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Biomedical subjects

W Nieuwenhuizen

Publications and source records attributed to W Nieuwenhuizen.

At least 19 recordsLinked to original sources
PubMed2006

Can we gain precision by sampling with probabilities proportional to size in surveying recent landscape changes in the Netherlands?

Seventy-two squares of 100 ha were selected by stratified random sampling with probabilities proportional to size (pps) to survey landscape changes in the period 1996-2003. The area of the plots times the urbanization pressure was used as a size measure. The central question of this study is whether the sampling with probabilities proportional to size leads to gain in precision compared to equal probability sampling. On average 1.03 isolated buildings per 100 ha have been built, while 0.90 buildings per 100 ha have been removed, leading to a net change of 0.13 building per 100 ha. The area with unspoiled natural relief has been reduced by 2.3 ha per 100 ha, and the length of linear relicts by 137 m per 100 ha. On average 74 m of linear green elements have been planted per 100 ha, while 106 m have been removed, leading to a net change of -31 m per 100 ha. For the state variables 'unspoiled natural relief', 'linear relicts', 'removed linear green elements', and 'new-removed linear green elements' there is a gain in precision due to the pps-sampling. For the remaining state variables there is no gain or even a loss of precision ('new buildings', 'removed buildings', 'new-removed buildings', 'new linear green elements'). Therefore, if many state variables must be monitored or when interest is not only in the change but also in the current totals, we recommend to keep things simple, and to select plots with equal probability.

Environmental Monitoring↗
PubMed2004

Two monoclonal antibodies to D-dimer-specific inhibitors of fibrin polymerization.

D-dimer of human fibrin was used as antigen to obtain monoclonal antibodies (mAbs). We have obtained 16 hybridomas producing mAbs of different specificity. Only two of these mAbs inhibited fibrin polymerization. They are of the IgG-class. One mAb (II-4d) inhibited fibrin polymerization to 100% and another (II-3b) to 60% at a molar ratio mAb/fibrin=1.0. Fab-fragments of these mAbs inhibited fibrin polymerization completely at the same molar ratio. The epitopes for the mAbs studied are situated in the NH2-terminal part of the gamma-chain in fibrin D-domain. Electron microscopy showed that fibrin was in monomeric form in the presence of these mAbs or their Fab-fragments. Thus, these mAbs stop the initial step of fibrin polymerization, i.e. protofibril formation. Only one site of protofibril formation is known now in COOH-terminal half of the D-domain gamma chain named "a" site, which is complementary to the "A" site in the central E-domain of fibrin molecule. Our experiment with immobilized GPRP showed that the "a" site in fibrin D-fragment preserved its binding activity to GPRP when the D-fragment was complexed with mAbs-inhibitors of fibrin polymerization. Thus, these two mAbs inhibit fibrin polymerization not by blocking the sites "a" but either by blocking another (not "a") specific site in D-domain or by steric hindrance of highly organized fibrin polymerization process.

Antibodies, Monoclonal↗
PubMed2003

Associations of plasma fibrinogen assays, C-reactive protein and interleukin-6 with previous myocardial infarction.

BACKGROUND: The association of plasma fibrinogen with myocardial infarction (MI) may (like that of C-reactive protein, CRP) be a marker of subclinical inflammation, mediated by cytokines such as interleukin-6 (IL-6). There are well-recognized discrepancies between commonly performed fibrinogen assays. Increased ratio of clottable fibrinogen to intact fibrinogen (measured by a recently developed immunoassay) has been proposed as a measure of hyperfunctional fibrinogen, and is elevated in acute MI. OBJECTIVE: To compare the associations of intact fibrinogen and four routine fibrinogen assays (two von Clauss assays; one prothrombin-time derived; and one immunonephelometric) in a case-control study of previous MI. PATIENTS/METHODS: Cases (n=399) were recruited 3-9 months after their event; 413 controls were age- and sex- matched from the case-control study local population. Intact fibrinogen was measured in 50% of subjects. RESULTS: All routine fibrinogen assays showed high intercorrelations (r=0.82-0.93) and significant (P<0.0001) increased mean levels in cases vs. controls. These four routine assays correlated only moderately with intact fibrinogen (r=0.45-0.62), while intact fibrinogen showed only a small, nonsignificant increase in cases vs. controls. Consequently, the ratio of each of the four routine assays to the intact fibrinogen assay was significantly higher (P<0.0003) in cases vs. controls. Each fibrinogen assay correlated with plasma levels of CRP and IL-6 (which were also elevated in cases vs. controls). Each routine fibrinogen assay remained significantly elevated in cases vs. controls after further adjustment for C-reactive protein and interleukin-6. CONCLUSIONS: These data provide evidence for acquired, increased hyperfunctional plasma fibrinogen in MI survivors, which is not associated with markers of inflammatory reactions. The causes and significance of these results remain to be established in prospective studies.

Biomarkers↗
PubMed2002

A neoantigenic determinant in the D-dimer fragment of fibrin.

Monoclonal antibody (mAb) III-3b binds D-dimer with K(d)=1.4 x 10(-10) M without cross-reaction with fibrin(ogen). The epitope for this mAb is in Bbeta134-190, presumably in Bbeta155-160. The latter site is buried in the coiled coil structure of fibrin(ogen) but it is exposed as a neoantigenic determinant in D-dimer upon plasmic lysis of fibrin. mAb III-3b may be used as a tool for immunodiagnostic quantification of D-dimer in blood plasma.

Antibodies, Monoclonal↗
PubMed2001

Fibrin-mediated plasminogen activation.

Fibrin, but not fibrinogen, enhances the rate of activation of plasminogen by tissue type plasminogen activator (t-PA). Studies with enzymatic and chemical fragments of fibrinogen showed that several sites in fibrinogen are involved in this rate enhancement; these are, A alpha 148-160 (located in CNBr fragment FCB-2), and FCB-5 (a CNBr fragment comprising gamma 312-324), and recently discovered sites in the fibrinogen alpha C domains. All these sites are buried in fibrinogen, but exposed in fibrin and some fibrinogen fragments. For the first two of these, located in the D-domains, this was shown by the fact that monoclonal antibodies against A alpha 148-160 and gamma 312-324 bind to fibrin and rate enhancing fibrin(ogen) fragments, but not to fibrinogen. Direct binding studies indicate that at physiological concentrations plasminogen binds to FCB-2, and t-PA to FCB-5. More detailed studies have demonstrated the importance of residues A alpha-157 and A alpha-152, and that the minimum stretch with rate enhancing properties is A alpha 154-159. The sites in the alpha C domains await further identification. With the recently reported three-dimensional structure of fragments D and D-dimer it is now possible to explain these findings at the molecular level. Molecular calculations and experimental data show that the site A alpha 148-160 in fibrinogen is covered among others by a part of the A alpha chain (A alpha 166-195) that forms an alpha-helix, and by a globular domain formed by the beta-chain. On fibrin formation, the last two may move away, and give access to A alpha 148-160. It is conceivable that in the alpha C domain sites are involved in the early phases of fibrinolysis. The site A alpha 148-160 and that in FCB-5 may be more important at later stages. It is also clear that fibrin polymerization is important. This polymerization has probably several effects: exposure of the rate enhancing sites; mutual positioning of the t-PA and plasminogen binding sites; a concentrating effect of t-PA and plasminogen on the fibrin surface; effects on the kinetic properties of t-PA and plasminogen. These effects together explain the rate enhancement.

Amino Acid Sequence↗
PubMed2000

Conversion of fibrinogen to fibrin: mechanism of exposure of tPA- and plasminogen-binding sites.

Conversion of fibrinogen into fibrin results in the exposure of cryptic interaction sites and modulation of various activities. To elucidate the mechanism of this exposure, we tested the accessibility of the Aalpha148-160 and gamma312-324 fibrin-specific epitopes that are involved in binding of plasminogen and its activator tPA, in several fragments derived from fibrinogen (fragment D and its subfragments) and fibrin (cross-linked D-D fragment and its noncovalent complex with the E(1) fragment, D-D. E(1)). Neither D nor D-D bound tPA, plasminogen, or anti-Aalpha148-160 and anti-gamma312-324 monoclonal antibodies, indicating that their fibrin-specific epitopes were inaccessible. The Aalpha148-160 epitope became exposed only upon proteolytic removal of the beta- and gamma-modules from D. At the same time, both epitopes were accessible in the D-D.E(1) complex, indicating that the DD.E interaction resulted in their exposure. This exposure was reversible since the dissociation of the D-D.E(1) complex made the sites unavailable, while reconstitution of the complex made them exposed. The results indicate that upon fibrin assembly, driven primarily by the interaction between complementary sites of the D and E regions, the D regions undergo conformational changes that cause the exposure of their plasminogen- and tPA-binding sites. These changes may be involved in the regulation of fibrin assembly and fibrinolysis.

Animals↗
PubMed2000

Performance of semiquantitative and quantitative D-dimer assays in the ECAT external quality assessment program.

D-dimer levels are used in clinical practice as markers for the presence or exclusion of venous thrombosis. Therefore, it is important that the performance of the D-dimer tests is well controlled. One of the components of a laboratory quality program is external quality assessment (EQA). The main aim of EQA is to identify the degree of agreement among laboratories. In addition to identifying the individual laboratory performance, it also identifies the characteristics of the different reagents and methods that are used in different laboratories. Recently, the D-dimer test was included in the ECAT External Quality Assessment program. Eighty-one laboratories in four rounds applied semiquantitative and quantitative D-dimer assays to three samples (concentrations normal, slightly elevated, and elevated). Although the reported values varied widely, the classification of the samples was mostly correct for the normal and the elevated samples. The slightly elevated sample was classified as normal by all laboratories using semiquantitative methods and by 60% of the laboratories using quantitative methods, and this varied between 45% and 86% for the different methods. In conclusion, D-dimer methods show a large variation, and the quality of the D-dimer assessment could be improved by standardization and by using cut-off ranges.

Antifibrinolytic Agents↗
PubMed2000

The effect of alcohol ingestion on the exercise-induced changes in fibrin and fibrinogen degradation products in man.

The present study examined the influence of ingesting a moderate dose of alcohol on plasminogen activator activity (t-PA), plasma fibrinogen (Fb), total degradation products (TDP) and the degradation products of fibrin (FbDP) and fibrinogen (FgDP) at rest and in response to exercise. Eleven male subjects performed two separate experimental trials at an exercise intensity corresponding to 70% maximal oxygen consumption for 35 min. Prior to trials, subjects were either given 0.5 g/kg alcohol in orange-flavoured drink or an equal volume of non-caloric non-alcoholic drink 45 min before exercise. Comparison of the levels of t-PA, Fb, TDP, FbDP, and FgDP at rest, before and 45 min after the ingestion of alcohol revealed no significant differences between alcohol and control experiments. Exercise resulted in a marked increase in t-PA, TDP, and FgDP, with no appreciable change in FbDP. Although plasma fibrinogen level showed significant decrease post-exercise when subjects ingested alcohol, this difference was small and its biological significance is questionable. While t-PA level increased similarly in response to exercise during alcohol and control trials, a significantly higher response of TDP was found during the control trial compared with alcohol trial. It was concluded that exercise with and without alcohol ingestion is followed by a substantial increase in t-PA, which coincided with an increase in TDP. The increase in TDP was mainly due to an increase in FgDP, but not to FbDP. These findings support the hypothesis that a significant fibrinogenolysis occurs in response to exercise, and moderate intoxication with alcohol prior to exercise reduced this response.

Adult↗
PubMed2000

Soluble fibrin species in arterial thrombi.

The aim of this study was to characterize soluble fibrin(ogen) species in human, arterial, in-vivo-formed thrombi, using the immunoblotting technique. Specimens were collected via intra-arterial catheters in six patients scheduled for catheter-directed thrombolysis. Unreduced and reduced samples of the supernatants from the arterial thrombi-derived specimens were electrophoresed on polyacrylamide gels and immunoblotted, using specific mono- and polyclonal anti-fibrin(ogen) antibodies. The reduced samples disclosed substantial amounts of high molecular weight material, consistent with alpha-chain polymers and gammagamma-dimers, as well as lower molecular weight material, such as alpha-, beta- and gamma-chains. No fibrinogen with intact fibrinopeptide A was detectable, and des-AABB fibrin represented a major fibrin derivative in the soluble part of the arterial thrombi. The alpha-chains were C-terminally degraded, most of them distal to position 259. In conclusion, we have demonstrated the presence of cross-linked fibrin derivatives in soluble, arterial thrombus-related material, without signs of fibrinogen-fibrin hybrids. The fibrin derivatives were C-terminally degraded, thus representing X-oligomeric material, most probably originating from plasmin degradation of insoluble thrombus fibrin. The present study supports the hypothesis of a dynamic equilibrium between clotting and lysis in thrombi.

Aged↗
PubMed2000

Clinical evaluation of a monoclonal antibody-based enzyme immunoassay for fibrin degradation products in patients with clinically suspected pulmonary embolism. ANTELOPE-Study Group.

We prospectively evaluated the diagnostic accuracy of the Fibrinostika FbDP assay in 304 consecutive patients with suspected pulmonary embolism and examined potentially useful cut-off points at which the disease can be excluded. The prevalence of pulmonary embolism was 31%. The assay generated an area under the Receiver Operating Characteristic curve of 0.79 (95% CI 0.73-0.84). A cut-off point of 0.05 microg/ml yielded a sensitivity, specificity, negative predictive value and an exclusion efficiency of 100% (95% CI 96-100), 5% (95% CI 2-9), 100% (95% CI 69-100) and 3% (95% CI 2-6), respectively. A clinically useful cut-off point seems to be 0.11 microg/ml which corresponded with a sensitivity, specificity, negative predictive value and an exclusion efficiency of 96% (95% CI 90-99), 27% (95% CI 24-28), 93% (95% CI 84-98) and 20% (95% CI 16-25), respectively. We conclude that the assay has potential clinical utility for the exclusion of pulmonary embolism, but it cannot be used as a sole test.

Adolescent↗
PubMed2000

Use of a new monoclonal antibody-based enzyme immunoassay for soluble fibrin to exclude pulmonary embolism. ANTELOPE-Study Group.

We prospectively evaluated the diagnostic performance of a new soluble fibrin assay in 303 consecutive patients with suspected pulmonary embolism and examined potentially useful cut-off levels at which this disease can be safely excluded. In addition, the diagnostic accuracy was calculated in the subgroups of in- and outpatients. The ROC curve of the assay in the total study cohort had an area under the curve of 0.69. The cut-off level associated with a sensitivity and negative predictive value of 100% was 20 ng/ml, but the specificity was only 4%. The cut-off level with a sensitivity of 90% was 30 ng/ml, which corresponded with a specificity and negative predictive value of 27% and 86%. respectively. The diagnostic performance was comparable in the subgroups of in- and outpatients. We conclude that the soluble fibrin assay has a low diagnostic accuracy and seems unsuitable as a screening test for the exclusion of pulmonary embolism.

Adult↗
PubMed1999

A new enzyme immunoassay for soluble fibrin in plasma, with a high discriminating power for thrombotic disorders.

Fibrin formation is a multistep process initiated by thrombin. At first thrombin converts fibrinogen to fibrin molecules which in vivo form soluble complexes with fibrinogen. Soluble fibrin is considered to be an early biochemical marker for intravascular fibrin formation and impending thrombotic events, such as deep venous thrombosis (DVT), pulmonary embolism (PE) and disseminated intravascular coagulopathy (DIC). A new enzyme immunoassay (EIA) was developed on the basis of a monoclonal antibody directed against a fibrin specific neo-epitope located on the gamma-chain of fibrinogen; gamma-(312-324). In addition, it was possible to prepare a lyophilized reference material of thrombin-generated soluble fibrin, that allowed for full antigen recovery after reconstitution with buffer. Assay conditions, e.g. solid phase-Ig concentration and buffer composition, sample and conjugate dilution, and incubation times were optimised. The present assay was found to be specific (no interference of homologous antigens) and reproducible (intra-assay CV 4-8%, interassay CV 4-9%), and therefore highly suited for measuring soluble fibrin levels in a plasma milieu. The median normal value for soluble fibrin was determined in plasma samples obtained from apparently healthy volunteers (n = 81) and found to be 0.040 microg/ml, with a range (10-90 percentiles) of 0.026-0.059 microg/ml. A retrospective study showed that soluble fibrin levels were highly significantly increased in patients with a confirmed diagnosis of DIC (median 1.042 microg FEU/ml, range 0.160-2.319 microg/ml, n = 21, P<0.0001 vs. normal). PE (median 0.527 microg FEU/ml, range 0.084-1.234 microg/ml, n = 29, P<0.0001 vs normal) and DVT (median 0.126 microg FEU/ml, range 0.059-0.878 microg/ml, n = 36, P<0.0001 vs. normal), as determined by the Mann-Whitney U-Test.

Fibrin↗
PubMed1998

Evaluation of the factors contributing to fibrin-dependent plasminogen activation.

Polymerized fibrin strongly enhances tissue plasminogen activator (tPA)-mediated plasminogen activation, concomitant with exposure of 'fibrin-specific' epitopes at 'Aalpha148-160' and 'gamma312-324'. To investigate which aspects of polymerization are involved in these activities, we explored the fibrin polymerization process by evaluating the ability of factor XIIIa-crosslinked fibrinogen polymers to expose 'fibrin-specific' epitopes and enhance plasminogen activation. Crosslinked normal fibrinogen, fibrinogen with deficient [des Bbeta1-42] or defective [Birmingham (AalphaR16H)] fibrin 'D:E' assembly sites ('E(A)'), or with defective end-to-end self-association sites ('D:D') [Cedar Rapids (gammaR275C)], exposed both 'fibrin-specific' epitopes and enhanced tPA-dependent plasminogen activation, whereas non-crosslinked fibrinogens showed minimal or no such activities. Epitope expression in crosslinked fibrinogen was retained in the presence of the fibrin E(A) site peptide homolog, gly-pro-arg-pro (GPRP), which inhibits fibrin D:E association, except for the Aalpha148-160 epitope in des Bbeta1-42 fibrinogen, which was not expressed. Fibrin prepared from crosslinked normal or abnormal fibrinogen, except for the des Bbeta1-42 fibrin epitopes, which were reduced or absent, expressed 'fibrin-specific' epitopes even in the presence of GPRP, which otherwise impairs such expression in non-crosslinked fibrin. Epitope exposure in fibrin prepared from non-crosslinked fibrinogen was nearly normal in Cedar Rapids fibrin (heterozygous D:D defect), but reduced in Birmingham fibrin (heterozygous E(A) defect), nil in des Bbeta1-42 fibrin (E(A) deficient), and absent in all cases in the presence of GPRP. In contrast, plasminogen activation stimulatory activity that had been exposed in crosslinked normal fibrinogen or in crosslinked des Bbeta1-42 or Cedar Rapids fibrin, was preserved to a large extent in the presence of GPRP, suggesting that once enhanced stimulatory activity and epitopes are exposed, they are not completely reversible. The findings indicate that end-to-end intermolecular associations (D:D) are not critical for 'fibrin-specific' epitope exposure, but that polymerization brought about in fibrinogen through factor XIIIa crosslinking, or in fibrin through 'D:E' interactions, is necessary for 'fibrin-specific' (more correctly, 'polymerization-specific') epitope exposure and enhancement of plasminogen activation.

Afibrinogenemia↗
PubMed1997

An enzyme immunoassay for polymorphonuclear leucocyte-mediated fibrinogenolysis.

Upon stimulation, polymorphonuclear leucocytes (PMNs) release potent serine proteases, i.e. elastase, cathepsin G and proteinase 3, which contribute to the degradation of tissue and plasma components. Here, we describe the development of a plasma test to assess PMN-mediated fibrinogenolysis as a biochemical marker for actual PMN-derived proteolysis in vivo, useful for monitoring therapeutic efficacy, i.e. of elastase inhibitors. We generated a monoclonal antibody (MAb), designated 1-1/B3, with a high affinity for elastase-degraded fibrinogen (EDF). The epitope for 1-1/B3 becomes exposed in a time-dependent manner during digestion of fibrinogen with purified PMN-derived serine proteases and with isolated PMNs in vitro. However, 1-1/B3 does not react with plasma fibrinogen or with fibrin(ogen) degradation products generated by plasmin or by other active proteases that may occur locally, i.e. metalloproteases and lysosomal cathepsins. On the basis of MAb 1-1/B3, we developed a plasma test for the assessment of PMN-mediated fibrin(ogen) degradation products (PMN-FDP). In a panel of control plasmas, we observed concentrations of PMN-FDP of 8.2 +/- 0.9 ng mL-1 (n = 18). These values were increased twofold in patients with alpha 1-proteinase inhibitor deficiency (18.6 +/- 3.3 ng mL-1; n = 12; P < 0.0001) and even more in patients with sepsis (365.7 +/- 97.7 ng mL-1; n = 16; P < 0.0001). Furthermore, synovial tissue extracts from patients with rheumatoid arthritis contained increased levels of PMN-FDP, compared with synovial tissue extracts (P < 0.005) from patients with osteoarthritis.

Antibodies, Monoclonal↗
PubMed1997

A reference material for harmonisation of D-dimer assays. Fibrinogen Subcommittee of the Scientific and Standardization Committee of the International Society of Thrombosis and Haemostasis.

The term "D-dimer assay" suggests, that these assays report the concentrations of the end-stage degradation product of crosslinked fibrin. This hardly occurs in patients. Degradation products of cross-linked fibrin rather occur with a wide range of molecular weights, and comprise various numbers of the D-dimer motif. Moreover, the numerical values obtained with different "D-dimer" assays vary widely. The variations are probably due to differences in reactivity of the various monoclonal antibodies used with the various D-dimer containing degradation products as they occur in patients; and to the various calibrators with a value assigned by the manufacturers. For the reasons indicated above a calibrator in the strict sense (e.g., pure D-dimer) is not feasible. This study shows that: it appears feasible to generate a conversion factor for each of the "D-dimer" assays studied, which will make the widely varying results obtained with these kits comparable; that the conversion factors can be based on a pool of real patient samples; and that the conversion factors are pool-independent. The next and final step in this study is to prepare and make available an international reference material for use by manufacturers and others facing a comparison problem. This is being carried out, in collaboration with the NIBSC (Dr. P. Gaffney), and the material is expected to be available in early 1997.

Antifibrinolytic Agents↗
PubMed1996

Aggregated, conformationally changed fibrinogen exposes the stimulating sites for t-PA-catalysed plasminogen activation.

The present paper shows that conformationally changed fibrinogen can expose the sites A alpha-(148-160) and gamma-(312-324) involved in stimulation of the tissue-type plasminogen activator (t-PA)-catalysed plasminogen activation. The exposure of the stimulating sites was determined by ELISA using mABs directed to these sites, and was shown to coincide with stimulation of t-PA-catalysed plasminogen activation as assessed in an assay using a chromogenic substrate for plasmin. Gel permeation chromatography of fibrinogen conformationally changed by heat (46.5 degrees C for 25 min) demonstrated the presence of both aggregated and monomeric fibrinogen. The aggregated fibrinogen, but not the monomeric fibrinogen, has exposed the epitopes A alpha-(148-160) and gamma-(312-324) involved in t-PA-stimulation. Fibrinogen subjected to heat in the presence of 3 mM of the tetrapeptide GPRP neither aggregates nor exposes the rate-enhancing sites. Thus, aggregation and exposure of t-PA-stimulating sites in fibrinogen seem to be related phenomena, and it is tempting to believe that the exposure of stimulating sites is a consequence of the conformational changes that occur during aggregation, or self-association. Fibrin monomers kept in a monomeric state by a final GPRP concentration of 3 mM do not expose the epitopes A alpha-(148-160) and gamma-(312-324) involved in t-PA-stimulation, whereas dilution of GPRP to a concentration that is not longer anti-polymerizing, results in exposure of these sites. Consequently, the exposure of t-PA-stimulating sites in fibrin as well is due to the conformational changes that occur during self-association.

Amino Acid Sequence↗
PubMed1995

Measuring plasma fibrinogen levels in patients with liver cirrhosis. The occurrence of proteolytic fibrin(ogen) degradation products and their influence on several fibrinogen assays.

In patients with liver cirrhosis the fibrinogen molecule is under constant attack of various proteolytic enzymes, which might affect results of the different assay systems for fibrinogen. We therefore studied the measurement of fibrinogen in the plasma of patients with mild, moderate and severe cirrhosis of the liver. Fibrinogen levels were measured with the Clauss method (functional fibrinogen); an enzyme immuno assay (EIA) for HMW + L MW fibrinogen; and an assay that measures the total clottable fibrinogen. With all three methods we found normal or slightly increased fibrinogen levels in patients with mild or moderate cirrhosis, whereas patients with severe cirrhosis had decreased levels. No evidence was found for increased partial fibrinogen proteolysis, resulting in increases of LMW'-fibrinogen in cirrhotic patients. We further observed that fibrinogen degradation products levels increased slightly with the severity of the disease, but were still in the normal range in patients with severe cirrhosis. This indicates a very low level of primary fibrinolysis. Fibrin degradation products levels increased much stronger, which points to intravascular coagulation. The levels of the fibrin degradation products remained below the level where they are expected to influence the Clauss assay. In patients with liver cirrhosis the measurement of plasma fibrinogen levels with the three studied methods give comparable results. We suggest to apply the Clauss assay in cirrhotic patients because of this and because it has good reproducibility and because the test is cheap, quick and easy to perform.

Child↗