Defective Activation of Clotting, Fibrinolytic, and Permeability-Enhancing Systems in Human Fletcher Trait Plasma

Abstract

When normal plasma is exposed to foreign surfaces, Hageman factor (HF, factor XII) is activated; under appropriate circumstances, it then initiates reactions leading to coagulation, fibrinolysis, increased vascular permeability, esterolytic activity, and kinin formation. However, coagulation, fibrinolysis, and increased vascular permeability were impaired in plasma from an individual with Fletcher trait, despite a normal concentration of HF that is functionally and immunologically indistinguishable from that in normal plasma. This defective clotting is completely repaired by the addition of small amounts of normal plasma, HF-deficient plasma, plasma thrombo-plastin antecedent (PTA)-deficient plasma, or activated PTA but only partially repaired by the addition of activated HF. Defective fibrinolysis and permeability-enhancing activity were partially corrected by the addition of small amounts of normal plasma, HF-deficient plasma, PTA-deficient plasma, or activated HF. A preparation of partially purified plasma kallikrein largely repaired defective coagulation and fibrinolysis in Fletcher trait plasma in the presence of kaolin. In immunodif fusion studies, no precipitin line formed between Fletcher trait plasma and monospecific antikallikrein serum. Fletcher trait plasma appeared to be deficient in a plasma prekallikrein, which most probably participates in the functioning of activated HF. These studies emphasize the intimate relationships among clotting, fibrinolysis, and enhancement of vascular permeability.