Congenital Coagulation Disorders Research Articles

Surgical management for ankle arthropathy in patients with hemophilia and other congenital coagulation disorders

Objective: Compare the surgical treatment options available in our institution and the postoperative outcomes during follow-up.Additionally, assess patient’s perception of their condition and its progression. Methods: This descriptive observational study is a case series with a narrative literature review. All patients who met the inclusion and exclusion criteria and received surgical management for ankle arthropathy due to ankle hemarthrosis between 1999 and 2022 at Hospital San José in Bogotá were included. A perception survey was conducted via teleconsultation to evaluate pain control, functional impact, and capacity for daily activities. Results: Fifteen patients were included in the study, 13 male (86.7%). The mean age at the time of surgical intervention was 33 years (range 25–68). Among the patients, eight (53.3%) were diagnosed with Hemophilia A, four (26.7%) with Hemophilia B, two with Von Willebrand disease (13.3%), and one (6.7%) with Factor VII deficiency. The most common surgical intervention was ankle arthroscopy, with nine cases (50%). No infectious or intraoperative complications were documented, but one case of Hemophilic Pseudotumor developed late. The mean follow-up time was 87.7 months (IQR 60–105, SD 56.17). All patients reported improved pain and resumed their daily activities after the surgical intervention. Conclusion: Surgical management, regardless of the technique used (joint preservation or sacrifice), had a positive impact on patients by reducing pain after conservative management failure and allowing them to regain their daily activities, improving their quality of life. Level of Evidence IV; Therapeutic studies - investigating the results of treatment; Case series.

Early Initiation of Breastfeeding Can Accelerate Uterine Involution in Postpartum Women

<div><table cellspacing="0" cellpadding="0" align="left"><tbody><tr><td align="left" valign="top"><p><em>Maternal Mortality Rate (MMR) in Indonesia is still high with the main causes of pre-eclampsia and postpartum hemorrhage, this occurs due to endometritis, congenital coagulation disorders as well as residual conception products, subinvolution of blood vessels at placental implantation. Therefore, efforts are needed to increase uterine contractions in the first minute after birth by stimulating the release of the hormone oxytocin so that the uterus contracts adequately with early initiation of breastfeeding (EIB). This study aims to determine the effect of EIB on uterine involution in postpartum mothers in Bengkulu Regency, Bengkulu Province. </em><em>Design</em><em> of research is cross sectional with independent variable of EIB, dependent variable of uterine involution. External variables measured include early mobilization, age and parity. The sample in this study were postpartum mothers on day 7, a total of 54 people selected by purposive sampling. The research site was located in Central Bengkulu Regency, Bengkulu Province. Data were analyzed univariate, bivariate with Mann Whitney and multivariate with ancova. There is an effect of EIB with uterine involution p=0.000. There is no relationship between parity and uterine involution p=0.100. There is a relationship between age and uterine involution p=0.00. There is a relationship between early mobilization and uterine involution p=0.00. EIB is the dominant factor affecting uterine involution in postpartum mothers. EIB is the dominant factor affecting uterine involution. Health care providers should perform EIB within the first hour after the birth of the baby to prevent sub involution in postpartum women</em><em>.</em></p><p><em> </em></p></td></tr></tbody></table></div><strong><em>Keywords: Breastfeeding, Early, Initiation, Involution, Uterine</em></strong>

Donor-derived disorders of hemostasis and thrombosis in liver transplantation: Considerations for deceased donor liver selection.

OLT is known to be associated with a precarious perioperative hemostatic state due to dysregulation of procoagulant and anticoagulant factors, endothelial injury, and inflammation. Transmission of inherited bleeding and clotting disorders from the liver donor to the recipient may further complicate hemostasis during and after transplantation. As a result, consideration of congenital coagulation disorders in the liver donor is a practical concern for donor selection. However, there is no clear consensus regarding the selection of donors with known or suspected thrombophilia or bleeding disorders. While multiple case reports and retrospective studies, subject to reporting bias, describe donor-derived thrombophilic and bleeding disorders, there are no large-scale studies in the adult liver transplant literature that examine the frequency of transmission, utility of donor screening, or clinical impact of donor hemostatic disorders. Based on the reported literature, we summarize our approach for donor selection with an aim to balance improved organ utility and optimal post-transplant outcomes.

Bleeding Disorders and Dental Implants: Review and Clinical Indications.

Bleeding disorders can be divided into three categories: congenital coagulation disorders (CCDs), antiplatelet-induced bleeding disorders (APBDs) and anticoagulant-induced bleeding disorders (ACBDs). Implant placement can be challenging in these kinds of patients. The aim of this study is to provide evidence on implant surgery in patients with bleeding disorders and to generate some practical recommendations for clinicians. Pubmed/MEDLINE, Scopus, Web of Science and Cochrane Library databases were screened. The latest search was performed in July 2022. Case reports, case series, cohort studies, cross-sectional studies, case control studies, reviews, consensus reports, surveys and animal studies were included in the analysis. Seventeen articles on CCDs were found, fourteen on APBDs and twenty-six on ACBDs. Most of these articles were case reports or case series. Patients with CCDs can be treated after the infusion of the missing coagulation factor. Patients with APBDs can be treated without withdrawing the therapy. Patients with ACBDs should be treated depending on the anticoagulative medication. Despite the low level of evidence, dental implants can be safely placed in patients with bleeding disorders. However, careful preoperative evaluation and the adoption of local and post-operative bleeding control measures are mandatory.

A rare case of an anaphylactic reaction to plasma and recombinant blood coagulation factor VIII in a child with severe hemophilia A

A rare case of anaphylactic shock after administration of 4 th generation recombinant blood coagulation factor VIII is presented. Anaphylactic shock is a life-threatening complication for a patient with hemophilia A. Temporarily refrain from re-administration of factor VIII, a skin test confirming drug choice, and a patient desensitization procedure provide the clinician with a chance to continue hemostatic replacement therapy for a patient with hemophilia A. The main purpose of this case report is to determine the algorithm of actions to overcome the consequences of anaphylactic shock and continue the prophylactic administration of coagulation factor VIII concentrate to prevent bleeding in a child with a rare random combination of an anaphylactic reaction and congenital coagulation disorders.

Intraoperative Bleeding Management: An Updating Literature Review: Review Article

Background: Intraoperative bleeding remains a major complication during and after surgery, leading to increased morbidity and mortality. Several influences determine the complex causes of bleeding in surgical patients. About 75 to 90% of early intraoperative and postoperative bleeding is due to technical factors. In some cases, however, acquired or congenital coagulopathies can stimulate, if not directly cause, surgical bleeding.
 Objectives: This paper aims to overview etiology, causes, diagnosis, and updated management of intraoperative bleeding.
 Methods: The review article ran from July 1, 2021 to October 31, 2021. We searched articles on etiology, causes, and treatments published in English worldwide in the Medline, EBSCO and PubMed databases. No software was used to analyze the data. Team members reviewed the data to determine initial results.
 Results: All patients scheduled for elective surgery should be screened for possible hemostatic defects using tests, and, if necessary, laboratory tests. Treatment of intraoperative bleeding consists of identifying patients at risk and understanding the effect of surgery on hemostasis. For patients at high risk of bleeding, a pre-operative meeting with a multidisciplinary team (anesthesiologist, surgeon, hematologist, radiologist) can discuss the correct surgical procedure.
 Conclusion: Technical variables account for 75-90% of initial intraoperative and postoperative bleeding. However, in other cases it is associated with acquired or congenital coagulation disorders. All patients scheduled for elective surgery should be checked for problems with hemostasis. Treatment of intraoperative bleeding involves identifying those at risk and understanding the effect of surgery on hemostasis.

Transjugular Liver Biopsy

Transjugular liver biopsy (TJLB) was first performed in 1970 and has since become a standard procedure in interventional radiology practices. TJLB can be used when a percutaneous liver biopsy is contraindicated, such as patients with ascites, coagulopathy, congenital clotting disorders or for patients undergoing concurrent evaluation for portal hypertension. While TJLB specimens tend to be smaller with less complete portal triads numerous studies have shown the samples to be adequate for diagnosis and staging. This article will review what the interventional radiologist needs to know about TJLB including indications/work-up, technical details, tips and tricks, and complications.

Integrated Hemophilia Patient Care via a National Network of Care Centers in the United States: A Model for Rare Coagulation Disorders.

Rare, chronic diseases such as hemophilia and other congenital coagulation disorders require coordinated delivery of services for optimal outcomes. Hemophilia Treatment Centers (HTCs) are specialized, multidisciplinary health-care centers providing team-based care to meet the physical, psychosocial, and emotional needs of people with hemophilia (PWH) and may serve as a model for other rare coagulation disorders. Health-care purchasers, as well as the general medical community, may not appreciate the breadth and quality of services provided by HTCs. They exemplify the acculturalization and actualization of integrated care by providing comprehensive diagnostic and treatment services that reduce morbidity, mortality, avoidable emergency room visits, hospitalizations, and overall costs, while promoting a longer lifespan and improved patient functioning and outcomes. This is accomplished by a team-based approach relying upon a shared decision-making model to effectively prevent complications and manage symptoms in PWH, who are dependent on high-cost treatments. This article provides a concise yet comprehensive description of the core components of an HTC and the regional and national networks in the United States, which together achieve their incomparable value for all stakeholders.

Prognostic Factors and Clinical Features of Neonatal Splenic Rupture/Hemorrhage: Two Cases Reports and Literature Review.

Background: Neonatal splenic rupture/hemorrhage (SRH), an extremely rare and potentially fatal presentation, can spontaneously resolve without surgical treatment; However, treatment approaches remain controversial. The present study aimed to describe and analyze the clinical features and therapies of neonatal SRH and therapeutic approaches.Methods: We present the cases of two patients and review another 37 cases reported in English-literature. The literature search included all articles published in PUBMED from inception between January 1968 and December 2019. Demographic data, precipitating factors, clinical characteristics including presenting symptoms and signs, presenting time, age at SRH presentation, imaging findings, as well as treatments and outcomes were analyzed.Results: In addition to the two cases treated at our hospital, 37 neonates with SRH were reported during the study period. The rate of full-term neonates was 72% (28/39). The cause was idiopathic in most cases, and congenital coagulation disorders were underlying causes in 13% (5/39) of the cases. The most common presenting symptom and sign of neonatal SRH were pallor or anemia, followed by abdominal discoloration/distension. Additionally, 18% (7/39) of the cases presented with scrotal hematoma or swelling. The age at SRH presentation ranged between 3 h and 5 days of age. Abdominal ultrasonography or computed tomography was used as the diagnostic tool. Twenty-seven cases (69%) received surgical management. The prognosis was comparable between the neonates treated with splenectomy and those treated with non-surgical approaches. The mortality rate was 18% (7/39) in the study cohort. SRH presentation at ≤12 h of age was associated with higher mortality compared to SRH presenting time at >12 h of age (odds ratio 25.0, 95% CI 2.514–248.575, p = 0.001).Conclusion: Our literature review revealed that the mortality rate of neonatal SRH was 18% and that the mortality risk was higher in neonates presenting with SRH symptoms and signs at ≤12 h of age.

Congenital coagulation disorders in neurosurgical patients. Literature review and case series

Congenital coagulation disorders account about 1-2% and can pose a serious risk for neurosurgical patients. Indeed, coagulation management in these patients is essential to ensure normal hemostasis. Analysis of available literature devoted to this issue and case series of neurosurgical patients with congenital coagulation disorders. Literature data were obtained from the PubMed, Cochrane Library, Medline and Google Scholar databases for the period from 2019 to 2020. Over 200 reports devoted to our scientific issue were selected. We determined the key features of perioperative management of neurosurgical patients with congenital coagulation disorders. We have also analyzed 10 similar patients for the period from 2008 to 2020. Comprehensive analysis of anamnesis, adequate diagnosis, perioperative planning and multidisciplinary approach are essential for successful elective surgery in patients with congenital coagulation disorders.

Analysis of the assortment of plasma-derived products on Ukraine pharmaceutical market

Increasing number of patients, who suffers from diseases such as immunodeficiency, autoimmune and inflammatory diseases, various congenital blood clotting disorders stimulate an increase in the pharmaceutical market in the number of drugs for treating these diseases. Providing high-quality, effective and safe drugs, obtained from blood is an urgent issue that can save lives.
 The purpose of the work was to study the range of biological drugs containing active substances obtained from human and animal blood plasma and analyze the segment of these drugs on the pharmaceutical market of Ukraine for 2020. To study this segment, was used data from the State Register of Medicinal Products of Ukraine, the information retrieval program «Morion» and the ATX classification system of the electronic resource Compendium.online. Research methods: structural, statistical, graphic, generalization and systematization.
 Established, that the segment of biologic drugs, derived from human and animal blood plasma, at the Ukrainian pharmaceutical market, are represented by 100 trade names of drugs, where 23% of the studied market segment is occupied by domestic manufacturers. The leaders of importing countries are Austria (31%) and Sweden (13%). Analysis of the nomenclature found, that the most common drug dosage form are lyophilized powders for injection and infusion solution (52%) and solutions for injection and infusion (35%).
 Studies have shown, that the active ingredient in the largest share of blood products is the coagulation factor of human blood VIII (36% of the total assortment). The range of drugs produced using plasma of animal origin is limited, makes up only 14% and is represented by preparations of immunoglobulins (horse, rabbit) and drugs containing deproteinization of dialysate from calf blood. The lack of domestic technologies for obtaining PDMPs from cattle plasma (RED) with a sufficient number of cattle was determined.
 Obtained data show, that blood is a strategic raw material for the production of a wide range of drugs for the treatment of diseases of various etiologies, interruptions in the blood supply can lead to regional and global deficiency of the main PDMPs, therefore, the development of drugs based on blood is relevant and promising.

Transfusion Transmitted Infections in Patients with Haemophilia, a Study from Western Rajasthan, India

Introduction: Haemophilia is one of the predominant congenital coagulation disorder and a disease without ethnic or geographic limitations with incidence approximately 20 per 100 000 male births. Haemophilic patients are in regular need of blood and blood products and prone to risk of acquiring infections such as hepatitis B, C (HBV, HCV) and human immunodeficiency virus (HIV). Materials and methods: In this descriptive study, 98 haemophilic patients were selected for screening of HIV I and II, HBV, and HCV through the rapid immunochromatographic test method. Positive cases were confirmed by third generation enzyme linked immunosorbent assay (ELISA). Results: In this study, prevalence of hepatitis B among haemophilia patient was zero and prevalence of hepatitis C and HIV was 1.02% each. Conclusion: Prevalence of transfusion transmitted infections is much lower in this study than previous studies. The use of advanced methods, more sensitive tests, and virally inactivated factor concentrates might contribute to this reduction of viral infections in these patients.

Nontraumatic Pediatric Intracerebral Hemorrhage.

Nontraumatic Pediatric Intracerebral Hemorrhage.

Professional functioning of young adults with congenital coagulation disorders in the Netherlands.

Introduction and AimSuboptimal health‐related quality of life and lowered employment rates found in a previous study in young adults (YA) with congenital coagulation disorders (CCD) in the Netherlands underline the need for more insight into professional functioning of YA with CCD and into determinants of professional functioning.MethodsYoung adults (18‐30 years) with CCD participated in a cross‐sectional study. Professional functioning was assessed with the Work Productivity and Activity Impairment questionnaire (WPAI). Potential determinants were assessed with the Course of Life Questionnaire (CoLQ), Pediatric Quality of Life Inventory Young Adult version (PedsQL_YA), Illness Cognition Questionnaire (ICQ) and Haemophilia Activities List (HAL). Logistic regression analyses were performed in the complete sample of YA with CCD, and in YA men with haemophilia separately, to examine determinants of WPAI outcomes.ResultsNinety‐four YA (77 men; mean age 24.1 years, SD 3.5 and 17 women; mean age 24.5 years, SD 3.8) with CCD (74% haemophilia A/B) participated. 74.5% of YA were paid employed for on average 30 hours per week. Of these, more than a quarter reported work impairment. Older age and a non‐severe type of haemophilia (in the sample of YA men with haemophilia) were associated with successful (paid) employment. No variables were associated with professional functioning (expressed as Presenteeism and Overall work impairment) in patients with CCD or haemophilia.ConclusionThree‐quarters of YA with CCD were successful in finding paid employment. Though absenteeism was low, YA with paid employment needs attention as a considerable part experienced work impairment.

Rola leczenia żywieniowego dzieci z wrodzonymi skazami krwotocznymi

Balancing diet in patients with congenital haemorrhagic diatheses is very important because of the need to eliminate excess weight and at the same time strengthen muscle mass. This has an important role in the treatment and prevention of strokes. The food provided to these children should secure the right amount of energy nutrients and fluids in the right proportions. After investigating the cause and complications associated with the course of the disease, we can reduce symptoms. An individual approach to each patient and the choice of a right diet will reduce the duration of treatment, ensure better development and growth, as well as improving quality of life. Additionally, it is necessary to assess the level of physical activity of each patient and, when it is too low, recommend them to increase it. Proper rehabilitation, which mainly concerns patients with congenital plasma diatoma, is especially important. Another symptom, occurring mainly in girls, is profuse menstruation and associated iron deficiency anemia. In this article we present the most important nutritional problems which a physician dealing with patients (both boys and girls) with congenital coagulation disorders should manage.

Congenital hemophilia: a new treatment paradigm

Hemophilia is the most common congenital coagulation disorder, characterized by a tendency to bleed severely. Treatment is based on the replacement of defective FVIII or FIX. Following the introduction of recombinant FVIII and FIX, the treatment paradigm of the disease is shifting from episodic to prophylactic treatment with regular the infusion of factor concentrates. Since 2000, several new recombinant FVIII and FIX products with longer half-life have been developed by pegylation protein modification and other technologies, resulting in improved quality of life for patients with hemophilia. Recently, therapeutics with novel hemostatic mechanisms have been developed to overcome several unmet needs. FVIII (a), mimicking bispecific antibody recognizing FIX (a) /FX, has been approved in Japan. The product has several advantages, including a much longer half-life spanning 30 days, subcutaneous injectability, and effectiveness irrespective of the presence of FVIII inhibitor. The paradigm of hemophilia treatment is now shifting towards intact joint function and higher activity.

Increased serum levels of progranulin (PGRN) in patients with haemophilic arthropathy.

Haemophilia A and B are rarely occurring X chromosome-linked congenital coagulation disorders dominated by spontaneous joint bleedings and chronic synovitis, leading to development of haemophilic arthropathy (HA). Progranulin (PGRN) is a growth factor with anti-inflammatory and immunomodulatory properties. PGRN is an important molecule in the pathogenesis of osteoarthritis (OA) and rheumatological disorders. This study was aimed at investigating the potential role of PGRN in the mechanisms underlying the pathogenesis of HA. The serum levels of PGRN were measured by enzyme-linked immunosorbent assay (ELISA) in patients with end-stage knee joint HA (n=20) and end-stage primary knee joint OA (n=20) who met the inclusion and exclusion criteria. The clinical and radiological assessment of disease severity was evaluated by the Knee Society Score (KSS) and Kellgren-Lawrence scale. Median PGRN levels in HA patients was 349.1ng/mL (232.8-415.6ng/mL) and in OA patients 148.3ng/mL (112.1-275.3ng/mL) with statistically significant differences between both groups (P<0.015). Further analysis revealed no correlation between PGRN levels and any of the patient demographics and clinical parameters. This study demonstrates increased PGRN serum levels in patients with HA and provides new insights into the mechanisms underlying the pathogenesis of HA indicating a new potential target for therapeutic intervention.

Diagnostic Single Gene Analyses Beyond Sanger

SummaryMolecular testing of congenital coagulation and platelet disorders offers confirmation of clinical diagnoses, supports genetic counselling, and enables predictive and prenatal diagnosis. In some cases, genotype-phenotype correlations are important for predicting the clinical course of the disease and adaptation of individualized therapy. Until recently, genotyping has been mainly performed by Sanger sequencing. While next generation sequencing (NGS) enables the parallel analysis of multiple genes, the cost-value ratio of custom-made panels can be unfavorable for analyses of specific small genes. The aim of this study was to transfer genotyping of small genes involved in congenital coagulation and platelet disorders from Sanger sequencing to an NGS-based method. A LR-PCR approach for target enrichment of the entire genomic regions of the genes F7, F10, F11, F12, GATA1, MYH9, TUBB1 and WAS was combined with high-throughput sequencing on a MiSeq platform. NGS detected all variants that had previously been identified by Sanger sequencing. Our results demonstrate that this approach is an accurate and flexible tool for molecular genetic diagnostics of single small genes.

Gene Therapy with BMN 270 Results in Therapeutic Levels of FVIII in Mice and Primates and Normalization of Bleeding in Hemophilic Mice.

Hemophilia A is an X-linked bleeding disorder caused by mutations in the gene encoding the factor VIII (FVIII) coagulation protein. Bleeding episodes in patients are reduced by prophylactic therapy or treated acutely using recombinant or plasma-derived FVIII. We have made an adeno-associated virus 5 vector containing a B domain-deleted (BDD) FVIII gene (BMN 270) with a liver-specific promoter. BMN 270 injected into hemophilic mice resulted in a dose-dependent expression of BDD FVIII protein and a corresponding correction of bleeding time and blood loss. At the highest dose tested, complete correction was achieved. Similar corrections in bleeding were observed at approximately the same plasma levels of FVIII protein produced either endogenously by BMN 270 or following exogenous administration of recombinant BDD FVIII. No evidence of liver dysfunction or hepatocyte endoplasmic reticulum stress was observed. Comparable doses in primates produced similar levels of circulating FVIII. These preclinical data support evaluation of BMN 270 in hemophilia A patients.

Change of Thrombelastography in Children's DIC and Analysis of Its Sensitivity and Specificity for Diagnosis of DIC

To investigate the influence of thrombelastography index changes on its sensitivity and specificity for diagnosis of disseminated intravascular coagulation (DIC) in children. A total of 149 children with DIC in our hospital from June 2013 to June 2016 were selected in DIC group, while 106 cases of non-DIC, including healthy children and children with diseases easily confused with DIC, were selected as non-DIC(control) group. The thrombelastography, D-dimer, coagulation functions including prothrombintime (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB) and fibin degradation product (FDP), congental coagulation disorders and platelet count were detected in DIC and non-DIC groups; the statistics of data was performed and the sensitivity and specificity of thromelastraphy indexes such as R time, α angle MA value and A value were evaluated; the relationship of DIC with indexes was analyzed. Moreover, the result difference of thromelastography and routine coagulation function test was compared at diagnosis of DIC. According to statistical analysis of clinical data in 2 groups, the average R time in non-DIC group was significantly less than that in DIC group (P<0.05); the average α angle in non-DIC group was larger than that in DIC group (P<0.05), both the MA and A values in the non-DIC group were significantly higher than those in DIC group (P<0.05). The specificity of routine coagulation function test for diagnosis of DIC was as follow: PT-27.2%, APTT-42.2%, international normalized ratio(INR)-47.9%, FIB-44.4%, FDP-42.7% and D-dimer-68.3%, which were significantly lower than that of R time,α angle and MA value for diagnosis of DIC (85.1%, 74.1% and 73%). The α angle and MA value of healthy children were greater than those of children with severe liver disease(P<0.05). while the average R time of healthy children was less than that of children with severe liver disease(P<0.05), but the difference of A value between them did not statistically significant (P>0.05) . The average R time of healthy children was less than that of children with congenital coagulation disorders (P<0.05). but there was no significant differences in α angle MA and Avalues between them. As compared with routine coagulation function test, the thrombelastography shows more high specificity for diagnosis of DIC, and can more precisely diagnose the DIC; moreover, the thrombelastography combined with roatime coagulation function test can more early find and diagnose the DIC in children, therefore it can improve the survival rate of children with DIC.