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At least 19 recordsLinked to original sources
PubMed1991

The rate of fibrinopeptide B release modulates the rate of clot formation: a study with an acquired inhibitor to fibrinopeptide B release.

An asymptomatic 50-year-old male with a gamma globulin paraprotein was found to have prolonged prothrombin time, activated partial thromboplastin time, and thrombin time but a normal reptilase time. The prolonged clotting times were not the result of a factor deficiency because they were not corrected by the addition of normal plasma. Instead, this patient had an antibody that delayed thrombin-mediated fibrinopeptide B release thereby producing an apparent dysfibrinogenaemia. His isolated IgG prolonged the thrombin clotting time of both normal plasma and fibrinogen. Precincubation of his IgG with fibrinopeptide B, but not with fibrinopeptide A or thrombin, decreased its ability to prolong the thrombin clotting time. The patient's purified IgG but not control IgG delayed thrombin-mediated fibrinopeptide B release from fibrinogen without affecting the release of fibrinopeptide A. These studies define a novel, clinically silent dysfibrinogenaemia due to an antibody that delays thrombin-mediated fibrinopeptide B release from fibrinogen thereby markedly prolonging the clotting times.

Blood Coagulation Disorders↗
PubMed1998

Substitution of tyrosine for phenylalanine in fibrinopeptide A results in preferential thrombin cleavage of fibrinopeptide B from fibrinogen.

Phenylalanine at residue 8 in the Aalpha chain of fibrinogen is a highly conserved amino acid that is believed to be critical for binding and catalysis by the serine protease thrombin. We have examined the requirement for Phe at this position by constructing a variant recombinant fibrinogen with a conservative substitution of tyrosine for phenylalanine, Aalpha F8Y fibrinogen. We found that the variant fibrinopeptide A (F8Y 1-16) was cleaved by thrombin, in contrast to the lack of cleavage of an Aalpha 1-23 peptide and an Aalpha 1-50 fusion protein with the same substitution. This result indicates that fibrinogen residues other than Aalpha 1-50 participate in thrombin binding and fibrinogen proteolysis. We found, for the first time, that thrombin-catalyzed lysis of the fibrinogen Bbeta chain preceded lysis of the Aalpha chain, such that fibrinopeptide B (FpB) was released prior to F8Y 1-16. Kinetic analysis demonstrated that F8Y 1-16 was a very poor substrate for thrombin, with a specificity constant 280-fold lower than normal fibrinopeptide A. FpB was also a poor substrate, but the specificity constant for FpB was only 4-fold lower than normal. Consequently, FpB was preferentially released from Aalpha F8Y fibrinogen. This "role reversal" had a dramatic effect on polymerization, such that the rate of Aalpha F8Y fibrinogen polymerization was 13% of the rate of normal recombinant fibrinogen. These results confirm the importance of phenylalanine at Aalpha chain residue 8 for efficient thrombin-catalyzed proteolysis of fibrinogen, and further demonstrate that sequential fibrinopeptide release has an important role in normal polymerization.

Amino Acid Substitution↗
PubMed1985

A monoclonal antibody, specific for human fibrinogen, fibrinopeptide A-containing fragments and not reacting with free fibrinopeptide A.

Spleen cells of BALB/c mice, immunized with fragments Y of normal human fibrinogen, were fused with P3 X 63 Ag 8653 myeloma cells. A clone was found which produces monoclonal antibodies (Mab-Y18) of the IgM kappa type. Mab-Y18 is immunoreactive with normal human fibrinogen, and its fragments X, Y, N-terminal disulphide knot, A alpha-chain, and A alpha stretch 1-51. The immunoreactivity with these same fragments disappears upon treatment with thrombin or arvin. This strongly suggests that fibrinopeptide A is an essential component of the Mab-Y18 epitope. This is supported by the finding that Mab-Y18 prolongs the thrombin and arvin clotting times of human fibrinogen by inhibition of the fibrinopeptide A release. More detailed information about the nature of the Mab-Y18 epitope was obtained from studies with genetic variants of human fibrinogen (especially fibrinogen Metz) and with fibrinogens from other mammalian species. These studies show that amino acid residue A alpha 16 (arginine) of fibrinopeptide A is essential for the Mab-Y18 epitope. Mab-Y18 does not react with free fibrinopeptide A.

Animals↗
PubMed1992

[Plasma fibrinopeptide A, fibrinopeptide B beta 15-42 and 4 other coagulation factors levels in patients with diabetic retinopathy].

Fibrinopeptide A (FPA), fibrinopeptide B beta 15-42 (FPB beta 15-42) and other coagulation factors (anti-thrombin III, thrombin-antithrombin complex, alpha 2-macroglobulin, plasmin inhibitor complex) were measured in the plasma of 101 patients with diabetes mellitus (DM). The levels in 80 healthy adults were also measured for comparative purposes. The mean levels of FPA, FPB beta 15-42 and the other 4 coagulation factors in the DM patients were significantly higher than in the controls (p < 0.05). The mean levels of FPA and FPB beta 15-42 in patients with diabetic retinopathy (DR) were higher than in those without DR, that is in those with proliferative diabetic retinopathy (PDR) higher than in those with simple diabetic retinopathy (SDR). In patients after panretinal photocoagulation (PRP), the mean level of FPA was higher and that of FPB beta 15-42 was lower than in patients before PRP. In the SDR group, the level of FPB beta 15-42 was significantly correlated with the progression of diabetic retinopathy. We suggest that there was a close correlation between plasma FPA and FPB beta 15-42 levels and activity or progression of disease, and that the investigation of these levels may be useful for the judging of prognosis or effect of therapies of diabetic retinopathy.

Blood Coagulation Factors↗
PubMed1987

[Effects of acid-base balance and Apgar score on fibrinopeptide A and fibrinopeptide B beta 15-42 in umbilical cord blood].

Previous studies on asphyxia neonatorum show that the infant's blood is in a state of hypercoagulability at such a time. In the present study, we determined the amount of fibrinopeptide A (FPA) and fibrinopeptide B beta 15-42 (FPB beta), new sensitive indicators of the coagulation-fibrinolytic system, in the newborn, and examined their relationship to the acid-base balance in umbilical artery blood in elective cesarean section and vaginal delivery, as well as to the Apgar score (Ap. S). In addition, the findings in umbilical cord blood were then compared with those in the blood of normal adults. The results were as follows: In vaginal delivery, infants with Ap. S at 5-7, pH, had significantly lower HCO-3 and BE readings lower while PCO2 was significantly increased, which indicated respiratory and metabolic acidosis. In the vaginal delivery group, FPA was significantly increased in infants with pH under 7.24, PCO2 over 50 mmHg, BE under -8 and Ap. S at 5-7, and as well as in infants in the elective cesarean section group with Ap. S at 5-7. This suggests that the production of thrombin is accelerated if the fetus is asphyxiated. FPB beta was not significantly different among groups. However, FPB beta was significantly higher in various vaginal delivery groups than in the elective cesarean section group (Ap. S greater than or equal to 8), which implies acceleration of the production of plasmin and fibrinolysis in vaginal delivery. FPA and FPB beta were markedly increased in umbilical cord blood as compared with the blood of normal adults. This suggests that blood coagulation and fibrinolysis were accelerated in umbilical cord blood.

Acid-Base Equilibrium↗
PubMed1986

Levels of fibrinopeptide A (FPA) and fibrinopeptide B beta 15-42 (FPB beta) in urine and plasma after urokinase administration in patients with chronic glomerulonephritis.

A study on the significance of the measurement of fibrinopeptide A (FPA) and fibrinopeptide B beta 15-42 (FPB beta) in urine and plasma before and after urokinase (UK) administration in patients with chronic glomerulonephritis is described. FPA and FPB beta in urine and plasma were measured by radioimmunoassay. The levels of fibrinogen degradation product (FDP) in urine and sera were also determined before and after the UK administration. UK was administered at a dose of 48,000 IU/20 ml in saline intravenously, followed by an intravenous infusion of 250 ml of 5% glucose for one hour. It was demonstrated that the levels of FPB beta in urine and plasma showed a significant increase after UK administration in patients with chronic glomerulonephritis. However, there was no significant difference in the levels of FDP in urine and sera before and after UK administration. It was concluded that the measurement of FPB beta in urine and plasma may be useful for evaluating the efficacy of UK therapy in patients with chronic glomerulonephritis.

Adult↗
PubMed1985

Plasma concentrations of fibrinopeptide A and fibrinopeptide B beta 15-42 in glomerulonephritis and the nephrotic syndrome.

Plasma fibrinopeptide A (FPA) and fibrinopeptide B beta 15-42 concentrations were determined by radioimmunoassay in 46 patients with glomerulonephritis and the nephrotic syndrome. An increase in plasma FPA and B beta 15-42 levels was noted in these patients; this increase was marked in the nephrotic patients. There was a positive correlation in these patients between plasma FPA and B beta 15-42 levels. The B beta 15-42/FPA ratio was significantly higher in nonnephrotic patients compared with controls. Intravascular coagulation with subsequent fibrinolysis to regulate fibrin formation may occur in patients. A positive correlation was found between plasma B beta 15-42 level and serum urea nitrogen or serum creatinine concentration, suggesting that plasma B beta 15-42 level is influenced not only by plasmin action, but also by renal dysfunction.

Adolescent↗
PubMed1976

Reactivity of fibrinogen and fibrinopeptide A containing fibrinogen fragments with antisera to fibrinopeptide A.

Two antisera used in the radioimmunoassay for human fibrinopeptide A (FPA) which appear to have different immunochemical specificities have been tested for cross-reactivity with fibrinogen and with three fragments of fibrinogen which contain the FPA sequence. These fragments were the three-chain, NH2-terminal disulfide knot (N-DSK) produced by CNBr cleavage of fibrinogen, the reduced, carboxymethyl Aalpha chain portion of the N-DSK, and fragment E produced by plasmin digestion of fibrinogen. One antiserum (R-2) showed high specificity for free FPA and less than 2% cross-reactivity with fibrinogen or the FPA-containing fragments. The other antiserum (R-33) possessed a much higher degree of cross-reactivity with the FPA-containing fragments. Synthetic and native fibrinopeptides were found to be indistinguishable in the assay system with either antiserum. As a result of these studies, an hypothesis has been developed concerning the nature of the antigenic determinants on FPA which favor measurement of free FPA and limit cross-reactivity with larger, FPA-containing peptides.

Amino Acid Sequence↗
PubMed1976

Specificity of antisera to human fibrinopeptide A used in clinical fibrinopeptide A assays.

Distinction between fibrinopeptide A (FPA) and larger polypeptides containing the FPA sequence is critical for the interpretation of clinical results with FPA immunoassay methods. Therefore, the immunochemical reactivity of 14 rabbit anti-FPA sera with six different FPA containing antigens was studied in detail. Antigens tested included: fibrinogen; fragment E of fibrinogen; the amino-terminal disulfide knot of fibrinogen; Aalpha 1(Ala)-51(Met); Aalpha 1(Ala)-23(Arg); and, FPA. Synthetic partial sequences of FPA were also tested. The 14 FPA-specific antisera were divided into 3 distinct categories with: I, FPA immunoreactivity of larger polypeptides containing FPA approximately 1/100 of FPA on a molar basis, II, FPA immunoreactivity of the larger polypeptides intermediate between I and III; and III, FPA immunoreactivity of the larger polypeptides approximately equal to that of FPA on a molar basis. The antigenic determinants of a category I antiserum (R 2) are included in Aalpha 7(Asp)-16(Arg) with Asp(7), Phe(8) and Arg(16) being essential. When attached to FPA, the sequence Gly(17)-Arg(23) decreases the immunoreactivity of FPA with category I antisera 100-fold. The practical consequence of these findings is that, when category III antisera are employed, both FPA and larger FPA-containing polypeptides are equally immunoreactive. Since thrombin treatment of the larger polypeptides does not alter their immunoreactivity, category III antisera cannot discriminate between FPA and the larger polypeptides. On the other hand, with category I antisera, although the immunoreactivity of FPA itself is unaltered by thrombin treatment, larger polypeptides [e.g., Aalpha 1(Ala)-23tArg)] show a 100-fold increase in immunoreactivity following thrombin treatment and thus can readily be identified and separately quantitated. It is concluded that antisera with the specificity of category I are essential for the specific and accurate measurement of FPA, and for its distinction from larger FPA-containing polypeptides, in clinical plasma samples.

Animals↗
PubMed1976

Fibrinopeptides. IV. Synthesis of human fibrinopeptide A.

Human fibrinopeptide A, a hexadecapeptide, released by the action of thrombin on fibrinogen during clotting of blood, has been synthesized by conventional methods. The synthetic peptide as well as some of the intermediates in the synthesis have been examined for anticoagulant activity. Though all of them were found to be active, the terminal carboxyl protected peptides are more potent inhibitors of clotting than the carboxyl free peptides.

Fibrinogen↗
PubMed1975

Radioimmunoassay of human fibrinopeptide B and kinetics of fibrinopeptide cleavage by different enzymes.

Thrombin converts fibrinogen to fibrin monomer by cleaving fibrinopeptides A and B (FPA and FPB) from the amino terminal ends of the A (alpha) and B (beta) chains. A radioimmunoassay capable of measuring the A peptide in human blood as an index of thrombin action in vivo has been described previously. This paper describes the development of a radioimmunoassay for FPB and the use of both assays in the demonstration of distinctive patterns of cleavage of the amino terminal ends of the A (alha) and B (beta) chains of fibrinogen by various enzymes. Antisera were raised in rabbits to a synthetic analogue of FPB coupled to bovine serum albumin. FPB analogue was couple to desaminotyrosine and radiolabeled with 125I by the chloramine-T technique. The radiolabeled peptide was bound by the antiserum, and binding was inhibited by synthetic or native FPB. Unbound tracer was separated from bound tracer by charcoal adsorption. The senistivity of the assay was such that 50% inhibition of binding of the tracer was caused by 1.25 ng of the native FPB. Fibrinogen was treated with thrombin, plasmin, trypsin, Reptilase, and an extract of the venom from Ancistrodon contortrix contortrix (ACC). After ethanol precipitation and centrifugation, dialysates of enzymatically altered fibrinogen were assayed for FPA and FPB. The action of thrombin on fibrinogen resulted in a rapid release of FPA and a slower release of FPB. Plasmin cleaved a segment(s) of the B (beta) chain which included FPB but cleaved no detectable FPA-containing material for the first 2 h of incubation. In the case of plasmin-treated fibrinogen, the dialysates had been further treated with thrombin before being assayed for FPA and FPB. Trypsin rapidly cleaved both peptides, the B before the A. Reptilase cleaved only FPA in 24 h. ACC cleaved FPB at a rapid rate, with a slowere cleavage of FPA. The distinctive cleavage patterns produced by the serine proteases may be useful in interpreting the levels of FPA and FPB measured in human blood and in studying the generation of FPA and FPB in clinical blood samples.

Alpha-Globulins↗
PubMed1988

Fibrinopeptide A and fibrinopeptide B beta 15-42 in patients with Behçet's disease.

Plasma levels of FPA and FPB beta 15-42 in patients with Behçet's disease were examined. In the patients, the mean levels of FPA and FPB beta 15-42 were significantly higher than controls (p less than 0.001). Fibrinolysis subsequent to coagulation may be activated in the patients. The levels of both FPA and FPB beta 15-42 were higher during attack than in remission. The caution should be taken these levels to understand the disease activity.

Behcet Syndrome↗