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Background: Previous observational studies have shown that Hypothyroidism is associated with Von Willebrand Disease (VWD), but the causal relationship has not been confirmed because of conflicting findings and confounding by mixing factors. There are also some studies suggesting that polyunsaturated fatty acids (PUFA) may be one of the potential mediators. In this study, we used a Mendelian randomization study to analyze the causal relationship between Hypothyroidism and VWD and to investigate whether polyunsaturated fatty acids mediate the effects of Hypothyroidism on VWD. Methods: Using a large publicly available genome-wide association study of predominantly European ancestry to obtain data on Hypothyroidism, VWD, and PUFA, we conducted a two-sample Mendelian randomization study to assess the causal relationship between Hypothyroidism and VWD and assess the potential role of Polyunsaturated fatty acids in mediating the causal pathway between Hypothyroidism and VWD. Finally, we also inferred reverse causality between VWD and Hypothyroidism. Inverse variance weighting (IVW) was the primary analytical method. Results: We found that Hypothyroidism may be negatively causally associated with the development of VWD and that PUFA have a role in mediating role in this process (the ratio of the mediating effect: 24.33%). The causal effects of Hypothyroidism and PUFA on VWD remained significant (p < 0.05) after correction of each other by MVMR. Conclusion: Our study unveils a novel negative correlation between hypothyroidism and VWD, further enriched by the discovery of partial mediation by PUFA. This groundbreaking finding not only advances our comprehension of VWD etiology but also opens promising avenues for its control and treatment. By elucidating the intricate interplay between hypothyroidism, PUFA, and VWD, our research pioneers a paradigm shift in therapeutic approaches, offering fresh perspectives for the management of this complex disorder. [ABSTRACT FROM AUTHOR]

The REAADS VWF activity assay is often assumed to be specific for the A1 domain, the portion of VWF that binds platelet GPIbα. We tested this assay on the A1A2A3 region of VWF with each domain expressed independently of one another and together in combination as a tri-domain. The monoclonal antibody used in this assay is found to be insensitive to the single A domains and does not recognize free A1 domains as it is often assumed. Rather, we find the assay to effectively recognize A1A2A3 with the domains together in their natural glycosylated sequence context. Furthermore, type 2M and 2B Von Willebrand Disease mutations differentially disrupt the sensitivity of the assay, indicating that mutational effects on the structure of A1 in the A1A2A3 context concomitantly disrupt the epitope of the antibody. The REAADS VWF activity assay therefore is conformationally sensitive to the native quaternary association of the A domains together and it is not specific to freely exposed A1 domains. [ABSTRACT FROM AUTHOR]

Importance: Polycythemia vera (PV), a myeloproliferative neoplasm characterized by an increased red blood cell mass and increased risk of thrombosis, affects approximately 65 000 people in the US, with an annual incidence of 0.5 to 4.0 cases per 100 000 persons. Observations: Erythrocytosis (hemoglobin >16.5 mg/dL in men or >16.0 mg/dL in women) is a required diagnostic criterion, although thrombocytosis (53%) and leukocytosis (49%) are common. Patients may have pruritus (33%), erythromelalgia (5.3%), transient visual changes (14%), and splenomegaly (36%) with abdominal discomfort. More than 95% of patients have a JAK2 gene variant, which helps distinguish PV from secondary causes of erythrocytosis, such as tobacco smoking or sleep apnea. Among 7 cohorts (1545 individuals), the median survival from diagnosis was 14.1 to 27.6 years. Prior to or at the time of PV diagnosis, arterial thrombosis occurred in 16% of patients and 7% had venous thrombotic events, which could involve unusual sites, such as splanchnic veins. PV is also associated with an increased bleeding risk, especially in patients with acquired von Willebrand disease, which can occur with extreme thrombocytosis (platelet count, ≥1000 × 109/L). All patients with PV should receive therapeutic phlebotomy (goal hematocrit, <45%) and low-dose aspirin (if no contraindications). Patients who are at higher risk of thrombosis include those aged 60 years or older or with a prior thrombosis. These patients and those with persistent PV symptoms may benefit from cytoreductive therapy with hydroxyurea or interferon to lower thrombosis risk and decrease symptoms. Ruxolitinib is a Janus kinase inhibitor that can alleviate pruritus and decrease splenomegaly in patients who are intolerant of or resistant to hydroxyurea. About 12.7% of patients with PV develop myelofibrosis and 6.8% develop acute myeloid leukemia. Conclusions and Relevance: PV is a myeloproliferative neoplasm characterized by erythrocytosis and is almost universally associated with a JAK2 gene variant. PV is associated with an increased risk of arterial and venous thrombosis, hemorrhage, myelofibrosis, and acute myeloid leukemia. To decrease the risk of thrombosis, all patients with PV should be treated with aspirin and therapeutic phlebotomy to maintain a hematocrit of less than 45%. Cytoreductive therapies, such as hydroxyurea or interferon, are recommended for patients at high risk of thrombosis. This narrative review investigates the diagnosis, symptoms, and management of polycythemia vera and explores the efficacy of treatments like low-dose aspirin, therapeutic phlebotomy, and cytoreductive therapies. [ABSTRACT FROM AUTHOR]

Background: Sickle cell anemia (SCA) is a hypercoagulable state characterized by a significant alteration in hemostatic parameters which may predispose an increased risk of vaso-occlusive crisis (VOC). Sickle cell disease (SCD) is the most common genetic disorder in sub-Saharan Africa. Nigeria bears a high disease burden with an estimated prevalence of 1%–3% of its population being affected by the disease. The study seeks to determine the role of von Willebrand factor (VWF), ADAMTS13, and the ratio of ADAMTS13:VWF antigen in the pathogenesis of VOC. Objective: The objective of this study is to evaluate the level of VWF, ADAMTS13, and their ratio in SCD subjects in Calabar and to determine their role in the pathogenesis of VOC. Methodology: This is a comparative study carried out at the University of Calabar Teaching Hospital (UCTH), Calabar. Sixty SCA patients were evaluated in VOC and steady states as well as five parented healthy controls. VWF: Ag and ADAMTS13:Ag were evaluated using Assaypro enzyme-linked immunosorbent assay kits with Lot nos. 01751728 and 04222167R, respectively. Data were analyzed by IBM SPSS Chicago software version 21. The study was approved by the UCTH Institution Ethical Review Board. Results: The mean ages of the SCA subjects and controls were 23.5 ± 7.2 years and 26.5 ± 5.6 years, respectively (P = 0.706). There were 23 (38.3%) males in the SCA group and 21 (42.0%) females in the controls. There was no significant difference in their sex distribution (P = 0.063). The mean (standard deviation [SD]) of VWF in VOC, steady state, and controls were 2.52 ± 0.34, 1.34 ± 0.23, and 1.41 ± 0.23 IU/mL, respectively. The differences in mean were significantly higher in VOC state (P = 0.003). The mean ± SD of ADAMTS13 in VOC, steady state, and controls were 0.61 ± 0.10, 0.44 ± 0.06, and 0.62 ± 0.10 µg/L, respectively. ADAMTS13 levels did not differ significantly across the groups (P = 0.270). Similarly, there was no significant difference between ADAMTS13:VWF ratios across the groups (P = 0.318). Conclusion: VWF level is elevated in VOC state and thus may be implicated in the pathogenesis of VOC. ADAMTS13 and the ratio of ADAMTS13:VWF are not significantly affected in VOC. [ABSTRACT FROM AUTHOR]

Background: New treatments for patients with bleeding disorders (PWB) have emerged, including products with extended half‐life and subcutaneous administration. These less frequent treatments can potentially enhance quality of life (QoL), but adherence becomes critically important. Aim: To investigate adherence and QoL among PWB and explore the correlation between treatment adherence and QoL in adult patients with haemophilia A (HA), haemophilia B (HB) and Von Willebrand disease (vWD) in Denmark. Method: This survey used disease‐specific patient‐reported questionnaires: Veritas‐PRO and Veritas‐PRN to measure adherence, and Haemo‐A‐QoL and VWD‐QoL to assess QoL. Results: Responses were obtained from 149 patients with HA, 32 with HB and 118 with vWD. Adherence was reported by 87.1% of patients on prophylaxis and 71.2% of patients treated on demand, according to Veritas‐PRO and Veritas‐PRN cut‐off scores. High QoL was generally reported, decreasing with age in HA and HB, but not in vWD. Conclusion: Danish patients with HA, HB and vWD reported high QoL and high adherence to prescribed treatments. There was no correlation between treatment adherence and QoL among the different patient groups. These findings highlight the need for further research to better understand adherence behaviours and identify opportunities to further improve QoL in PWB. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion Heavy menstrual bleeding (HMB) is a significant health concern that may lead to critical medical care and impaired quality of life. The aim of the present study was to identify the clinical indicators of common causes of HMB in adolescents and evaluate the factors influencing the treatment preferences of clinicians.Between 2010 and 2022, the electronic medical records of adolescents between the ages of 10–18 with HMB were reviewed, and a final of 205 adolescents was included. Clinical, laboratory, and treatment data were retrospectively analyzed.Hypothalamic–pituitary‐ovarian (HPO) axis immaturity was diagnosed in 63.9%, bleeding disorders (BD) in 13.7%, and polycystic ovary syndrome (PCOS) in 12.2% of the patients. The presence of “heavy bleeding” and the bleeding length at presentation were not different between the groups. Patients with a BD presented with lower hemoglobin (Hb) levels (P = 0.019), and more frequently required inpatient admissions (P = 0.005). Of all patients, 34.6% were given only iron, 44.9% were given a low dose, and 15.6% were given a high‐dose hormone treatment. Factors influencing high‐dose hormone regimens were lower Hb levels (P < 0.001), the place of visit (ER rather than the clinic) (P < 0.001), and the presence of multiple ER visits (P < 0.001).Physicians base their decisions to start high‐dose hormonal therapy on objective parameters such as Hb levels and the need for hospitalization, while more precise guidelines are deemed necessary for initiating low‐dose hormonal therapy. Standardized protocols and their practical implementation at the clinical level are needed for the management of HMB in adolescence. [ABSTRACT FROM AUTHOR]

Objective: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease that is challenging to treat. This study aimed to identify the effect of sodium ferulate on endothelial dysfunction mediated by neutrophil extracellular trap (NET)–platelet activation in AAV to provide potential strategies for AAV treatment. Material and Methods: An animal model of myeloperoxidase (MPO)-AAV passive immune vasculitis was established using anti-MPO immunoglobulin G and Rag2 knockout mice. The efficacy and mechanism of action of sodium ferulate in AAV were explored in cultured and isolated endothelial progenitor cells (EPCs), and messenger ribonucleic acid gene expression, relative protein expression, and protein fluorescence intensity were determined through quantitative polymerase chain reaction, Western blotting, and immunofluorescence, respectively. Serum antibody concentrations were determined by enzyme-linked immunosorbent assay, and flow cytometry was used in determining the expression levels of platelet-selectin (CD62p) and procaspase-activating compound-1 (PAC-1) on the surfaces of the platelets. The EPCs' ultramicroscopic structure was observed through transmission electron microscopy. Results: The expression levels of ANCA, histone H3 citrullinated, and MPO protein fluorescence intensity in MPO-AAV mice were inhibited by sodium ferulate, and the expression levels of CD62p and PAC-1 on the cell surface were reduced. The relative expression levels of β-trace protein (β-TG), soluble thrombomodulin, inducible nitric oxide synthase (iNOS), and tumor necrosis factor α decreased. We found that sodium ferulate inhibited NETs' free DNA and mitigated damage in EPCs. In addition, relative expression levels of von Willebrand Factor, β-TG, and iNOS and serum concentrations of PAC-1, β-TG, and iNOS were inhibited. Conclusion: Sodium ferulate can treat AAV by inhibiting NET release and platelet activation and reducing endothelial cell damage. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Clinical Considerations Conclusions This clinical case describes a multidisciplinary retreatment of a patient with anterior fixed dental prostheses (FDPs) using minimally invasive restorations and a biologically oriented preparation technique (BOPT).A 56‐year‐old female patient, treated 30 years ago with a metal‐ceramic FDP due to dental agenesis, presented a misfit prosthesis at the gingival margin, black spaces, and food retention at the pontics. Notably, tooth number 2.6 was absent, and she exhibited a left crossbite. Her chief complaint was the compromised esthetics of her restorations. Given her coagulation disorder, von Willebrand disease, she declined mucogingival surgery. A diagnostic wax‐up and mock‐up was performed to establish treatment goals. The initial phase involved periodontal, orthodontic, and implant treatment. The orthodontic treatment with aligners to correct the crossbite. Subsequently, bleaching and a second mock‐up were conducted to guide prosthetic treatment. In the prosthodontic treatment, the abutment teeth were prepared using a vertical BOPT to remodel the gingival tissues, achieving the esthetic goal of repositioning the gingival margin without surgery. The provisional phase was critical for soft tissue remodeling and ensured clinical success. After stabilization of the soft tissues, a monolithic zirconia FDP was delivered, with a follow‐up of 2 years.A multidisciplinary treatment plan, utilizing a digital workflow, resulted in stable clinical and esthetic outcomes at the two‐year follow‐up, effectively retreating an anterior bridge using BOPT in a patient with a coagulation disorder that contraindicated complex surgical interventions. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Aim Methods Results Conclusions Maintaining the balance between procoagulant and anticoagulant factors is essential for effective haemostasis. Emerging evidence suggests a modulation of bleeding tendency by factors in the anticoagulant and fibrinolytic systems.This study investigates the clinical and laboratory characteristics of a family with combined von Willebrand disease (VWD) and antithrombin (AT) deficiency.The study focused on a 38‐year‐old female index patient (IP) with severe type 3 VWD and a history of bleeding disorders. Coagulation assays included VWF antigen, platelet‐dependent VWF activity, factor VIII activity, thrombin generation assay (TGA) and AT activity. Molecular genetic analyses were conducted by a targeted DNA custom next generation sequencing (NGS) panel.The IP and one of her sisters suffered type 3 VWD. While the IP presents with a classical severe bleeding phenotype, the sister (II‐2) exhibited less severe bleeding symptoms. Extended family members showed type 1 VWD with mild presentations. NGS revealed a homozygous deletion of exon 6 in the VWF gene in the IP and her sister (II‐2). All other family members carry this genetic variant in a heterozygous state. Additionally, II‐2 has a heterozygous variant in the SERPINC1 gene (c.133C>T, p.Arg45Trp). Both IP and II‐2 carry a homozygous prothrombin G20210A variant. TGA results indicated reduced thrombin generation in severe VWD patients, with a pronounced thrombin burst in those with the AT and prothrombin G20210A variant.AT deficiency appears to modulate bleeding symptoms in severe VWD. This study emphasizes the importance of comprehensive genetic and phenotypic evaluation in managing complex coagulation disorders. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aim Materials & methods Results Discussion & conclusion A wide variety of laboratory hemostasis tests is available, but the majority is plasma‐based, static and unable to assess platelet function and fibrin formation simultaneously. The Total Thrombus‐Formation Analysis System (T‐TAS) is a microchip‐based flow chamber system that simulates in vivo conditions for evaluating whole blood thrombogenicity.A comprehensive overview of its applicability in different thrombosis and hemostasis related clinical situations is lacking and therefore this scoping review was performed.A literature search was done using the electronic databases PubMed, Scopus and Embase on January 7, 2024. Original studies assessing the usefulness of the T‐TAS in thrombosis and hemostasis related clinical situations were eligible for this scoping review.A total of 28 studies were included; six studies investigating the role of the T‐TAS in congenital bleeding disorders, five studies using the T‐TAS to assess 1‐year bleeding risk in patients on antiplatelet or anticoagulant medications, four studies investigating the effects of thrombocytopenia and hemodialysis on thrombus formation as measured by the T‐TAS, 11 studies testing the applicability of the T‐TAS in the monitoring of anticoagulant and antiplatelet therapies and eventually two studies on the ability of the T‐TAS to assess the thrombogenicity in different disease entities.The T‐TAS method is an interesting technology that mimics the complex biological coagulation process using shear forces, creating a “blood vessel component on a chip”. More research is needed, but it could eventually function as a screening test for platelet function and coagulation. Moreover, it could be used to detect the presence of anticoagulant and/or antiplatelet medication. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Aim Methods Results Conclusion The 2024 ISTH clinical practice guideline (CPG) for treatment of congenital haemophilia, the NBDF‐McMaster Guideline on Care Models for Haemophilia Management, and ASH ISTH NBDF WFH guidelines on the diagnosis and management of VWD all utilised GRADE methodology.Discuss missed opportunities and the methodological approach of the ISTH Guideline in contrast to how GRADE was previously applied in rare diseases.Critically analyse the methodology of each guideline along with best practices in the use of GRADE. Where applicable, the WFH Guidelines for the Management of Haemophilia were analysed.Important differentiating features in applying GRADE were identified. Where a strong evidence base is lacking, data other than those from randomized controlled trials, which may not always be justified, need to be considered, including incorporation of outcomes important to people living with the disease. Justification and stakeholder input to prioritize questions requiring a new guideline, panel composition with necessary patient participation and content expertise were also found to be significant differentiating features.The puristic approach taken in the ISTH Guideline development process, without consideration of accepted adaptations to GRADE implementation, created a missed opportunity for progressing haemophilia care, leading to guideline recommendations that have been widely deemed invalid and obsolete by expert healthcare professionals and by those living with the condition, the very people who are expected to implement or bear the impact of the recommendations. Lessons learnt from this comparative analysis should guide future guideline development and encourage collaboration to further advance haemophilia. [ABSTRACT FROM AUTHOR]

Background: Lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) is a rare autoimmune condition characterized by acquired prothrombin (FII) deficiency associated with antiphospholipid syndrome (APS) and life-threatening bleeding. We present the case of a 34-year-old woman with heavy menstrual bleeding (HMB), positive Lupus anticoagulant (LA) test, and high titer anticardiolipin antibodies Immunoglobulin G (ACA IgG) and anti-β2 glycoprotein I antibodies IgG (antiB2GPI IgG). Severe iron deficiency anemia necessitated recurrent blood transfusions and intravenous iron infusions from 2018 to 2021. Results: In January 2022, she was admitted to our clinic. Von Willebrand disease screening and platelet function analysis (PFA100) were normal. FII and FIX deficiencies were detected, without factor IX inhibitors. Anti-phosphatidylserine/prothrombin antibodies were confirmed by Padua University lab. To reduce antibody titers and menstrual bleeding, immunosuppressive therapy (Rituximab 375 mg/m2 weekly ×4 weeks) and hormonal therapy (desogestrel 75 mcg/day) were initiated. Conclusion: After 1-year, complete remission of clinical symptoms was achieved, with normalization of FII and FIX values and moderate reduction of aPS/PT titers, especially IgM isotype. [ABSTRACT FROM AUTHOR]

Background: Dental implants are commonly employed to address edentulism, while orthodontic treatments often incorporate mini-screws to enhance tooth movement and provide stable anchorage. Both procedures are integral to modern dental practice and frequently interact in comprehensive care scenarios. While oral health professionals routinely assess patients' medical histories before procedures, undiagnosed coagulopathies, such as Von Willebrand Disease (VWD), can present significant challenges when invasive procedures are carried out, such as the insertion of implants or mini-implants. Case description: This case report discusses the surgical placement of dental implants and orthodontic mini-screws in a patient with previously undiagnosed VWD, underscoring the potential complications and the importance of recognizing bleeding disorders in clinical practice, and provides some advice on the management of patients with previously undiagnosed VWD after/during surgical procedures. Conclusions: To prevent the risk of excessive bleeding, before surgery, all patients should be screened through precise questions on bleeding history. [ABSTRACT FROM AUTHOR]

The article discusses the use of menstrual suppression to reduce intrauterine device expulsion in adolescents with inherited bleeding disorders. The study found that hormonal menstrual suppression was effective in preventing early device expulsion due to excessive bleeding. The research suggests that concurrent menstrual suppression for at least 30 days after insertion may enhance safety and minimize complications in this vulnerable population. The authors emphasize the importance of managing heavy menstrual bleeding in adolescents with inherited bleeding disorders to improve outcomes and reduce expulsion rates. [Extracted from the article]

Introduction: Treatment options are expanding for von Willebrand disease (VWD). A core outcome set (COS)—a minimum set of agreed‐upon outcomes to be used in every clinical trial for a given condition—provides guidance on which outcomes are most important to measure to ensure necessary data is collected for a variety of stakeholders and enable comparison across products and trials. Aim: coreVWD aimed to develop a COS for trials for prophylaxis and perioperative treatments for VWD. Methods: A modified Delphi consensus process was used to condense/prioritize a long list of potential outcomes. Over three Delphi rounds, a multi‐stakeholder panel (patients, clinicians, pharmaceutical company representatives, HTA organizations, payer, and government organization representatives) rated each outcome from 1 (not important to include in a COS) to 9 (essential to include). Outcomes were eliminated or retained based on pre‐determined criteria; a special provision to elevate patient priorities was included. An in‐person consensus meeting was held after Delphi round 2. Results: Thirty‐nine panellists participated. The final COS for prophylaxis treatment included 18 outcomes, seven of which are part of a special subset selected for women, girls and people with the potential to menstruate. There were 11 outcomes in the final perioperative branch COS. Six outcomes overlapped both COS. Conclusions: The coreVWD COS represents a consensus list of outcomes for clinical trials for both factor and non‐factor VWD therapies. These outcomes will be useful across the lifecycle of a product, from clinical development through regulatory and market access phases and into patient‐provider decision‐making. [ABSTRACT FROM AUTHOR]

Introduction: The severity of Von Willebrand disease (VWD) is currently based on laboratory phenotype. However, little is known about the severity of the patient's experience with the disease. The most recent VWD guidelines highlight the need for patient‐reported outcomes (PROs) in VWD. Aim: The study aimed to investigate the patient‐perspective on VWD severity and to identify key factors that determine the severity of disease experienced by patients. Materials and methods: Patients participated in a nationwide cross‐sectional study on VWD in the Netherlands (WiN‐study). Patients filled in a questionnaire containing questions on the experienced severity of VWD (4‐point scale), bleeding score (BS) and quality of life (QoL). Results: We included 736 patients, median age of 41.0 years (IQR 23.0–55.0) and 59.5% were women. A total of 443 had type 1, 269 type 2 and 24 type 3 VWD. Self‐reported severity of VWD was categorized as severe (n = 52), moderate (n = 171), mild (n = 393) or negligible (n = 120). Classification by historically lowest FVIII:C levels < 0.20 IU/mL as a proxy for severe VWD aligned with patient‐reported severity classification with a 72% accuracy. Type 3 VWD (OR = 4.02, 95%CI: 1.72–9.45), higher BS (OR = 1.09, 95%CI: 1.06–1.11), female sex (OR = 1.36, 95%CI: 1.01–1.83), haemostatic treatment in the year preceding study inclusion (OR = 1.53, 95%CI: 1.10–2.13) and historically lowest VWF:Act levels (OR = 0.26, 95%CI: 0.07–1.00) were independent determinants of patient‐reported severity. Conclusion: This study shows that patient‐reported data provide novel insights into the determinants of experienced disease severity. Our findings highlight the need for studies on PROs with validated questionnaires to assess the burden of VWD. [ABSTRACT FROM AUTHOR]

Introduction: Acquired von Willebrand syndrome (AVWS) is a rare haemorrhagic disorder. The prophylaxis and treatment of bleeding before surgery are complex. Since 2018, a new recombinant VWF (rVWF) concentrate that contains no factor VIII (FVIII) but a high amount of high molecular weight VWF multimers has been available in France. Aim: To describe the real‐world experience of using rVWF in non‐surgical bleeding and surgical procedures in patients with AVWS. Methods: Fifteen bleeding episodes in seven patients and 16 surgeries in 10 patients were retrospectively analysed in t French haemostasis centres. Results: During bleeding, the median number of infusions was only 1 (range 1–27) with a median loading dose of 58 IU/kg (range 17–116) rVWF and a total median dose of 65 IU/kg (range 35–1488) rVWF. Bleeding control was rated markedly effective in 73% (11/15) of the cases and ineffective in 27% (4/15). During surgeries, the median number of infusions was 3 (range 1–8) with a preoperative loading dose of 60 IU/kg (range 23–118) rVWF and a total median dose of 123 IU/kg (range 31–542). The overall clinical efficacy was qualified as excellent, good and poor (ISTH criteria) in respectively 7 (43%), 6 (38%) and 3 (19%) procedures. There was no accumulation of VWF or FVIII during postoperative monitoring. No thromboembolic events nor adverse events were reported. Conclusion: This French 'real‐world' experience shows that rVWF could be of interest in the treatment and prophylaxis of bleeding in patients with AVWS, with no clinically significant safety concern. [ABSTRACT FROM AUTHOR]

Purpose: Platelets are key mediators in cardiovascular disease (CVD). Low cardiorespiratory fitness (CRF) is a risk factor for CVD. The purpose of our study was to assess if CRF associates with platelet function. Methods: Platelet assays and cardiopulmonary exercise testing were conducted in the Framingham Heart Study (N = 3014). Linear mixed effects models estimated associations between CRF (assessed by peak oxygen uptake [V̇O2]) and multiple platelet reactivity assays. Models were adjusted for multiple medications, risk factors, relatedness, and prevalent CVD. Results: Nineteen associations passed the significance threshold in the fully adjusted models, all indicating higher CRF associated with decreased platelet reactivity. Significant traits spanned multiple platelet agonists. Strongest associations were observed in multiplate whole blood testing after TRAP-6 (e.g., velocity, beta = -0.563, 95% CI = -0.735 to -0.391, P = 1.38E-10), ADP (e.g., velocity, beta = -0.514, 95% CI = -0.681 to -0348, P = 1.41E-09), collagen (e.g., velocity, beta = -0.387, 95% CI = -0.549 to -0.224, P = 3.01E-06), ristocetin (e.g., AUC, beta = -0.365, 95% CI = -0.522 to -0.208, P = 5.17E-06) and arachidonic acid stimulation of platelets (e.g., velocity, beta = -0.298, 95% CI = -0.435 to -0.162, P = 3.39E-04), and light transmission aggregometry (LTA) after ristocetin stimulation (e.g., max aggregation, beta = -0.362, 95% CI = -0.540 to -0.184, P = 6.64E-05). One trait passed significance threshold in the aspirin subsample (LTA ristocetin primary slope, beta = -0.733, 95% CI = -1.134 to -0.333, P = 3.30E-04) and another in a model including von Willebrand Factor levels as a covariate (U46619, a thromboxane receptor mimetic, AUC in the Optimul assay, beta = -0.36, 95% CI = -0.551 to -0.168, P = 2.35E-04). No strong interactions were observed between the associations and sex, age, or body mass index in formal interaction analyses. Conclusions: Our findings build on past work that shows CRF to be associated with reduced CVD by suggesting decreased platelet reactivity may play a mechanistic role. We found significant associations with multiple platelet agonists, indicating higher CRF may globally inhibit platelets; however, given multiple strong associations after TRAP-6 and ADP stimulation, PAR-1 and purinergic signaling may be most heavily involved. This is notable because each of these receptor pathways are tied to anticoagulant (DOAC/thrombin inhibitors) and antiplatelet therapies (P2Y12/PAR1/PAR4 inhibitors) for CVD prevention. [ABSTRACT FROM AUTHOR]

The underlying mechanisms and clinical impact of portal microthrombosis in severe COVID-19 are unknown. Intrapulmonary vascular dilation (IPVD)-related hypoxia has been described in severe liver diseases. We hypothesised that portal microthrombosis is associated with IPVD and fatal respiratory failure in COVID-19. Ninety-three patients who died from COVID-19 were analysed for portal microvascular damage (histology), IPVD (histology and chest-computed tomography, CT), and hypoxemia (arterial blood gas). Seventeen patients who died from COVID-19-unrelated pneumonia served as controls. Vascular lesions and microthrombi were phenotyped for endothelial (vWF) and pericyte (αSMA/PDGFR-β) markers, tissue factor (TF), viral spike protein and nucleoprotein (SP, NP), fibrinogen, and platelets (CD41a). Viral particles in vascular cells were assessed by transmission electron microscopy. Cultured pericytes were infected with SARS-CoV-2 to measure TF expression and tubulisation of human pulmonary microvascular endothelial cells was assessed upon vWF treatment. IPVD was present in 16/66 patients with COVID-19, with available liver and lung histology, and was associated with younger age (62 vs. 78 years-old), longer illness (25 vs. 14 days), worsening hypoxemia (PaO 2 /FiO 2 from 209 to 89), and an increased requirement for ventilatory support (63% vs. 22%) compared to COVID-19/Non-IPVD. IPVD, absent in controls, was confirmed by chest CT. COVID-19/IPVD liver histology showed portal microthrombosis in >82.5% of portal areas, with a thicker wall of αSMA/PDGFR-β+/SP+/NP+ pericytes compared with COVID-19/Non-IPVD. Thrombosed portal venules correlated with αSMA+ area, whereas infected SP+/NP+ pericytes expressed TF. SARS-CoV-2 viral particles were observed in portal pericytes. In vitro SARS-CoV-2 infection of pericytes upregulated TF and induced endothelial cells to overexpress vWF, which expanded human pulmonary microvascular endothelial cell tubules. SARS-CoV-2 infection of liver pericytes elicits a local procoagulant response associated with extensive portal microthrombosis, IPVD and worsening respiratory failure in fatal COVID-19. Vascular involvement of the liver represents a serious complication of COVID-19 infection that must be considered in the work-up of patients with long-lasting and progressively worsening respiratory failure, as it may associate with the development of intrapulmonary vascular dilations. This clinical picture is associated with a procoagulant phenotype of portal venule pericytes, which is induced by SARS-CoV-2 infection of pericytes. Both observations provide a model that may apply, at least in part, to other vascular disorders of the liver, featuring obliterative portal venopathy, similarly characterised at the clinical level by development of hypoxemia and at the histological level by phlebosclerosis and reduced calibre of the portal vein branches in the absence of cirrhosis. Moreover, our findings shed light on an overlooked player in the pathophysiology of thrombosis, i.e. pericytes, which may present a novel therapeutic target. [Display omitted] • Portal vein microthrombosis is associated with IPVD in fatal COVID-19-related hypoxia. • In thrombosed portal venules, pericytes are preponderantly infected by SARS-CoV-2. • Pericytes embedding the thrombosed portal vein radicles overexpress tissue factor. • SARS-CoV-2 induces infected pericytes to overexpress tissue factor. • Infected pericytes kindle endothelial cells to overexpress von Willebrand factor. [ABSTRACT FROM AUTHOR]

This document is an editorial announcing the new Journal Impact Factor (IF) for Seminars in Thrombosis and Hemostasis (STH) for the year 2023. The 2023 IF for STH is 3.6, which is a decrease from previous years. The decrease in IF is attributed to changes in calculation methods, the inclusion of additional journals, and the impact of the COVID-19 pandemic. The document also highlights the impact of COVID-19 on research and publishing, with STH publishing four issues focused on COVID-19. It emphasizes that the IF is just one measure of journal quality and provides rankings of STH in relevant categories. The document lists the most highly cited papers contributing to the 2023 IF, many of which are related to COVID-19. The inclusion of Young Investigator winners and original studies on the list is noted. The article also discusses the success of select original studies published in STH and the support provided for the Young Investigator Awards. It provides information on submission and acceptance rates for unsolicited manuscripts, as well as data on the number of issues, pages, and cumulative count of papers published in STH. The article concludes by celebrating the 50th anniversary of STH and expressing hopes for its continued success. [Extracted from the article]

The article announces the winners of the Eberhard F. Mammen Young Investigator Awards, which recognize outstanding presentations or meeting abstracts in the fields of thrombosis and hemostasis. The winners receive a cash prize and are selected by the Senior Editors of Seminars in Thrombosis & Hemostasis. The article also provides a list of previous award winners and their resulting publications. Additionally, the article lists various articles published in the journal Seminars in Thrombosis and Hemostasis, covering topics such as primary immune thrombocytopenia, heparin-induced thrombocytopenia, hemophilia, von Willebrand disease, platelet function, and anticoagulant therapy. The articles offer insights into the causes, diagnosis, and treatment of these conditions. [Extracted from the article]

Patients with hemophilia frequently require supplementary interventions, either invasive (suturing, gel foam, or cauterization) or non-invasive (fibrin sealant/glue), to attain hemostasis post dental procedures. This study aimed to compare the efficacy of fibrin sealant against traditional methods for achieving hemostasis post dental surgery. The medical records of patients with factor VIII or IX deficiency, or von Willebrand disease, who underwent dental procedures in the Department of Dentistry, Seth GSMC and KEM Hospital, were evaluated for inclusion in this retrospective matched cohort study. Cohort-1 included those treated with a fibrin sealant (Tisseel Lyo) with/without traditional hemostatic measures post-procedure, while cohort-2 (controls) included those in whom no fibrin sealant was used. A total of 128 patients, 64 in each group, were evaluated. There was no statistically significant difference in demographics, disease-related variables, dental complaints, or preoperative treatment given between the groups. However, there was a significant reduction (P < 0.001) in the requirement for secondary procedures for hemostasis (suturing, gel foam application, and/or cauterization) and postoperative requirement for factor replacement (P = 0.003) in the fibrin glue group as compared to the controls. In this study, fibrin sealant demonstrated superior efficacy in mitigating the necessity for active hemostasis control. [ABSTRACT FROM AUTHOR]

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BACKGROUND: Menorrhagia, or excessive menstrual bleeding, is a common symptom in women with inherited bleeding disorders; they are conditions where the blood ability to clot is impaired. Some of the common bleeding disorders include von Willebrand disease (VWD), clotting factor deficiencies, and platelet function disorders. OBJECTIVE: To assess different types of inherited bleeding disorders in women with menorrhagia referred to the National Center of Hematology/Mustansiriyah University in Baghdad/Iraq. PATIENTS AND METHODS: A prospective study was carried out on 193 women who had experienced menorrhagia for a duration of 3 years, from 2020 to 2023. These women sought consultation at the National Centre of Hematology/Mustansiriyah University. All participants were diagnosed through various laboratory tests, including complete blood count, blood film, blood group and Rh, bleeding time, prothrombin time, activated partial thromboplastin time, fibrinogen level, factor assay, von Willebrand factor antigen using ELISA technique, ristocetin cofactor, and platelet function test. RESULTS: Out of the 193 women with menorrhagia who participated in this study, the majority of whom had an unidentified cause (36.3%), followed by VWD (30.1%) and platelet function disorders (21.2%). Other bleeding disorders ( thrombocytopenia and factors deficiencies) were 5.7% and 6.7%, respectively. Furthermore, the results showed that there was a significant difference in family history and consanguinity between patients with a hereditary bleeding disorder and nonhereditary bleeding disorder (P < 0.001). CONCLUSIONS: Fifty eight percent of females with Menorrhagia in this study have inherited bleeding disorders(IBDs), VWD, and thrombasthenia account for 51.3% are the most common causes of inherit bleeding disorder (IBD). Consanguineous marriage should be discouraged in Iraqi society to reduce such inherited diseases.

The American Society of Hematology–International Society on Thrombosis and Haemostasis–National Hemophilia Foundation–World Federation of Hemophilia 2021 International Guidelines (IGL) on von Willebrand disease (VWD) have pointed out many challenges, mainly in the diagnostic approach of VWD patients. To determine the impact of these IGL on the current clinical and laboratory diagnosis of Italian VWD patients, we have recently conducted a survey among 43 centers affiliated with the Italian Association of Hemophilia Centers (AICE). Directors and colleagues responsible for the management of VWD patients were invited to report in a detailed questionnaire how IGL recommendations about the assessment of the specific activities of von Willebrand Factor (VWF) could be applied at their local sites. Results from such a survey showed that bleeding assessment tools, VWF antigen, and factor VIII procoagulant are currently in use in all centers. The automated assays for platelet-dependent VWF activity with or without ristocetin described in IGL have been used since 2021 in 37/43 (86%) centers. Among other laboratory tests, VWF collagen binding, ristocetin-induced platelet agglutination, multimeric analysis, VWF propeptide, VWF:FVIII binding assay were available in 49, 63, 26, 7, and 28% of AICE, respectively. Analyses of VWF gene defects are available only at 3/43 (7%) centers. Desmopressin (DDAVP) infusion trials at diagnosis, with measurements of VWF activities at 1 and 4 hours post-DDAVP, is currently performed at 38/43 (88%) centers. Based on this information, a simplified clinical diagnosis using a few automated tests before and after DDAVP has been proposed. Such a diagnostic approach will be validated prospectively in a large cohort of Italian VWD patients. [ABSTRACT FROM AUTHOR]

The article "Welcome to Seminars in Thrombosis and Hemostasis 2025: Toward the Next 50 Years of Publishing and Announcement of New Online Manuscript Submission System" reflects on the 50th anniversary of Seminars in Thrombosis & Hemostasis (STH) and introduces changes to the editorial board. The impact factor trends and publication metrics of STH are discussed, with a focus on online publication. The article also announces the launch of a new online manuscript submission system for STH, marking a significant milestone after 50 years of publishing. [Extracted from the article]

Type 3 von Willebrand disease (VWD), the most severe form of VWD, is an inherited recessive bleeding disorder caused by the complete deficiency of von Willebrand factor (VWF). The reported prevalence is 1 per million but varies worldwide according to the frequency of consanguineous marriages. The clinical phenotype is characterized not only by mucocutaneous bleedings, but also by hemarthroses and muscle hematoma, as in patients with moderate hemophilia. Long-term prophylaxis with factor (F)VIII/VWF concentrates is recommended in patients with a history of severe and frequent bleeds. A rare complication of replacement therapy is the development of alloantibodies against VWF, with the consequences of an ineffective therapy and risk of anaphylactic reactions upon treatment. Emicizumab is the first bispecific monoclonal antibody that mimics FVIII coagulant activity and is approved for prophylaxis of bleeding in patients with inherited hemophilia A with or without inhibitors and recently also for acquired hemophilia. In this manuscript we report and discuss available data in the literature on the use of emicizumab in type 3 VWD and describe the case of a female patient with type 3 VWD with a history of alloantibodies against VWF and posttransfusion anaphylaxis, recently and successfully put on off-label prophylaxis with emicizumab. [ABSTRACT FROM AUTHOR]

Abstract Treatment of type 3 von Willebrand disease by infusion of von Willebrand factor (VWF) and factor VIII (FVIII) concentrates may lead to the development of anti‐VWF antibodies, challenging haemostasis management. The systematic review of the literature presented here retrieved 15 such cases (surgery n = 11, bleeding n = 4). The heterogeneous patient management mostly involved continuous infusion of FVIII, or recombinant FVIIa together with various other strategies. Off‐label infusion of the bispecific monoclonal antibody emicizumab was prescribed in three cases and in a complex local case, ultimately well‐controlled with emicizumab. This illustrates the fact that emicizumab appears as a therapeutic option in this context of allo‐immunisation.

Heyde syndrome, marked by aortic stenosis, gastrointestinal bleeding from angiodysplasia, and acquired von Willebrand syndrome, is often underreported. Shear stress from a narrowed aortic valve degrades von Willebrand factor multimers, leading to angiodysplasia formation and von Willebrand factor deficiency. This case report aims to raise clinician awareness of Heyde syndrome, its complexity, and the need for a multidisciplinary approach. We present a 75-year-old man with aortic stenosis, gastrointestinal bleeding from angiodysplasia, and acquired von Willebrand syndrome type 2A. The patient was successfully treated with argon plasma coagulation and blood transfusions. He declined further treatment for aortic stenosis but was in good overall health with improved laboratory results during follow-up. Additionally, we provide a comprehensive review of the molecular mechanisms involved in the development of this syndrome, discuss current diagnostic and treatment approaches, and offer future perspectives for further research on this topic. [ABSTRACT FROM AUTHOR]

Background: Females with rare bleeding disorders who suffer from mild bleeding symptoms and extra bleeding symptoms related to menstruation are usually delayed in their diagnosis, necessitating early evaluation for an underlying bleeding diathesis based on clinical suspicion. Objectives: We aimed to assess the frequency of rare bleeding disorders among female children and adolescents presenting with bleeding symptoms and to evaluate their health-related quality of life. Patients and methods: Sixty females with bleeding symptoms younger than 18 years old were recruited and were subjected to detailed medical assessment and evaluation of different bleeding symptoms using the ISTH-BAT, the menstrual pictogram for assessing menstrual blood loss in pubertal females, and the Arabic version of the pediatric quality of life multidimensional fatigue scale. Laboratory investigations are tailored according to the institutional guidelines. Results: The median age of the studied population was 8.25 years and 48.3% had a positive family history of bleeding. The mean age of presentation/diagnosis of Von Willebrand disease and Glanzmann disease were 6.1/8.2 and 5.3/7.6 years, respectively. Forty-five females had inherited bleeding disorders, and 15 had acquired ones. The most common diagnosis was Von Willebrand disease (30%), followed by Glanzmann disease (18.3%). The most common acquired disorder was aplastic anemia (13.3%). There was a higher ISTH-BAT total score in those with inherited disorders than in those with acquired disorders (P =0.006). Conclusion: Adolescent females who present to a tertiary pediatric or gynecology service with bleeding manifestations should be screened for underlying bleeding disorders. [ABSTRACT FROM AUTHOR]

Background: The use of recombinant coagulation factors has reduced the incidence of hepatitis B and C infections in hemophilia patients. As recombinant von Willebrand factor is not easily available, patients with von Willebrand disease (VWD) may be at higher risk for acquiring hepatitis B and C infections. The prevalence of hepatitis B and C infections in the Indian population is ~0.95% and ~0.3%, respectively. Aims: This single tertiary center study aimed to assess the prevalence of hepatitis B and C infections and the profile of liver disease caused by these viruses among patients with VWD. Methodology: We retrospectively enrolled VWD patients treated in our center from January 2012 to December 2022 and analyzed the prevalence of hepatitis B and C infection and stage of liver disease. Results: Among 189 patients with VWD during the study period, 5 of 61 (8.1%) VWD patients screened were hepatitis B surface antigen positive (age: 34 [24–42] years; median (range); plasma VWF antigen: 10.1, [0–40] IU/dL). One patient had cholangiohepatoma at presentation, whereas none had chronic liver disease. Four of five patients received multiple bloodproduct transfusions before coming to our institution, with 10 (7–18) years interval between 1st transfusion and to detection of hepatitis B infection. Four of the 47 VWD patients (8.5%) screened were positive for hepatitis C virus antibody (48 [43–59] years, plasma VWF antigen: 20 [0–21.5] IU/dL). One patient had chronic liver disease. All four patients received multiple blood product transfusions before coming to our institution, with 15.5 (2–39) years interval between 1st transfusion and to the detection of hepatitis C infection. Conclusions: The prevalence of hepatitis B infection (8.1%) and hepatitis C infection (8.5%) was 8-fold and 28-fold higher, respectively, in VWD patients than the general population in India. VWD patients remain at high risk for acquiring transfusion-transmitted viral infections and appropriate interventions are needed to address this. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: Heyde syndrome is characterized by anemia due to angiodysplasia, aortic valve stenosis, and acquired von Willebrand syndrome. However, the awareness regarding Heyde syndrome in clinical practice is low. We report the case of an older woman with severe refractory iron-deficiency anemia and severe aortic stenosis who was diagnosed with Heyde syndrome. Case Report: A 70-year-old woman who had been experiencing exertional dyspnea for 3 months prior to presentation was diagnosed with iron-deficiency anemia, with a hemoglobin level of 69 g/L. She did not experience any episodes of bleeding, such as nosebleeds, gum bleeding, abnormal bleeding, or melena. Upper and lower gastrointestinal endoscopy revealed no evidence of bleeding, and oral iron supplementation failed to improve the anemia. Auscultation of the chest identified an ejection systolic murmur. Chest and abdominal computed tomography showed no significant lesions or active bleeding. Capsule endoscopy of the small intestine revealed capillary dilation. Echocardiography detected severe aortic valve stenosis. Blood test results revealed a deficiency in large von Willebrand factor multimers. Therefore, Heyde syndrome was diagnosed. Aortic valve replacement surgery was performed, which resulted in an improvement in anemia and the associated symptoms. Conclusions: In cases of unexplained and treatment-resistant iron-deficiency anemia, especially if careful auscultation detects aortic stenosis, Heyde syndrome should be considered a differential diagnosis. Furthermore, screening for angiodysplasia in the gastrointestinal tract and prompt diagnosis through measurement of large von Willebrand factor multimers are imperative when investigating potential sources of bleeding. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Methods Results Conclusion Trial Registration The entity entitled bleeding disorder of unknown cause (BDUC) qualifies individuals displaying a mild haemorrhagic profile but normal routine coagulation tests. This study was designed to evaluate whether collagen‐binding assay for von Willebrand Factor (VWF) measurement (VWF:CB) could allow to diagnose VW disease in such patients.A large screening was conducted prospectively in two University Hospitals, using the bleeding assessment tool (BAT) recommended by the International Society of Thrombosis and Hemostasis. Patients with an abnormal BAT were confirmed to have a normal complete hemostatic evaluation. A large range of VWF assays was then carried out on a new blood sample for the 68 individuals (91% women) thus identified. Of note, five VWF:CB using different types of collagen were performed, as well as a comprehensive sequencing of the VWF gene.Of this cohort, only 3 individuals (all blood group O), had a VWF:CB between 40 and 50 IU/dL. No unknown anomaly of the VWF gene was disclosed. Of note, 54% of these patients had unexplained abnormal occlusion times on PFA‐200.This study identified 68 cases of BDUC, after screening of a large population, indicating a low incidence. Only 3 cases were potentially confirmed as displaying moderate von Willebrand disease. VWF:CB tests were globally normal in the 65 other patients of the cohort.ClinicalTrials.gov identifier: NCT0279220. [ABSTRACT FROM AUTHOR]

Background: Coronavirus-19 disease (COVID-19) frequently causes coagulation disturbances. Data remains limited on the effects of microRNAs (miRNAs) on coagulation during COVID-19 infection. We aimed to analyze the comprehensive miRNA profile as well as coagulation markers and blood count in hospitalized COVID-19 patients. Methods: Citrated plasma samples from 40 patients (24 men and 16 women) hospitalized for COVID-19 were analyzed. Basic coagulation tests, von Willebrand factor (VWF), ADAMTS13, blood count, C-reactive protein, and 27 miRNAs known to associate with thrombosis or platelet activation were analyzed. MiRNAs were analyzed using quantitative reverse transcription polymerase chain reaction (RT qPCR), with 10 healthy controls serving as a comparator. Results: Among the patients, 15/36 (41%) had platelet count of over 360 × 109/L and 10/36 (28%) had low hemoglobin of < 100 g/L, while 26/37 (72%) had high VWF of over 200 IU/dL. Patients had higher levels of the miRNAs miR-27b-3p, miR-320a-3p, miR-320b-3p, and miR-424-5p, whereas levels of miR-103a-3p and miR-145-5p were lower than those in healthy controls. In total, 11 miRNAs were associated with platelet count. Let-7b-3p was associated with low hemoglobin levels of < 100 g/L. miR-24-3p, miR-27b-3p, miR-126-3p, miR-145-5p and miR-338-5p associated with high VWF. Conclusion: COVID-19 patients differentially express miRNAs with target genes involved in fibrinolysis inhibition, coagulation activity, and increased inflammatory response. These findings support the notion that COVID-19 widely affects hemostasis, including platelets, coagulation and fibrinolysis. [ABSTRACT FROM AUTHOR]

Introduction: Acquired von Willebrand syndrome (AvWS) is a rare entity with approximately 700 cases described in the literature. A number of etiologies are responsible for this condition, mainly lymphoproliferative, myeloproliferative syndromes and cardiac diseases. Management is aimed at preventing and treating bleeds, as well as treating the underlying pathology. In the case of a monoclonal gammopathy, there are limited evidence and high heterogeneity only based on old case reports, resulting in poor quality recommendations. It seems essential in 2023 to take into account and offer the new anti-myeloma treatments available. Case Presentation: We describe the case of a patient with an AvWS secondary to an IgG smoldering multiple myeloma, experiencing multiple bleeding, treated successfully with daratumumab, lenalidomide, and dexamethasone, after multiple treatment failure. Conclusion: Daratumumab, lenalidomide, and dexamethasone was demonstrated as a rapid and effective treatment for a patient with severe AvWS and multiple bleeding complications. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Women with VWD have an increased risk of gynaecological complications due to haemostatic challenges of menstruation. Aim: Review gynecological bleeding symptoms and their management in women with moderate‐severe VWD. Materials and Methods: Retrospective cohort analysis of prospectively collected data for women with moderate and severe VWD attending a joint multidisciplinary clinic between January 2010 and December 2020. Data was collected from electronic patient records on response to treatment options using PBAC, quality of life (QoL) assessment using SF‐36 scores, haemoglobin and ferritin in comparison to pre‐treatment values. Results: Of the 67 women managed in the clinic; all reported heavy menstrual bleeding (HMB). Combination therapy with concurrent hormonal agents and tranexamic acid was required in 80% of women. There was an overall 64% improvement in PBAC scores in the first year, reflecting on QoL with 35% improvement in SF‐36 score and correction of anaemia in 21% of cases. The cumulative effect of continued treatment culminated in greater reduction of blood loss, with an overall 71% improvement in PBAC scores by 5 years. One in 10 women required surgical treatment for a gynaecological pathology. Non‐compliance was the cause of excessive unscheduled bleeding in 50% of adolescents. After 3 years, one in five women experienced a relapse of symptom, of whom 46% became perimenopausal and 54% discontinued hormonal treatments due to concerns about fertility, hair loss and weight gain. Conclusion: Management of HMB requires careful monitoring and follow‐up by MDT with close collaboration between the gynaecology team and HTC. Control of HMB often requires a combination therapy. [ABSTRACT FROM AUTHOR]

A study conducted in Sweden examined the bleeding risk associated with intramuscular COVID-19 vaccination in patients with hemophilia and von Willebrand disease (VWD). The study found that vaccination coverage was high among patients with bleeding disorders, and the risk of bleeding from intramuscular vaccination was low. The study emphasized the importance of following treatment recommendations and using premedication when necessary. Overall, the study concluded that intramuscular COVID-19 vaccination is safe for patients with hemophilia or VWD, particularly for those with mild hemophilia and non-type 3 VWD. [Extracted from the article]

Objective Von Willebrand factor (VWF) antigen plays a role in vascular inflammation and thrombosis, both of which are important in the pathogenesis of ANCA-associated vasculitis (AAV). Previous work found that VWF correlates with disease activity in childhood-onset primary CNS vasculitis. We sought to determine the relationship between VWF and disease activity over time in children with AAV. Methods AAV patients with more than one VWF level measured were included in this retrospective study, and the relationships between active vasculitis, VWF and other disease measures were analysed. Generalized estimating equations analysis was used to account for repeated VWF measurements within a patient. Repeated measures correlation was used to determine associations of paired laboratory observations. Diagnostic performance was evaluated using receiver operating curve analysis. Results A total of 732 total VWF measurements were collected in 33 AAV patients. VWF antigen levels were higher during active disease [median 2.03 IU/ml, interquartile range (IQR) 1.35, 2.55] compared with inactive disease (median 1.18 IU/ml, IQR 0.94, 1.53). VWF antigen was the only variable that was significantly associated with active disease (odds ratio 3.01, P  < 0.001, 95% CI 2.3, 3.93). The effect of VWF did not show a substantial difference between the disease subtypes. There was a moderate positive correlation between VWF antigen and disease activity, with an acceptable sensitivity and specificity rates. Conclusion Increased VWF antigen levels correlate with active vasculitis in this paediatric-onset AAV cohort and may be used as an additional biomarker in childhood AAV. [ABSTRACT FROM AUTHOR]

Background: Historically, von Willebrand factor (VWF) activity assays utilized ristocetin despite limitations including poor limits of detection and high imprecision. Newer VWF activity assays such as the INNOVANCE® VWF Ac assay, however, do not rely on ristocetin to measure platelet-dependent VWF function. The purpose of this study was to evaluate the analytical and clinical performance of the Siemens Healthineers INNOVANCE VWF Ac Assay on the Siemens BCS® XP and the Sysmex® CS-2500 systems in a large reference laboratory setting. Methods: Performance indicators for the INNOVANCE VWF Ac assay were the limit of quantitation (LoQ), precision, and method comparison. Method comparison studies were performed using remnant plasma patient samples from routine coagulation tests and analyzed using both the INNOVANCE VWF Ac assay and the Siemens Healthineers ristocetin-dependent BC von Willebrand Reagent. Results: Evaluation of the INNOVANCE VWF Ac assay on the BCS® XP and CS-2500 systems demonstrated good precision and a lower LoQ compared to the BC von Willebrand Reagent. Method comparisons support the use of the INNOVANCE VWF Ac assay on the BCS® XP and CS-2500 systems to measure platelet-dependent VWF function. The INNOVANCE VWF Ac assay was able to further assist in von Willebrand disease classification in 6/7 (86%) samples when the result was below the LoQ for the BC von Willebrand Reagent (ristocetin cofactor activity). Conclusions: These data are consistent with the 2021 American Society of Hematology/International Society on Thrombosis and Haemostasis/National Hemophilia Foundation/World Federation of Hemophilia von Willebrand disease guidelines that suggest using newer assays such as the INNOVANCE VWF Ac assay in place of ristocetin cofactor activity assays. [ABSTRACT FROM AUTHOR]

Objective: Unusual clinical course Background: Classical hemophilia A, an X-linked recessive disorder, is characterized by an inability to produce factor VIII in normal quantities. This condition, also leading to factor IX deficiency, underpins the bleeding disorder known as hemophilia A. Among the complications of this illness, spontaneous retroperitoneal hematoma is rare but can be associated with congenital coagulopathies such as von Willebrand disease or hemophilia A. This type of spontaneous internal bleeding has been the subject of a limited number of studies. Case Report: A 38-year-old man with a known diagnosis of hemophilia A presented to the Emergency Department exhibiting acute pain in the right lower abdomen. A computed tomography scan of the abdomen identified a rightsided retroperitoneal mass, suspected to be a hematoma. Within 7 h after admission, the patient experienced significant drops in the hemoglobin level and platelet count. He was administered packed red blood cells, fresh frozen plasma, and platelet transfusions prior to transfer to the Intensive Care Unit. There, he was treated with factor VIII and recombinant factor VIIa, coupled with stringent monitoring. Following clinical and laboratory findings and stabilization, he was discharged with specific medications, and a follow-up appointment was scheduled. Conclusions: Spontaneous retroperitoneal hematoma in patients with hemophilia A is a rare and grave emergency. This case underscores the need for precise diagnostic approaches, tailored management strategies, and vigilant surveillance to prevent and mitigate the potentially life-threatening complications associated with spontaneous hemorrhage in this population. [ABSTRACT FROM AUTHOR]

Von Willebrand disease (VWD) is the most common congenital bleeding disorder. This autosomal dominant condition arises from quantitative or qualitative defects of Von Willebrand factor. To our knowledge, this study leveraged a national database to characterize the largest VWD cohort of total hip arthroplasty (THA) patients to date, assessing 90-day postoperative adverse events and 5-year revision-free survival. Adult patients who underwent primary THA for osteoarthritis were identified from January 2010 to October 2021 in a nationwide database. Patients who had and did not have VWD were matched (4:1) on age, sex, and Elixhauser Comorbidity Index and compared with multivariable logistic regression. Patients were then categorized based upon venous thromboembolism (VTE) chemoprophylaxis prescription patterns to compare bleeding and thrombotic adverse events. Of 544,851 THA patients, VWD was identified in 309 patients (0.06%). The matched cohorts contained 1,221 patients who did not have VWD and 306 patients who have VWD. On multivariable analysis, VWD patients had increased odds of 90-day VTE (odds ratio [OR] = 1.86) and hematoma (OR = 3.40) (P <.05 for all). No difference in 5-year revision-free survival was found. The VWD patients receiving aspirin or no prescriptions had greater odds of VTE (OR = 2.39, P =.048). Those on other chemoprophylaxis agents had greater odds of hematoma (OR = 4.84, P =.006). Patients with VWD undergoing THA had increased odds of 90-day VTE if using aspirin or no prescriptions, or hematoma if using other chemoprophylaxis. There is a delicate balancing act of clotting versus bleeding that must be considered in managing such patients, but it was reassuring that no difference in overall 5-year revision-free survival was found. [ABSTRACT FROM AUTHOR]

Introduction: Von Willebrand disease (VWD) is the most common inherited bleeding disorder, affecting about 0.6% to 1.3% of the population, and is characterized primarily by mucocutaneous bleeding secondary to defective platelet adhesion and aggregation. Current therapeutic options for those with severe disease are limited and require frequent intravenous infusions. Areas covered: This review discusses the current and recently completed clinical trials involving pathways to FVIII augmentation for the treatment of VWD. Clinical trials registered on clinicaltrials.gov and published data via PubMed searches through June 2024 were included. Expert opinion: Available treatment options to those with VWD are limited in part due to limited clinical trials, the complexity of VWD types, and the pharmacokinetics of current treatment options. The development of therapeutic options that reduce treatment burden is necessary to improve quality of life and reduce bleeding complications and in recent years there has been an increased interest from industry to apply novel therapeutics for VWD. The FVIII mimetic, emicizumab, has demonstrated early success in patients with severe VWD and is a promising treatment option for those who require prophylaxis. Furthermore, products like efanesoctocog alfa (Altuviiio®) and BT200 have achieved enhanced VWF/FVIII half-life extension could expand the current treatment landscape while concurrently minimizing treatment burden. [ABSTRACT FROM AUTHOR]

Background: Type 2B von Willebrand disease (VWD) is a less common subtype and is difficult to diagnose. This case report and literature review highlights a rare neonatal onset of type 2B VWD initially misdiagnosed as neonatal alloimmune thrombocytopenia (NAIT). Methods: The neonate presented with severe thrombocytopenia and was unresponsive to NAIT treatments. Genetic testing was conducted because of the unclear family history of thrombocytopenia. Results: Next-generation sequencing revealed a p.Arg1306Trp von Willebrand factor variant, confirming type 2B VWD. Conclusions: This study underscores the critical role of genetic testing in diagnosing challenging cases of neonatal thrombocytopenia, irrespective of family history, and aims to elucidate the clinical manifestations and course of neonatal onset type 2B VWD [ABSTRACT FROM AUTHOR]

BackgroundPrevious observational studies have shown that Hypothyroidism is associated with Von Willebrand Disease (VWD), but the causal relationship has not been confirmed because of conflicting findings and confounding by mixing factors. There are also some studies suggesting that polyunsaturated fatty acids (PUFA) may be one of the potential mediators. In this study, we used a Mendelian randomization study to analyze the causal relationship between Hypothyroidism and VWD and to investigate whether polyunsaturated fatty acids mediate the effects of Hypothyroidism on VWD.MethodsUsing a large publicly available genome-wide association study of predominantly European ancestry to obtain data on Hypothyroidism, VWD, and PUFA, we conducted a two-sample Mendelian randomization study to assess the causal relationship between Hypothyroidism and VWD and assess the potential role of Polyunsaturated fatty acids in mediating the causal pathway between Hypothyroidism and VWD. Finally, we also inferred reverse causality between VWD and Hypothyroidism. Inverse variance weighting (IVW) was the primary analytical method.ResultsWe found that Hypothyroidism may be negatively causally associated with the development of VWD and that PUFA have a role in mediating role in this process (the ratio of the mediating effect: 24.33%). The causal effects of Hypothyroidism and PUFA on VWD remained significant (p < 0.05) after correction of each other by MVMR.ConclusionOur study unveils a novel negative correlation between hypothyroidism and VWD, further enriched by the discovery of partial mediation by PUFA. This groundbreaking finding not only advances our comprehension of VWD etiology but also opens promising avenues for its control and treatment. By elucidating the intricate interplay between hypothyroidism, PUFA, and VWD, our research pioneers a paradigm shift in therapeutic approaches, offering fresh perspectives for the management of this complex disorder.

The article discusses a case study of a patient with Acquired von Willebrand Syndrome (AVWS) associated with Monoclonal Gammopathy of Undetermined Significance (MGUS). The study highlights the challenges in diagnosing AVWS and the importance of pharmacokinetic studies in identifying the etiopathogenesis of anti-von Willebrand factor (VWF) antibodies. The research emphasizes the role of IVIG in managing AVWS and the need for collaboration between hematologists and laboratory experts for accurate diagnosis. The study provides valuable insights into the treatment and diagnostic approaches for AVWS associated with MGUS. [Extracted from the article]

The article discusses a case report of a patient with severe haemophilia and a haemophilia pseudotumor who developed a severe pulmonary embolism and cardiac arrest during surgery, ultimately leading to death. The patient had a large pseudotumor in the left pelvis, severe bone erosion, and compression of the abdominal cavity. Despite rescue efforts, including ECMO treatment, the patient did not survive. The study highlights the challenges of surgical treatment for pelvic haemophiliac pseudotumors and the rare occurrence of serious pulmonary embolism in such cases. [Extracted from the article]