fibrinopeptide-b and Hemorrhagic-Disorders

A congenitally abnormal fibrinogen was isolated from the blood of a young woman with a severe bleeding diathesis. Coagulation tests showed a prolonged Thrombin and Reptilase time partially corrected by Ca2+. Polymerization of thrombin induced preformed fibrin monomers was severely impaired. Thrombin caused the release of fibrinopeptides with normal retention times on HPLC. However, the rate of release was abnormally slow and the total amount of fibrinopeptide A (FpA) released reached only approximately 50% of the theoretical maximum. The rate and quantity of FpA release was normal when Reptilase was used. Transmission Electron Microscopy (TEM) of Thrombin induced clots showed an altered clot structure characterized by a reduced mean fiber diameter. The mother has a polymerization defect similar to the propositus, her fibrinopeptide release is unaffected however. The father has a minor fibrinopeptide release defect suggesting the presence of two populations of fibrinogen. This study supports the idea that the fibrinogen isolated from the propositus has two defects inherited as separate genetic traits. This fibrinogen has been named Fibrinogen Guarenas I.

Topics: Adolescent; Afibrinogenemia; Biopolymers; Female; Fibrin; Fibrinogens, Abnormal; Fibrinopeptide A; Fibrinopeptide B; Hemorrhagic Disorders; Humans; Kinetics; Male; Metrorrhagia; Microscopy, Electron; Thrombin; Thrombin Time

We have determined the extent of fragment X formation during thrombolytic therapy by integration over time of the plasma fibrinopeptide B beta 1-42 concentration. This peptide is quantitatively released when fragment X is formed by plasmin action on fibrinogen or fibrin I. In response to streptokinase (SK) and rt-PA, 264 +/- 54 and 95 +/- 12 mg/dl respectively of fibrinogen was converted to fragment X. By immunoblotting, fragment X was demonstrated as early as 5 min after SK and 30 min after rt-PA, and was still evident 24 h after treatment. Patients treated with SK showed extensive further plasmin degradation of fragment X to fragments Y and D. Thus fragment X concentrations tend to be more similar in the two groups than would be expected from the extent of fibrinogen breakdown. Fragment X forms clots, but these have lower tensile strength and are more susceptible to further plasmin lysis than clots of fibrin. Thus the similar bleeding observed in the two treatment groups might be a reflection of their similar plasma fragment X concentrations.

Topics: Fibrin Fibrinogen Degradation Products; Fibrinolysin; Fibrinolytic Agents; Fibrinopeptide B; Hemorrhagic Disorders; Humans; Myocardial Infarction; Recombinant Proteins; Streptokinase; Tissue Plasminogen Activator

A new case of congenital dysfibrinogenemia has been discovered in a 20 year old woman, who suffered from a severe postpartal hemorrhage after the delivery of her first child, followed by episodes of thrombosis. Coagulation studies reveal a prolongation of thrombin time, reptilase time was immeasurable. Thromboplastin time and partial thromboplastin time were slightly prolonged. Low fibrinogen levels were obtained by techniques, which depend on the coagulation velocity following addition of thrombin, while immunological procedures gave slightly diminished values of fibrinogen. Patients's fibrinogen had a moderate inhibitory effect on the fibrin formation in normal plasma. However, inhibitors of the fibrinogen-fibrin conversion could not be detected. Coagulation factors were normal, fibriolysis as well. The cause of the coagulation disorder was found to be a defect of the fibrinogen molecule, leading to an abnormal fibrin polmerization of patient's fibrin monomers. The release of the fibrinopeptides in the paperelectrophoresis was normal. The defect of the fibrinogen molecule did not protect from thrombotic complications. The same defect could be found in the lower scale in patient's father, 4 of her 7 brothers and sisters, and her son.

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Tests; Female; Fibrinogen; Fibrinolysis; Fibrinopeptide A; Fibrinopeptide B; Hemorrhagic Disorders; Humans