Inhibitory antibodies to FVIII in severe HA and AHA: clinical, laboratory, and treatment assessment
| FVIII deficiency . | X-linked . | Acquired . |
|---|---|---|
| Antibody | Alloantibodies | Autoantibodies |
| Sex | Mostly male | Male and female |
| Family history | Usually present | Absent |
| Risk factors | Genetic and environmental | Malignancy, autoimmune disease, postpartum period, drug-induced, ∼50% idiopathic |
| Age onset | First 2 decades (20 exposure days) | Biphasic Female*: 20-30 y Male: >60 y |
| Bleeding phenotype | Recurrent hemarthrosis and hematomas not responsive to FVIII replacement therapy | Sudden onset of bleeding, >80% major hemorrhages mucocutaneous, extensive bruises, hematomas, and rarely hemarthrosis |
| Immunoglobulin type | IgG1 and 4 | IgG1 and 4, IgA |
| Inhibitor type: inhibition of FVIII activity | Type I, linear-kinetics inhibition correlated with inhibitor titers | Type II, rapid initial inactivation phase followed by a slower equilibrium phase with some residual FVIII activity |
| Bypass agents for hemostasis† | Formal indication | Risk and benefit ratio: risk of bleeding and underlying cardiovascular risk |
| FVIII concentrate protein infusion (ITI) | Commonly indicated | No standard but used occasionally |
| Immunosuppression | Occasionally | Commonly indicated |
| Mortality risk in patients with current inhibitors | Threefold higher than noninhibitor due to bleeding (US data) | ∼15-20% due to severe infection, bleeding, and cardiovascular complications |
| Spontaneous remission | Rarely, low titers (transient inhibitors) | 20-30% usually in postpartum inhibitors |
| FVIII deficiency . | X-linked . | Acquired . |
|---|---|---|
| Antibody | Alloantibodies | Autoantibodies |
| Sex | Mostly male | Male and female |
| Family history | Usually present | Absent |
| Risk factors | Genetic and environmental | Malignancy, autoimmune disease, postpartum period, drug-induced, ∼50% idiopathic |
| Age onset | First 2 decades (20 exposure days) | Biphasic Female*: 20-30 y Male: >60 y |
| Bleeding phenotype | Recurrent hemarthrosis and hematomas not responsive to FVIII replacement therapy | Sudden onset of bleeding, >80% major hemorrhages mucocutaneous, extensive bruises, hematomas, and rarely hemarthrosis |
| Immunoglobulin type | IgG1 and 4 | IgG1 and 4, IgA |
| Inhibitor type: inhibition of FVIII activity | Type I, linear-kinetics inhibition correlated with inhibitor titers | Type II, rapid initial inactivation phase followed by a slower equilibrium phase with some residual FVIII activity |
| Bypass agents for hemostasis† | Formal indication | Risk and benefit ratio: risk of bleeding and underlying cardiovascular risk |
| FVIII concentrate protein infusion (ITI) | Commonly indicated | No standard but used occasionally |
| Immunosuppression | Occasionally | Commonly indicated |
| Mortality risk in patients with current inhibitors | Threefold higher than noninhibitor due to bleeding (US data) | ∼15-20% due to severe infection, bleeding, and cardiovascular complications |
| Spontaneous remission | Rarely, low titers (transient inhibitors) | 20-30% usually in postpartum inhibitors |