Factor VIII Levels and Hemophilia A

Inheritance:

(1) factor 8 is encoded on the X-chromosome (sex-linked)

(2) affects approximately 1 in 5,000-10,000 male births

(3) only rarely affects females

 

Clinical severity of disease correlates with the plasma factor 8 activity.

 

Level of Factor 8	Clinical Severity
> 50%	no bleeding
30 - 50%	may bleed after significant trauma or major surgery
10 - 30%	mild disease, with bleeding after trauma or surgery
2 - 10%	moderately severe disease; can have spontaneous hemorrhage or severe hemorrhage after minor trauma
< 2%	severe disease, with spontaneous hemorrhage into muscles or joints

 

Factor 8 Replacement Dosing

 

dose of factor 8 concentrate =

= (body weight in kilograms) * 0.5 * (increment in percent activity as whole number)

 

The dose can be administered:

(1) as intermittent intravenous infusion every 12 hours (half-life of infused factor 8)

(2) as a continuous infusion (approximately 2 units per hour per kg body weight will raise factor 8 level by 50% activity)

 

Product options include:

(1) cryoprecipitate (contains 90-100 units of factor 8 in approximately 20 mL)

(2) kogenate (recombinant factor 8 concentrate)

(3) helixate (recombinant factor 8 concentrate)

(4) recombinate (recombinant factor 8 concentrate)

(5) alphanate (solvent detergent treated concentrate from pooled human plasma)

(6) humate (pasteurized concentrate from pooled human plasma)

(7) koate (concentrate from pooled human plasma)

(8) monoclate (pasteurized concentrate from pooled human plasma)

 

Target Levels and Duration for Hemophilic Conditions

 

Clinical Condition	Target Plasma Level	Duration
hemarthroses	5 - 10%	2 - 3 days
hematuria	5 - 10%	2 - 3 days
hematomas	10 - 20%	4 - 7 days
moderately severe bleeding	40%	7 days
major surgery	> 60%	10-14 days

 

Anti-Factor 8 Inhibitors

 

Some patients with hemophilia A have circulating antibodies to factor 8, which act as inhibitors. Infusion of prothrombin complex concentrate can help to control hemorrhage related to circulating inhibitors.

 

dose of anti-inhibitor complex =

= (body weight in kilograms) * (number of units based on bleeding)

 

where:

• 25 units/kg are administered for mild bleeding, up to 100 units/kg for severe hemorrhaging

 

Contraindications: DIC

 

If bleeding has not been reduced at 6 hours, then the dose can be repeated.