Presence Of Fibrinogen Degradation Products Research Articles

Interaction of plasminogen and fibrin in plasminogen activation.

Glu1-, Lys77-, miniplasminogens, kringle 1-3, kringle 1-5A, and kringle 1-5R were able to bind with fibrin, while microplasminogen and kringle 4 did not bind significantly. Kringle 1-5A, but not kringle 1-3, effectively inhibited the binding of Glu1-, Lys77-, and miniplasminogens with fibrin. Miniplasminogen also inhibited the binding of Glu1-plasminogen with fibrin. The binding of kringle 1-3 with fibrin was blocked by mini- or Glu1-plasminogen. It is therefore evident that there are two fibrin-binding domains in plasminogen and that the one in kringle 5 is of higher affinity than that in kringle 1-3. CNBr cleavage products of fibrinogen effectively enhanced the activation of Glu1-, Lys77-, or miniplasminogens, but not microplasminogen, by tissue-type plasminogen activator. Kringle 1-5, but not kringle 1-3, dose-dependently inhibited the enhancement by fibrinogen degradation products of Glu1-plasminogen activation by the activator. Lysine and epsilon-aminocaproic acid could inhibit the binding of plasminogens and plasminogen derivatives with fibrin and block the enhancement effect of fibrinogen degradation products on plasminogen activation. The data clearly illustrate that the binding of plasminogen with fibrin, mainly determined by kringle 5, is essential for effective activation by tissue-type plasminogen activator. However, the presence of kringle 1-4 in the plasminogen molecule is required for the full enhancing effect since the kcat/Km of miniplasminogen activation in the presence of fibrinogen degradation products was 8.2 microM-1 min-1 which is significantly less than 52.0 microM-1 min-1 of Glu1-plasminogen.

A latex agglutination assay for D dimer: evaluation and application to the diagnosis of thrombotic disease.

Although latex agglutination assays have been used for some years to diagnose thrombotic disorders, only recently has it been possible to measure specifically the products of fibrin breakdown in the presence of fibrinogen degradation products, by using monoclonal antibodies. We have evaluated a preparation of latex particles coupled to the monoclonal antibody DD-3B6/22, which is specific for cross-linked fibrin degradation products (XDP) and allows accurate discrimination between normal and pathological conditions. Of samples from 515 apparently healthy volunteers, 97.7% failed to agglutinate the latex; the normal reference interval for XDP determined by enzyme immunoassay was less than 78-320 micrograms/L. The use of different anticoagulants with or without the addition of a protease inhibitor had no significant effects on the results of the latex assay. The latex preparation provides a useful, rapid diagnostic tool for assaying small numbers of samples or as an emergency test.

Disseminated Intravascular Coagulation and Antiprotease Activity in Acute Human Pancreatitis

The coagulation and fibrinolytic systems were analysed parallel to the clinical evaluation in 27 attacks of acute human pancreatitis of different severity. Consumptive coagulopathy was evident from decreased platelet counts, decreased prothrombin values and consumption of fibrinogen during the first days in severe attacks. Fibrinolysis was suggested by decreased plasminogen values and the presence of fibrinogen degradation products. All main protease inhibitors of the two systems showed protease-antiprotease complexation and lower functional than quantitative values. Functional levels of the protease inhibitors were almost zero in the peritoneal fluid in severe attacks. It is concluded that severe acute pancreatitis results in consumptive coagulopathy and fibrinolysis together with a local antiprotease deficiency. All the changes are closely correlated to the severity of the disease.

Potentiation of the activation of glu-plasminogen by streptokinase and urokinase in the presence of fibrinogen degradation products

When Glu-plasminogen was activated by streptokinase (SK), the presence of early degradation products of fibrinogen (FgDP) enhanced the rate of activation. When various fragments of FgDP were fractionated, FgDP-Y and E fragments had a potentiating activity while D fragment did not. When Glu-plasminogen was activated by urokinase (UK), the activation rate was enhanced by every fragment of FgDPs, i.e. X, Y, D and E. Although both D and E fragments seem to be able to bind with lysine binding sites of Glu-plasminogen, and to enhance the activation rate by UK, only binding of E fragment with plasminogen can result in enhancement of the activation of Glu-plasminogen by SK.

The sulphite precipitation method for fibrinogen measurement; Its use on small samples in the presence of fibrinogen degradation products

A technique based on precipitation by sodium sulphite (Na 2SO 3) has been developed for measuring the fibrinogen concentration of small (100 μ1) samples. This technique offers technical advantages over the throm bin-clotting method, especially when measuring dilute solutions. Measurements made with the sulphite technique on fibrinogen solutions and on plasma samples were not significantly different from those obtained with the thrombin-clotting method. The effect of fibrinogen degradation products (FDP) on the two methods was investigated. Sulphite was found to precipitate fibrinogen fragments X and Y in conjunction with fibrinogen, but not D or E; thrombin clotted some forms of fragment X and fibrinogen but its action was inhibited in the presence of substantial amounts of Y, D or E. Neither technique was very sensitive to the presence of FDP in plasma, concentrations of at least 15% of that of the fibrinogen being required in order to affect the measurement of fibrinogen. The most prevalent FDP in plasma, namely fragments X and Y, are measured together with fibrinogen by the sulphite method, their effect on the thrombin-clottable fibrinogen is difficult to predict. Thus, the sulphite method could prove useful for measuring fibrinogen in plasma samples containing high levels of FDP.

Disseminated intravascular coagulation after excision of giant hemangioma

The importance of recognizing disseminated intravascular coagulation as the cause of severe bleeding diathesis in a patient with giant hemangioma is illustrated. A sixteen year old boy with multiple giant cavernous hemangiomas had massive local bleeding after each of the three times surgical excision of the hemangiomas was carried out. Detailed laboratory studies performed on the third occasion provided evidence of disseminated intravascular coagulation as shown by the decreased platelet counts and plasma levels of fibrinogen and factors V and VIII, the prolongation of prothrombin time, partial thromboplastin time, thrombin time, and arvin time, the presence of fibrinogen degradation products, and the increased fibrinolytic activity. Cessation of bleeding accompanied by a return of the laboratory values to within normal limits occurred after correction of the disseminated intravascular coagulation with heparin and acetylsalicylic acid. The use of epsilon aminocaproic acid is contraindicated in this situation.

The Measurement of Heparin

SummaryA method for the measurement of heparin utilising the potentiating effect of heparin on the action of anti-factor Xa is described. The effect on the assay of platelet contamination of plasma, the presence of fibrinogen degradation products and low levels of anti-factor Xa have been studied. The assay method has been compared with the calcium thrombin time method and a group of obstetrical patients have been studied using both methods.

The Effect of Fibrinogen Degradation Products on Plasmin Activity

SummaryPurified fibrinogen degradation products Y, D or E were not found to exert antiplasmin activity as measured by the clot lysis time.Spontaneous inactivation of plasmin was observed during incubation at 37° C. This inactivation was partly prevented by the presence of fibrinogen degradation products, as well as by other proteins.

Influence of pH on the Incorporation of Fibrinogen Degradation Products into Fibrin Clots as Studied by Tracer Technique

Fibrinogen degradation products (FDP) interfere with coagulation of fibrinogen and may lead to incorrect estimates of fibrinogen in plasma and of FDP in serum. At pH 7.8 as much as 50–60 % of early FDP were incorporated into clots made from whole blood or from plasma, whereas late FDP were incorporated to minor extent. By lowering pH to 6.3, incorporation of early FDP was markedly reduced. The amount of unclotted fibrin due to the presence of FDP was also reduced. Thus, for a more correct estimate of FDP in serum, it is suggested that pH of blood or plasma should be lowered prior to clotting. Estimation of fibrinogen according to the Jacobsson assay (pH 6.3) is fairly exact in the presence of FDP, except at very high FDP concentrations.

Parallel Determinations of FDP and Fibrin Monomers with Various Methods

SummaryThe following tests were performed in 305 persons with one or other of the following conditions: malignant disease, postoperative complications, sepsis or multiple fractures, liver disease, pregnancy, the puerperium, renal disease, dysproteinaemia and different blood disorders : 1. fibrinogen degradation products (FDP) with Niléhn’s immunochemical method; 2. the thrombin time; 3. the Reptilase time; 4. the ethanol gelation test; 5. the protamine sulphate precipitation test. It was found that a prolonged thrombin time or Reptilase time in a given case was not necessarily a sign of the presence of FDP. Thus, neither determination of the thrombin time nor of the Reptilase time can substitute for specific determination of FDP. A positive ethanol gelation test was found in only 5 out of 17 patients with a low platelet count, low P & P test, low factor V, low fibrinogen and clinical signs of disseminated intravascular coagulation such as shock, disturbance of the periphery circulation, oliguria or anuria. No association was found between a positive ethanol gelation test and the presence of FDP. The protamine sulphate precipitation test was positive in only one of the 305 patients.

Fibrinogen degradation products in serum and urine of patients with systemic lupus erythematosus. Relation to renal disease and pathogenetic mechanism.

AbstractSerum and concentrated urine from blood donors, patients with rheumatoid arthritis and SLE patients with and without renal disease were tested for the presence of fibrinogen degradation products (FDP), using the tanned red cell hemagglutination inhibition immunoassay. The majority of blood donors had serum titers of 1:2 to 1:4, while the majority of patients with rheumatoid arthritis and systemic lupus erythematosus had titers of 1:8 to 1:32. FDP were detected in low titers in urine of nearly all blood donors, patients with rheumatoid arthritis and SLE patients without renal disease, whereas elevated titers were found in SLE patients with active renal disease. Several possible sources of the urinary FDP are discussed, and the role of fibrin deposition in glomerular injury is reviewed.

The Effects of Infusing Thrombin and Its Acetylated Derivative

Summary and ConclusionsDogs and rabbits were infused with acetylated thrombin (thrombin E) and clotting thrombin (thrombin C). Similar effects were noted in both animal series. Very large amounts of thrombin E could be tolerated, but resulted in defibrination. Following a transient hypercoagulable state, the blood became unclottable. The platelets and factors I, V, and VIII were markedly decreased. Factor II was moderately affected and factor VII-X showed no significant changes in most experiments. The presence of fibrinogen degradation products was indicated by a delay in the polymerization of fibrin monomers.Based on the shortening of the euglobulin lysis time, a decrease in the proactivator, and the appearance of inhibitors of fibrin monomer polymerization, it is concluded that transient fibrinolysis is induced by the infusion of thrombin. Its immediate mechanism could not be determined.

Soluble Unclottable Complexes Formed in the Presence of Fibrinogen Degradation Products (FDP) during the Fibrinogen-Fibrin Conversion and Their Potential Significance in Pathology

Summary1. With the aid of isotopie technique, it was shown, that fibrinogen, fibrinogen-fibrin intermediates and fibrinogen degradation products (FDP) may form soluble complexes, which are unclottable by thrombin.2. These complexes may be precipitated by protamine sulphate or by cooling to 4° C (par a coagulation),3. The above findings are discussed in regard to their significance in the pathology of the acute defibrination syndrome :a) Paracoagulation by protamine sulphate without addition of thrombin occurs when defibrination is caused by excessive intravascular clotting, while in cases of the syndrome due to proteolytic digestion of fibrinogen, paracoagulation occurs after combined action of thrombin and protamin sulphate.b) Formation of the complexes described above may explain the occurence of cryofibrinogens in various pathological states.c) Formation of these complexes is postulated to be an important factor involved in the development of the hemostatic defect. It may be as well the expression of a defence mechanism against intravascular fibrin formation by rendering unclottable the intermediates of the fibrinogen-fibrin conversion.