Autoantibodies in Autoimmune Coagulation Factor Deficiencies: A Review of Inhibitory and Clearance-Accelerating Mechanisms from Japanese Practice.

Autoimmune acquired coagulation factor deficiency (AiCFD) represents a rare coagulation disorder that primarily affects older people and sometimes causes fatal bleeding; therefore, clinicians need to consider this when encountering patients with unexplained bleeding. AiCFD is caused by the production of autoantibodies against one's own coagulation factor, which markedly inhibit its function, or accelerate its clearance from plasma, resulting in hemostatic failure. The plasma of affected patients shows various abnormal findings, because anti-coagulation factor autoantibodies are polyclonal, and each clone has different properties. First, inhibitor type autoantibodies target the functional sites of coagulation factors, thereby considerably reducing their activity. Second, clearance-accelerating autoantibodies bind to non-functional sites and cause rapid removal of coagulation factors from the blood, thereby reducing their levels (and their activity in parallel). Third, mixed type autoantibodies (inhibitory clearance-accelerating) substantially reduce coagulation factor activity and level to various degrees. Most anti-coagulation factor autoantibodies are inhibitory clearance-accelerating types, although pure inhibitor types remain clinically significant; however, the pure clearance-accelerating type appears to be rare, possibly because the autoantibody is not detected unless it exceeds the level of the target coagulation factor (pseudo-autoantibody negative). Moreover, anti-factor XIII autoantibodies are particularly complex, as they interfere with the A subunit (Aa type), its activated form (Ab type), and/or the B subunit (B type). Of the three types, Aa type anti-factor XIII autoantibodies contain a mixture of different inhibitor type autoantibodies in various ratios in plasma, resulting in an extremely diverse range of test findings. Therefore, care must be taken when diagnosing and assessing the efficacy of treatment.