Transthyretin amyloidosis (ATTR) is a group of diseases caused by the deposition of insoluble fibrils derived from misfolded transthyretin, which compromises the structure and function of various organs, including the heart. Thromboembolic events and increased bleeding risk are among the most important complications of ATTR, though the underlying mechanisms are not yet fully understood. Transthyretin plays a complex role in the coagulation cascade, contributing to the activation and regulation of the coagulation and fibrinolytic systems. The prevalence of atrial fibrillation, cardiac mechanical dysfunction, and atrial myopathy in patients with ATTR may contribute to thrombosis, though such events may also occur in patients with a normal sinus rhythm and rarely in properly anticoagulated patients. Haemorrhagic events are modest and mainly linked to perivascular amyloid deposits with consequent capillary fragility and coagulation anomalies, such as labile international-normalised ratio during anticoagulant therapy. Therefore, it is paramount to carefully stratify the thrombotic and haemorrhagic risks, especially when initiating anticoagulant therapy. Our review aims to ascertain the prevalence of thromboembolic and haemorrhagic events in ATTR and identify potential risk factors and predictors and their impact on antithrombotic therapy.

Background and Aims. Advances in hemophilia care have significantly improved life expectancy, thereby increasing exposure to cardiovascular risk. Although hemophilia has traditionally been considered protective against thrombosis, cardiovascular events are increasingly recognized in this population. This study aims to evaluate the prevalence and predictors of cardiovascular events in patients with hemophilia A and B, and to investigate their association with both clinical and subclinical atherosclerosis.Methods. We conducted a multicenter ambispective observational cohort study including 163 patients aged >40 years with hemophilia A or B (139 hemophilia A; 24 hemophilia B), followed at the Hemophilia Centers of Padua and Castelfranco Veneto, in North-East Italy. Patients were divided into two groups according to the occurrence of clinical events (myocardial infarction, stroke/TIA, and venous thrombosis). Demographic, clinical, laboratory, and treatment-related variables were collected. ROTEM and Multiplate assays were performed. All participants underwent carotid ultrasound, abdominal aorta diameter measurement, and ankle-brachial index (ABI) assessment. Associations with outcomes were evaluated using univariate analyses and multivariable logistic regression models.Results. A total of 16.6% of patients (27/163) experienced at least one event, which occurred more frequently in patients with mild compared to severe hemophilia (70.4% vs 40.4%; p = 0.0199), with no significant difference between hemophilia A and B (p = 0.545). Patients with events were significantly older than those without (67.8 ± 12.2 vs 55.7 ± 10.7 years; p = 0.001). Patients with events showed a higher prevalence of cardiovascular and metabolic comorbidities, including hypertension (66.6% vs 38.2%; p = 0.01), dyslipidemia (59.3% vs 38.2%; p = 0.04), and cancer (37% vs 13.2%; p = 0.004). In multivariable analysis, events were independently associated with HIV infection (OR 6.51; 95% CI 1.38–30.77), hypertension (OR 3.17; 95% CI 1.31–7.68), and dyslipidemia (OR 2.38; 95% CI 1.02–5.56). Imaging and vascular assessments showed greater carotid plaque thickness, larger abdominal aorta diameter, and a higher prevalence of abnormal ABI (<1) in patients with events (p = 0.006, p = 0.03, and p = 0.001, respectively).Laboratory analyses revealed significantly lower hemoglobin (p = 0.0076) and platelet counts (p = 0.0037) in patients with events. Renal function was also impaired, as indicated by higher creatinine levels (p = 0.0182). In addition, NT-proBNP (p = 0.02) and troponin I (p = 0.004) were significantly increased in patients with events. Thromboelastometry demonstrated a shorter INTEM clotting time in patients with events (p = 0.0037), while platelet function testing showed significantly reduced ASPI AUC (p = 0.03) and TRAP AUC (p = 0.002).Kaplan–Meier analysis showed no significant difference in event-free survival between patients with mild and severe hemophilia (p = 0.94) (Figure 1).Conclusions. Thrombotic and cardiovascular events occurred in a minority of patients with hemophilia A and B and were more frequent among older individuals, patients with mild disease, and those with HIV infection. Events were associated with traditional cardiovascular risk factors and markers of subclinical atherosclerosis, emphasizing the importance of comprehensive cardiovascular evaluation in this population.

Background and Clinical Significance: Hemophilia A presents a considerable challenge in cardiac surgery due to the elevated risk of perioperative bleeding, particularly during procedures involving cardiopulmonary bypass. Standard management typically involves standard half-life (SHL) factor VIII (FVIII) concentrates, which require frequent dosing. Extended half-life (EHL) FVIII products offer theoretical advantages, including prolonged action and reduced infusion frequency, but their use in cardiac surgery remains largely undocumented. Case Presentation: We report the case of a 73-year-old male with mild Hemophilia A who underwent successful aortic valve replacement using a 25 mm Carpentier-Edwards Magna Ease biological prosthesis. The patient was managed perioperatively with an anti-hemorrhagic protocol based on EHL recombinant FVIII. The surgery and postoperative course were uneventful, with no bleeding complications or need for transfusion. Conclusions: This case illustrates the potential role of EHL FVIII in safely managing hemophilic patients undergoing major cardiac surgery. Given the lack of existing reports in the literature, further studies are warranted to evaluate the efficacy and safety of EHL FVIII in this setting and to potentially optimize perioperative care protocols for this patient population.

Background and Aims. Hemophilia is classically characterized by hypocoagulability; however, patients remain susceptible to atherosclerosis due to the presence of conventional cardiovascular risk factors. Data on global hemostasis and platelet function in hemophilia patients with arterial disease are still limited. This study aimed to compare clinical characteristics, laboratory parameters, ROTEM findings, and platelet function between hemophilia patients with and without atherosclerosis, and to explore potential differences in their hemostatic profiles.Methods. This cross-sectional study included 105 adult patients with hemophilia A and B, of whom 77 had no evidence of atherosclerosis and 28 had atherosclerosis. Atherosclerosis was defined as ≥50% carotid artery stenosis on Doppler ultrasound, the presence of any aortic plaque on imaging, or a pathological ankle–brachial index (ABI ≤ 0.9) consistent with peripheral arterial disease. Clinical history, comorbidities, medications, laboratory parameters, ROTEM, and Multiplate assays were collected. Continuous variables were expressed as mean ± standard deviation or median [IQR], and categorical variables as counts and percentages. Group comparisons were performed using the t-test, Mann–Whitney U test, or chi-square test, with p < 0.05 considered statistically significant.Results. Patients with atherosclerosis were older than those without (63 ± 12.4 vs. 55.5 ± 10.9 years; p = 0.007) and showed a higher prevalence of hypertension (60.7% vs. 33.7%; p = 0.013), dyslipidemia (75% vs. 35%; p < 0.001), use of antihypertensive therapy (53.6% vs. 28.6%; p = 0.018), lipid-lowering therapy (46.4% vs. 16.9%; p = 0.002), and prior cardiovascular or cerebrovascular events (28.6% vs. 6.5%; p = 0.002). No significant differences were observed in hemophilia type or severity, obesity, diabetes, alcohol consumption, or presence of inhibitors. Routine laboratory parameters, including hemoglobin, platelet count, renal function, lipid profile, lipoprotein(a), hs-CRP, and HbA1c, were comparable between groups. NT-proBNP differed significantly between groups but remained within normal ranges. ROTEM analysis showed a shortened INTEM clotting time in patients with atherosclerosis (254.9 ± 47.8 vs. 294.3 ± 140.1 s; p = 0.04) and increased FIBTEM maximum clot firmness (14 ± 3.7 vs. 12.2 ± 3.6 mm; p = 0.031), suggesting subtle procoagulant changes. No significant differences were observed in EXTEM parameters or in Multiplate ADP and ASPI assays, indicating preserved platelet function (Table 1). Kaplan–Meier analysis showed no significant difference in survival between groups (p = 0.93).Conclusions. Despite their inherent hypocoagulable state, hemophilia patients with atherosclerosis display a cardiovascular risk profile similar to that of the general population. ROTEM analysis suggests early and subtle shifts toward a procoagulant state, characterized by faster clot initiation and increased fibrin-based clot firmness. These findings highlight the importance of comprehensive cardiovascular risk assessment and global hemostasis evaluation in hemophilia patients, and support ROTEM as a sensitive tool for detecting subclinical prothrombotic changes associated with atherosclerosis.

Background and Aims. Hypercoagulability is a well-recognized feature of cancer and may play a role in tumor development and progression. Hereditary thrombophilia confers a lifelong predisposition to thrombosis, yet its relationship with cancer risk remains uncertain. This study aims to compare the prevalence of cancer among patients with venous thromboembolism (VTE) with and without hereditary thrombophilia.Methods. Consecutive patients with a history of venous thromboembolism (VTE) who underwent hereditary thrombophilia testing were enrolled. Patients were classified into three groups: no thrombophilia, mild thrombophilia, and severe thrombophilia (n = 200 each). The primary outcome was a history of cancer, defined as any solid or hematological malignancy diagnosed at any time. Age at first VTE was used as age at inclusion. Prevalence ratios (PRs) for cancer were estimated using Poisson regression with a log link and robust standard errors, adjusted for age and sex. Incident post-VTE cancer was analyzed after excluding pre-VTE cancer cases, using Cox regression adjusted for age and sex.Results. Cancer prevalence was 12.5% (25/200) in patients without thrombophilia, 14.0% (28/200) in those with mild thrombophilia, and 11.0% (22/200) in those with severe thrombophilia. Adjusted Poisson regression showed no association between thrombophilia status and overall cancer prevalence (mild vs no thrombophilia: PR 1.31, 95% CI 0.74–2.32, p = 0.362; severe vs no thrombophilia: PR 1.06, 95% CI 0.59–1.91, p = 0.839), while increasing age was independently associated with cancer (p = 0.001). Pre-VTE cancer prevalence was 9.0% (18/200) in patients without thrombophilia, 2.5% (5/200) in mild thrombophilia, and 6.5% (13/200) in severe thrombophilia. However, thrombophilia was not independently associated with pre-VTE cancer after adjustment for age and sex (overall p = 0.212). In sensitivity analyses based on thrombophilia subtypes, an overall association between subtype and pre-VTE cancer was observed (p = 0.041), mainly driven by protein C deficiency (PR 2.19 vs no thrombophilia; p = 0.032). Median age at cancer diagnosis was 64.5 [54.0–73.0] years in patients without thrombophilia, 61.5 [53.5–69.0] in mild thrombophilia, and 58.0 [47.0–66.8] in severe thrombophilia. Incident cancer occurred in 6.9% (39/564) over 5,722 person-years (0.68 per 100 person-years, 95% CI 0.47–0.90), with no association with thrombophilia in adjusted Cox regression, while age remained an independent risk factor.Conclusions. In VTE patients, hereditary thrombophilia was not independently associated with overall cancer prevalence. Cancer risk was mainly driven by age. Subtype analyses suggested a possible signal for protein C deficiency and pre-VTE cancer, but this finding requires confirmation.