Prekallikrein deficiency in man

Area of Science:

• Biochemistry
• Hematology
• Physiology

Background:

• Fletcher factor deficiency causes abnormal thromboplastin formation and kinin generation.
• The precise role and identity of Fletcher factor in coagulation pathways were not fully understood.

Purpose of the Study:

• To investigate the identity of Fletcher factor.
• To elucidate the role of Fletcher factor in kinin and plasmin generation.

Main Methods:

• Assessing plasma correction with normal, Hageman factor-deficient, or PTA-deficient plasma.
• Evaluating correction with purified human or rabbit prekallikrein.
• Measuring kinin generation upon kaolin exposure.
• Assessing PF/dil generation in Fletcher factor-deficient plasma.
• Analyzing plasmin formation in dilute, acidified plasma with kaolin.

Main Results:

• Fletcher factor-deficient plasma was corrected by normal plasma and purified prekallikrein.
• Prekallikrein addition corrected the defect in kinin generation.
• Prekallikrein antigen was undetectable in deficient plasma.
• Fletcher factor-deficient plasma showed defects in PF/dil and plasmin generation, which were corrected by prekallikrein or Hageman factor-deficient plasma.

Conclusions:

• The data strongly support the identity of Fletcher factor and prekallikrein.
• Fletcher factor (prekallikrein) plays a crucial role in kinin and plasmin generation.
• Understanding Fletcher factor's identity clarifies its function in hemostasis and inflammation.