Clotting factor concentrates given to prevent bleeding and bleeding-related complications in people with hemophilia A or B.
BACKGROUND
People with severe hemophilia A or B, X-linked bleeding disorders due to decreased blood levels of coagulants, suffer recurrent bleeding into joints and soft tissues. Before clotting factor concentrates were available, most people with severe hemophilia developed crippling musculoskeletal deformities. Clotting factor concentrate prophylaxis aims to preserve joint function by converting severe hemophilia (factor VIII or IX less than 1%) into a clinically milder form of the disease. Prophylaxis has long been used in Sweden, but not universally adopted because of medical, psychosocial, and cost controversies. Use of clotting factor concentrates is the single largest predictor of cost in treating hemophilia.


OBJECTIVE
To determine the effectiveness of clotting factor concentrate prophylaxis in the management of people with hemophilia A or B.


METHODS
We searched the Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references from comprehensive electronic database searches and handsearches of journals and abstract books. Reference lists of relevant articles were reviewed. Most recent search: November 2005.


METHODS
Randomized controlled trials (RCTs) evaluating people with severe hemophilia A or B, receiving prophylactic clotting factor concentrates.


METHODS
Two authors independently reviewed studies for eligibility, assessed methodological quality and extracted data.


RESULTS
Twenty-nine studies were identified; four studies (including 37 participants) were eligible for inclusion. Three studies evaluated hemophilia A; one showed a decrease in frequency of joint bleeds with prophylaxis compared to placebo (non-physiological dose), with a rate difference (RD) -10.80 (95% confidence interval (CI) -16.33 to -5.27) bleeds per year. The remaining two studies evaluating hemophilia A compared two prophylaxis regimens, one study showed no difference in joint bleed frequency, RD -5.04 (95%CI -17.02 to 6.94) bleeds per year and another failed to demonstrate an advantage of factor VIII dosing based on individual pharmacokinetic data over the standard prophylaxis regimen with RD -0.14 (95% CI -1.34 to 1.05) bleeds per year. The fourth study evaluated hemophilia B and showed fewer joint bleeds with weekly (15 IU/kg) versus bi-weekly (7.5 IU/kg) prophylaxis, RD -3.30 (95% CI -5.50 to - 1.10) bleeds per year.


CONCLUSIONS
There is insufficient evidence from randomised controlled trials to determine whether prophylactic clotting factor concentrates decrease bleeding and bleeding-related complications in hemophilia A or B, compared to placebo, on-demand treatment, or prophylaxis based on pharmacokinetic data from individuals. Well-designed RCTs are needed to assess the effectiveness of prophylactic clotting factor concentrates. Two clinical trials are ongoing.
Stobart
K
K
Walter Mackenzie Health Sciences Centre, Department of Pediatrics, 2C3.88, University of Alberta, 8440 - 112 Street, Edmonton, Alberta, Canada T6G 2B7. kstobart@cha.ab.ca
Iorio
A
A
Wu
J K
JK
D001779:Blood Coagulation Factors / Q000627:therapeutic use*; D005169:Factor VIII / Q000627:therapeutic use*; D006395:Hemarthrosis / Q000517:prevention & control*; D006467:Hemophilia A / Q000150:complications*; D002836:Hemophilia B / Q000150:complications*; D006801:Humans; D016032:Randomized Controlled Trials as Topic
D001779:Blood Coagulation Factors; D005169:Factor VIII