PRIMARILY A MALE DISEASE
MONOCLONAL ANTIBODY PURIFIED FACTOR VIII & RECOMBINANT FACTOR VIII ARE AVAILABLE NOW AS REPLACEMENT THERAPY
GENERAL MEASURES
o Avoid aspirin or aspirin-containing drugs
o Treat early. Symptoms often precede obvious bleeding.
o An uncomplicated, soft tissue bleeding or an early hemarthrosis requires a single infusion to 20-30% activity
o More extensive hemarthrosis or retroperitoneal bleeding requires bid infusions for 72 or more hours to 25-50% activity
o Life-threatening bleeding into the CNS requires maintaining levels greater than 50% activity for 2 weeks
o Major surgery requires greater than 50% activity preoperatively, continued for 1-2 weeks postoperatively
o Orthopedic care and physical therapy to prevent contractures and maintain joint mobility
o Vaccinate against hepatitis B at time of diagnosis
o Maintain good dental care
o Annual evaluation in a comprehensive hemophilia center
o Consideration for three times weekly prophylaxis in severe factor VIII deficiency
SURGICAL MEASURES
o Surgical or radionucleotide synovectomy, in selected patients
o Joint replacement, in selected patients
ACTIVITY
o Attempt to lead as normal a life as possible
o Restrict activities in proportion to the degree of factor deficiency, but maintaining a trim physical condition is
important
DIET No special diet
PATIENT EDUCATION
o Teach patient and family about signs and symptoms to watch for
o Genetic counseling
o Home care with self administered replacement therapy is often used
DRUG(S) OF CHOICE
o Hemophilia A: Recombinant or monoclonal factor VIII is treatment of choice for hemophilia A patients
who are HIV negative and who have had minimal prior concentrate exposure. Less optimal are plasma products enriched in factor VIII [cryoprecipitate, factor VIII concentrate]
? 1 unit of factor VIII (the amount in 1 mL of plasma) per kg of body weight will raise the plasma level of the recipient by 2%
? Number units = [(desired percent activity - current percent activity) times (body weight in kilograms)] Γ· 2
? For example: 70 kg patient with 5% activity needs to be taken to 25% activity. Units needed: [(25% - 5%)
x (70 kg)] Γ· 2 = [(25 - 5) x (70)] Γ· 2 = 700 units of factor VIII needed
? Half-life of factor VIII is 8-12 hours, therefore need to infuse at least bid to maintain a chosen factor VIII
level, and tid when tight control of the level is needed
o Hemophilia B: Recombinant factor IX became available in mid 1997 and is treatment of choice for hemophilia B
patients who are HIV negative and who have had minimal prior concentrate exposure. Monoclonal antibody
purifi ed factor IX is an effective and apparently safe plasma derived product
? For mild patients: Desmopressin (DDAVP); 0.3 mcg/kg diluted in 10-20 mL of saline IV over 20 minutes. An intranasal preparation is also available.
? Factor IX concentrate for moderate to severe hemorrhage and patients to undergo surgery. One unit/kg
will raise levels 1%
? Number units = [(desired percent activity - current percent activity) times (body weight in kilograms)] Γ· 1
? For example: 70 kg patient with 5% activity needs to be taken to 25% activity. Units needed: [(25% - 5%)
x (70 kg)] Γ· 1 = [(25 - 5) x (70)] Γ· 1 = 1400 units of factor IX needed
ALTERNATIVE DRUGS
o Aminocaproic acid (epsilon-aminocaproic acid, EACA) can be used for minor dental work following a single
factor VIII infusion. Aminocaproic acid greatly enhances the risk of thromboembolism and should be used with
caution with factor IX concentrates.
o Patients with inhibitors to factor VIII may require intensive plasmapheresis, large doses of concentrate,
infusion of prothrombin complex concentrates (bypassing products), porcine factor VIII, or recombinant factor
VIIA
PATIENT MONITORING Regular evaluations every 6 to 12 months include a musculoskeletal evaluation, an inhibitor screen, liver tests, and tests for antibodies to hepatitis viruses and human immunodeficiency virus (HIV)
PREVENTION/AVOIDANCE Genetic Counseling
POSSIBLE COMPLICATIONS
o Factor VIII and IX preparations and transfusions may result in viral hepatitis, chronic liver disease, and acquired immunodeficiency syndrome (AIDS). However, recent advances in factor VIII concentrate preparation should prevent future HIV infection and hepatitis B and C.
o Hemophilia A - 10-20% of patients develop inhibitors to factor VIII, typically those with severe disease receivingmultiple transfusions. Type I (high responders) inhibitors to factor VIII rapidly neutralize factor VIII and prevent effective transfusion therapy. Type II (low responders) inhibitors are low-titer and may respond to
higher than normal doses of factor VIII.
EXPECTED COURSE/PROGNOSIS
o Repeated hemarthroses result in eventual deformity and crippling
o Survival is normal for those with mild disease, and mortality is increased 2 to 6 fold in those with moderate
to severe disease, primarily due to complications of infection
o Median life expectancy with this condition peaked in late 1970's at 68 years, and is now declining due to the AIDS epidemic
o Up to 70% are HIV seropositive, especially those with severe disease, and 4% with severe disease develop
AIDS. Younger patients whose treatment began since the mid-late 80's are largely HIV negative and are
not expected to be exposed by modern replacement products. The proportion of HIV positive hemophiliacs
is therefore declining.
PREGNANCY
o The vast majority of females are asymptomatic carriers, although an occasional carrier will bleed at time of
surgery. They require no specific treatment during pregnancy or delivery.
o Prenatal diagnosis previously required sampling fetal blood for coagulant activity. Newer prenatal detection
schemes detect an identifi able restriction fragment length polymorphism or a gene deletion or rearrangement
in a sample of chorionic villus or from fluid obtained at amniocentesis.
OTHER NOTES Recombinant factor VIII is available. It has biologic activity and clinical efficacy comparable to plasma factor VIII, while posing no risk of transmitting hepatitis viruses or HIV. There are factor VIII and factor IX concentrates prepared from human plasma using a monoclonal antibody method plus either heat or detergent treatment of the concentrate. These monoclonal-prepared concentrates have the lowest risk for hepatitis B and essentially no risk for HIV infection. (Recombinant factor IX became available in mid 1997, and has no risk of viral infection.)