White cell-associated procoagulant activity induced by ABO incompatibility

Area of Science:

• Hematology
• Immunology
• Transfusion Medicine

Background:

• Disseminated intravascular coagulation (DIC) is a known complication of acute hemolytic transfusion reactions (aHTRs).
• Immune hemolysis, particularly ABO incompatible red blood cell (RBC) reactions, can activate coagulation.
• Peripheral blood white cells, especially monocytes, can express procoagulant activity (PCA) under inflammatory conditions.

Purpose of the Study:

• To investigate the expression of PCA by peripheral blood white cells in ABO RBC incompatibility.
• To elucidate the mechanisms of coagulation activation during immune hemolysis.

Main Methods:

• Incubation of group O whole blood with incompatible (group A) or compatible (group O) RBCs.
• Separation, washing, and lysis of white cells for PCA assay using a clotting time method.
• Investigation of coagulation activation pathways using factor-deficient plasmas, anti-tissue factor antibodies, and anti-CD11b antibodies.

Main Results:

• Significant white cell-associated PCA was observed in response to incompatible RBCs, but not compatible RBCs.
• PCA generation required complement and protein synthesis, and was dependent on tissue factor and a CD11b-mediated mechanism.
• PCA was reduced by factor VII-deficient plasma and factor X-deficient plasma, implicating the extrinsic pathway of coagulation.

Conclusions:

• White cell-associated PCA is generated during ABO RBC incompatibility.
• This PCA may contribute to DIC in acute hemolytic transfusion reactions.
• Mechanisms involve tissue factor expression and CD11b-dependent activation of factor X.