Comparative analysis of chromogenic vs clot.based one stage APTT assay for determination of factor VIII level.

BACKGROUND: In the laboratory, factor VIII can be measured by three different methodologies, such as one-stage clotting assay, two-stage clotting assay, and chromogenic assay. These assays differ in ease of use, variety of reagents available, sensitivity to mild hemophilia A, and interference from lupus anticoagulants (LACs). Certain factor VIII gene mutations can cause discrepancy in results between one-stage activated partial thromboplastin time (APTT) and chromogenic assays. MATERIALS AND METHODS: The coagulometer for factor VIII assay is Sysmex CS-5100. All data were expressed as mean ± standard deviation (SD). RESULTS: A total of 135 cases were studied. Of these, 100 cases were of mild hemophilia A diagnosed by molecular genetics and, 15 cases were positive for LAC, which were confirmed by dilute Russell Viper venom test. Clot-based one-stage APTT assay showed 65% sensitivity and 80% specificity in diagnosing mild hemophilia A cases and out of 15 LAC cases, it showed false positivity in five cases. Chromogenic assay showed 85% sensitivity and 90% specificity in diagnosing mild hemophilia cases and was 100% specific in excluding LAC cases. CONCLUSIONS: One-stage APTT assay is the most commonly used test for determining factor VIII levels but chromogenic assay are considered as the gold standard and recommended as the reference method by European Pharmacopoeia and ISTH subcommittee. Mild hemophilia A patients with missense mutations show discrepancy between the one-stage clot-based APTT assay and chromogenic assays for determination of factor VIII level and this can lead to misdiagnosis or misclassification of mild hemophilia A. Therefore, it is recommended that both the assays should be used in the evaluation of mild hemophilia cases.

Discrepant Hemophilia A: An Underdiagnosed Disease Entity.

OBJECTIVES: The term discrepant hemophilia A (DHA) denotes the discrepancy between factor VIII activity (FVIII:C) measured by different assay methodologies in patients with nonsevere hemophilia A (HA). The objective was to review the characteristics and the current understanding of mechanisms contributing to assay discrepancy in DHA. METHODS: Characteristics of the DHA patients treated were examined by retrospective chart review. In addition, a literature review was performed to determine the current understanding of DHA. RESULTS: Three cases of DHA were diagnosed based on bleeding phenotype: 2 cases represented missed diagnoses of HA, and 1 represented misclassification of hemophilia severity. The revised diagnosis and classification of hemophilia directly affected clinical management. Review of the literature identified 18 articles with an estimated pooled prevalence of 36% (95% CI, 23%-56%; I2 = 85%; P < .01) among nonsevere HA. Furthermore, literature indicated that DHA is a feature of how different FVIII gene mutations affect FVIII:C activity within different assay methodologies. CONCLUSIONS: Our experience and literature review suggested that DHA is not only a laboratory phenomenon-it can affect clinical management in a subset of patients. A high index of suspicion for DHA is necessary while evaluating bleeding patients and/or classifying nonsevere HA.

Analysis of Sasang Constitutional Medicine as an Optimal Preventive Care Strategy for Hemophilia Patients.

Introduction. Medical improvements have allowed hemophilia patients to anticipate an increased quality of life and life expectancy similar to that of the general population. Analysis of the potential disease symptoms of hemophilia patients based on a survey of Sasang Constitutional Medicine (SCM) is important for optimal preventive care and adjunctive therapy to avoid life-threating complications. AIM: To predict potential disease symptoms from the viewpoint of SCM as a preventive care strategy for hemophilia patients. METHODS: Sixty-one hemophilia patients responded to a survey on Sasang constitutional classification, hemophilia disease pattern, and original symptoms. RESULTS: In terms of SCM type, the 61 of hemophilia patients included 37 Tae-Eum (60.7%), 18 So-Yang (29.5%), and 6 So-Eum (12.5%). Hemophilia was found to be higher in Tae-Eum type and lower in So-Yang and So-Eum types, while considering the distributional rate of Korean Sasang types. Most of the patients with Tae-Eum type had Joyeol or Ganyeol. Furthermore, the incidences of diabetes and high blood pressure were greater in Tae-Eum type than in those of other types. CONCLUSION: In order to increase the quality of life and overall life expectancy, hemophilia patients with Tae-Eum type should be treated through management according to SCM along with medicine against hemophilia as long-term preventive care. Diabetes and high blood pressure should be regularly monitored in patients with Tae-Eum type.

Major and Minor Classifications for Surgery in People With Hemophilia: A Literature Review.

Agents that control bleeding and the usage of bypassing agents have made surgery an option to consider in people with hemophilia. However, the lack of consistent definitions for major or minor surgery may lead to inconsistencies in patient management. This literature review has evaluated how surgical procedures in people with hemophilia were categorized as major or minor surgery and assessed the consistency across publications. After screening 926 potentially relevant articles, 547 were excluded and 379 full-text articles were reviewed. Ninety-five articles categorized major or minor surgical procedures; of these, 35 publications categorized three or more major or minor surgical procedures and were included for analysis. Seven (20%) publications provided varying criteria for defining major or minor surgery, five of which defined surgery according to the level of surgical invasiveness. Across all 35 publications, there was considerable variance in the categorization of major and minor surgical procedures and some overlap in surgical nomenclature (eg, type of synovectomy, arthroscopy, and central venous access device insertion/removals). The lack of consistent guidance when referring to major or minor surgery in people with hemophilia needs to be addressed. Clear and consistent definitions, achieved by consensus and promoted by relevant international hemophilia committees, are desirable, to provide guidance on appropriate treatment, to increase the accuracy of trial data and may confound the interpretation of surgical outcomes.

A comparison between MRI, sonography and Functional Independence Score in Haemophilia methods in diagnosis, evaluation and classification of arthropathy in severe haemophilia A and B.

Evaluation of joints in children with haemophilia is important in detecting abnormalities, staging their severity and following the effects of treatment. The aim of this study is to evaluate the correlation of FISH score (Functional Independence Score in Haemophilia) with the scores obtained by MRI and sonography for the diagnosis, evaluation and classification of arthropathy in severe haemophilia. In this cross-sectional study on 25 severe haemophilia patients, FISH, MRI and sonography procedures were performed in the elbow or knee joint. All patients' information, including age, type of haemophilia, affected joint, scores of MRI, sonography and FISH, dose of factor consumed, weight and prophylaxis protocol were collected and analysed. Among the 25 patients (age range of 11-70 years), 22 patients were haemophilia A and three patients were haemophilia B. Affected joints were right knee in 12 patients, left knee in nine and right elbow in four. There was only a statistically significant negative correlation between FISH and MRI Additive (A) scale (rs = -0.537, P = 0.006). Considering cartilage loss domain (related MRI A scale: 13-20), 20 patients (80%) were classified in this group with FISH scores ranged from 17 to 22. On the basis of our results, FISH scores in severe haemophilia patients were negatively correlated with MRI A scale. Also, it seems that a FISH score less than 22 could be considered as loss of cartilage; however, due to the small number of our patients, it needs further assessment in different populations.

Hemophilia and oral health.

OBJECTIVE: The aim was to overview the oral health aspects in hemophilia patients. MATERIAL AND METHODS: An electronic search of Medline (Pub Med), Cochrane, SSCI (Social Citation Index), SCI (Science Citation Index) databases from 1982 to the present, using the following search words: hemophilia, oral health, dental caries, dental caries prevalence, gingivitis, periodontitis, primary dentition, permanent dentition, dental treatment and review, was performed. The search yielded 196 titles and abstracts on chosen words. All articles were full-text reviewed and 40 of publications were included. RESULTS: Nowadays coagulation factor abnormalities are the most common of inherited bleeding disorders, but occur much less frequently approximating 10000-50000 male births than acquired coagulation defects. Von Willebrand disease, Hemophilia A and Hemophilia B account for 95-97% of all coagulation deficiencies. Hemophilias A and B are subdivided according to the factor's activity levels in the blood: mild, moderate or severe. The two main oral diseases affecting patients with hemophilia are the same as for the rest of population, i.e. dental caries and gingivitis/periodontitis. Only a few studies concerning oral health aspects in hemophilia patients were carried out. Some controversy exists concerning caries prevalence in both primary and permanent dentitions in children with hemophilia. People with congenital hemorrhagic diatheses constitute a very small proportion of the total population. Due to that fact treatment of such patients becomes a challenge to the most of dentists due to the fact that most of them have no experience in dealing with dental problems in such patients. CONCLUSION: There is a lack of epidemiological studies in oral health status of hemophilia patient.

Hemophilia a and hemophilia B: different types of diseases?

Hemophilia A and B are traditionally considered clinically indistinguishable; however, differences in bleeding frequency, clinical scores, use of prophylaxis, and need for orthopedic surgery have been reported, suggesting that the bleeding tendency associated with factor IX deficiency may be less severe with consequent better outcomes in the long term.Hemophilia A and B show their own peculiar aspects, not only in terms of epidemiological and clinical features, including inhibitor incidence and associated symptoms, but also with respect to molecular defects. The type of factor VIII/IX mutation is a major determinant of the bleeding tendency as well as of the risk of inhibitor formation; thus, there is a biological plausibility behind the different clinical expression of these two forms of congenital hemophilia. The distinction of various bleeding phenotypes in hemophilia has considerable therapeutic implications; therefore, further research in this field is required to optimize treatment regimens.

[Diagnosis of mild hemophilia A made by massive intraabdominal bleeding in a 13-year-old boy].

We report a 13-year-old boy who had massive intra-abdominal bleeding without a history of bleeding episodes or traumatic cause of bleeding. The patient underwent surgical treatment because bleeding was not controlled after treatment with tranexamic acid and transfusions including fresh-frozen plasma. Bleeding was traced to the lower left lobe of the liver. The mother's side of the family had a history of bleeding episodes in the boy's grandfather, great uncle, and son of a great aunt. A low level of plasma factor VIII coagulant activity (22%) led to a diagnosis of mild hemophilia A. Compared with severe hemophilia, mild hemophilia is more difficult to diagnose because bleeding episodes are less frequent. Most cases are found after incidental trauma or uncontrolled surgery-related bleeding, there is rarely a family history of hemophilia and activated partial thromboplastin time is normal or slightly prolonged. However, bleeding episodes in mild hemophilia may result in excessive, sometimes life-threatening hemorrhage and require early diagnosis and replacement treatment with adequate amounts of factor VIII, as in severe hemophilia.

Bleeding disorders seen in the dental practice.

Dentists may encounter patients with various types of bleeding disorders in their daily practice. Initial recognition of such bleeding disorders and their possible systemic causes, as well as knowing when to refer those cases to secondary care, plays a crucial and important role in reducing potential complications and negative side-effects. This article will give an account of the most common bleeding disorders that dentists might find in their daily dental practice. This will be followed by another article that will cover the management of congenital and acquired disorders found in the dental practice.

Clinical severity of haemophilia A: does the classification of the 1950s still stand?

The classification of haemophilia originates from 1950s and has been adopted unchallengedly by the ISTH in 2001. The aim of this study was: does the current classification compare onset of bleeding and age at first treatment, as well as annual joint bleeding frequency according to baseline FVIII activity? Data on age and reason of diagnosis, onset of treatment, onset of bleeding and bleeding frequency from 411 patients with haemophilia A born after 1970 were collected. Data were analysed according to base-line FVIII activity levels. Age at diagnosis, onset of bleeding and start of treatment according to FVIII activity were compared with the current classification. Overall, the distinction between severe and non-severe haemophilia was clear. The distinction between mild and moderate haemophilia was more difficult, mostly due to the wide variability in the group of patients with moderate haemophilia. Patients with severe haemophilia experienced their milestones like diagnosis, first treatment and joint bleed earliest, mostly as infants aged 0-3 years, whereas patients with moderate haemophilia reached these milestones around toddler age, 2-7 years, and patients with mild haemophilia reached them when they were in elementary school, around the ages of 5-14 years. This study confirms the clinical distinction between severe and non-severe haemophilia A. However, the group of moderate haemophilia patients showed a wide variability, warranting close follow-up and individualized treatment.

[Haemophilia A and haemophilia B. Are there relevant clinical differences?]. / Hämophilie A und Hämophilie B. Gibt es relevante klinische Unterschiede?

UNLABELLED: Haemophilia B (HB) was described in 1952 as a single disease for the first time. In comparison to haemophilia A (HA) the bleeding tendency seemed to be less severe. The aim of this study was to investigate this hypothesis in all patients with HA and HB treated in the haemophilia care center of the Vivantes Klinikum. PATIENTS, METHODS: All patients with severe HA and HB treated at the haemophilia care center were included. We evaluated the regimen of replacement therapy and factor concentrate consumption within the last 5 years (1/2004 to 12/2008). Intracerebral bleeds were analysed over the whole life span of the included patients. RESULTS: 111/181 patients with HA had the severe form and 12/34 patients severe HB. 4/12 patients with severe HB had a history of intracerebral bleeding in comparison to 5/111 patients with severe HA. 2/8 adult patients with severe HB used a prophylactic treatment with factor concentrates (mean consumption 1289 IU factor IX/kg BW/year) in contrast to 60/95 adult patients with HA (mean consumption 2109 IU factor VIII /kg BW/year). CONCLUSION: The data suggest a milder bleeding type of patients with severe HB in comparison to patients with severe HA but may be patients with severe HB are at higher risk for intracerebral bleeds.

[Haemophilia in the German risk adjustment scheme]. / Die Hämophilie im morbiditätsorientierten Risikostrukturausgleich.

Haemophilia presents a challenge to every risk adjustment scheme even if it uses diagnostical or pharmaceutical data. The German adjustment scheme developed by the Bundesversicherungsamt realizes fairly cost homogenous groups for many expensive diseases. It does not regard haemophilia. This holds true for the original classification system (grouper) from 2009 and for the improved classification procedure in 2010. The extreme peak costs that can originate from haemophilia cases can present a existential risk for small health plans. The chances to form cost-homogeneous subgroups of the haemophilia disease by more specific coding or other measures seem low because of the small number of cases affected by this disease. The complementary (re-)installation of a expenditure-oriented risk sharing is regarded as suited for improvement of the performance of the German risk adjustment scheme. This also corresponds to international experience and practice.