Fibrinogen Sevilla, a congenital dysfibrinogenemia characterized by an abnormal monomer aggregation and a defective plasmin lysis

Abstract

A dysfibrinogenemia (fibrinogen Sevilla) was detected in a 64-yr-old woman with no previous history of hemorrhagic diathesis or thrombosis. Thrombin and reptilase times were prolonged. The aggregation of fibrin monomers showed a prolonged latency time with a defective slope although fibrinopeptide release and clot stabilization were found to be normal. Plasmin proteolysis was abnormal with a much slower plasmic degradation in patient's purified fibrinogen. By chromatofocussing the patient's fibrinogen showed an abnormality in pattern elution with a second peak eluting at a pH slightly more basic than the normal one @H 5.5). Likewise, the isoelectrofocussing of purified non-reduced patient's fibrinogen in agarose gel showed an abnormal distribution in its focussed bands, especially in a group which focussed in a p&interval between 5.20-5.85. By two-dimensional electrophoresis we did not find any abnormality in the fibrinogen-reduced chains. These results could indicate that the abnormal monomer aggregation, as well as the defective plasmin lysis, could be due to conformational aspects of fibrinogen rather than to structural defects.

Fibrinogen longmont: A dysfibrinogenemia that causes prolonged clot‐based test results only when using an optical detection method

“…Dysfibrinogenemias with resistance to plasmin lysis have been reported to be associated with thrombotic symptoms [3]. However, there have been case reports indicating that this is not always so [9]. Our patient, to date, has not displayed any history of thrombosis.…”

Dysfibrinogenemia: A case with thrombosis (fibrinogen richfield) and an overview of the clinical and laboratory spectrum

“…The clinical and laboratory data suggest that the abnormal fibrin clots, while slow to form and initially susceptible to digestion, acquire secondary resistance to plasmin ly sis due to the architecture of the abnormal fibrin clot. Fibrinogen Richfield joins a subset of dysfibrinogenemias with abnormal polymerization, thrombosis, and plasmin resistance (e.g., Fibrinogen Haifa [50], Chapel Hill I11 [53], Dusard [54], and Sevilla [55]).…”

“…The pathophysiology of thrombotic dysfibrinogens has been attributed to various aspects of clot dissolution. These defects can be classified as abnormalities of fibrindependent plasmin generation or insensitivity of the clots to plasmin digestion [1,55]. Specific domains on fibrin (ogen) are required to bind thrombin, plasminogen, and tPA, and a dysfibrinogenemia with thrombosis has been reported to have reduced binding of tPA [73] and plasmin generation.…”