Urinary fibrinopeptide-A as a predictive biomarker of exacerbation in asthma

SummaryIncreased fibrinopeptide A (FPA) levels have been reported in various non-thrombotic disorders, including cancer, acute myocardial infarction, liver cirrhosis and collagen vascular diseases. To investigate the significance of these findings, the present study combined the radioimmunoassay of FPA with that of fibrinogen/fibrin degradation fragment E (FgE) in the aforementioned disorders and compared the results with those observed in healthy subjects as well as in patients with thromboembolism and overt disseminated intravascular coagulation (DIC). Mean FPA and FgE in malignancy were 6.3 and 305 ng/ml, in myocardial infarction 5.6 and 98 ng/ml, in liver cirrhosis 2.7 and 132 ng/ml and in collagen vascular diseases 5.6 and 142 ng/ml. All these values were significantly higher than in healthy controls (mean FPA 1.6 ng/ml, mean FgE 49 ng/ml) but significantly lower than in thromboembolism (mean FPA 10.7 ng/ml, mean FgE 639 ng/ ml) and DIC (mean FPA 22.0 ng/ml, mean FgE 1041 ng/ml). The overall correlation between FPA and FgE was highly significant. Elowever, different disorders showed peculiar patterns in FPA, FgE and fibrinogen levels. In malignancy, a definite increase of FPA, FgE and plasma fibrinogen levels was observed. This finding probably indicates a compensated state of (intra- or extravascular) fibrin formation and lysis. Acute myocardial infarction was characterized by a high FPA to FgE ratio, which is interpreted to reflect acute thrombin generation and fibrin formation. FPA in cirrhosis was only marginally elevated with most single values within the normal range, indicating that intravascular coagulation was infrequent and unimportant in quantitative terms.

Download Full-text

Apolipoprotein(a), Fibrinopeptide A and Carotid Atherosclerosis in Middle-Aged Men

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648915 ◽

1994 ◽

Vol 72 (04) ◽

pp. 563-566 ◽

Cited By ~ 16

Author(s):

Tuomo Rankinen ◽

Sari Väisänen ◽

Michele Mercuri ◽

Rainer Rauramaa

Keyword(s):

Risk Factors ◽

Cardiovascular Diseases ◽

Carotid Atherosclerosis ◽

Intima Media Thickness ◽

Carotid Bifurcation ◽

Carotid Intima Media Thickness ◽

Fibrinopeptide A ◽

Carotid Imt ◽

Apolipoprotein A ◽

The Difference

SummaryThe association between apolipoprotein(a) [apo(a)], fibrinogen, fibrinopeptide A (FPA) and carotid intima-media thickness (IMT) was analyzed in Eastern Finnish men aged 50 to 60 years. Apo(a) correlated directly with carotid bifurcation (r = 0.26, p = 0.001), but not with common carotid IMT. Men in the lowest quartile of apo(a) had thinner (p = 0.013) IMT in bifurcation [1.59 mm (95% Cl 1.49; 1.68)] compared to the men in the highest [1.91 mm (95% Cl 1.73; 2.09)] apo(a) quartile. The difference remained (p=0.038) after adjusting for confounders. Plasma fibrinogen was not related to carotid IMT, whereas FPA correlated with common carotid (r = 0.21, p = 0.016) and carotid bifurcation (r = 0.21, p = 0.018) IMT. These associations abolished after adjusting for the confounders. The data suggest that apo(a) associate with carotid atherosclerosis independent of other risk factors for ischemic cardiovascular diseases.

Download Full-text

Studies on the Functionality of Newly Synthesized Fibrinogen after Treatment of Acute Myocardial Infarction with Streptokinase, Increase in the Rate of Fibrinopeptide Release

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649710 ◽

1993 ◽

Vol 70 (06) ◽

pp. 0978-0983 ◽

Cited By ~ 7

Author(s):

Edelmiro Regano ◽

Virtudes Vila ◽

Justo Aznar ◽

Victoria Lacueva ◽

Vicenta Martinez ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Molecular Weight ◽

Steady State ◽

High Molecular Weight ◽

Coronary Arteries ◽

Risk Index ◽

Weight Fraction ◽

High Molecular Weight Fraction ◽

Fibrinopeptide A

SummaryIn 15 patients with acute myocardial infarction who received 1,500,000 U of streptokinase, the gradual appearance of newly synthesized fibrinogen and the fibrinopeptide release during the first 35 h after SK treatment were evaluated. At 5 h the fibrinogen circulating in plasma was observed as the high molecular weight fraction (HMW-Fg). The concentration of HMW-Fg increased continuously, and at 20 h reached values higher than those obtained from normal plasma. HMW-Fg represented about 95% of the total fibrinogen during the first 35 h. The degree of phosphorylation of patient fibrinogen increased from 30% before treatment to 65% during the first 5 h, and then slowly declined to 50% at 35 h.The early rates of fibrinopeptide A (FPA) and phosphorylated fibrinopeptide A (FPAp) release are higher in patient fibrinogen than in isolated normal HMW-Fg and normal fibrinogen after thrombin addition. The early rate of fibrinopeptide B (FPB) release is the same for the three fibrinogen groups. However, the late rate of FPB release is higher in patient fibrinogen than in normal HMW-Fg and normal fibrinogen. Therefore, the newly synthesized fibrinogen clots faster than fibrinogen in the normal steady state.In two of the 15 patients who had occluded coronary arteries after SK treatment the HMW-Fg and FPAp levels increased as compared with the 13 patients who had patent coronary arteries.These results provide some support for the idea that an increased synthesis of fibrinogen in circulation may result in a procoagulant tendency. If this is so, the HMW-Fg and FPAp content may serve as a risk index for thrombosis.

Download Full-text

Comparison of the Actions of Thrombin and the Thrombin-Like Venom Enzymes Ancrod and Batroxobin

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648004 ◽

1976 ◽

Vol 36 (01) ◽

pp. 009-013 ◽

Cited By ~ 32

Author(s):

D. L Aronson

Keyword(s):

Factor Viii ◽

Fibrinopeptide A ◽

Enzymic Reaction

SummaryThrombin acts on several coagulant proteins to produce products with physiologic, pharmacologic and pathologic potential. The most sensitive thrombin substrate seems to be factor VIII. Some thrombin dependent reactions studied in vitro and proposed as control reactions seem too insensitive to the action of thrombin to be of in vivo significance.The only enzymic reaction the thrombin-like venom enzymes, Ancrod and Batroxobin, have in common with thrombin is the removal of fibrinopeptide A.

Download Full-text

Cross-Linked αsγt-Chain Hybrids in Plasma Clots Studied by 1D- and 2D Electrophoresis and Western Blotting

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649601 ◽

1993 ◽

Vol 70 (03) ◽

pp. 438-442 ◽

Cited By ~ 6

Author(s):

B Grøn ◽

C Filion-Myklebust ◽

S Bjørnsen ◽

P Haidaris ◽

F Brosstad

Keyword(s):

Molecular Weight ◽

Monoclonal Antibodies ◽

Human Plasma ◽

Western Blotting ◽

Isoelectric Point ◽

Factor Xiii ◽

Cross Linking ◽

2D Electrophoresis ◽

Complex Phenomenon ◽

Fibrinopeptide A

SummaryFibrinogen and fibrin related chains in reduced human plasma as well as the bonds interlinking partially cross-linked fibrin from plasma clots have been studied by means of 1D- and 2D electrophoresis and Western blotting. Immunovisualization of reduced plasma or partially cross-linked fibrin with monoclonal antibodies specific for the α-chains or the γ-chains have shown that several bands represent material belonging to both chains. In order to decide whether these bands constitute αγ-chain hybrids or superimposed α- and γ-chain dimers, the cross-linked material was separated according to both isoelectric point (pI) and molecular weight (MW) using Pharmacia’s Multiphor II system. Western blotting of the second dimension gels revealed that partially cross-linked fibrin contains αsγt-chain hybrids and γ- polymers, in addition to the well-known γ-dimers and α-polymers. The main αsγt-chain hybrid has a pI between that of the α- and the γ-chains, a MW of about 200 kDa and contains Aα-chains with intact fibrinopeptide A (FPA). It was also observed that soluble fibrinogen/fibrin complexes as well as partially cross-linked fibrin contain degraded α-dimers with MWs close to the γ-dimers. These findings demonstrate that factor XIII-catalyzed cross-linking of fibrin is a more complex phenomenon than earlier recognized.

Download Full-text

Fibrinopeptide A (FPA) Level and Fibrinogen Kinetics in Patients with Malignant Disease

Thrombosis and Haemostasis ◽

10.1055/s-0038-1653457 ◽

1981 ◽

Vol 46 (04) ◽

pp. 706-709 ◽

Cited By ~ 51

Author(s):

Yasuhiro Yoda ◽

Tsukasa Abe

Keyword(s):

Fibrinolytic Activity ◽

Turnover Rate ◽

Malignant Disease ◽

Major Determinant ◽

Fibrinopeptide A

SummaryFPA level, fibrinogen turnover rate, and fibrinolytic activity were studied on 18 patients with malignant disease. It was found that the FPA levels were significantly elevated and were correlated with fibrinogen turnover rate (r=0.74, p<0.001) and FDP (r = 0.58, p<0.02). Estimated FPA turnover rate was also correlated with fibrinogen turnover rate (r = 0.70, p<0.001). These results suggest that fibrinogen catabolism in patients with malignant disease is related with thrombin proteolysis. However, ratios of 1/2 FPA turnover rate to fibrinogen turnover rate suggest that intravascular thrombin proteolysis is not the major determinant of fibrinogen catabolism. It is suspected that extravascular thrombin proteolysis is responsible for the elevation of plasma FPA level which is correlated with acceleration of fibrinogen catabolism.

Download Full-text

The Action of Thrombin on Modified Fibrinogen

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657364 ◽

1983 ◽

Vol 49 (03) ◽

pp. 208-213

Author(s):

A J Osbahr

Keyword(s):

Physical Properties ◽

Negative Charge ◽

Lysine Residue ◽

Fibrinopeptide A ◽

Amino Groups ◽

Lysine Residues ◽

Citraconic Anhydride

SummaryThe modification of canine fibrinogen with citraconic anhydride modified the ε-amino groups of the fibrinogen and at the same time generated additional negative charges into the protein. The addition of thrombin to the modified fibrinogen did not induce polymerization; however, the fibrinopeptide was released at a faster rate than from the unmodified fibrinogen. The physical properties of the citraconylated fibrinogen were markedly altered by the modification of 50-60 lysine residues in one hour. A modified fibrinopeptide-A was released by thrombin from the modified fibrinogen and was electrophoretically more anionic than the unmodified fibrinopeptide-A. Edman analysis confirmed the modification of the lysine residue present in the peptide. The rate of removal of citraconylated fibrinopeptide-A from modified fibrinogen by thrombin was 30 to 40 percent greater than the cleavage of unmodified fibrinopeptide-A from unmodified fibrinogen. However, the modification of 60 or more lysine residues in the fibrinogen produced a decrease in the rate of cleavage of citraconylated fibrinopeptide-A. The results suggest that additional negative charge in the vicinity of the attachment of fibrinopeptide-A to canine fibrinogen aids in the removal of the peptide by thrombin.

Download Full-text

Effects of Intermittent Pneumatic Calf Compression On Postoperative Thrombin and Plasmin Activity

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661639 ◽

1986 ◽

Vol 56 (02) ◽

pp. 198-201 ◽

Cited By ~ 25

Author(s):

Jeffrey Weitz ◽

Jost Michelsen ◽

Kenneth Gold ◽

John Owen ◽

Duncan Carpenter

Keyword(s):

Enzyme Activity ◽

Fibrinopeptide A ◽

Plasmin Activity ◽

Neurosurgical Patients ◽

The Mean ◽

Calf Compression

SummaryA previous study of neurosurgical patients demonstrated an imbalance between thrombin and plasmin action following surgery. The present study was designed to determine the effect of intermittent pneumatic calf compression on postoperative enzyme activity. Fibrinopeptide A (FPA) and Bβ 1-42 levels, reflecting thrombin and plasmin action respectively, were measured daily in patients undergoing elective craniotomy. Two of 9 patients not receiving calf compression developed positive fibrinogen leg scans, while none of 5 patients receiving prophylaxis had positive scans. Calf compression was associated with a markedly altered pattern of changes in the fibrinopeptide values following surgery. Without compression, there was perturbation of the balance between thrombin and plasmin action on the day after surgery as reflected by an increase in the FPA/Bβ 1-42 ratio. In contrast, in those receiving prophylaxis there was no change in this ratio on the first postoperative day. Calf compression both blunted the mean postoperative increase in the FPA level (1.8 nM vs 4.7 nM; p <.05) and augmented the mean Bβ 1-42 value (3.0 nM vs 0.2 nM; p <.05) so that the mean increase in the FPA/ Bβ 1-42 ratio was only 0.1 with calf compression as compared to 2.2 without it (p <.05). Systemic modulation of both the coagulation and fibrinolytic pathways thus occurred in association with calf compression.

Download Full-text

Plasma Fibrinopeptide A and Beta-Thromboglobulin in Patients with Chest Pain

Thrombosis and Haemostasis ◽

10.1055/s-0038-1665250 ◽

1983 ◽

Vol 50 (02) ◽

pp. 541-542 ◽

Cited By ~ 13

Author(s):

J T Douglas ◽

G D O Lowe ◽

C D Forbes ◽

C R M Prentice

Keyword(s):

Myocardial Infarction ◽

Chest Pain ◽

Unstable Angina ◽

Plasma Levels ◽

Thrombin Generation ◽

Acute Chest Pain ◽

Fibrinopeptide A ◽

Control Hospital ◽

Hospital Patients ◽

Platelet Release

SummaryPlasma levels of β-thromboglobulin (BTG) and fibrinopeptide A (FPA), markers of platelet release and thrombin generation respectively, were measured in 48 patients within 3 days of admission to hospital for acute chest pain. Twenty-one patients had a confirmed myocardial infarction (MI); 15 had unstable angina without infarction; and 12 had chest pain due to noncardiac causes. FPA and BTG were also measured in 23 control hospital patients of similar age. Mean plasma BTG levels were not significantly different in the 4 groups. Mean plasma FPA levels were significantly higher in all 3 groups with acute chest pain when compared to the control subjects (p < 0.01), but there were no significant differences between the 3 groups. Increased FPA levels in patients with acute chest pain are not specific for myocardial infarction, nor for ischaemic chest pain.

Download Full-text