Quantitative Estimation of Split Products of Fibrinogen in Human Serum, Relation to Diagnosis and Treatment

Abstract

Split products of fibrinogen and fibrin are found in the sera of patients with defibrination syndrome and/or fibrinolysis. They may result from spontaneous (primary) fibrinolysis or secondary fibrinolysis of intravascular fibrin deposits. The split products can be detected by several immunologic methods. Both immunodiffusion and immunoelectrophoresis in agar gel show abnormal bands in high-titer pathologic serum samples (usually more than 12 µg./ml.). One of the lines present on immunodiffusion is closer to the point of application than is the other. The position of the closer band might result from the presence of small amounts of fibrinogen-sized molecules or from moderate amounts of partially polymerized or digested fibrin. A precipitin test in a capillary tube offers a simple and sensitive method for demonstrating split products; immediate precipitin occurs with high-titer products but lesser amounts may require up to 18 hours incubation. The Fi test, agglutination of antibody-coated latex particles, is simple, rapid, moderately sensitive, and commercially available but sometimes yields false-positive results. The precipitin or Fi test on thrombin-treated blood, plasma, or serum may be positive when split products are present in high titer, can be read immediately, and thus provides a rapid bedside test. Neither the precipitin nor the Fi test is as sensitive as the tanned red-cell hemagglutination inhibition immunoassay (TRCHII) for the quantitation of fibrinogen and its split products. This test is sensitive to 2.0-5.0 µg./ml. of fibrinogen or split products and much more reliable than the other methods. For example, 13 of 22 samples with up to 24 µg./ml. of split products yielded negative results with the Fi test and positive results with TRCHII. Because defective and incomplete coagulation may coexist with fibrinolysis in these clinical syndromes, an excess of thrombin must be added to remove thrombin-clottable fibrinogen and establish the presence of nonclottable split products. It was necessary to demonstrate split products to diagnose occult fibrinolysis; throm-treated normal serum was found to contain up to 2.0-5.0µg./ml. of split products. Up to 768 µg./ml. split products were detected in serum from patients with reduced fibrinogen with associated primary fibrinolysis (idiopathic, hepatic disease), induced fibrinolysis (streptokinase, urokinase) or in defibrination syndrome with secondary fibrinolysis (metastatic cancer, abruptio placentae, diffuse allergic vasculitis). In other patients with secondary fibrinolysis, up to 96 µg./ml. were occasionally encountered during and following obstetrical delivery of normal or dead fetus, in pulmonary embolism, myocardial infarction, and rheumatoid arthritis. The actual quantity of split products was of greatest value in assessing clinical progress. Heparin therapy in patients with defibrination syndrome, for example, was associated with a rise in plasma fibrinogen and a fall in the concentration of split products. The data indicate that trace amounts of fibrinolytic split products may occur in normal serum. Larger amounts are found both in primary and secondary fibrinolysis, which are relatively common disorders.

Mesterolone: thrombosis during treatment, and a study of its prothrombotic effects.

“…by the Laurell technique as adapted by Zimmerman, Ratnoff & Powell (1971); antithrombin III activity by the method of Howie, Prentice & McNicol (1973); and fibrinogen by the thrombin-time method of Clauss (1957) using a Dade fibrometer. Fibrinogen-fibrin degradation products (FDP) were measured in serum by the method of Merskey, Kleiner & Johnson (1966). Plasminogen was determined by the method of Remmert & Cohen (1949) as modified by Alkjaersig, Fletcher & Sherry (1959); euglobulin lysis time by the method of Buckell (1958), and urokinase sensitivity by the method of McNicol & Douglas (1964).…”

Isolation of Fibrinogen–Fibrin Related Antigen from Human Plasma by Immunoaffinity Chromatography: its Characterization in Normal Subjects and in Defibrinating Patients with Abruptio Placentae and Disseminated Cancer

“…About 3% ofthe contaminating protein was probably cold-insoluble globulin. Antisera to the fibrinogen were raised in white New Zealand rabbits and in a donkey (Merskey et al, 1966). Repeated adsorption (about 10 times) with normal aged human serum was performed in the presence of 2% PEG, mol wt 4000.…”

“…Binding capacity and specijcity ofthe antiserum. (a) Purified fibrinogen and fragments D and E, respectively, were coupled to formalinized, tanned sheep red cells (Merskey et al, 1966). The antiserum reacted with these cells to a titre of at least 1:2000 in each of three instances.…”

Failure of Heparin Therapy to Affect the Clinical Course of Severe Pre‐eclampsia

“…The coagulation and fibrinolytic tests were : fibrinogen (Ratnoff and Menzie, 1951), cryofibrinogen (Howie et al, 1971), plasminogen (Remmert andCohen, 1949), serum fibrinolytic degradation products (FDPs) (Merskey et al, 1966), urinary FDPs (Howie et al, 1971), euglobulin lysis time (Nilsson and Olow, 1962) and platelet count (Dacie and Lewis, 1963). Platelet adhesiveness to a renal dialysis membrane was measured in citrated whole blood, using the test-cell system described by Lindsay et al…”