Immunological assay for a carboxyterminal peptide of the fibrinogen aalpha-chain in normal and pathological human sera.
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Biomedical subjects
Publications and source records attributed to R Hafter.
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Soluble oligomers of fibrin were produced by limited incubation of fibrinogen with thrombin in the presence of calcium2 positive earth, cysteine and factor XIII. They were separated from fibrinogen by gel filtration. Gamma-gamma dimers were demonstrated in fractions from the void volume and the shoulder prior to the fibrinogen peak. These fractions were subjected to affinity chromatography on agarose-coupled fibrinogen and fibrin. Cross-linked oligomers of fibrin were adsorbed to agarose-coupled fibrin, whereas no adsorption occured during affinity chromatography on agarose-coupled fibrinogen. This indicates that crosslinked fibrin oligomers have no affinity to fibrinogen, yet readily form complexes with fibrin.
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Soluble fibrin monomer complexes (SFMC) were determined in 12 patients following delivery, 2, 4, 6 days and 3 months post partum. Quantitative gel filtration (1 per cent agarose) of the beta-alanine-precipitated plasma samples yielded the relative (per cent of the total fibrinogen content) and absolute (milligrams per 100 ml. of plasma) amount of SFMC. During the early puerperium the amount of SFMC remained essentially constant, with average postpartum values of 6.3 +/- 1.2 per cent and 27.6 +/- 9.1 mg. per 100 ml. (mean and standard deviation). Three months after delivery the level of SFMC was significantly (p less than 0.001) decreased (3.3 +/- 1.3 per cent and 8.4 +/- 3.4 mg. per 100 ml.). The quantitative estimation of SFMC in the early puerperium as presented in this study indicates that a state of hypercoagulability can be evaluated by measuring the thrombin-mediated catabolic products of fibrinogen.
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Soluble fibrin monomer complexes (SFMC) were determined in patients with septic abortion (body temperatures of more than 39 degree C and/or chills without apparent signs of endotoxic shock), with infected abortion, with non-infected abortion and with normal pregnancies. Quantitative gel filtration (4% agarose) of beta-alanine precipitated plasma samples yielded the relative (percent of total fibrinogen content) and absolute (mg/100 ml plasma) amount of SFMC. The relative (5.5+/-1.4%, mean+/-SD) and absolute (21.5+/-8.6 mg/100 ml) amount of SFMC was significantly increased in patients with septic abortion compared to patients with normal pregnancies or non-infected abortion (p less than 0.001). Patients with infected abortion (p less than 0.001). Patients with infected abortion already revealed increased levels of SFMC (4.3+/-1.2%, 14.2+/-6.8 mg/100 ml) though their platelet count was still unaltered (infected abortion: 221+/-47 X 10(3) platelets/mm3; septic abortion; 99+/-36 X 10(3) platelets/mm3). The use of heparin in patients with septic abortion resulted in a decrease in SFMC. Chain characterization of SFMC frequently revealed a slight degradation of the alpha-chains probably due to fibrinolytic activity in vivo; gamma-gamma dimers representing intermolecular covalent bindings were not observed. The findings are in agreement with our former assumption that patients with septic abortion have a pronounced state of hypercoagulability.
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The quantitative estimation of soluble fibrin monomer complexes (SFMC) was applied to evaluate the state of hypercoagulability during pregnancy and delivery. Blood samples from 67 healthy primi and multiparae, 6 to 40 weeks pregnant, and from a group of 8 women in labour and after delivery of the placenta were examined. Fibrinogen and SFMC were precipitated from plasma by precipitation with beta-alanine. Gel filtration (4% agarose) of the redissolved precipitate resulted in a separation of SFMC and fibrinogen. This enabled a quantitative estimation of the SFMC concentration (with-in assay precision: coefficient of variation=8%). The % amount SFMC of the total fibrinogen content increased from 2.6 +/- 0.4 to 4.9 +/- 1.3% (mean and standard deviation) to week 40 of pregnancy. During delivery an additional statistically significant increase occurred. Chain analysis of SFMC showed a decreased amount of alpha-chain indicating plasmin activity. gamma-gamma-dimers as residuals of intermolecular covalent bonding were not observed. The quantitative estimation of SFMC during pregnancy and delivery demonstrates that a state of hypercoagulability during gestation can be evaluated by measuring the catabolic products of fibrinogen. This may lead to a differentiation from severe intravascular coagulation and to an early diagnosis of thromboembolic disease or consumption coagulopathy.