Relevance of Thrombophilic Risk Factors on Clinical Phenotype in Patients with Haemophilia A.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3981-3981
Author(s):  
Manuela Krause ◽  
Anika Hahn ◽  
Ferrial Peyvandi ◽  
Inge Scharrer
Keyword(s):  
Factor Viii ◽  
Healthy Subjects ◽  
Clinical Phenotype ◽  
Treatment Center ◽  
Study Group ◽  
Haemophilia A ◽  
Bleeding Tendency ◽  
Factor Viii Activity ◽  
On Demand ◽  
Bleeding Episodes

Abstract Introduction: By assuming the hypothesis, that a high coinheritance of genetic haemostatic abnormalities influences the clinical phenotype in patients with coagulation disorders, we analysed the bleeding tendency in adult patients with haemophilia A. Patients: A total of 49 patients with haemophilia A (severe:20 patients, moderate:12 patients, mild:17 patients; median age:44 years, range:22–78 years) and 80 sex-matched healthy subjects (median age:26 years, range:16–58 years) were studied in our haemophilia treatment center. Two of this patients have an inhibitor against factor VIII. 10 of 49 patients receive the factor VIII replacement therapy on demand. In addition to factor VIII activity, FV G1691A mutation and the FII G20210A variant were investigated. Results: In our study the prevalence of FV G1691A was significantly higher among patients 6/49 (severe:5, moderate:1) than among control subjects 2/80 [12% vs 2.5%; p=0.03 OR 4.9]. We found no differences in the FII G20210A variant in 2/49 patient (moderate:1, mild:1) as compared to 2/80 among controls [4% vs 2.5%; p=0.62 OR 1.63 ]. In none of our patients both defects together were identified. Within the last year the onset of bleeding was not different in thrombophilic haemophilia patients (n=8) 64 bleeding episodes/year compared with non-carriers (n=41) 284 bleeding episodes/year [8 vs 7 bleeding episodes/year/patient; p=0.72; OR 1.15]. Conclusion: The FV G1691A was found significantly more frequent in the thrombophilic haemophiliacs than in the general population. In our smal study group we could not demonstrate a relevant influence of the FV G1691A and FII G20210A on bleeding tendency. Further studies are needed to confirm whether FV G1691A and FII G20210A plays a role on the influence of bleeding tendency in haemophilia A patients.

Clinical Profile of Haemophilia in a Tertiary Care Hospital in Pune, Maharashtra, India

2021 ◽  
Vol 8 (15) ◽  
pp. 968-971
Author(s):  
Sadiq Yunus Mulla ◽  
Sachin Sitaram Pandit ◽  
Sachin Kisan Shivnitwar
Keyword(s):  
Factor Viii ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Factor Ix ◽  
Clinical Profile ◽  
Factor Viii Inhibitor ◽  
Haemophilia A ◽  
Care Hospital ◽  
Factor Viii Activity ◽  
Viii Inhibitor

BACKGROUND Haemophilia’s are X-linked hereditary blood clotting disorders due to deficiency of factor VIII (haemophilia A) or factor IX (haemophilia B) & also has identical clinical manifestations, screening tests abnormalities and sex-linked genetic transmission. Haemophilia’s result from defects in the factor VIII / IX gene that lead to decreased amount of factor VIII / IX protein, the presence of a functionally abnormal protein, or combination of both. Haemophilia A is a classic example of an X-linked recessive trait. The severity of their bleeding depends on their factor VIII activity level; and, rarely, a woman can have very low factor VIII activity, and present with symptoms of moderate or even severe haemophilia. We wanted to study the clinical profile of patients of haemophilia admitted in a tertiary care hospital. METHODS This is a cross-sectional study enrolling 60 known cases of haemophilia A & B admitted in wards & ICU / attending OPD of a tertiary care hospital. History was obtained in detail & thorough clinical examination was carried out. Precipitating factors for bleeding (spontaneous / minor trauma / major trauma / surgical operation / dental procedure / others), family h / o bleeding were studied in detail. RESULTS Of the total 60 cases of haemophilia, majority (49) of cases were of haemophilia A and 11 cases were of haemophilia B. In the study, majority (28.33 %) of cases belonged to 12 - 20 years age group and the most common presentation was haemarthrosis (61.67 %). 6 patients had factor VIII inhibitor antibodies and all of them were of haemophilia A. CONCLUSIONS Haemarthrosis is the most common clinical presentation of haemophilia and most common cause for haemarthrosis is spontaneous bleeding. Most common joint involved in bleeding was knee joint (target joint). Presence of factor VIII inhibitor antibodies specially in haemophilia A patients is not uncommon. KEYWORDS Haemophilia, Factor VIII, Factor IX

Effects of primary and secondary prophylaxis on the clinical expression of joint damage in children with severe haemophilia A

2008 ◽  
Vol 99 (01) ◽  
pp. 71-76 ◽  
Author(s):  
Karin Kurnik ◽  
Frauke Friedrichs ◽  
Susan Halimeh ◽  
Anne Krümpel ◽  
Christoph Bidlingmaier ◽  
...  
Keyword(s):  
Bleeding Episode ◽  
Joint Damage ◽  
Primary Prophylaxis ◽  
Secondary Prophylaxis ◽  
Outcome Variable ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
On Demand ◽  
Haemophilic Arthropathy ◽  
Bleeding Episodes

SummaryPatients with severe haemophilia A (HA) can either be treated by regular FVIII infusions twice or three times per week (prophylaxis), or only in case of bleeding episodes (on-demand). Whereas prophylaxis reduces the number of bleeding episodes and may therefore prevent the development of haemophilic arthropathy, there is still a lot of controversy surrounding recommendations on age and dose at start of prophylactic regimens. The present database study was performed to investigate the role of primary versus secondary prophylaxis in HA children. The outcome variable was imaging-proven haemophilic joint damage. Forty-two children were initially treated with primary prophylaxis following the first bleeding episode, and were frequency-matched (year of birth, catchment area) to 67 pa- tients receiving “on-demand” therapy with an early switch to “secondary prophylaxis”. In multivariate analysis adjusted for the HA mutation type and the presence or absence of thrombophilia, the Pettersson score investigated at a median age of 12.5 years in joints with at least one documented bleeding episode was not significantly different between the two patient groups (p=0.944),and no statistically significant differences were found in patients with target joints (p=0.3), nor in children in whom synovitis had occurred (p=0.77). No conclusion can be drawn from the data presented herein whether primary prophylaxis or an early start of secondary prophylaxis is superior with respect to joint outcome in children with severe HA.

Increased Thrombin Generation in Severe Hemophiliacs with Mild Clinical Phenotype

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 515-515
Author(s):  
Elena Santagostino ◽  
Maria Elisa Mancuso ◽  
Armando Tripodi ◽  
Veena Chantarangkul ◽  
Gianluigi Pasta ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Clinical Phenotype ◽  
Platelet Rich Plasma ◽  
Gene Mutations ◽  
Clinical Score ◽  
Bleeding Tendency ◽  
Spontaneous Bleeding ◽  
Chromogenic Assay ◽  
Bleeding Episodes ◽  
The Impact

Abstract Introduction: Some severe hemophiliacs (FVIII/FIX<1%) exhibit a mild bleeding tendency, but the basis for this clinical heterogeneity is poorly understood. This study investigated the relationship between the values of endogenous thrombin potential (ETP) and clinical phenotype in severe hemophiliacs. The impact of FVIII/FIX gene mutations and thrombophilic polymorphisms was also evaluated. Methods: severe hemophiliacs older than 18 years without inhibitor history and treated on demand were eligible. Mild bleeders (MB) and severe bleeders (SB) were defined as follows: spontaneous bleeding episodes per year ≤2 (MB) or 25 (SB) and concentrate consumption <500 (MB) or >2000 (SB) IU/Kg/year. Patients who did not fit these criteria were considered as intermediate bleeders (IB). FVIII was measured by chromogenic assay and ETP was measured in platelet-rich plasma after addition of tissue factor. Results: 22MB, 22SB and 28IB were enrolled. MB had lower clinical and radiological scores when compared with both IB and SB (p<0.005). MB showed an older age at first bleed compared to SB (p < 0.005) and p for trend among the 3 groups was also significant (p < 0.05). The prevalence of severe FVIII/FIX gene defects (null mutations) was lower and ETP values were higher in MB compared with both IB and SB (p<0.05; table 1). Conclusions: our results indicate an extremely low prevalence of null mutations in severe hemophiliacs with mild bleeding diathesis. The measurement of thrombin generation in platelet-rich plasma may allow to identify this subgroup of patients, not otherwise distinguishable by conventional functional assays. SB (#22) IB (#28) MB (#22) p Age (yr) 38 (21–76) 38 (23–62) 32 (22–73) NS Age 1st bleed (yr) 1 (0–4) 2 (0–6) 3 (1–10) < 0.005 Bleeding episodes/yr 36 (25–60) 10 (3–20) 0 (0–2) < 0.0005 Factor use (IU/Kg/yr) 2207 (2040–8696) 1068 (207–2400) 60 (25–487) < 0.0005 Clinical score 18 (10–35) 10 (0–34) 3 (0–17) < 0.005 Pettersson score 44 (14–62) 28 (0–48) 17 (3–40) < 0.0005 Null mutations (%) 59 70 6 < 0.005 PTG20210A (%) 0 7 5 NS FV Leiden (%) 5 7 0 NS Median ETP (nM) 414 478 850 < 0.05

scholarly journals Haemophilia A in a Female Patient with Turner Syndrome

2019 ◽  
Vol 1 (01) ◽  
pp. 26-27
Author(s):  
Salma Afrose
Keyword(s):  
Family History ◽  
Turner Syndrome ◽  
Haemophilia A ◽  
Bleeding Tendency ◽  
Factor Viii Activity ◽  
Sexual Character ◽  
Negative Family History ◽  
Primary Amenorrhoea ◽  
First Case ◽  
History Of

A 28-year-old female presented with occasional swelling of knees and prolonged bleeding after trauma. She also complained of gum bleeding in few occasions. She also gave history of primary amenorrhoea and failure of development of secondary sexual character. There was negative family history of bleeding tendency in both maternal and paternal family. Her investigation profile showed prolonged Partial Thromboplastin Time and reduced factor VIII activity (2.5%). Karyotyping showed (45 XO) Turner syndrome. This is the reported first case of association of Turner syndrome with moderate Haemophilia A in Bangladesh.

scholarly journals CLINICAL EFFICACY OF RECOMBINANT FACTOR VIII FC FUSION PROTEIN IN HAEMOPHILIA A PATIENT RECEIVING ON DEMAND TREATMENT ONLY

2021 ◽  
Vol 71 (1) ◽  
pp. 62-66
Author(s):  
Saima Zahir ◽  
Tahira Zafar ◽  
Altaf Hussain ◽  
Hamid Saeed Malik ◽  
Pervez Ahmed ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Factor Viii ◽  
Armed Forces ◽  
Recombinant Factor Viii ◽  
Haemophilia A ◽  
On Demand ◽  
Group I ◽  
Fc Fusion Protein ◽  
Male Patients ◽  
Group Ii

Objective: To evaluate the efficacy of recombinant factor VIII FC fusion protein in haemophilia A patientreceiving on demand treatment only. Study Design: Comparative cross sectional study. Place and Duration of Study: Department of Hematology, Armed Forces Institute of Pathology and PakistanHemophilia Welfare Society, Rawalpindi, from Jun to Dec 2017. Methodology: Eighty-nine male patients of Hemophilia A already receiving recombinant factor VIII (20-30 Units/kg) on demand, with no history of inhibitors were included in study. Patients were divided as per age into paediatric and adult group and also on the basis of their basal factor VIII levels into severe, moderate and mild groups. Same patients were switched to recombinant factor VIII FC fusion protein (20-30 Units/kg) and its efficacy was measured and compared with recombinant Factor VIII in terms of dose requirement, injections, bleeds in six month period, presence of inhibitors and side effects. Results: Eighty nine male patients were studied. There was significant reduction in dose from median value of5750 units for group I to 4000 units for group II. Number of bleed in six month period were reduced from 5.3 ingroup I to 4.5 in group II. Number of injections were reduced on average to 1-2 injection per bleed in group II. No inhibitors were detected in group II. Conclusion: rFVIII Fc fusion protein has prolong activity and results in reduction of total dose, number of bleed,dose per bleed and has reduced antigenecity.

Evaluation of the Cuticle Bleeding Time in Canine Haemophilia A

1986 ◽  
Vol 55 (01) ◽  
pp. 070-073 ◽  
Author(s):  
M I M Pijnappels ◽  
E Briët ◽  
G Th van der Zwet ◽  
R Huisden ◽  
N H van Tilburg ◽  
...  
Keyword(s):  
Factor Viii ◽  
Bleeding Time ◽  
Severe Bleeding ◽  
Suitable Model ◽  
Haemophilia A ◽  
Bleeding Tendency ◽  
The Central Nervous System ◽  
Time Test ◽  
Labrador Retrievers

SummaryIn this paper we describe our clinical experience and results with the cuticle bleeding time test in a colony of cross-bred Labrador retrievers with severe haemophilia A. The dogs have a severe bleeding tendency with a high incidence of fatal haemorrhages in the central nervous system. Homozygous females appeared to be especially prone to this lethal complication. Factor VIII recovery and half-life determinations yielded results similar to the data from human studies. The cuticle bleeding time proved to be a good measure of the coagulation defect. The prolongation of the bleeding time could be completely abolished by administration of 10 to 15 units of canine factor VIII per kg body weight. We conclude that the cuticle bleeding time in canine haemophilia provides us with a suitable model for the in vivo study of new therapeutic materials.

A Post-Marketing Surveillance Study of the Safety and Efficiacy of Refacto® (Moroctocog Alfa, B-Domain Deleted Recombinant Factor VIII) (St. Louis-Derived Active Substance in the Treatment and Prevension of Bleeding Episodes in Hemophilia a Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4023-4023
Author(s):  
Jay M. Feingold ◽  
Mark P. Smith ◽  
Richard Littlewood ◽  
Paul Giangrande ◽  
Keyword(s):  
Factor Viii ◽  
Active Substance ◽  
Hemophilia A ◽  
High Titre ◽  
Surveillance Study ◽  
Point Scale ◽  
On Demand ◽  
Post Marketing Surveillance ◽  
Post Marketing ◽  
Bleeding Episodes

Abstract This was an open-label, multicenter, post-marketing surveillance study conducted in Belgium, France, Germany, Italy, Netherlands, New Zealand, Switzerland, and UK. The objectives were to assess the safety and clinical efficacy of ReFacto St Louis-derived active substance (STL) in the treatment and prevention of bleeding episodes in patients with hemophilia A in the usual care setting. 60 patients with moderate to severe hemophilia A (FVIII:C <5%) with no history of FVIII inhibitor were enrolled (58 were previously treated patients and 2 were previously untreated patients). Data on infusions, concomitant medications, adverse events, and inhibitor development were collected from patients at regular intervals. Efficacy for prophylaxis was assessed by the investigator approximately every 3 months until 50 exposure days, 6 months or study termination using the number of breakthrough bleeding episodes and the 3-point scale (excellent, effective, and inadequate). The efficacy of each on-demand treatment administered was assessed using the 4-point scale (excellent, good, moderate, and no response). The investigator and surgeon assessed efficacy of surgical prophylaxis jointly after each surgery using the 4-point scale (excellent, good, moderate, and no response). Factor VIII inhibitor (using local laboratory Bethesda assay) was evaluated at screening, after 10 EDs, after 30 EDs, and at the end of treatment. The investigator determined all dosing and treatment regimens. In the prophylaxis treatment group, no particular prophylaxis regimen was enforced. A total of 32 patients aged 0–66 years initially received prophylaxis treatment: 10 (31%) patients reported no breakthrough bleeds. A median of 6.25 bleeds per year occurred in all prophylaxis patients. Twenty-nine assessments of the prophylactic treatment final outcome were made: 93% of these assessments were excellent or effective. A total of 28 patients aged 1–71 years initially received on-demand treatment with ReFacto STL. 95.2% of bleeds were resolved with 1 or 2 infusions. The assessment of treatment response was excellent or good in 98% of cases. Seven patients underwent 7 surgical procedures, haemostasis was achieved all cases and ReFacto STL was rated as providing an excellent or good response as the final outcome in each case. As this was a post-marketing study, safety evaluation was focused on collection of serious AEs and product-related non-serious AEs. One PTP (1/58, 1.7%) developed a high titre inhibitor and 1/58 (1.7%) developed a low titre transient inhibitor. One PUP developed a low titre transient inhibitor (0.4 BU). SAEs included 1 fatal intracranial hemorrhage (considered unrelated to ReFacto), 5 preplanned surgeries, 1 episode of gastroenteritis, and 1 hemorrhage. There were no allergic events. Three patients were withdrawn from treatment for safety reasons (1 patient due to death, 1 PTP due to high titre inhibitor and 1 PTP due to low titre transient inhibitor). The nature and incidence of non-serious AEs did not raise new safety concerns. The majority of AEs were mild or moderate in severity.

Coated-Platelet Levels May Explain Some Variability in Clinical Phenotype of Severe Hemophilia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1018-1018 ◽  
Author(s):  
Kapil Saxena ◽  
Kalpana Pethe ◽  
George L. Dale
Keyword(s):  
Factor Viii ◽  
Clinical Phenotype ◽  
Factor V ◽  
Healthy Controls ◽  
Severe Hemophilia ◽  
High Concentration ◽  
Co Activation ◽  
Bleeding Episodes ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Objective: To determine if variability in clinical phenotype of severe hemophilia patients is influenced by the percentage of coated-platelets. Background: Co-activation of platelets with thrombin and collagen results in a unique subset of platelets, with high levels of alpha granule proteins on their surface, such as Factor V, fibrinogen, von Willebrand factor, and thrombospondin. This subset of activated platelets is referred to as coated-platelets (J. Thromb. Haemostasis3:2185, 2005). The high concentration of adhesive and prohemostatic proteins observed on coated-platelets provides a unique procoagulant locus that may influence the number of bleeding episodes in patients with severe hemophilia. Methods: After informed consent, 3–5 ml of blood was drawn from patients with severe hemophilia (Factor VIII &lt;1%) and healthy controls. The number of bleeding episodes reported in the last 6 months was taken as an indicator of clinical phenotype. Results: In 6 patients with more than 3 bleeds reported in the last 6 months (14 ± 4.9 bleeds; mean ± 1SD), the average coated-platelets percentage was 22.3 ± 11.2%. In 17 patients with 3 or less bleeds (1.6 ± 1.3) in the last 6 months, the average coated-platelets percentage was 37.6 ± 12.0%, a difference that was statistically significant (p=0.012). In healthy controls (n=12), the mean coated-platelets were 30.2 ± 9.5%. Conclusion: A higher percentage of coated-platelets may provide a better procoagulant locus for residual Factor VIII, thereby reducing the number of clinical bleeding episodes and partially explaining some variability observed in clinical phenotype of severe hemophilia.

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