Factor VIII inhibitor: Difference between revisions
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==Background== | ==Background== | ||
*Autoantibodies (IgG) directed against Factor VIII, causing an acquired coagulopathy | |||
*Also called '''acquired hemophilia A''' — distinct from congenital [[hemophilia]] | |||
*Rare but potentially life-threatening; mortality 8-22% | |||
*'''Associations:''' autoimmune diseases, malignancy, pregnancy/postpartum, medications (penicillin, sulfonamides), idiopathic (~50%) | |||
*Most common in elderly patients (median age 60-70) | |||
==Clinical Features== | ==Clinical Features== | ||
*Spontaneous soft tissue bleeding, ecchymoses, hematomas (often extensive) | |||
*Mucosal bleeding, GI bleeding, [[hematuria]] | |||
*'''Unlike congenital hemophilia:''' hemarthrosis is uncommon | |||
*May present with life-threatening hemorrhage without prior bleeding history | |||
==Differential Diagnosis== | ==Differential Diagnosis== | ||
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==Evaluation== | ==Evaluation== | ||
*PTT does | *'''Isolated prolonged PTT''' with normal PT and platelet count | ||
*'''Mixing study:''' PTT does NOT correct (distinguishes inhibitor from factor deficiency) | |||
*Factor VIII activity level markedly reduced | |||
*'''Bethesda assay:''' Quantifies inhibitor titer (Bethesda Units) | |||
*CBC, fibrinogen, DIC panel to assess for concurrent coagulopathy | |||
==Management== | ==Management== | ||
* | *'''Acute bleeding:''' | ||
** | **'''Bypassing agents''' (first-line for significant hemorrhage): | ||
***Recombinant Factor VIIa (NovoSeven) 90 mcg/kg IV q2-3h | |||
***Activated prothrombin complex concentrate (FEIBA) 50-100 units/kg IV q8-12h | |||
**High-dose Factor VIII concentrate may be tried but often ineffective if high-titer inhibitor | |||
**[[Desmopressin]] (DDAVP) for low-titer inhibitors only | |||
*'''Inhibitor eradication''' (in consultation with hematology): | |||
**Immunosuppression: corticosteroids ± cyclophosphamide | |||
**Rituximab for refractory cases | |||
*Avoid procedures and IM injections; hold anticoagulants | |||
==Disposition== | ==Disposition== | ||
*Admit all patients — hematology consult urgently | |||
*ICU for significant hemorrhage | |||
==See Also== | ==See Also== | ||
*[[Hemophilia]] | |||
*[[Coagulopathy (Main)]] | *[[Coagulopathy (Main)]] | ||
*[[DIC]] | |||
==References== | ==References== | ||
<references/> | <references/> | ||
[[Category:Heme/Onc]] | [[Category:Heme/Onc]] | ||
Revision as of 01:41, 21 March 2026
Background
- Autoantibodies (IgG) directed against Factor VIII, causing an acquired coagulopathy
- Also called acquired hemophilia A — distinct from congenital hemophilia
- Rare but potentially life-threatening; mortality 8-22%
- Associations: autoimmune diseases, malignancy, pregnancy/postpartum, medications (penicillin, sulfonamides), idiopathic (~50%)
- Most common in elderly patients (median age 60-70)
Clinical Features
- Spontaneous soft tissue bleeding, ecchymoses, hematomas (often extensive)
- Mucosal bleeding, GI bleeding, hematuria
- Unlike congenital hemophilia: hemarthrosis is uncommon
- May present with life-threatening hemorrhage without prior bleeding history
Differential Diagnosis
Coagulopathy
Platelet Related
- Too few
- Nonfunctional
Factor Related
- Acquired (Drug Related)
- Warfarin (Coumadin)
- Unfractionated heparin
- Low molecular weight heparin (i.e. enoxaparin (Lovenox), dalteparin)
- Factor Xa Inhibitors (e.g. rivaroxaban, apixaban, fondaparinux, edoxaban)
- Direct thrombin inhibitors (e.g. dabigatran, argatroban, bivalirudin)
- Illness induced
- Genetic
Evaluation
- Isolated prolonged PTT with normal PT and platelet count
- Mixing study: PTT does NOT correct (distinguishes inhibitor from factor deficiency)
- Factor VIII activity level markedly reduced
- Bethesda assay: Quantifies inhibitor titer (Bethesda Units)
- CBC, fibrinogen, DIC panel to assess for concurrent coagulopathy
Management
- Acute bleeding:
- Bypassing agents (first-line for significant hemorrhage):
- Recombinant Factor VIIa (NovoSeven) 90 mcg/kg IV q2-3h
- Activated prothrombin complex concentrate (FEIBA) 50-100 units/kg IV q8-12h
- High-dose Factor VIII concentrate may be tried but often ineffective if high-titer inhibitor
- Desmopressin (DDAVP) for low-titer inhibitors only
- Bypassing agents (first-line for significant hemorrhage):
- Inhibitor eradication (in consultation with hematology):
- Immunosuppression: corticosteroids ± cyclophosphamide
- Rituximab for refractory cases
- Avoid procedures and IM injections; hold anticoagulants
Disposition
- Admit all patients — hematology consult urgently
- ICU for significant hemorrhage