Blood diffusion to novel therapies: A quantitative analysis of scholarly output in Haemophilia from India

Lack of specific protein factors, such as factor VIII and factor IX, results in haemophilia, a genetic bleeding condition. Due to its genetics, haemophilia affects an individual, but we can see how it has an impact on a whole generation. The goal of this study is to determine the extent to which our Indian researchers have been able to advance this highly sought-after field. Although this study was intended to last 75 years, it had to be restricted to the years 1991 to 2021 due to a shortage of publications at the time of data mining. There was a total of 81 publications found, and after analysing them, it was found that India and the USA collaborated more frequently than France and the UK. The National Institute of Immunohaematology (NIIH), located in Mumbai, is India's most productive institution in terms of the number of publications or ongoing work. Haemophilia, factor viii, and gene therapy were the most commonly used keywords. Indian researchers still need to put in a lot of effort in this area because, according to studies from around the world, haemophilia is spreading like a fire. Continuous research and knowledge of the needs of the population are required if we are to improve not only our position in the world but also the way we are treated, which would make life better.

Haemophilia management programme: Transformation during COVID-19

Background & objectives: Haemophilia is a debilitating bleeding disorder with significant comorbidities affecting the quality of life. In India, the management of these individuals is still limited to on-demand institutional treatment with coagulant factors. In this study, we highlighted the problems faced by these patients in the COVID-19 period due to nationwide lockdown. Methods: A retrospective study was done to ascertain the trend in the number of patients with haemophilia A and B visiting the hospital, those succumbing to haemophilic complications and indications for factor requirement in the pre-COVID (October 2019-March 2020) and during the COVID-19 period (April-September 2020). Representative cases with unusual complications were described along with significant challenges faced in providing standard care of treatment to these individuals due to the COVID-19 pandemic. Results: A total of 818 and 162 individuals with haemophilia A and B, respectively, were registered with the department. The overall number of patient visits to the hospital significantly reduced from an average of 6.9 outpatient department (OPD) visits per patient in the pre-COVID-19 period to an average of 3.9 OPD visits per patient and admissions reduced to 50 per cent during the COVID-19 period. This led to a reduction in utilization of factors VIII and IX except VIIa for haemophilia with inhibitors. There was no factor utilization for elective surgeries during the COVID-19 period. A total of eight patients succumbed to haemophilia-related complications during the COVID-19 period due to delay in reaching the hospital. The challenges faced in the management of three cases with musculoskeletal bleeds, one case with scrotal haematoma and one with haemothorax during the COVID-19 period were also highlighted. Interpretation & conclusions: COVID-19 pandemic has unveiled the need for on-demand home treatment with coagulant factors and has also brought to light the existing need for primary prophylaxis, especially for younger individuals with haemophilia.

Epistaxis in a Pediatric Outpatient Clinic: Could It be an Alarming Sign?

Abstract Introduction Epistaxis is a common presentation among children. Objective To investigate the suitability of a simple tool of assessment for patients with epistaxis that could guide in subgrouping those with possible bleeding tendencies who may need further assessment. Methods Children who presented to a tertiary outpatient clinic with epistaxis of an unknown cause were recruited. They underwent thorough clinical assessment and answered the pediatric bleeding questionnaire and the epistaxis severity score. All patients underwent complete blood count as well as coagulation profile, and confirmatory diagnostic tests were performed as needed. Results Among the 30,043 patients who presented to the outpatient clinic over a year, 100 children had epistaxis, with an estimated annual frequency of 1 in 300. A total of 84% of the patients were younger than 12, and nearly half of these were younger than 6 years. Seventy-six patients had recurrent epistaxis, and 12 had systemic comorbidities. A significant higher percentage of patients presented with epistaxis in the hot months of the year. A total of 90% of the patients presented anterior bleeding, and the majority were treated with nasal compression only. Forty-three patients presented with epistaxis only; 37 of them were diagnosed as idiopathic epistaxis, and 6 had local causes. Fifty-seven patients presented with other bleeding manifestations, 47 of whom had a definite bleeding disorder and the other 10 had undiagnosed bleeding tendency. Those with other bleeding manifestations showed a higher frequency of positive family history of epistaxis; of being referred from a primary care physician; of having alarming low platelet count, and of presenting less seasonal variability. A bleeding score ≥ 2 showed significant value in suspecting an underlying systemic pathology as a cause of epistaxis. Conclusion The pediatric bleeding questionnaire is a useful and simple tool in the identification of pediatric patients who need further diagnostic testing to detect any underlying bleeding tendency.

Haemophilia care and outcome in a major haemophilia treatment centre in Malaysia

@#Introduction/Objective: The management of potential treatment-related complications and bleeding events in haemophilia is challenging in developing countries. Providing optimal care among these patients improve their quality of life (QOL) and life expectancy. This study explores the demographic characteristics and treatment outcome in a major haemophilia treatment centre in Malaysia. Materials and Methods: A total of 260 patients were recruited in this retrospective cross-sectional analysis. Clinical data, including treatment regimens and outcome, were collected and analysed. Results: A total of 211 patients were diagnosed with haemophilia A (HA) (severe disease, 72.5%) and 49 patients had haemophilia B (HB) (severe disease, 65.3%). The median age was 31 (IQR;2-84) years. Majority of the patients had at least one episode of musculoskeletal bleeding since diagnosis. The mean annual bleeding event (ABE) was 4.91 (SD±6.07) in 2018. Target joints were identified in 80.4% of the patients. Chronic arthropathy and synovitis collectively accounted for more than half of the musculoskeletal complications. 30.1% of the patients had contracted hepatitis C with less than half received treatment. Thirty-one patients (16.8%) with severe haemophilia developed inhibitor and 12 patients successfully underwent immune tolerance induction. More than three-quarters of the severe haemophilia patients were treated with factor concentrate prophylaxis. The mean prophylaxis dose for HA and HB were 41.3 (SD±19.1) and 48.6 (SD±21.5) IU/kg/week, respectively. In patients with severe disease, prophylaxis significantly reduced the ABE (5.45,9.03;p=0.005). Conclusion: The importance of utilising a low to moderate dose regimen as prophylaxis in haemophilic patients is highlighted in our study. Future studies should include QOL assessment will further improve the management in haemophilia.

Screening and quantitative estimation of factor VIII inhibitors by Nijmegen-Bethesda assay in hemophilia a patient of Southern Odisha, India

Background: The current treatment of haemophilia is replacement of factor VIII or IX which is effective till development of inhibitor against factors. There has been no study on factor VIII inhibitors in Southern Odisha using Nijmegen朆ethesda assay. This study was planned with objectives to screen factor VIII inhibitors in hemophilia-A patients, to do quantitative estimation of it using Nijmegen-Bethesda assay and to explore factors associated with development of inhibitors. Methods: This cross-sectional study was carried out from September 2016 to August 2018 in Department of pathology, MKCG medical college, Berhampur. Haemophilia-A patients coming to MKCG medical college and registered Haemophilia-A cases under Haemophilia society of Berhampur were included. Patients denying consent and having multiple clotting factors deficiencies were excluded. 1.8ml blood was collected. Mixing study was done to screen factor VIII inhibitors and then in positive cases inhibitors level measured by Nijmegen-Bethesda method. All data were analysed using SPSS (version 16.0).Results: 70 cases of Hemophilia-A patients were studied. Majority (50%) were with severe hemophilia-A. 7 patients developed inhibitors where 3 were high and 4 were low responders. Inhibitor level ranged from 0.8 to 64 Nijmegen-Bethesda units. Patients with severe hemophilia A, more than 10 transfusions and who switched to receive recombinant FVIII from other blood products developed inhibitors which were significant.Conclusions: Severity of hemophilia, increase frequency of transfusion and switching of blood products significantly increases chances of inhibitor development and hence intensive inhibitor screening is needed in these cases. Quantification of inhibitor is needed to monitor treatment and to manage bleeding episodes effectively.

Análisis general del brote epidemiológico causado por los virus Zika y chikunguña en Colombia / General Analysis of the Epidemiological Outbreak Caused by the Zika and Chikungunya Viruses in Colombia / Análise geral do surto epidemiológico causado pelos vírus Zika e Chikungunya na Colômbia

Resumen: Los virus son agentes infecciosos, causantes de diversas enfermedades en los seres humanos, comportamiento demostrado, por ejemplo, con el brote de viruela en los nativos americanos que causó la muerte de miles de ellos en la época de la Conquista. En los últimos años, se ha reportado la reaparición de algunos padecimientos causados por virus en países tropicales, que amenazan con convertirse en pandemias. Padecimientos como las fiebres del Zika y el chikunguña han afectado a varios países de América del Sur, principalmente, Brasil, Perú y Colombia, donde se reportaron miles de contagios y algunos casos de desenlace fatal. Debido a la importancia del tema, se realizó una revisión crítica para evidenciar las características de los virus, las manifestaciones clínicas del contagio, estadísticas de los afectados y los tratamientos disponibles. Asimismo, se analizaron las acciones preventivas propuestas por la OMS y el Instituto Nacional de Salud (INH). Finalmente, se consultaron algunas propuestas en el desarrollo de vacunas, de donde se concluye que, a pesar de los significativos avances y cuantiosas posibilidades en fases clínicas, aún no hay ningún producto comercial para ninguno de los dos virus analizados, pero se proyecta tenerlos después de 2020.

Abstract: Viruses are infectious agents causing various diseases in humans; this behavior is demonstrated by, for example, the outbreak of smallpox in Native Americans that resulted in the death of thousands at the time of the Conquest. In recent years, the reappearance of some diseases caused by viruses has been reported in tropical countries, which threaten to become pandemics. Conditions such as Zika and chikungunya fevers have affected several countries in South America, mainly Brazil, Peru, and Colombia, where thousands of infections and some fatal outcomes were reported. Due to the importance of the matter, the characteristics of the viruses, clinical manifestations of the infection, statistics on those affected, and treatments available are critically reviewed. Likewise, the preventive actions proposed by the WHO and the National Institute of Health (NIH) are discussed. Finally, some proposals in the development of vaccines are checked to conclude that, despite the significant advances and considerable possibilities in clinical phases, there is still no commercial products for either of the two viruses analyzed, but they are planned for after 2020.

Resumo: Os vírus são agentes infecciosos que causam várias doenças nos seres humanos, esse comportamento pode ser demonstrado, por exemplo, com o surto de varíola que causou a morte de milhares de nativos americanos na época da conquista. Nos últimos anos, o reaparecimento de algumas doenças causadas por vírus tem sido relatado em países tropicais, emergindo a ameaça delas se tornarem pandemias. Doenças como a febre zika e a febre Chikungunya afetaram vários países da América do Sul, principalmente o Brasil, o Peru e a Colômbia, onde milhares de infecções e alguns casos de resultados fatais foram relatados. Devido à importância desse tema, realizamos uma revisão crítica para mostrar as características dos vírus, as manifestações clínicas da infecção, as estatísticas sobre os afetados e os tratamentos disponíveis. Além disso, as ações preventivas propostas pela Organização Mundial da Saúde (OMS) e pelo Instituto Nacional de Saúde (INH) também foram analisadas. Finalmente, a partir da consulta de algumas propostas no desenvolvimento de vacinas, concluímos que, apesar dos avanços significativos e das possibilidades consideráveis nas fases clínicas, ainda não existe nenhum produto comercial para enfrentar os vírus analisados neste estudo. Porém, depois de 2020, é provável que algum produto seja disponibilizado no mercado.

Rare post-operative complications in a previously undiagnosed Congenital Factor X deficiency patient

Factor X (FX) deficiency is a rare autosomal recessive congenital bleeding disorder. The clinical presentation is among the most severe among the rare coagulation defects. Thus, majority of diagnosed patients will receive factor replacement therapy before surgical manipulation. However, the diagnosis of FX deficiency may be overlooked because it is a rare entity. This is a case report of a 15-year-old male patient who was diagnosed with FX deficiency after developing post-operative complications. With regular fresh frozen plasma infusion given, the patient responded well and recovered. However, had he been diagnosed earlier pre-operatively, the post-operative complication could have been prevented. Therefore, pre-operative coagulation screening should be performed in patients with significant bleeding history in both emergency and elective situations to prevent surgical morbidity related to post-operative bleeding.

A Clinico-Pathological Study of Hemophilia in Rural Set up of Karnataka.

Haemophilia is the most common inherited coagulation disorders, with X linked recessive inheritance, affecting the males while females are the carriers of the disease. Haemophilia A and Haemophilia B are the commonest form of Haemophilia encountered and they result from defect in Factor VIII and Factor IX gene respectively. A clinico hematological study with suspected coagulation disorder was conducted over a period of two years, from June 2008 to July 2010. Of the 76 patients visited OPD, based on clinical presentation and family history, 50 cases were categorized as Hemophilia A or B after laboratory investigations. Majority (41) of the cases were categorized as Hemophilia A & only 7 cases were Hemophilia B. The mean age group of the patients was 2.87 years with an age of onset ranged between 3rd day to 5.6 years. All the cases were males and only a very rare case of female Hemophilia patient was noted. Thirty five (52.23%) patients had positive family history of bleeding. In 12 families (18.75%) there had been consanguineous marriage. Spontaneous bleeding was the predominant presenting symptom followed by Hemarthrosis and prolonged post traumatic bleeding. The knee joint was most commonly involved. Coagulation screening tests showed that 60% patients had prolonged activated partial thromboplastin time (APTT) with an average of 88 seconds. Mixing and substitution studies were very useful in distinguishing between Hemophilia A & B. Factor assays in both Hemophilia A & B showed 66% of cases with severe factor deficiency, 26% moderate and 8% with mild deficiency. In the present study an effort is made to explore, elucidate and document the clinico haematological correlation of Hemophilia in this part of Karnataka.

Disorders in Hemostasis

Neonatal bleeding is a common problem encountered in nursery rooms or neonatal intensive care units, especially among premature infants. Furthermore, owing to recent remarkable improvement of neonatology, survival rates of preterm neonates have increased; hence, neonatal bleeding cannot be emphasized enough. Since the total blood volume of neonates is small, bleeding can be one of the causes of morbidities and mortalities. Therefore, rapid diagnosis and immediate therapy is urgently needed. The patient's medical history including a familial history of a bleeding disorder or of a previously affected infant who suffered from bleeding along with maternal and neonatal drugs can provide important diagnostic clues. Presence of bleeding with or without petechiae and ecchymoses in a healthy term or late preterm infant with thrombocytopenia but normal prothrombin time and activated partial thromboplastin time strongly suggests a congenital bleeding disorder. For a sick infant who is bleeding from multiple sites, an acquired disorder such as disseminated intravascular coagulation is suspected. Intracranial hemorrhage in term or late preterm infants without a history of birth trauma is highly suggestive of coagulation disorders. The purpose of this review is to summarize recent advances in diagnostic methods is as well as basic concepts of neonatal hemostatic disorders. First, an outline of background information will be presented followed by a discussion of primary and secondary hemostatic disorders as well as inherited and acquired disorders.

Prevalence and spectrum of von Willebrand disease in Eastern Uttar Pradesh.

Context: Von Willebrand disease is the most common inherited bleeding disorder with a prevalence of ≈ 1% in the general population. Studies available from India are limited, showing a prevalence of ≈ 10% of vWD amongst inherited bleeding disorders. Aims: This study aims to know the prevalence and subtypes of vWD in patients presenting with various bleeding manifestations to university hospital. Settings and Design: We investigated 840 patients presenting with bleeding manifestations in the period from August 2004 to August 2008 for bleeding disorders. Materials and Methods: Tests performed for the diagnosis of vWD included platelet count, bleeding time (BT), prothrombin time (PT), activated partial thromboplastin time (APTT), Factor VIII:C assay, von Willebrand Factor Antigen assay and Ristocetin-induced platelet aggregation. Results: Amongst 840 patients, 230 (27.38%) had inherited bleeding disorder. Out of these, 40 (17.39%) patients were identified as vWD. Type 1 in 17 (42.5%), Type 2 in 11 (27.5%) and Type 3 vWD was present in 12 (30.0%) patients. Patients' age ranged from five months to 45 years, with 17 males and 23 females. Positive family history was seen in 12 patients (30%). Muco-cutaneous bleeding was the most common presentation. Menorrhagia was present in 100% women of reproductive age group, and hemarthrosis was seen in two male patients. Conclusions: We felt that Type I vWD with infrequent and mild bleeding episodes remain undiagnosed either because of unawareness of the disease in society or due to paucity of diagnostic facilities available in our country. Therefore, an awareness program along with enhancement of diagnostic facilities for vWD is required in our country to identify these patients for proper management thus avoiding hemorrhagic complications.

Riesgo de sangrado y complicaciones ginecoobstétricas en una paciente con déficit de factor XIII. Presentación de un caso y revisión de la literatura / Risk of bleeding and gyneconstetric complications in a patient with factor XIII deficiency. Case report and literature review

La deficiencia de factor XIII de la coagulación es un trastorno raro de la coagulación, entre los que están la afibrinogenemis y los de factor II, V, V+VIII, VII, X y XI. Estos son son anormalidades de la hemostasia con herencia autosómica recesiva; su prevalencia es de 1 en 500,000 a 2 millones de personas. Por su rareza, tipo y severidad de las hemorragias y lo poco claro que es el defecto molecular y su manejo son un reto diagnóstico y terapéutico. Para algunas de estas deficiencias no existen concentrados del factor de coagulación implicado disponibles, por lo que es necesario utilizar derivados sanguíneos o medicamentos hemostáticos alternativos, lo que puede generar complicaciones, en ocasiones fatales; estas complicaciones pueden ser minimizadas evaluando en cada caso el riesgo de sangrado o de trombosis seleccionando como tratamiento alternativas diferentes a los derivados de la sangre, o incluso no administrando tratamiento en los episodios hemorrágicos leves. En este artículo se describe el caso de una paciente con diagnóstico de déficit de factor XIII que debutó con hematuria y complicaciones ginecoobstétricas; hay historia familiar de consanguinidad y de déficit de factor XIII; recibió manejo con crioprecipitados y antifibrinolíticos y profilaxis con crioprecipitados durante el transcurso de su segundo embarazo, lográndose un producto a término con un parto por cesárea sin complicaciones hemorrágicas o trombóticas.

The factor XIII deficiency is a rare clotting disorder, among which are afibrinogenemia and factor II, V, V+VIII, VII, X and XI ones. These are hemostasis anomalies with autosomal recessive herency; its prevalence is 1 in 500,000 to 2 million people. For its rarity, type and bleeding severity, and its unclear molecular defect, this is a challenge diagnostic and therapeutic effort. The are not clotting factor concentrates available, reason what it is necessary to use blood derivatives or alternative hemostatic agents, which can generate complications, sometimes fatal; these complications can be minimized assessing in each case its bleeding or thrombosis riks to select alternatives to blood or not to do treatment in mild bleeding episodes. This paper describes a case of a women diagnosed with XIII deficiency that began with hematuria and gynocobstetric complications; she received plasma concentrates and antifibrinolytic agents, plus prophylaxis with these products in her second pregnancy, achieving a at term product by caesarean section without any complications.

Battered child: A case report.

A four year old Muslim female child came with alleged h/o fall in school with bluish discoloration around the left eye, neck, back and limbs. The paediatrician suspected this to be a case of bleeding disorder because of family history as her elder sister was suffering from platelet disorder. Finally it turned out to be a physical assault case with no any ill or evil intention.