Integrated Approach to Highlighting the Molecular Bases of a Deep Vein Thrombosis Event in an Elite Basketball Athlete.

Acute or intense exercise can result in metabolic imbalances, muscle injuries, or reveal hidden disorders. Laboratory medicine in sports is playing an increasingly crucial role in monitoring athletes' health conditions. In this study, we designed an integrated approach to explore the causes of a deep venous thrombosis event in an elite basketball player. Since the complete blood count revealed a marked platelet count (838 × 103 µL), and thrombophilia screening tests did not reveal any significant alteration, we evaluated the thrombin generation, which highlights a state of hypercoagulability. First-level haemostasis exams showed only a slight prolongation of the activated Partial Thromboplastin Time (aPTT). Thus, screening tests for von Willebrand Disease showed a reduction in vWF parameters. Therefore, we directed our hypothesis towards a diagnosis of acquired von Willebrand disease secondary to Essential Thrombocythemia (ET). To confirm this hypothesis and highlight the molecular mechanism underlying the observed phenotype, molecular tests were performed to evaluate the presence of the most common mutations associated with ET, revealing a 52-bp deletion in the coding region of CALR exon 9. This case report highlights the importance of an integrated approach to monitoring the athletes' health status to personalise training and treatments, thus avoiding the appearance of diseases and injuries that, if underestimated, can undermine the athlete's life.

Validation of PLASMIC score in a cohort of patients with suspected thrombotic microangiopathy in an academic medical centre.

BACKGROUND: The PLASMIC score is a rapid and inexpensive clinical assessment tool for predicting severe ADAMTS13 deficiency (<10% activity) in patients with suspected thrombotic thrombocytopenic purpura (TTP). The score includes 7 parameters: absence of active cancer, patient not having received stem cell transplant or organ transplant, platelet count <30×109/L, hemolysis, mean corpuscular volume <90 fl, International Normalized Ratio <1.5, and serum creatinine <2 mg/dL. MATERIALS AND METHODS: In this retrospective study, we evaluated a cohort of 59 consecutive patients with suspected thrombotic microangiopathy who had been referred to the Hemostasis and Thrombosis Center of the "Federico II" University of Naples, Italy, for measurement of ADAMTS13 activity. Relevant clinical and laboratory information were collected for all patients. RESULTS: The PLASMIC score was calculated in 52 of the 59 patients included in the study. In the high-risk group (PLASMIC score 6 or 7), 12 out of 20 patients (60%) had ADAMTS13 <10%. Interestingly, all 6 patients (100%) with PLASMIC score 7 had ADAMTS13 <5%. In the intermediate risk group (score 5), only one case out of 17 (5.9%) had ADAMTS 13 <10%. In the low-risk group (score 0-4), none of the patients had severe ADAMTS13 deficiency. The collected data enabled the sensitivity and specificity of PLASMIC score in TTP to be calculated, achieving 92% (95% CI: 0.80-0.98) and 79% (95% CI: 0.66-0.89), respectively. The PLASMIC score was seen to be a very efficient tool in distinguishing between patients with severe ADAMTS13 deficiency from those without, with an AUC of 0.92 (95% CI: 0.82-1.0; p<0.001). DISCUSSION: In our cohort, a high-risk PLASMIC score successfully predicted patients with severe ADAMTS13 deficiency, allowing the clinician to quickly define the best therapeutic approach, especially useful for those clinicians not used to the diagnosis and treatment of thrombotic microangiopathies.

Secondary prophylaxis of venous thromboembolism with direct oral anticoagulants: comparison between patients with major congenital thrombophilia versus non-thrombophilic patients.

Direct oral anticoagulants (DOACs) are widely used for the treatment and secondary prophylaxis of venous thromboembolism (VTE). Congenital thrombophilia is a condition that predisposes to a higher incidence of VTE and often requires long-term anticoagulation for secondary prophylaxis. It is less clear the efficacy of DOACs in patients with major thrombophilia. The aim of our study was to evaluate the efficacy and safety of full and reduced DOACs dose for VTE secondary prophylaxis, in patients affected by major congenital thrombophilia compared to a control group of patients with idiopathic recurrent VTE without thrombophilia. We retrospectively evaluated consecutive patients who required long-term anticoagulation for recurrent VTE, treated with DOACs, and compared the outcomes between patients affected by major thrombophilia and the control group. The examined patients were 209. The median time of DOACs therapy was 20 months (range 6-90). Two (2.7%) thrombotic events were observed in the subset affected by major congenital thrombophilia (n = 72) and five (3.6%) in the control group (n = 137) (p 0.73). Four (5.5%) hemorrhagic events were reported in the group with major thrombophilia; 21 (15.3%) in the other group (p 0.039). No statistically significant differences were observed in terms of efficacy and safety between DOACs at full and reduced dose. Our data suggest that DOACs may be effective and safe in the secondary VTE prophylaxis in patients affected by major congenital thrombophilia, also at reduced dose.

Safety of Switching Factor VIII Products in the Era of Evolving Concentrates: Myths and Facts.

Recent advances in the development of factor VIII (FVIII) concentrates offer patients with hemophilia the opportunity to switch to products considered safer or with improved properties. In some cases, product switch occurs due to side effects, convenience issues, or economic reasons affecting clinical choices. Reluctance to change FVIII concentrates is shown by patients and also by their physicians, because of concerns in particular about the risk of inhibitor development. A literature review was performed to retrieve the best evidence regarding safety issues of switching FVIII concentrate in patients with severe hemophilia A. Product switch was not associated with an increased inhibitor risk in four studies in patients during the first 50 to 75 exposure days, or in three studies reporting national switches in Canada and United Kingdom. The latter, the only available study comparing switcher and nonswitcher patients, showed an inhibitor incidence similar to that historically reported in the United Kingdom. In 16 phase III clinical trials and 6 postmarketing studies of FVIII concentrates, few de novo inhibitors were detected in previously treated patients, mostly transient and low-titer, with some additional recurrent inhibitors in patients with previous positive testing. On the whole, although rigorous controlled studies are lacking, literature data do not support increased risk of inhibitor development or other safety issues related to product switch. Therefore, in the presence of clinical needs, the advantages of switching FVIII products should not be missed because of perceived more than evidence-based challenges, in particular in this era of products with improved properties recently introduced or available in few years. Caution, however, is suggested in patients with high inhibitor risk, including in those in concomitance with surgery or intensive treatment. A careful inhibitor testing prior to and after product switch is always needed, to identify real de novo inhibitors and to gather further information in the current evolving scenario, in particular comparing switch and nonswitch patients.