The Medical Directors of nine Italian Hemophilia Centers reviewed and discussed the key issues concerning the replacement therapy of hemophilia patients during a one-day consensus conference held in Rome one year ago. Particular attention was paid to the replacement therapy needed for surgery using continuous infusion (CI) versus bolus injection (BI) of standard and extended half-life Factor VIII (FVIII) concentrates in severe hemophilia A patients. Among the side effects, the risk of development of neutralizing antibodies (inhibitors) and thromboembolic complications was addressed. The specific needs of mild hemophilia A patients were described, as well as the usage of bypassing agents to treat patients with high-responding inhibitors. Young hemophilia A patients may take significant advantages from primary prophylaxis three times or twice weekly, even with standard half-life (SHL) rFVIII concentrates. Patients affected by severe hemophilia B probably have a less severe clinical phenotype than severe hemophilia A patients, and in about 30% of cases may undergo weekly prophylaxis with an rFIX SHL concentrate. The prevalence of missense mutations in 55% of severe hemophilia B patients allows the synthesis of a partially changed FIX molecule that can play some hemostatic role at the level of endothelial cells or the subendothelial matrix. The flow back of infused rFIX from the extravascular to the plasma compartment allows a very long half-life of about 30 h in some hemophilia B patients. Once weekly, prophylaxis can assure a superior quality of life in a large severe or moderate hemophilia B population. According to the Italian registry of surgery, hemophilia B patients undergo joint replacement by arthroplasty less frequently than hemophilia A patients. Finally, the relationships between FVIII/IX genotypes and the pharmacokinetics of clotting factor concentrates have been investigated.

Background: atrial fibrillation (AF) patients with obesity and high thromboembolic risk need oral anticoagulant therapy. Limited data are available on direct oral anticoagulants (DOACs) in this population, and a point-of-care method has been validated to support rapid clinical decisions and to identify on-off plasma concentration thresholds. Methods: This is a monocentric, cross-sectional diagnostic accuracy study on obese AF outpatients referred to Policlinico Umberto I of Rome. Urinary Dipsticks were assessed with separate pads for factor Xa (FXA-i) and thrombin inhibitor (THR-i) and compared to the reference standard of trough and peak plasma concentrations with chromogenic assays/dTT and prespecified plasma thresholds for each DOAC. Study endpoints were the sensitivity, specificity, positive and negative predictive values (PPV and NPV) of DOACs Dipstick compared to plasma concentrations. Sub-analyses according to obesity severity and type of DOAC were performed. Results: 320 paired plasma and urine samples were available from 160 enrolled patients (mean age 73.2 ± 9.1 years). Compared to trough plasma concentrations, DOACs Dipstick showed a sensitivity of 99.24% (mean, 95% confidence interval, CI 95.82–99.98), specificity of 6.89% (0.85–22.76), PPV 82.80% (81.32–84.18), NPV 66.67% (15.79–95.52). On the other hand, compared to peak plasma concentrations, DOACs Dipstick showed a sensitivity of 97.8% (93.7–99.5), specificity of 0% (0.0–15.4), and PPV of 85.9% (85.6–86.2). Urinary Dipstick showed a sensitivity of 99.10% (95.4–100.0), specificity of 4.70% (0.60–16.20) and a PPV and NPV of 74.50% (73.2–75.8) and 66.70 (15.7–95.6), compared to plasma thresholds > 30 ng/mL of FXA-I and THR-I. Sub-analyses showed similar results between FXA-i and THR-i. Conclusions: The urine point-of-care has high sensitivity, acceptable PPV, but low specificity and NPV in AF obese patients and may be useful only in selected clinical scenarios.

Background: An appropriate and effective management of haemophilia is currently based on a multidimensional evaluation of treatment adequacy. Current clinical practice however is still lacking standardised tools able to combine clinical, functional, and patient-reported outcomes. In this study a structured Monitoring Tool for haemophilia A and B was developed and validated through a Delphi-based expert consensus process. This study represents an expert consensus-based validation of a monitoring framework, rather than a clinical validation in patient cohorts. The tool is intended for use by haemophilia treaters during routine follow-up visits to support structured treatment reassessment. Score categories reflect the need for clinical re-evaluation or potential treatment optimisation, rather than disease severity. Methods: Italian haemophilia specialists were asked to participate to a panel over a two-round Delphi process. Experts rated the relevance of several predefined clinical domains—pharmacokinetics, bleeding episodes, joint health, adherence and quality of life (QoL)—and the individual items within each domain for patients on prophylactic or on-demand treatment. Consensus was defined by responses within an interquartile range (IQR) < 8. Section and item weights and Likert-based scoring values were used to reach a composite score between 0 and 100. Results: Consensus was achieved for all domains and items across haemophilia types and treatments, prophylaxis and on demand (Haemophilia A: 16 and 12 participants; Haemophilia B: 12 and 9, respectively). With reference to prophylaxis domains, bleeding episodes received the highest domain weight (31–32%), followed by joint health (27–29%) and adherence/QoL (21–23%) and pharmacokinetics (18–19%). For on-demand treatment, pharmacokinetics was excluded; bleeding episodes (38–40%) and joint health (35–37%) remained dominant. At the item level, dynamic joint health indicators (HJHS and HEAD-US changes) and longitudinal QoL changes consistently received the highest weights. The final scoring system categorised results as Excellent (0–25), Suboptimal (26–50), Poor (51–75), or Critical (76–100). Conclusions: The Delphi-validated Monitoring Tools provide a structured, weighted, and clinically relevant framework for assessing treatment adequacy in haemophilia A and B across prophylactic and on-demand settings. These tools allow multidimensional outcome assessment and may support a more consistent, personalised therapeutic decision-making. A prospective validation of the tool in clinical cohorts is warranted.