Hemophilia A

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Description from OMIM

Hemophilia A is an X-linked recessive bleeding disorder caused by a deficiency in the activity of coagulation factor VIII. The disorder is clinically heterogeneous with variable severity, depending on the plasma levels of coagulation factor VIII: mild, with levels 6 to 30% of normal; moderate, with levels 2 to 5% of normal; and severe, with levels less than 1% of normal. Patients with mild hemophilia usually bleed excessively only after trauma or surgery, whereas those with severe hemophilia have an annual average of 20 to 30 episodes of spontaneous or excessive bleeding after minor trauma, particularly into joints and muscles. These symptoms differ substantially from those of bleeding disorders due to platelet defects or von Willebrand disease (193400), in which mucosal bleeding predominates (review by Mannucci and Tuddenham, 2001).

Prevalence of clinical parameters (%)

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List of symptoms

Symptom/sign Organ system Percent affected Pubmed id Added on(yyyy-mm-dd) Edit/add reference
Muscle haematoma skeletal 93 % 11167767 2012-01-11
Joint bleeding skeletal 86 % 11167767 2012-01-11
Joint bleeding skeletal 72 % 11886463 2011-10-27
Oral cavity bleeding digestive 64 % 11167767 2012-01-11
Post-operative bleeding multi 36 % 11167767 2012-01-11
Epistaxis respiratory 20 % 11167767 2012-01-11
Haematuria urinary 12 % 11167767 2012-01-11
Intracranial haemorrhage circulatory 11 % 21114482 2011-10-27
Gastrointestinal bleeding digestive 10 % 11167767 2012-01-11
Synovitis skeletal 7 % 12648975 2011-10-27
Intracranial haemorrhage nervous 4 % 11167767 2012-01-11

List of references:

Clinical manifestations and complications of childbirth and replacement therapy in 385 Iranian patients with type 3 von Willebrand disease.
M Lak, F Peyvandi, P M Mannucci,

Type 3 is the most severe form of von Willebrand disease (VWD) transmitted as an autosomal recessive trait. We collected data on the clinical manifestations of type 3 VWD by examining 385 patients from 300 Iranian kindreds, who were compared with 100 age-matched patients with severe haemophilia A. Joint and muscle bleeding was less frequent than in haemophiliacs, perhaps because factor VIII levels were in general higher (median value 4% vs. 1% or less). Mucosal tract haemorrhages such as epistaxis and menorrhagia were the most prevalent symptoms in VWD. Post-circumcision and oral cavity bleeding occurred frequently when prophylactic replacement therapy was not carried out or was inadequate. The course of pregnancy was usually uneventful, but increased bleeding occurred at parturition when affected women were treated with replacement therapy for less than 3-4 d. Ten of 385 (2.6%) of these multitransfused patients developed an alloantibody to VWF and 55% are chronically infected with the hepatitis C virus.

British journal of haematology - Dec 2000

Clinical outcomes and resource utilization associated with haemophilia care in Europe.
W Schramm, S Royal, B Kroner, E Berntorp, P Giangrande, C Ludlam, A Gringeri, K Berger, T Szucs, ,

We conducted a multicentre, cross- sectional study of 1042 haemophilia subjects across Europe to compare various health outcomes associated with on-demand vs. prophylactic factor-substitution therapy. Demographic, medical history, and healthcare resource utilization data were analysed along with the number of bleeding events over the past 6 months. Treatment-cost data were also examined to provide preliminary information for future economic studies. A logistic regression analysis, controlling for other statistically significant covariates, showed that patients treated on demand were 3.4 times more likely to have had a joint bleed over the previous 6 months than those treated with prophylaxis. Multiple regression analyses further confirmed these findings, because on-demand subjects had, on average, 5.15 more joint bleeds over the reporting period than patients treated with prophylaxis. Notably, these findings were even more dramatic for younger haemophilia patients when our study sample was stratified by age. Due to the high cost of factor replacement, healthcare costs were significantly higher for subjects treated prophylactically. While hospital costs for prophylaxis subjects were, on average, lower, statistically significant cost savings for prophylactic subjects were not noted. These results suggest that clinicians and health policy decision-makers should consider the advantages of prophylactic therapy for haemophilia patients in formulating treatment protocols and allocating health resources.

Haemophilia : the official journal of the World Federation of Hemophilia - Jan 2002

Associations between intracranial haemorrhage and prescribed prophylaxis in a large cohort of haemophilia patients in the United States.
Char Witmer, Rodney Presley, Roshni Kulkarni, J Michael Soucie, Catherine S Manno, Leslie Raffini,

Intracranial haemorrhage (ICH) is the most serious type of bleeding for patients with haemophilia. Prior published reports regarding ICH predate the widespread provision of prophylaxis. Our study objectives were to determine risk factors for ICH and whether prophylaxis reduces ICH occurrence. We performed a nested case-control study of persons with haemophilia, ≥2 years of age enrolled in the Centers for Disease Control and Prevention Universal Data Collection project. Of 10 262 patients 199 (1·9%) experienced an ICH for an incidence rate of 390/10⁵ patient years. Head trauma was reported in 44% (88/199). ICH mortality was 19·6% (39/199). Significant risk factors for ICH included a high titre inhibitor [odds ratio (OR) = 4·01, 95% confidence interval (2·40-6·71)], prior ICH [OR = 3·62 (2·66-4·92)] and severe haemophilia [OR = 3·25 (2·01-5·25)]. Prophylaxis was associated with a significant risk reduction for ICH occurrence in patients with severe haemophilia who were negative for human immunodeficiency virus or an inhibitor, with an OR of 0·52 (0·34-0·81) and 0·50 (0·32-0·77) respectively. The most significant risk factors for ICH included the presence of an inhibitor, prior ICH, severity of haemophilia and reported head trauma. This is the first study to demonstrate that prescribed prophylaxis conferred a protective effect against ICH in patients with uncomplicated severe disease.

British journal of haematology - Jan 2011

Chronic synovitis and HLA B27 in patients with severe haemophilia.
Kanjaksha Ghosh, Umapathy Shankarkumar, Shrimati Shetty, Dipika Mohanty,

Chronic synovitis affects about 10% of patients with severe haemophilia in India. This disease has some features in common with ankylosing spondylitis, which has been linked to HLA B27. We therefore aimed to test whether there is an association between HLA B27 and chronic synovitis. We studied 473 patients with severe haemophilia (33 of whom had chronic synovitis), and 1175 healthy controls using a standard serological technique and the reverse line strip assay. 64% (21 of 33) of patients with haemophilia and chronic synovitis were positive for HLA B27, compared with 5% (23 of 440) of those with severe haemophilia, but not chronic synovitis (odds ratio 31.6 [95% CI 9.28-39.38], p<0.0001), and 9% (100 of 1175) of healthy controls (18.81 [9.6-27.7], p<0.0001). We conclude that there is a strong association between HLA B27 and chronic synovitis in Indian patients with severe haemophilia and screening in this population could allow treatment and prevention of the complication.

Lancet (London, England) - Mar 2003