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

Author(s):  
Yasuhiro Yoda ◽  
Haruo Nakamura ◽  
Tsukasa Abe
1981 ◽  
Vol 46 (04) ◽  
pp. 706-709 ◽  
Author(s):  
Yasuhiro Yoda ◽  
Tsukasa Abe

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.


1979 ◽  
Author(s):  
F.W. Peuscher ◽  
W.G. van Aken ◽  
A.L. Armstrong ◽  
E. A. Stoepman-van Dalen ◽  
J.A. van Mourik

Hypercoagulability, known to complicate malignant disease, can be detected by the measurement of fibrinopeptide A (FPA). The aim of the present study was to establish the significance of FPA production in. patients (n = 113) with various types of malignancy, without clinical signs of DIC, venous thromboembolism, not receiving cytostatic, anticoagulant or radiotherapy or bedrest. 8 patients presented laboratory abnormalities compatible with DIC; In this group mean FPA was 9.8 ng/ml (normal 1.4±0.9.2SD) and FPA generation In vitro (ΔFPA) was 15 ng/ml/10 min (normal 0.4±0.8, 230). In the remaining 105 patients, mean FPA was 5.2 ng/ml andFPA was 1.8 ng/ml/10 min. Of the 20 patients with both normal FPA and ΔFPA, 13 were clinically in remission, 5 had malignancies without detectable metastases and only 2 showed metastases. In 2 patients FPA was normal but ΔFPA was slIghtLy accelerated. 50 patients had elevated ΔFPA but normal FPA and in 33 cases both FPA and ΔFPA were increased; in these groups the majority of patients had a metastatic malignancy In 22 patients mean FPA before (4.9 ng/ml) and 20 mln after(4.2 ng/ml) receiving heparin (7500 U, i.v.) was not significantly different. These results suggest that apart from DIC tumor cells or the adjacent inflammatory area of tumors may trigger FPA generation, not being affected by heparin. It Is postulated that “heparin resistant” FPA generation Is potentially a sensitive marker of tumor activity.


1981 ◽  
Vol 26 (2) ◽  
pp. 133-134
Author(s):  
E. James Anthony

1987 ◽  
Vol 58 (02) ◽  
pp. 758-763 ◽  
Author(s):  
G Mombelli ◽  
R Monotti ◽  
A Haeberli ◽  
P W Straub

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.


1994 ◽  
Vol 72 (04) ◽  
pp. 563-566 ◽  
Author(s):  
Tuomo Rankinen ◽  
Sari Väisänen ◽  
Michele Mercuri ◽  
Rainer Rauramaa

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.


1993 ◽  
Vol 70 (06) ◽  
pp. 0978-0983 ◽  
Author(s):  
Edelmiro Regano ◽  
Virtudes Vila ◽  
Justo Aznar ◽  
Victoria Lacueva ◽  
Vicenta Martinez ◽  
...  

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.


1976 ◽  
Vol 36 (01) ◽  
pp. 009-013 ◽  
Author(s):  
D. L Aronson

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.


1993 ◽  
Vol 70 (03) ◽  
pp. 438-442 ◽  
Author(s):  
B Grøn ◽  
C Filion-Myklebust ◽  
S Bjørnsen ◽  
P Haidaris ◽  
F Brosstad

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.


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