Pro-coagulant haemostatic factors for the prevention and treatment of bleeding in people without haemophilia.
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ABSTRACT:
SUBMITTER: Fabes J
PROVIDER: S-EPMC6517302 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Acquired haemophilia A (AHA) is a rare and possibly fatal autoimmune disorder that is challenging to treat. Although a majority of cases are idiopathic, AHA can also be associated with an underlying malignancy, autoimmune disorder, pregnancy, infection or certain medications. The diagnosis and treatment of AHA require a specialist with both clinical and laboratory expertise. The goal of treatment is aimed at achieving haemostasis as well as eradicating factor inhibitors. We present a patient with AHA and life-threatening haemorrhage who was successfully treated with a combination of haemostatic agents and a triple-drug immunosuppressive regimen. In reviewing recent studies and published guidelines, we advocate that a newer agent, emicizumab, can potentially be incorporated into the treatment protocol for AHA given its promising performance in the realm of congenital haemophilia.
| S-EPMC8217947 | biostudies-literature
Project description:Acquired haemophilia A (AHA) is an autoimmune bleeding disorder caused by autoantibodies blocking coagulation factor VIII (FVIII). Haemostatic management of AHA and concomitant thrombotic risk is difficult. We cover the management of a 75-year-old male with severe Covid-19, a prothrombotic disease, and de novo AHA with severe muscle bleeding, a disease requiring highly thrombogenic haemostatic therapy and immunosuppression-a challenging combination. FVIII activity was measured using human and bovine reagents to differentiate between endo- and exogenous FVIII activity. For haemostatic control, recombinant human activated FVII was given, followed by emicizumab, as a less thrombogenic long-term haemostatic agent. Steroids were used as initial immunosuppressive therapy. Later, rituximab was used for inhibitor eradication. No thromboembolic events occurred, and bleeding was effectively controlled. Emicizumab achieved haemostatic balance in a patient under haemorrhagic and thrombogenic conditions. Individual risk assessment is needed to guide treatment decisions in patients threatened by simultaneous bleeding and thrombosis.
| S-EPMC9877795 | biostudies-literature
Project description:IntroductionAlthough the measurement of physical activity (PA) amongst people with haemophilia (PWH) has become increasingly widespread in recent years, the relationship between PA and bleeding phenotype remains poorly understood. In addition, the influence of various treatment regimens on this relationship has not been defined.AimThis review aimed to systematically assess the data that are available regarding PA levels amongst PWH, as well as the relationship between PA and bleeding.MethodsA systematic search of the online databases EMBASE, Cochrane, MEDLINE Ovid, CINAHL and Web of Science was conducted by two independent reviewers. Quality assessment was undertaken using the AXIS Critical Appraisal Tool for Cross-sectional Studies and the STROBE checklist.ResultsOf 1902 sources identified overall, 36 articles were included. Low-to-moderate transparency of reporting and various sources of bias were identified. PA levels varied amongst heterogeneous samples of PWH. The relationship between PA and bleeds was inconclusive, although there was evidence that improvements in treatment over recent decades have appeared to enable PWH to become more physically active.ConclusionBased upon the limited available evidence, the relationship between PA and bleeding phenotype in PWH remains unclear. However, with the development of improved prophylaxis treatment regimens in recent years, there is evidence that PA levels have increased, especially amongst people with severe haemophilia. The use of validated outcome measures of PA and more robust reporting of bleeds and treatment regimen are warranted in future research, especially in a rapidly evolving era of new treatments for PWH.
| S-EPMC8359343 | biostudies-literature
Project description:BackgroundAcquired haemophilia A (AHA) is a rare bleeding disorder due to autoantibodies to coagulation factor VIII that may be secondary to autoimmune diseases, cancer, drugs, pregnancy, infections, or be idiopathic. Recurrent bleeding, often severe, mostly in muscles and soft tissues, and isolated prolonged activated partial thromboplastin time (aPTT), in the absence of personal and family history of bleeding, are typical features that should raise the suspicion of AHA. Poor awareness of the disease results in diagnostic delays and inappropriate treatment.Materials and methodsThe Italian Association of Haemophilia Centres (AICE) developed consensus recommendations in cooperation with the Italian Society on Thrombosis and Haemostasis (SISET). The document was shared with scientific societies of specialist physicians, laboratory professionals and pharmacists to spread knowledge about AHA and promote appropriate diagnosis/treatment.ResultsReady availability of the aPTT mixing test is crucial, although diagnostic confirmation and optimal management require prompt referral of patients to specialised centres with rapidly available diagnostic and therapeutic facilities. If immediate referral is unfeasible, treatment must be undertaken early, under guidance of specialised centres or based on shared protocols. Recommendations about diagnosis, general management and, in bleeding patients, haemostatic therapy using bypassing agents or replacement treatment, including the recently available recombinant porcine factor VIII, are provided, considering the different clinical settings and laboratory facilities.DiscussionThis consensus document aims to improve the overall healthcare pathways for AHA, harmonise the management and therapeutic approaches to newly diagnosed patients and reduce the still relevant complications and mortality in this setting.
| S-EPMC9068356 | biostudies-literature
Project description:IntroductionThe impact of bleeding for women with bleeding disorders (WBD) is of increasing focus and importance. Despite this, optimal management strategies are unclear and knowledge gaps persist.AimTo examine practices and define research priorities on diagnosis and management of WBD in Europe.MethodsAn electronic survey on clinical management of WBD was sent to 136 European haemophilia treatment centres (HTCs), including open questions on knowledge gaps and research priorities.ResultsFifty-nine HTCs from 12 Western (WE) and 13 Central/Eastern European (CEE) countries completed the survey. Less than half runs a joint clinic (24 HTCs, 42%). Most centres without a joint clinic have a named obstetrician (81%) and/or gynaecologist (75%) available for collaboration. Overall 18/54 (33%) European HTCs do not offer preimplantation genetic diagnosis. Third trimester amniocentesis to guide obstetric management is available 28/54 HTCs (52%), less frequent in CEE compared to WE countries (5/17 vs 23/37, P = .03). 53% of HTCs (28/53) reported that only 0%-25% of WBD seek medical advice for heavy menstrual bleeding (HMB). An algorithm managing acute HMB in WBD is lacking in 22/53 (42%) HTCs. The main reported knowledge and research gaps are lack of awareness & education on WBD among patients and caregivers, optimal diagnostic strategies and effective multidisciplinary management of pregnancy & HMB.ConclusionJoint clinics, prenatal diagnostics and algorithms for managing acute HMB are lacking in many European HTCs. HMB may be an underestimated issue. This survey highlights the need to prioritize improvement of knowledge and patient care for WBD across Europe.
| S-EPMC7497252 | biostudies-literature
Project description:IntroductionValoctocogene roxaparvovec is an investigational AAV5-based factor VIII (FVIII) gene therapy that has demonstrated sustained clinical benefit in people with severe haemophilia A.AimTo report safety, tolerability, efficacy, and quality of life (QOL) among participants who received valoctocogene roxaparvovec in a phase 1/2 clinical study (NCT02576795).MethodsMen ≥18 years of age with severe haemophilia A (FVIII ≤1 IU/dl) without history of FVIII inhibitors or anti-AAV5 antibodies received a single infusion of valoctocogene roxaparvovec and were followed for 5 years (6 × 1013 vg/kg dose, n = 7) and 4 years (4 × 1013 vg/kg dose, n = 6).ResultsOver the past 2 years, few adverse events and no FVIII inhibitors were reported. Per chromogenic substrate (CSA) assay at years 5 and 4, four of seven and three of six participants in the 6 × 1013 and 4 × 1013 vg/kg cohorts, respectively, maintained median FVIII levels >5 IU/dl, corresponding to mild haemophilia. By regression analysis, rate of change in FVIII activity was -0.14 (95% confidence interval [CI]: -.32 to .03) IU/dl/wk in the 6 × 1013 vg/kg cohort in year 5 and -.06 (95% CI: -.14 to .01) IU/dl/wk in the 4 × 1013 vg/kg cohort in year 4. No participants resumed FVIII prophylaxis, and eight of 13 participants reported zero bleeds in the past 2 years. Improved QOL from baseline persisted in the 6 × 1013 vg/kg cohort; all six Haemo-QOL-A domain scores increased. For the 4 × 1013 vg/kg cohort, high baseline Haemo-QOL-A scores persisted.ConclusionThese results demonstrate transgene expression and haemostatic response for up to 5 years in individuals with haemophilia A.
| S-EPMC9291073 | biostudies-literature
Project description:ObjectiveTo identify risk factors for bleeding in atrial fibrillation (AF) patients treated with anti-coagulants such as warfarin, apixaban, edoxaban, dabigatran, rivaroxaban using a large claims database.MethodsA claims database for 8926 AF patients from 2004 to 2016 was obtained from JMDC. Inc. We performed a retrospective cohort study in 2796 Japanese AF patients with 4-month screening and 12-month observation periods. Polypharmacy was defined as prescription of over six drugs. Logistic regression analysis was conducted after stratification based on the presence and absence of cerebrovascular diseases to detect the predictive factors for bleeding.ResultsPolypharmacy was observed in 815 of 2796 (29.1%) patients. A total of 371 AF patients (13.3%) experienced bleeding in the 12-month observation period. Bleeding risk assessment using multiple logistic regression analysis revealed that the odds ratio for the number of co-administered drugs in the elderly (age for ≥60, ≤74) was not significant in those without and with cerebrovascular diseases (1.05 [0.99-1.12], N.S. and 1.10 [0.96-1.27], N.S.). In contrast, in the young (age for <60), the number of co-administered drugs was a significant predictive factor in those without and with cerebrovascular diseases (1.09 [1.03-1.16], p = 0.0054 and 1.20 [1.05-1.36], p = 0.0059). Other observed predictors were"history of bleeding" in young and elderly, but "polypharmacy" and "start from warfarin" were observed in only young.ConclusionWe determined the bleeding risk in the clinical setting using a large claims database. Physicians and pharmacists need to monitor patients for the initial bleeding signs, particularly in those with these predictive risk factors.
| S-EPMC7458330 | biostudies-literature
Project description:BackgroundGastrointestinal bleeding is a rare but severe complication of pancreatic ductal adenocarcinoma.ObjectiveThe purpose of this study was to describe the causes and treatments of non-postoperative gastrointestinal bleeding in patients with pancreatic ductal adenocarcinoma, and explore the parameters associated with therapeutic effectiveness.MethodsThis was a single-centre observational retrospective study (2000-2017) with data collected from the prospectively coded diagnostic hospital's database system including patients with pancreatic ductal adenocarcinoma who had a gastrointestinal bleeding episode. Effectiveness of haemostatic treatment was assessed according to transfusion requirements and immediate and long-term haemostatic efficacy; the latter defined as no bleeding recurrence.ResultsThe population included 72 patients with pancreatic ductal adenocarcinoma who had 94 episodes of gastrointestinal bleeding. The main causes of gastrointestinal bleeding were gastroduodenal tumour invasion (56.4%) and oesophageal variceal bleeding due to left-sided portal hypertension (19.1%). In cases of gastrointestinal bleeding caused by tumour invasion, the main treatment was therapeutic endoscopy (41.5%). Among patients who had gastrointestinal bleeding by tumour invasion treated by endoscopy or radiation therapy, haemostatic immediate efficacy rates were 70.6% and 100%, respectively. Bleeding recurrence rates were 35.3% and 25.0%, for patients treated by endoscopy or radiation therapy, respectively, for a first episode of gastrointestinal bleeding by tumour invasion. Transfusion requirements, before and after treatment, were not different in patients treated by haemostatic radiation therapy for gastrointestinal bleeding by tumour invasion compared to other treatments (odds ratio 0.3, 95% CI (0.06-1.59); p = 0.16). The median survival after all-cause gastrointestinal bleeding was 2.72 months (1.43-4.01).ConclusionGastroduodenal tumour invasion was the main cause of gastrointestinal bleeding in patients with pancreatic ductal adenocarcinoma; haemostatic radiation therapy is a potential interesting option for gastrointestinal bleeding treatment in this context.
| S-EPMC7724548 | biostudies-literature
Project description: Not available
| S-EPMC6472507 | biostudies-literature
Project description:BackgroundIn people with haemophilia, therapeutic clotting agents might be recognised as a foreign protein and induce anti-factor VIII antibodies, known as 'inhibitors'. Drugs insensitive to such antibodies, either recombinant or plasma-derived, are called factor VIII 'by-passing' agents and used for treatment of bleeding in people with inhibitors.ObjectivesTo determine the clinical effectiveness of recombinant factor VIIa concentrate compared to plasma-derived concentrates for treating acute bleeding episodes in people with haemophilia and inhibitors.Search methodsWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Coagulopathies Trials Register which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Coagulopathies Trials Register: 23 September 2015.Selection criteriaRandomised and quasi-randomised controlled clinical trials comparing recombinant factor VIIa concentrate to human plasma-derived concentrates (high-dose human or recombinant factor VIII or factor IX concentrate; non-activated prothrombin complex concentrates; activated prothrombin complex concentrates) in people with haemophilia. Comparisons with animal-derived products were excluded.Data collection and analysisTwo authors independently assessed the trials (eligibility and risk of bias) and extracted data. No combined meta-analyses were performed due to the unavailability of outcomes and comparisons common to the included trials.Main resultsA total of 15 trials were identified, two of which (with data for a total of 69 participants) were eligible for analysis. Both trials showed methodological flaws and did not show superiority of one treatment over the other. Both the treatments showed that recombinant factor VIIa and activated prothrombin complex concentrate appeared to have a similar haemostatic effect in both trials, without increasing thromboembolic risk.Authors' conclusionsBased on the separate analysis of the two available randomised trials, recombinant factor VIIa and activated prothrombin complex concentrate were found to be similar in efficacy and safety. However, there is a need for further, well-designed, adequately-powered, randomised controlled trials to assess the relative benefits and risks of using recombinant factor VIIa compared to human plasma-derived concentrates in people with haemophilia with inhibitors. It is advisable that researchers in the field define commonly agreed objective outcome measures in order to enable the pooling of their results, thus increasing the power of comparisons. To date, data could not be combined in a formal meta-analysis. For the same reason reporting concordant and discordant pairs in cross-over trials is recommended.
| S-EPMC7137678 | biostudies-literature