HEMOGLOBIN INHIBITION OF FIBRIN POLYMERIZATION AND CLOTTING

Clotting of human plasma by human alpha-thrombin was prolonged in the presence of haemoglobin as was human and bovine fibrinogen. Specifical ly, the clot time doubled for human plasma, human fibrinogen and bovin e fibrinogen at 483, 233, and 116 mu M haemoglobin, respectively. Fibr inopeptide A release was not inhibited at concentrations in similar to 16000 molar excess compared with alpha-thrombin. Turbidometric analys is of fibrin polymerization showed a lengthening of the lag phase as w ell as the fibrin assembly process in the presence of haemoglobin. The se findings suggested that neither fibrinogen recognition nor catalyti c efficiency of thrombin was affected, implying that haemoglobin inter feres with fibrin polymerization. Since human blood contains sufficien t haemoglobin in erythrocytes to generate concentrations of up to 2.3 mM upon cell lysis, and haemoglobin concentrations of 0.16-0.48 mM cau sed 1.25 to two times longer clotting times in fresh human plasma, res pectively, haemoglobin may act to modulate clot formation under condit ions of haemolysis.