DEFICIENCY OF FACTOR VIII (HEMOPHELIA A) WITH
FACTOR VIII INHIBITOR
Andy Nguyen,M.D./ UT-Medical School at Houston, Pathology/
Last Revision on: 9/10/06
Only factor VIII inhibitor is discussed in this section. For further
information on hemophelia A, please refer to that section.
- Biochemical aspects:
- Antibodies to factor VIII are almost exclusively of the IgG
class. The antibodies form a complex with factor VIII in a
time-and-temperature dependent neutralization reaction that
may take 1 to 2 hours to complete (this is the basis for
anticoagulant screenning procedure).
- The antibodies inactivate factor VIII activity but have no
effect on von Willebrand factor.
- Pathological Basis:
- The incidence of antibodies to factor VIII has been reported
to vary between 5% to 15% of persons with severe hemophelia A.
In approximately 70% of the cases, inhibitors in develop by 20
of age. Development of the antibodies is related to exposure
to factor VIII infusion.
- The level of the inhibitor is expressed in Bethesda units.
By definition, an inhibitor plasma that contains 1 Bethesda unit
of antibodies per milimeter will neutralize 50% of factor VIII
activity in an equal volume of pooled normal plasma after
incubation of the mixture at 37 degrrees C for 2 hours.
- The pattern of response of antibodies on exposure to factor
VIII may be classified into two main types: "high responder"
and "low responder". High responders show a rise in antibody
titer on the 3rd or 4th day after infusion of blood products
that contain factor VIII. Low responders tend not to show
increases in inhibitor titers in excess of 2 to 5 Bethesda units.
- Treatment:
- For low responders: factor VIII concentrates.
- For high responders:
- Prothrombin complex concentrates.
- Activated F VII.
- Plasmapheresis may be helpful in acute bleeding.
- Porcine factor VIII concentrates.
- Massive doses of factor VIII concentrates.
Diagnostic Criteria:
- Family_history_of_coagulation_disorders:positive
- APTT:abnormal
- Factor_VIII:C_activity:abnormal
- Factor_VIII_inhibitor(Bethesda_assay):abnormal
- APTT_does_not_respond_to_Factor_VIII_replacement_therapy
- Mixing_APTT:not_corrected