicted VE/VCO2 affected HF prognosis prediction (composite of cardiovascular mortality + urgent transplant or left ventricular assist device). We did so in the entire cardiac and kidney indexes score population and separately in HF patients with severe (peakVO2 < 14 mL/min/kg, n = 2919, 61.1 events/1000 pts/year) or moderate (peakVO2 ≥ 14 mL/min/kg, n = 3183, 19.9 events/1000 pts/year) HF. In the healthy population, we obtained the following equations: female, VE/VCO2 = 0.052 × Age + 23.808 (r = 0.192); male, VE/VCO2 = 0.095 × Age + 20.227 (r = 0.371) (P = 0.007). We applied these formulas to calculate the percentages of predicted VE/VCO2 values. The 2-year survival prognostic power of VE/VCO2 slope was strong, and it was similar if expressed as absolute value or as a percentage of predicted value (AUCs 0.686 and 0.690, respectively). In contrast, in severe HF patients, AUCs significantly differed between absolute values (0.637) and percentages of predicted values (0.650, P = 0.0026). Moreover, VE/VCO2 slope expressed as a percentage of predicted value allowed to reclassify 6.6% of peakVO2 < 14 mL/min/kg patients (net reclassification improvement = 0.066, P = 0.0015). CONCLUSIONS: The percentage of predicted VE/VCO2 slope value strengthens the prognostic power of VE/VCO2 in severe HF patients, and it should be preferred over the absolute value for HF prognostication. Furthermore, the widespread use of VE/VCO2 slope expressed as percentage of predicted value can improve our ability to identify HF patients at high risk, which is a goal of utmost clinical relevance.