Coagulation abnormalities in renal pathology are associated with a high thrombotic and hemorrhagic risk. This study aims to investigate the hemostatic abnormalities that are related to the interaction between soluble coagulation factors and blood cells, and the effects of hemodialysis (HD) on it, in end stage renal disease (ESRD) patients. Thirty-two ESRD patients under HD treatment and fifteen healthy controls were included in the study. Whole blood samples from the healthy and ESRD subjects were collected before and after the HD session. Evaluation of coagulation included primary and secondary hemostasis screening tests, proteins of coagulation, fibrinolytic and inhibitory system, and ADAMTS-13 activity. Phosphatidylserine (PS) exposure and intracellular reactive oxygen species (iROS) levels were also examined in red blood cells and platelets, in addition to the platelet activation marker CD62P. Platelet function analysis showed pathological values in ESRD patients despite the increased levels of activation markers (PS, CD62P, iROS). Activities of most coagulation, fibrinolytic, and inhibitory system proteins were within the normal range, but HD triggered an increase in half of them. Additionally, the increased baseline levels of ADAMTS-13 inhibitor were further augmented by the dialysis session. Finally, pathological levels of PS and iROS were measured in red blood cells in close correlation with variations in several coagulation factors and platelet characteristics. This study provides evidence for a complex coagulation phenotype in ESRD. Signs of increased bleeding risk coexisted with prothrombotic features of soluble factors and blood cells in a general hyperfibrinolytic state. Hemodialysis seems to augment the prothrombotic potential, while the persisted platelet dysfunction might counteract the increased predisposition to thrombotic events post-dialysis. The interaction of red blood cells with platelets, the thrombus, the endothelium, the soluble components of the coagulation pathways, and the contribution of extracellular vesicles on hemostasis as well as the identification of the unknown origin ADAMTS-13 inhibitor deserve further investigation in uremia.

Patients with hemophilia have a life-long risk of developing neutralizing antibodies (inhibitors) against clotting factor concentrates. After the first 50 exposure days (EDs), ie, in previously treated patients (PTPs), data on inhibitor development are limited. To report inhibitor development according to factor (F)VIII or FIX concentrate use in PTPs with severe hemophilia A and B. Inhibitor development in PTPs was collected since 2008 from 97 centers participating in European HAemophilia Safety Surveillance. Per concentrate, inhibitors were reported quarterly and the number of PTPs treated annually. Incidence rates (IRs)/1000 treatment years with 95% CIs were compared between concentrate types (plasma derived FVIII/FIX, standard half-life recombinant FVIII/FIX, and extended half-life recombinant (EHL-rFVIII/IX) concentrates using IR ratios with CI. Medians and IQRs were calculated for inhibitor characteristics. For severe haemophilia A, inhibitor rate was 66/65,200 treatment years, IR 1.00/1000 years (CI 0.80-1.30), occurring at median 13.5 years (2.7-31.5) and 150 EDs (80-773). IR on plasma-derived pdFVIII (IR, 1.13) and standard half-life recombinant FVIII (IR, 1.12) were similar, whereas IR on EHL-rFVIII was lower at 0.13 (incidence rate ratio, 0.12; 95% CI, <0.01-0.70; P < .01). For severe hemophilia B, inhibitor rate was 5/11,160 treatment years and IR was 0.45/1000 years (95% CI, 0.15-1.04), at median 3.7 years (95% CI, 2.1-42.4) and 260 EDs (95% CI, 130 to >1000). Data were insufficient to compare by type of FIX concentrates. Low inhibitor rates were observed for PTPs with severe hemophilia A and B. Data suggested reduced inhibitor development on EHL-rFVIII, but no significant difference between plasma-derived FVIII and standard half-life recombinant FVIII. FIX inhibitor rates were too low for robust statistical analysis.

Background: The platelet functionality of cold-stored platelets remains a subject of debate. Our aim was to investigate the effect of temperature on the hemostatic properties of stored platelets. Methods: Ten split pooled platelets stored at cold and at room temperature were evaluated in vitro on storage days 1, 5, 10, and 15 for metabolic, physiological, and vesiculation parameters, as well as their hemostatic profile using rotational thromboelastometry (ROTEM^®). Results: The integrity profile was better preserved in the cold-stored platelets, as lower lactate dehydrogenase levels were documented (e.g., day 10: 261 ± 46 vs. 572 ± 220 U/L, 4 vs. 22 °C, p = 0.004). A time-dependent decrease in hemostatic capacity was evident regardless of the temperature, but the cold-stored units were linked to shorter clot initiation times and increased elasticity, strength, and firmness parameters, especially during extended storage (e.g., maximum clot firmness, INTEM day 15: 81 ± 2 vs. 19 ± 4 mm, 4 vs. 22 °C, p = 0.0008). Additionally, the aggregation of cold-stored platelets was superior after the addition of any agonist tested. Regarding vesiculation parameters, the extracellular vesicles of the units at 4 °C were characterized by a larger size from day 10 onwards, when they also presented higher procoagulant activity (e.g., phospholipid-dependent clotting time of day 15: 21.4 ± 2.3 vs. 25.0 ± 3.0 s, 4 vs. 22 °C, p = 0.016). Conclusion: Our results indicate that cold-stored platelets perform better than those stored at room temperature, demonstrating superior clot formation and stability. This suggests that cold storage may more effectively preserve platelet function, potentially offering advantages for transfusion therapy and the extension of shelf-life. However, the clinical relevance of these findings requires further investigation.

Factor XII (FXII) deficiency is a coagulation factor disorder inherited in an autosomal recessive manner that causes prolonged activated partial thromboplastin time (aPTT). Although it is clinically benign without additional bleeding risk, it has been associated with paradoxical thrombosis. We report the case of a 38-year-old woman who presented with cardiac arrest secondary to spontaneous coronary artery dissection (SCAD) in the absence of identifiable risk factors. Laboratory investigations revealed an isolated prolonged aPTT, which was corrected with mixing studies, and a severe FXII deficiency with activity levels < 1%. Molecular analysis identified two homozygous FXII gene variants: the 46C>T polymorphism and the c.619G>C (p.Ala207Pro) variant. The two variants are considered clinically benign, although the combination of both in a single individual has not been previously reported. The coexistence of FXII deficiency in this case may be of clinical and hypothesis-generating interest.

Introduction: Extended half-life (EHL) factor VIII (FVIII) products aim to reduce treatment burden and improve bleeding control in hemophilia A. Real-world evidence remains essential to complement clinical trials. Aim: To evaluate clinical outcomes following switching from standard half-life (SHL) rFVIII to efmoroctocog alfa in routine clinical practice in Greece. Methods: Multicenter observational pre–poststudy including patients with moderate to severe hemophilia A. Outcomes were assessed during the 12 months before and after switching. The primary endpoint was change in annualized bleeding rate (ABR). Secondary endpoints included annualized joint bleeding rate (AjBR), infusion frequency, joint health, pain, and FVIII consumption. Results: Sixty patients were included. Following switching, ABR decreased from 6.8 to 3.2 (53%), and AjBR from 6.4 to 2.9 (55%), p < 0.001. Reductions were more pronounced in patients switching from on-demand treatment, while more modest improvements were observed among patients already on prophylaxis. HJHS significantly decreased from 17.9 to 11.5 (p < 0.007), accompanied by a decrease in pain scores (p < 0.001), in available paired subsets. Weekly infusion frequency decreased (3.2 to 2.2; p < 0.001), while mean dose per infusion increased, resulting in no consistent reduction in total annual FVIII consumption. No inhibitor or treatment-related adverse events have been observed. Conclusions: Switching to efmoroctocog alfa in routine practice was associated with improved bleeding outcomes, reduced infusion frequency, and better joint-related parameters. These findings support the real world feasibility and clinical utility οf EHL FVIII therapy, while further controlled studies are needed to better define the independent effect of product switching from changes in treatment regimen and other potential confounders.