FIBRINOGENS NEW YORK II, III, AND IV : RELATIONSHIP BETWEEN ABNORMAL FIBRIN MONOMER POLYMERIZATION, BLEEDING TENDENCY, AND THROMBOTIC TENDENCY

Abstract

It has been proposed that a normal fibrin monomer polymerization is required for a normal fibrin potentiation of tPA-induced plasminogen activation. Accordingly, an abnormal fibrin moncmer polymerization may contribute to a thrombotic tendency. To investigate this possibility, three abnormal plasma fibrinogens (dysfibrinogenemia) have been studied and tentatively designated New York II (NY-II), New York III (NY-III), and New York IV (NY-IV) after the city where they were described.Each of these patients has a long thrombin clotting time (TCT), a long Reptilase clotxing time, and an abnormal fibrin monomer polymerization. The abnormal fibrin moncmer polymerization can be corrected by addition of Ca2+. NY-II is characterized by a normal level of plasma fibrinogen, but delayed fibrino-peptide release and marked prolongation of the TCI; NY-III, by a normal level of plasma fibrinogen and a normal fibririopeptide release; and NY-IV, by a low level of plasma fibrinogen, a normal fibrinopeptide release, and marked prolongation of the TCT. Each of these cases appears to be congenital, not acquired although the absence of data on relatives prevents definite conclusions. SDS-PAGE analysis of the mobility of the reduced abnormal fibrinogens shows no detectable abnormality, indicating no significantly altered molecular size of Aα, Bβ, and γ chains.No patient appears to be associated with either a bleeding or a thrombotic tendency. Thus, no direct association is observed between an abnormal fibrin monomer polymerization and a thrombotic tendency. Accordingly, fibrin monomer polymerization is not a function absolutly required for potentiation of plasminogen activation. However, based on the present observations and the observations previously described of abnormal fibrinogens with abnormal fibrin monomer polymerization from patients associated with bleeding and/or thrombotic tendency, a bleeding tendency seems to be correlated with a condition in which both a long TCT and an abnormal fibrin moncmer polymerization can not be normalized by addition of Ca2+.