Can Hemophilia Impact on the Oral Health Conditions of Children and Adolescents? A Systematic Review and Metanalysis

Abstract Objective: To analyze if the oral health conditions in children and adolescents are associated with hemophilia (PROSPERO-42020168192). Material and Methods: The search strategy was performed in PubMed, Scopus, Lilacs/BBO, Web of Science, Cochrane, and Grey literature databases. Two independent researchers assessed the risk of bias in these studies by the Newcastle-Ottawa Scale. For the meta-analysis, the clinical conditions data were extracted as numerical variables according to their indexes, such as dental caries experience (dmft/DMFT), gingival condition (Modified Gingival Index - IGM), and oral hygiene (Plaque Index - PI). The quality of the evidence of the meta-analysis was evaluated by the GRADE tool (GRADEproGDT). Results: From a total of 431 studies, 27 were included, and 10 were included in the meta-analysis. The studies presented a moderate risk of bias, ranging from 2 to 7 points. The dental caries experience in primary (-0.62; CI95%: -1.68-0.43) and permanent dentitions (-0.05; CI95%: -0.69-0.59), gingival condition (-0.12; CI95%: -0.27-0.03), and oral hygiene (0.36; CI95%: -0.06-0.77) did not differ between the groups. Conclusion: Based on studies with very weak evidence, there were no differences in the oral health conditions of children and adolescents with and without hemophilia (AU).

A homozygous female hemophilia A.

BACKGROUND: Hemophilia A (HA), being an X-linked recessive disorder, females are rarely affected, although they can be carriers. AIMS: To study the mutation in F8 gene in an extended family with a homozygous female HA. MATERIALS AND METHODS: All the seven affected members (six males and one female) were initially screened by Conformation Sensitive Gel Electrophoresis (CSGE) and direct DNA sequencing. RESULTS: A homozygous missense mutation c.1315G>A (p.Gly420Ser) was identified in exon 9 of F8 gene in homozygous state in the affected female born of 1° consanguinous marriage and in all the affected male members of the family. Her factor VIII levels was found to be 5.5%, vWF:Ag 120%. CONCLUSION: In India, as consanguineous marriages are very common in certain communities (up to 30%), the likelihood of encountering female hemophilia is higher, although this is the first case of HA out of 1600 hemophilia families registered in our Comprehensive Haemophilia Care Center. Genetic diagnosis in such cases is not necessary as all the male children will be affected and daughters obligatory carriers.

Reliability of agglutination test to detect alloantibodies in patients with repeated blood transfusion

Blood transfusion is an integral part in the management of sickle cell disease patients. Allogeneic blood transfusion is a form of temporary transplantation. A recipient often mounts an immune response to the donor antigens resulting in various clinical consequences including delayed hemolytic transfusion reactions. Delayed reaction is often seen in individuals who have received repeated transfusion of ABO compatible blood that incompatible for other blood group antigens because of minor allelic difference stimulate the production of IgG antibodies. In the patients who have sickle cell disease the majority of tests may have low sensitivity and in turn may fail to show the autoantibodies. This study has been conducted for detection of allo-antibodies in patient with sickle cell anaemia and hemophilia who received repeated blood transfusions using newly introduced test system; the DiaMed-Immuno-Diffusion microtyping system. Samples were collected randomly from 60 patients with repeated blood transfusions. Micro column gel test as well as agglutination method were performed for all samples. All the results were analyzed using Statistical Packages of Social Sciences [SPSS]. This test provides clear and stable reactions that improve result interpretation. It proved to be more sensitive than the conventional tube agglutination technique as it captures agglutinate in a semi solid medium and on the other hand it has the capacity to detect unexpected antibodies. This in turn enhances visibility of agglutination compared to the traditional Tube techniques

Comparative Measurement of FVIII Inhibitors in Hemophilia A Patients Using ELISA and the Bethesda Assay / 대한진단검사의학회지

Factor VIII inhibitors are produced during or after coagulation factor VIII (FVIII) therapy in hemophilia A patients. These inhibitors are usually detected by a modified Bethesda assay or an enzymelinked immunosorbent assay (ELISA). In this study, we used the Bethesda assay to determine the incidence of FVIII inhibitors in 75 fresh plasma samples obtained from 50 hemophilia A patients, and then used ELISA and the Bethesda assay to determine the titres of these inhibitors after the samples had been frozen and thawed. The samples from the screening Bethesda assay were centrifuged and stored at -70degrees C in accordance with the assay guidelines. Subsequently, these samples were thawed and analyzed using ELISA and the Bethesda assay. The incidence of inhibitors in hemophilia A patients was 20.0%. Among the 35 inhibitor-positive samples identified in the screening Bethesda assay, 16 were positive in ELISA while only 4 were positive in the repeated Bethesda assay. In this study, the ELISA technique showed a higher sensitivity than the Bethesda assay in the detection of FVIII inhibitors in samples that were subjected to freezing and thawing procedures; this was because the Bethesda assay could not identify the FVIII inhibitors that were degraded after freezing and thawing.

Plasma protein variations in hemophiliacs receiving factor replacement therapy.

OBJECTIVE: Post transfusion manifestations and its affiliated factors are vital to understand in a disease like hemophilia where multi-transfusions are given to the patients. METHODS: To investigate the implications of factor replacement therapy on plasma proteins, 52 hemophiliacs and 68 carrier females were examined for 12 plasma proteins using various electrophoretic techniques. RESULTS: Severe hemophiliacs showed raised levels ( p< 0.05) of a2 M, IgG and Albumins where values were found to be 4.78 +/- 0.865 g/l, 21.48 +/- 3.38 g/l, 66.26 +/- 11.92 g/l respectively at 95% confidence intervals however, controls and carriers showed trivial variations. CONCLUSION: Juxtaposing the dissimilarities of 12 plasma proteins in carriers, controls and hemophiliacs, it has been gleaned that factor replacement therapy do play role when seen in severe hemophiliacs with raised levels.

Relation of factor VIII and IX inhibitors with ABO blood groups in 150 patients with haemophilia A and B

Many investigations have proved relations between ABO blood groups with some diseases and factor VIII and von willebrand level in plasma. In this study we investigated a relation between ABO blood groups and factor VIII and IX inhibitors in 102 patients with haemophilia A and 48 patients with haemophilia B. The assay of inhibitor was done by Bethesda method. There were no relation between ABO blood groups and factor VIII and IX inhibitors

Prevalence of hepatitis C virus infection and HCV genotypes among hemophiliacs in the State of Bahia, Northeastern Brazil: analysis of serological and virological parameters

O objetivo deste estudo foi analisar parâmetros sorológicos e virológicos em hemofílicos no Estado da Bahia. O anti-VHC foi investigado por ELISA em uma coorte de 268 hemofílicos A/B sob acompanhamento em uma unidade de referência do Estado da Bahia. A viremia do VHC e genótipos foram determinados em um subgrupo de 66 hemofílicos soropositivos para o anti-VHC. A soroprevalência do anti-VHC entre os hemofílicos foi de 42,2% (IC 95% 36,5-48,1) e foi associada significativamente (p<0,05) a idade >10 anos, presenca de anticorpos antifator VIII/IX e outros marcadores sorológicos de infeccão. Nenhum dos hemofílicos com idade inferior a 5 anos foram anti-VHC positivos. A viremia foi detectada em 77,3% (51/66), sendo o genótipo 1 do VHC (74%) o mais prevalente, seguido pelos genótipos 3 (22%) e 2 (4%). Nossos resultados indicam que a prevalência do VHC é ainda alta entre os hemofílicos, muito embora a transmissão não tenha sido observada entre os menores de 5 anos.

Treatment of patients with haemophilia and inhibitory antibodies.

The development of inhibitory antibodies is a complication which arise in approximately 10% of patients with haemophilia A. The underlying genetic mutation is the single most important predisposing cause, although other risk factors have been identified. Periodic screening for inhibitors is a vital aspect of haemophilia care. The consequences of inhibitor development are very significant in terms of morbidity and cost. Several agents are now available for control of bleeding, but these are often very expensive. The most useful agents include recombinant activated factor VII, prothrombin complex concentrates and porcine factor VIII. It is possible to suppress antibody production with immune tolerance, which is successful in approximately 85% of cases and relapse is rare.

Epidemiologia molecular do vírus da hepatite C (VHC) na cidade de Salvador-BA / Molecular epidemiology of hepatitis C virus (HCV) in the city of Salvador-BA

O VHC é um vírus RNA (VHC-RNA) hepatotrópico associado com um alto risco à cronificação, cirrose e carcinoma hepatocelular. Nos últimos anos, técnicas moleculares para a detecção do VHC-RNA e a genotipagem têm se tomado ferramentas indispensáveis para a avaliação de pacientes com hepatite crônica C. O objetivo principal foi realizar um estudo de epidemiologia molecular para determinar a prevalência de infecção e a distribuição dos genótipos do VHC em uma amostra de base populacional e em populações sob risco. Para o estudo de base populacional foram coletados 1308 amostras de soros de indivíduos selecionados através de uma aleatorização estratificada da população de Salvador (amostra do Programa Bahia Azul). Para o estudo em grupos sob risco, foram coletadas amostras de soro de 127 pacientes com anticorpo anti- VHC positivo provenientes do HUPESIUFBA, de 66 hemofilicos da HEMOBA e de 97 hemodialisados de sete clínicas de Salvador, voluntários na pesquisa. A prevalência de infecção pelo VHC foi estimada a partir da avaliação dos resultados de soroprevalência do anticorpo anti-VHC obtidos através do ELISA de 2ana. geração e confirmação pelo RIBA e/ou RT-PCR, método in-house. Quando possível, foi colhida uma segunda amostra de soro para confirmação dos resultados de RIBA ou RT-PCR negativos. Nas amostras VHC-RNA positivas foi realizada a genotipagem através da R T - PCR, utilizando-se primers genótipo-específicos dirigidos contra a região do core ou através da análise do RFLP da região 5'UTR do VHC-RNA. A prevalência de infecção pelo VHC na população em geral de Salvador, em hemofilicos e hemodialisados foi de 1,5%, 32,6% e 7,1 %, respectivamente. A infecção na população em geral foi associada com idade superior a 20 anos (p<0,05), 12 ou mais anos de escolaridade p<0,01), nível de renda mediano (p<0,05) e residência no bairro da Barra (p<0,05), uma vizinhança de classe média-alta da cidade de Salvador...

Hereditary combined coagulation factor V and factor VIII deficiency: report of two Indian families from Varanasi.

Hereditary deficiencies of blood coagulation factors usually involve a single protein defect. Herewith we are describing clinical features and laboratory approach for the diagnosis of combined coagulation factor V/VIII deficiency which we encountered in 3 patients from 2 unrelated Hindu families of Varanasi.

An unusual case of haemophilia--a case report.

Haemophilia in a female is very rare. We report a case of haemophilia in a female with a male sex chromosome pattern.

Clinicohaematological profile of two cases of inhibitors to factor VIII.

Bleeding is a common manifestation of inherited and acquired disorders of haemostasis. Acquired disorders of haemostasis can be of varied etiology like liver disease, DIC, haemorrhagic disease of newborn and inhibitors to coagulation factors. Inhibitors to coagulation factors are an unusual cause of bleeding which can be superimposed on inherited factor deficiencies or sometimes resembles them. The clinical and haematological profile to two cases of factor VIII inhibitors are being presented here, one of which was a known haemophiliac receiving factor VIII therapy and another was a elderly lady with no other apparent underlying disorder. Hence any case of factor VIII deficiency who becomes refractory to factor VIII replacement therapy or those who are detected to have factor deficiency late in life should be investigated for inhibitors.

Doenças hemorrágicas no atendimento odontológico em crianças / Hemorrhagic diseases in pediatric dentistry

O atendimento odontológico a pacientes com doenças hemorrágicas confere grande responsabilidade ao profissional, para a identificaçäo do problema e adequada atuaçäo, numa atitude multidisciplinar com os demais membros da equipe de saúde. Este aspecto é bem enfatizado na prática da Odontopediatria, em que o bebê ou criança pode estabelecer um primeiro contato sem o diagnóstico prévio de qualquer distúrbio na hemostasia. Por esta razäo, as autoras efetuaram uma revisäo da literatura sobre as patologias mais frequentes observadas, subordinadas ao tema abordado, com base em levantamento piloto das crianças atendidas no setor de Odontologia da Fundaçäo Hemope

Interleukin-2 restores natural killer activity inhibited by sera from HIV + Hemophilic patients

Natural killer (NK) activity is impaired in patients with positive serology for the human immunodeficiency virus (HIV). We previously found an inhibitory effect of sera from hemophilic (He) HIV+ patients on normal NK activity. In the present study, we have further characterized this effect by studying its reversibility, temperature and time incubation dependence. Since interleukin 2 (IL-2) is able to enhance NK levels, we analized the capacity of this lymphokine to reverse the effect of He HIV+ sera. We found that when IL-2 activation of NK activity occurred simultaneously or after HIV+ serum-treatment, a significant restoration of NK function was observed. In contrast, preincubation with IL-2 did not affect the inhibitory effect exerted by HIV+ sera.