Direct reinfusion of pericardial blood complications: A case of acute respiratory distress syndrome and disseminated intravascular coagulation.

Background: Direct reinfusion of pericardial blood during cardiac surgery triggers a systemic inflammatory response. Although various inflammatory mediators have been identified as triggers, the role of damage-associated molecular patterns (DAMPs) remains poorly understood. Despite guidelines recommending against this practice owing to its harmful effects, it is sometimes used in emergencies. Case Presentation: A 72-year-old man with atrial fibrillation and cerebral infarction developed cardiac tamponade during catheter ablation. He underwent pericardial drainage and direct blood reinfusion. He was transferred to our ICU, where he developed acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC). Despite aggressive management, the patient died 41 days after admission. Conclusion: This case highlights severe adverse events following direct reinfusion of pericardial blood. These findings suggest a significant role for DAMPs in mediating these inflammatory responses. Direct reinfusion of pericardial drainage blood should be avoided during emergencies to prevent life-threatening complications.

Rapid diagnosis of coagulopathies from vitamin K deficiency in a consecutive case cohort evaluated by comparative assessment of factor II by 1-stage assays with prothrombin time vs Ecarin reagents.

BACKGROUND: Vitamin K (VK) deficiency (VKD) impairs γ-carboxylation of VK-dependent factors (VKDFs), resulting in higher factor (F)II levels measured by Ecarin (FIIE) reagents (that convert des-γ-carboxylated FII to meizothrombin) than by prothrombin time (FII) reagents. OBJECTIVES: To evaluate FII/FIIE abnormalities among patients assessed for coagulopathies and identify findings predictive of coagulopathy improvement after VK. METHODS: We retrospectively assessed consecutive cases from 2002 to 2021 with FII/FIIE tests and the sensitivity and specificity of FII/FIIE ratios and FIIE-FII differences for VKD defined as international normalized ratio correction/improvement of ≥0.5 after VK. RESULTS: Two hundred ninety-two patients (males, 58.2%; adults, 85.6%; median age, 73 years) were evaluated (84.2% hospitalized, 48.3% in intensive care, 71.6% with active liver disease, and 28% deceased at discharge) and 25% to 38% had FII/FIIE findings suggestive of VKD. Among 170 patients assessed for response to VK, FII/FIIE ratios of ≤0.84 to 0.91 and FIIE-FII differences of >0.04 U/mL had similar modest sensitivity (47.7%-69.3%) and modest to good specificity (67.1%-91.5%) for VKD. FII/FIIE ratios of <0.86, suggestive of VKD (sensitivity, 47.7%; specificity, 90.2%), were more common in patients deficient in only VKDF (P = .0001), but were detected in 16% with non-VKDF deficiencies. Low FIIE was commonly associated with active liver disease (P = .0002). Patients with and without probable VKD (based on FII/FIIE ratios of <0.86) had similar mortality, bleeding, and rates of prothrombin complex concentrate and red cell transfusions (P ≥ .78), but fewer with probable VKD received plasma and fibrinogen replacement (P ≤ .024). CONCLUSION: FII/FIIE comparison aids the diagnosis of VKD and predicts clinical responses to VK treatment among patients with coagulopathies.

Sensitivity and specificity of strategies to identify patients with hemostasis abnormalities leading to an increased risk of bleeding before scheduled intervention: the Hemorisk study.

BACKGROUND: Preoperative identification of patients with hemostasis abnormalities leading to an increased bleeding risk is based on routine hemostasis tests: prothrombin time (PT), activated partial thromboplastin time (APTT), and platelet count. Because of their low predictive performance, guidelines recommend replacing them with structured bleeding risk questionnaires, but none is validated in this population. OBJECTIVES: To assess the diagnostic accuracy of 3 strategies, performed at the preanesthesia visit before scheduled interventions, and to identify patients with hemostasis abnormalities leading to an increased bleeding risk METHODS: A multicenter study was performed in 7 French academic hospitals, involving patients scheduled for surgical intervention, without antiplatelet/anticoagulant treatment. The 3 strategies consisted of 1-a structured screening questionnaire; 2-PT, APTT, and platelet count ordered in selected patients; and 3-systematic PT, APTT, and platelet count. The reference standard comprised von Willebrand factor activity/antigen, factor (F)VIII, FIX, FXI, platelet function analyzer, and, when required, FII, FV, FX, and FVII and hemostasis consultation. RESULTS: Eighteen (1.2%) of 1484 patients had a hemostasis abnormality leading to an increased bleeding risk according to reference standard. In the overall cohort, sensitivity of the questionnaire-based strategy was 50% (95% CI, 26%-74%; specificity, 87% [95% CI, 85%-88%]); sensitivity was 0% (95% CI, 0%-41%) in men vs 82% (95% CI, 48%-98%) in women. For selective routine tests, sensitivity was 33% (95% CI, 13%-59%) and specificity 97% (95% CI, 96%-98%). Corresponding values for systematic routine tests were 44% (95% CI, 22%-69%) and 93% (95% CI, 91%-94%). CONCLUSION: Sensitivity was low for all 3 strategies investigated. The structured screening questionnaire had clinically acceptable diagnostic accuracy only in women.

[Haemophilia B therapy: impact of the reimbursability of a long-acting recombinant factor on pharmaceutical expenditure in Italy]. / Terapia dell'emofilia B: impatto dell'ammissione alla rimborsabilità di un fattore ricombinante long-acting sulla spesa farmaceutica in Italia.

OBJECTIVES: to assess the variability in expenditure compared to 2022 assuming different rates of shifting of therapy days from current active ingredients used for the treatment of haemophilia B to nonacog beta pegolDesign: descriptive cross-sectional study. SETTING AND PARTICIPANTS: consumption in the year 2022 (data source: Medicines Utilisation Monitoring Centre, Italian Medicines Agency) of all medicinal products available in Italy containing coagulation factor IX. MAIN OUTCOMES MEASURES: for each active ingredient, the total number of therapy days and the variability in expenditure compared to 2022 were estimated on the basis of a switch of therapy days, between 5% and 20%, to nonacog beta pegol. RESULTS: on the basis of considered scenarios, the analysis shows that the total annual expenditure for clotting factors used in the treatment of haemophilia B could remain at most unchanged or reduced. Particularly, the extent of the reduction in spending could vary from 0.11% to 2.26%. This trend would be in contrast to the stable increase seen in recent years, particularly in 2022. CONCLUSIONS: this predictive spending assessment may be useful in evaluating the economic impact from new treatment options, such as etranacogene dezaparvovec gene therapy already approved by the European Medicines Agency and the Food and Drug Administration, and to improve pharmaceutical governance.

Efficacy of a 1:1 ratio VWF/FVIII concentrate in patients with von Willebrand disease.

INTRODUCTION: Patients with von Willebrand disease (VWD) require administration of von Willebrand factor (VWF) concentrates peri-operatively. Concerns about FVIII accumulation after repetitive injections of a 1:1 ratio VWF/FVIII clotting factor concentrate (CFC) led this study to explore the recovery and FVIII accumulation over time. METHODS: This monocentre study examined patients with VWD receiving perioperative 1:1 ratio CFC infusions. CFC dosing was based on body weight and endogenous VWF/FVIII activity. FVIII and VWF activity was monitored at T0 (baseline), T1 (15 min postinfusion), and trough levels at T2-T6 (24-120 h). RESULTS: We included 125 patients, undergoing 125 procedures (63 major surgeries, 62 minor), with a median of two CFC infusions (IQR 1-3). With a mean administered dose of 35.7 IU/kg CFC, recovery rates of FVIII and VWF were 2.6 IU/dL per IU/kg and 2.4 IU/dL per IU/kg, respectively. Mean FVIII levels at T0 were 62 (SD 51.9), T1: 164 (SD 80.4), T2: 155 (SD 62.8), T3: 162 (SD 59.8), T4: 124 (SD 78.4), and T5: 120 (SD 65.3) IU/dL. Mean VWF activity levels at T0 were 29 (SD 25.0), T1: 133 (SD 43.7), T2: 92 (SD 37.2), and T3: 86 (SD 37.5) IU/dL. Subgroup analysis in 47 patients with more than three infusions, showed no accumulation of mean FVIII levels. CONCLUSION: This perioperative study demonstrated excellent FVIII and VWF recovery of a 1:1 ratio VWF product in patients with VWD. Stable FVIII and VWF activity levels were observed after repeated infusions, without accumulation. Most major surgeries required only three CFC infusions.

Protein C Pretreatment Protects Endothelial Cells from SARS-CoV-2-Induced Activation.

SARS-CoV-2 can induce vascular dysfunction and thrombotic events in patients with severe COVID-19; however, the cellular and molecular mechanisms behind these effects remain largely unknown. In this study, we used a combination of experimental and in silico approaches to investigate the role of PC in vascular and thrombotic events in COVID-19. Single-cell RNA-sequencing data from patients with COVID-19 and healthy subjects were obtained from the publicly available Gene Expression Omnibus (GEO) repository. In addition, HUVECs were treated with inactive protein C before exposure to SARS-CoV-2 infection or a severe COVID-19 serum. An RT-qPCR array containing 84 related genes was used, and the candidate genes obtained were evaluated. Activated protein C levels were measured using an ELISA kit. We identified at the single-cell level the expression of several pro-inflammatory and pro-coagulation genes in endothelial cells from the patients with COVID-19. Furthermore, we demonstrated that exposure to SARS-CoV-2 promoted transcriptional changes in HUVECs that were partly reversed by the activated protein C pretreatment. We also observed that the serum of severe COVID-19 had a significant amount of activated protein C that could protect endothelial cells from serum-induced activation. In conclusion, activated protein C protects endothelial cells from pro-inflammatory and pro-coagulant effects during exposure to the SARS-CoV-2 virus.

Targeted exome analysis in patients with rare bleeding disorders: data from the Rare Bleeding Disorders in the Netherlands study.

Background: Rare coagulation factor deficiencies and disorders of fibrinolysis (defined as rare bleeding disorders [RBDs]) present with a heterogeneous bleeding phenotype, and bleeding severity is difficult to predict. Objectives: Describe underlying rare genetic variants in the Dutch RBD population and investigate the relationship between genotype, laboratory phenotype, and clinical phenotype. Methods: The Rare Bleeding Disorders in the Netherlands is a cross-sectional, nationwide study conducted between October 1, 2017, and November 30, 2019. Bleeding scores and blood samples were collected during a single study visit. Coagulation factor levels were measured centrally, and targeted exome analysis was performed on 156 genes involved in thrombosis and hemostasis. Pathogenicity was assigned according to the Association for Clinical Genetic Science guidelines. Results: Rare genetic variants specific to the diagnosed RBD were found in 132 of 156 patients (85%). Of the 214 rare genetic variants identified, 57% (n = 123) were clearly pathogenic, 19% (n = 40) were likely pathogenic, and 24% (n = 51) were variants of unknown significance. No explanatory genetic variants were found in patients with plasminogen activator inhibitor type 1 deficiency or hyperfibrinolysis. A correlation existed between factor activity levels and the presence of a genetic variant in the corresponding gene in patients with rare coagulation factor deficiencies and alpha-2-antiplasmin deficiency. Co-occurrence of multiple genetic variants was present in a quarter of patients, but effect on phenotype remains unclear. Conclusion: Targeted exome analysis may offer advantages over single-gene analysis, emphasized by a number of combined deficiencies in this study. Further studies are required to determine the role of co-occurring hemostasis gene variants on the bleeding phenotype in RBDs.

Assessing the impact of severe acute respiratory syndrome coronavirus 2 infection on hematological parameters.

BACKGROUND: The current study is a retrospective study designed to evaluate changes in complete blood count and coagulation parameters in adult coronavirus disease 2019 (COVID-19) patients at a prominent Saudi tertiary center to predict disease severity and mortality. METHODS: The cohort consisted of 74 800 adult patients divided into four groups based on a COVID-19 test and the patient's sex: 35 985 in the female negative COVID-19 group, 23 278 in the male negative COVID-19 group, 8846 in the female positive COVID-19 group and 6691 in the male positive COVID-19 group. RESULTS: Patients with COVID-19 demonstrated decreased white blood cell counts and increased red blood cell counts. Also, COVID-19-positive participants exhibited more prolonged partial thromboplastin time and lower D-dimer levels than those of COVID-19-negative subjects (p<0.05). The study also revealed gender-dependent impacts on platelet counts, implying a possible relationship with the greater infection mortality rate in men than in women (p<0.001). In addition, the study found a link between changes in coagulation test results and death in COVID-19 patients (p<0.001). The evidence regarding the effects of COVID-19 on blood cell counts and coagulation, on the other hand, is conflicting, most likely due to variances in study populations and the timing of testing postinfection. CONCLUSIONS: According to the findings, COVID-19-related alterations in blood cell count and clotting ability may be risk factors for death.

Factor XIII in major burns coagulation.

BACKGROUND: In the days following a burn injury, major burn patients (MBP) present a multifactorial coagulation disorder known as acute burn-induced coagulopathy. Several studies have investigated coagulation in MBPs; however, Factor XIII (FXIII), which converts fibrin monomers into a stable clot and promotes wound healing, has not yet been studied. OBJECTIVE: To determine the kinetics of FXIII and other coagulation factors and cofactors in MBPs in order to clarify coagulopathy in these patients and its potential relationship with surgical bleeding. METHODS: Prospective observational pilot study of the kinetics of FXIII and other coagulation factors and cofactors in MBPs during the first 30 days of burn injury. RESULTS: FXIII levels show a significant decline of 75.10% in the interval between the burn injury and surgery, and a decline of 87.70% in the 24 h following surgery. Patients undergo surgery with a median antigenic FXIII of 32%. Plasma levels of most factors decrease significantly 24 h after the burn injury. CONCLUSION: MBPs experience a significant decrease in plasma levels of FXIII from the time of admission up to 24 h after surgery. Abnormally low levels were observed at the time of surgery that could not be detected by other coagulation tests. The decrease in most factors at 24 h seems to be associated with dilution due to intensive fluid resuscitation.

Comparison of coagulation and fibrinolysis in Irish Wolfhounds and age-matched control dogs using tissue plasminogen activator-augmented viscoelastic testing.

OBJECTIVE: To determine if Irish Wolfhounds (IWs), like other sighthounds, are hyperfibrinolytic compared with nonsighthound dogs using 2 native and tissue plasminogen activator (tPA)-enhanced viscoelastic assays, one that is whole blood-based (viscoelastic coagulation monitor [VCM]) and the other that is plasma-based thromboelastography (TEG). DESIGN: Cohort study. SETTING: University teaching hospital. ANIMALS: A convenience sample of 27 IWs recruited from the Irish Wolfhound Association of New England Specialty and the local community, and 27 healthy, age-matched, large-breed control dogs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood samples including CBC, biochemistry, traditional coagulation, and viscoelastic testing were collected from IWs and control dogs. Twelve IWs had viscoelastic testing. IWs had lower fibrinogen concentrations (215.5 ± 57.8 vs 251.4 ± 64.5 mg/dL, P = 0.034) and formed weaker clots on both whole-blood VCM and plasma TEG assays (maximum clot firmness [VCM-MCF] = 39.4 [25.1-48.8] vs 48.5 [34.6-57.3], P = 0.0042; maximum amplitude [TEG-MA] = 22.7 [14.7-33.6] vs 32.2 [26.9-42.0], P < 0.0001). IWs were hyperfibrinolytic compared with control dogs on VCM whole-blood assays, with 25 U/mL tPA (lysis at 30 min [VCM-LI30] = 68.1 [0-100] vs\ 99.9 [63.3-100], P = 0.0009; lysis at 45 min [VCM-LI45] = 31.0 [0-100] vs 98.1 [38.4-100], P = 0.0002) but hypofibrinolytic compared with controls on TEG plasma assays with 50 U/mL tPA (lysis at 30 min [TEG-LY30] = 45.7 [4.6-94.6] vs 93.7 [12.3-96.5], P = 0.0004; lysis at 60 min [TEG-LY60] = 68.7 [29.7-96.8] vs 95.7 [34.4-97.6], P = 0.0003). Minimal fibrinolysis was measured on whole-blood VCM or plasma TEG assays without the addition of tPA, and there were no differences between the 2 groups. CONCLUSIONS: Weaker clots were found in IWs than control dogs. With the addition of tPA, IWs had evidence of hyperfibrinolysis on whole-blood VCM assays and hypofibrinolysis on plasma TEG assays compared with control dogs. Without the addition of tPA, however, both groups of dogs showed minimal fibrinolysis on viscoelastic testing.

Cost-effectiveness of emicizumab prophylaxis for haemophilia A with inhibitors: an adaptive health technology assessment for the Indian setting.

OBJECTIVE: To assess the cost-effectiveness of emicizumab prophylaxis for patients having haemophilia A with inhibitors in the Indian context using an adaptive health technology assessment (aHTA) methodology. DESIGN: Economic evaluation using multiple approaches aimed at adjusting previously generated cost-effectiveness results based on (1) price differences only ('simple') and (2) differences in cost and expected treatment duration ('moderate') and differences in cost, inflation and life expectancy ('complex'). SETTING: Typical haemophilia care in India. PARTICIPANTS: Patients with haemophilia A and inhibitors. INTERVENTION: Emicizumab prophylaxis using two vial strengths (30 or 150 mg/mL) in comparison to no prophylaxis. MAIN OUTCOME MEASURES: Adjusted incremental cost-effectiveness ratio (ICERa), incremental costs and incremental quality-adjusted life years associated with emicizumab prophylaxis from both the health system and societal perspectives. RESULTS: Using the simple ICER adjustment method, emicizumab prophylaxis resulted in potential cost savings from the payers' perspective for both vial strengths in patients aged ≥12 and <12 years. However, from a societal perspective, emicizumab prophylaxis was not cost-effective. Using the moderate adjustment method, emicizumab prophylaxis showed potential cost saving from the health system perspective. The complex adjustment method also revealed cost savings for emicizumab prophylaxis from the health system and societal perspectives across different age groups. CONCLUSION: We found that implementing emicizumab prophylaxis for patients with haemophilia A and inhibitors in India has the potential to result in cost savings. This study highlights the feasibility of using the expanded aHTA methodology for rapid evidence generation in the Indian context. However, it is crucial to address certain research gaps, including data limitations, challenges in translating international evidence to Indian context and associated uncertainties. Additionally, conducting a comprehensive budget impact analysis is necessary. These findings hold significant implications for decision-making regarding the potential provision of emicizumab prophylaxis through federal or/and state government-funded programmes and institutions in India.

Comprehensive genomic filtering algorithm to expose the cause of skewed X chromosome inactivation. The proof of concept in female haemophilia expression.

BACKGROUND: Exploring the expression of X linked disorders like haemophilia A (HA) in females involves understanding the balance achieved through X chromosome inactivation (XCI). Skewed XCI (SXCI) may be involved in symptomatic HA carriers. We aimed to develop an approach for dissecting the specific cause of SXCI and verify its value in HA. METHODS: A family involving three females (two symptomatic with severe/moderate HA: I.2, the mother, and II.1, the daughter; one asymptomatic: II.2) and two related affected males (I.1, the father and I.3, the maternal uncle) was studied. The genetic analysis included F8 mutational screening, multiplex ligation-dependent probe amplification, SNP microarray, whole exome sequencing (WES) and Sanger sequencing. XCI patterns were assessed in ectoderm/endoderm and mesoderm-derived tissues using AR-based and RP2-based systems. RESULTS: The comprehensive family analysis identifies I.2 female patient as a heterozygous carrier of F8:p.(Ser1414Ter) excluding copy number variations. A consistent XCI pattern of 99.5% across various tissues was observed. A comprehensive filtering algorithm for WES data was designed, developed and applied to I.2. A Gly58Arg missense variant in VMA21 was revealed as the cause for SXCI.Each step of the variant filtering system takes advantage of publicly available genomic databases, non-SXCI controls and case-specific molecular data, and aligns with established concepts in the theoretical background of SXCI. CONCLUSION: This study acts as a proof of concept for our genomic filtering algorithm's clinical utility in analysing X linked disorders. Our findings clarify the molecular aspects of SXCI and improve genetic diagnostics and counselling for families with X linked diseases like HA.

Laboratory assessment of antiphospholipid syndrome: Laboratory data.

INTRODUCTION: Thorough assessment of the antiphospholipid syndrome (APS) includes retesting of positive antiphospholipid antibody (aPL) tests after at least 12 weeks, and a full antiphospholipid antibody profile. To what extent this work-up is done in clinical practice is unknown. METHODS: Data on 25 116 in- and out-hospital patients tested for the presence of lupus anticoagulant (LA), the aPL which most strongly correlates with thrombosis, was extracted from the laboratory information system of the only laboratory that performs LA tests in the Capital Region, Denmark. We estimated fraction of repeated tests, tests repeated within the recommended time span, and fraction with a full aPL profile. RESULTS: Out of 25 116 patients, 843 were positive for LA (3.3%), and 3948 results were inconclusive (16%). Only 51% (95% CI of the proportion: 48%-54%) (n = 431) of positive tests were repeated. The proportion of inconclusive LA test results increased from 13% (12%-15%) in 2009 to 20% (19%-22%) in 2020. Out of the positive tests repeated within the first year, only 60/353 (17%; 13%-21%) were repeated within 12-16 weeks; 177/353 (50%; 45%-55%) were re-tested within the first 12 weeks of first positive test result. The proportion of patients with a full antiphospholipid antibody profile increased from 161/1978 (8%) in 2010 to 1041/1978 (43%) in 2020. CONCLUSION: We found several issues with the laboratory workup of APS. This indicates a need for increased awareness of comprehensive laboratory assessment of possible APS as well as a closer collaboration between the laboratory and clinicians.

Association between loss of hypercoagulable phenotype, clinical features and complement pathway consumption in COVID-19.

Background: Coronavirus disease 2019 (COVID-19) features a hypercoagulable state, but therapeutic anticoagulation effectiveness varies with disease severity. We aimed to evaluate the dynamics of the coagulation profile and its association with COVID-19 severity, outcomes, and biomarker trajectories. Methods: This multicenter, prospective, observational study included patients with COVID-19 requiring respiratory support. Rotational thromboelastometry findings were evaluated for coagulation and fibrinolysis status. Hypercoagulable status was defined as supranormal range of maximum clot elasticity in an external pathway. Longitudinal laboratory parameters were collected to characterize the coagulation phenotype. Results: Of 166 patients, 90 (54%) were severely ill at inclusion (invasive mechanical ventilation, 84; extracorporeal membrane oxygenation, 6). Higher maximum elasticity (P=0.02) and lower maximum lysis in the external pathway (P=0.03) were observed in severely ill patients compared with the corresponding values in patients on non-invasive oxygen supplementation. Hypercoagulability components correlated with platelet and fibrinogen levels. Hypercoagulable phenotype was associated with favorable outcomes in severely ill patients, while normocoagulable phenotype was not (median time to recovery, 15 days vs. 27 days, P=0.002), but no significant association was observed in moderately ill patients. In patients with severe COVID-19, lower initial C3, minimum C3, CH50, and greater changes in CH50 were associated with the normocoagulable phenotype. Changes in complement components correlated with dynamics of coagulation markers, hematocrit, and alveolar injury markers. Conclusions: While hypercoagulable states become more evident with increasing severity of respiratory disease in patients with COVID-19, normocoagulable phenotype is associated with triggered by alternative pathway activation and poor outcomes.

Benefits of physical activity self-monitoring in patients with haemophilia: a prospective study with one-year follow-up.

INTRODUCTION: Activity wristbands have been shown to be effective in relation to self-monitoring activity levels and increasing exercise adherence. However, previous reports have been based on short-term follow-ups in people with haemophilia (PWH). AIM: (1) To evaluate compliance with physical activity (PA) recommendations in PWH during a 1-year follow-up period using activity wristbands to record daily steps and intensity; (2) To determine the effect of PA self-monitoring on clinical outcomes. METHODS: A prospective observational study was conducted in 27 adults with severe haemophilia undergoing prophylactic treatment. The Fitbit Charge HR was used to track daily PA for an entire year. The participants were encouraged to try to reach a goal of 10,000 steps/day and to track their progress. The pre- and post-evaluation included quality of life (A36 Hemophilia-QoL Questionnaire), joint health (Haemophilia Joint Health Score), functionality (Timed Up and Go test), and muscle strength. RESULTS: A total of 323.63 (95%CI: 194-364) valid days (i.e., > 2000 steps) were recorded. The annual average number of steps per day taken by participants was 10,379. Sixteen (59%) PWH reached 10,000 steps/day at baseline and 17 (63%) at 1 year follow-up, with no significant differences (x2 = .33; p = .56). A statistically significant improvement was observed in daily moderate activity time (p = .012) and in the 'physical health' quality of life subscale (mean difference: 2.15 points; 95%CI: .64-3.65; p = .007). CONCLUSION: Our results suggest that patients with severe haemophilia who self-managed their PA can improve their long-term quality of life in the domain of physical health and also the daily time spent in moderate-intensity PA.

Use of crushed tranexamic acid tablets in water for paediatric patients with bleeding disorders.

BACKGROUND: Ε-Aminocaproic acid oral solution (EACA OS) is the only commercially available antifibrinolytic for patients who cannot swallow tablets. Insurance denials and high costs remain barriers to its use. OBJECTIVES: To determine the safety and efficacy of crushed tranexamic acid tablets in water (cTXAw) for children with bleeding disorders. METHODS: We retrospectively reviewed records of children (<10 years) with bleeding disorders who received cTXAw or EACA OS from 1 December 2018, through 31 July 2022, at Mayo Clinic (Rochester, Minnesota). Bleeding outcomes were defined according to ISTH criteria. RESULTS: Thirty-two patients were included (median age, 3 years; male, n = 23). Diagnoses were VWD (n = 17), haemophilia (n = 5), FVII deficiency (n = 3), inherited platelet disorder (n = 4), ITP (n = 2), and combined FV and FVII deficiencies (n = 1). Thirty-two courses of cTXAw (monotherapy 24/32; mean duration 6 days) and fifteen courses of EACA (monotherapy 12/15; mean duration 5 days) were administered. No surgical procedures (n = 28) were complicated by bleeding. Of the 19 bleeding events, 16 had effective haemostasis, two had no reported outcome, and one had no response. cTXAw and EACA were equally effective in preventing and treating bleeding (p value > .1). No patients had adverse effects. Eight of 19 patients (42%) who were initially prescribed EACA OS did not receive it because of cost or insurance denial. The estimated average wholesale price of one treatment was $94 for cTXAw and $905 for EACA OS. CONCLUSIONS: CTXAw appears to be an effective, safe, and low-cost alternative option to EACA OS for young children with bleeding disorders.

The role of the specialist nurse in comprehensive care for bleeding disorders in Europe: An integrative review.

INTRODUCTION: Managing bleeding disorders (BDs) is complex, requiring a comprehensive approach coordinated by a multidisciplinary team (MDT). Haemophilia nurses (HNs) play a central role in the MDT, frequently coordinating care. As novel treatments bring change to the treatment landscape, ongoing education and development is key. However, understanding of the roles and tasks of HNs is lacking. AIM: The EAHAD Nurses Committee sought to identify and describe the roles and tasks of the European HN. METHODS: A five-step integrative review was undertaken, including problem identification, literature search, data evaluation, data synthesis and presentation. Relevant literature published from 2000 to 2022 was identified through database, hand and ancestry searching. Data were captured using extraction forms and thematically analysed. RESULTS: Seven hundred and seventy-seven articles were identified; 43 were included. Five main roles were identified, with varied and overlapping associated tasks: Educator, Coordinator, Supporter, Treater and Researcher. Tasks related to education, coordination and support were most frequently described. Patient education was often 'nurse-led', though education and coordination roles concerned both patients and health care practitioners (HCPs), within and beyond the MDT. The HN coordinates care and facilitates communication. Long-term patient care relationships place HNs in a unique position to provide support. Guidelines for HN core competencies have been developed in some countries, but autonomy and practice vary. CONCLUSION: As the treatment landscape changes, all five main HN roles will be impacted. Despite national variations, this review provides a baseline to anticipate educational needs to enable HNs to continue to fulfil their role.

The role of viscoelastic hemostatic assays for postpartum hemorrhage management and bedside intrapartum care.

Viscoelastic hemostatic assays are point-of-care devices that assess coagulation and fibrinolysis in whole blood samples. These technologies provide numeric and visual information of clot initiation, clot strength, and clot lysis under low-shear conditions, and have been used in a variety of clinical settings and subpopulations, including trauma, cardiac surgery, and obstetrics. Emerging data indicate that these devices are useful for detecting important coagulation defects during major postpartum hemorrhage (especially low plasma fibrinogen concentration [hypofibrinogenemia]) and informing clinical decision-making for blood product use. Data from observational studies suggest that, compared with traditional formulaic approaches to transfusion management, targeted or goal-directed transfusion approaches using data from viscoelastic hemostatic assays are associated with reduced hemorrhage-related morbidity and lower blood product requirement. Viscoelastic hemostatic assays can also be used to identify and treat coagulation defects in patients with inherited or acquired coagulation disorders, such as factor XI deficiency or immune-mediated thrombocytopenia, and to assess hemostatic profiles of patients prescribed anticoagulant medications to mitigate the risk of epidural hematoma after neuraxial anesthesia and postpartum hemorrhage after delivery.

Hemostatic effect of fibrinogen concentrate on traumatic massive hemorrhage: a propensity score matching study.

Background: Fibrinogen concentrate (FC) can be administered during massive transfusions to manage trauma-induced coagulopathy. However, its effectiveness in survival remains inconclusive due to scarce high-level evidence. This study aimed to investigate the hemostatic effects of FC regarding mortality in massive hemorrhage caused by trauma. Methods: This retrospective study analyzed 839 patients who received massive transfusions (red blood cells (RBCs) ≥5 units in 4 hours or ≥10 units in 24 hours) at a level I trauma center between 2015 and 2022. Patients who were transferred to other hospitals or were deceased upon arrival, suffered or died from severe brain injury, and were aged 15 years or less were excluded (n=334). 1:2 propensity score matching was performed to compare the 'FC (+)' group who had received FC in 24 hours (n=68) with those who had not ('FC (-)', n=437). The primary outcome was mortality, and the secondary outcomes included transfusion volume. Results: The variables for matching included vital signs, injury characteristics, prehospital time, implementation of resuscitative endovascular balloon occlusion of the aorta, and blood gas analysis results. The administration of FC did not significantly reduce or predict mortality (in-hospital, 24 hours, 48 hours, or 7 days). The FC (-) group received more units of RBC (25.69 units vs. 16.71 units, p<0.001, standardized mean difference [SMD] 0.595), fresh frozen plasma (16.79 units vs. 12.91 units, p=0.023, SMD 0.321), and platelets (8.76 units vs. 5.46 units, p=0.002, SMD 0.446) than the FC (+) group. Conclusion: The use of FC did not show survival benefits but reduced transfusion requirements in traumatic massive hemorrhages, highlighting a need for future investigations. In the future, individualized goal-directed transfusion with FC may play a significant role in treating massive bleeding. Level of evidence: IV, retrospective study having more than one negative criterion.

Fibrin glue in managing intractable gingival bleeding in patients with inherited bleeding disorders-a quasi-experimental pilot study.

This study presents the clinical outcomes of using inhouse prepared fibrin glue for controlling gingival bleeding in patients with inherited bleeding disorders (IBD). The objective of the study was to assess the reduction in transfusion days and improvement in compliance for dental evaluation over a one-year period in a low-to-middle-income country. The quasiexperimental pilot study included 40 IBD patients with gingival bleeding. These were divided into two groups: Group A received fibrin glue (n=20), while Group B did not (n=20). The study compared outcome metrics, including the number of treatment days and blood components transfused, using non-parametric tests with a significance threshold of p<0.05. Results showed that Group A required fewer blood components (n=154) as compared to Group B (n=204) (p<0.001). Patients in Group A with Glanzmann thrombasthenia (GT) had a shorter treatment duration (one day) than those in group B (three days) (p<0.01). In conclusion, the application of fibrin glue effectively managed intractable gingival bleeding in IBD patients.