High Molecular Weight Fibrinogen Research Articles

Fibrinogen heterogeneity in horses.

BackgroundFibrinogen heterogeneity has been observed in humans and can influence fibrinogen measurements when using the modified Clauss assay. We hypothesized that fibrinogen heterogeneity also exists in horses.ObjectivesTo determine whether fibrinogen heterogeneity exists in horses.AnimalsFive clinically healthy horses from the university equine teaching herd.MethodsPresumed fibrinogen was purified from pooled citrated plasma and electrophoresis performed. The purified protein was subjected to Western blotting using sheep antiserum against human fibrinogen, and liquid chromatography‐tandem mass spectrometry (LC‐MS/MS).ResultsGel electrophoresis of nonreduced equine purified protein yielded 2 protein bands (approximately 377 and 318 kDa) that corresponded with the molecular weights of human high molecular weight fibrinogen and low molecular weight fibrinogen fractions, respectively. Electrophoretograms of reduced purified protein, Western blots, and LC‐MS/MS supported that the purified nonreduced protein bands were fibrinogen.ConclusionFibrinogen heterogeneity exists in horses.

Hypochlorite-induced aggregation of fibrinogen underlies a novel antioxidant role in blood plasma

Fibrinogen, a major constituent of blood plasma, is highly susceptible to reaction with biological oxidants. It has been proposed that fibrinogen plays a role in antioxidant defence, but oxidation of fibrinogen is also known to disrupt normal blood clotting and is implicated in the pathology of atherosclerosis. In the present study, we show that the biological oxidant hypochlorite promotes the formation of soluble high molecular weight fibrinogen assemblies ≥40 × 106 Da, that do not accumulate when fibrinogen is induced to aggregate by other stresses such as heating or hydroxyl-mediated damage in vitro. Hypochlorite-modified fibrinogen is stable at 37 °C as assessed by precipitation assays, and has reduced susceptibility to iron-induced (hydroxyl-mediated) precipitation compared to native fibrinogen. In contrast to hypochlorite-modified albumin, which is known to be immunostimulatory, hypochlorite-modified fibrinogen does not induce RAW 264.7 (macrophage-like) cells or EOC 13.31 (microglia-like) cells to produce reactive oxygen species or induce cell death. Furthermore, depletion of fibrinogen from human blood plasma increases the immunostimulatory property of blood plasma after it is supplemented with hypochlorite in situ. We propose that reaction of hypochlorite with fibrinogen in blood plasma potentially reduces the accumulation of other hypochlorite-modified species such as immunostimulatory hypochlorite-modified albumin. The latter represent a novel role for fibrinogen in blood plasma antioxidant defence.

Investigation of Hemostasis Using Plantain Sheath/Stem, Cassava Leaf and Snail Juices in Human Blood in-vitro

Inhabitants of most rural communities of West Africa have limited health care facilities and walk long distances to seek medical attention when injured. This sometimes lead to loss of blood and death. To minimize loss of blood from injured individuals by clot formation, juices from plantain sheath/stem, cassava leaf and snail are applied on injured areas. The present work therefore investigated Musa paradisiaca sheath/stem, Manihot essculanta leaf and Achatina marginata juices for hemostatic property using human blood in-vitro. Screening indicated these juices contain tannins, flavonoids and other secondary metabolites. Morphological studies showed formation of a protein network on adding each of the three juices to fresh whole blood, plasma and serum respectively. The protein network formed was as a result of interactions between tannins found in the juices and proteins in the blood components. Microscopic analysis revealed aggregation of red blood cells as each of the juices was added to whole blood. High molecular weight fibrinogen found in whole blood, could have been caused by tannins and flavonoids found present in the juices. Insoluble proteins increased blood viscosity and inhibited movement of the red blood cells. Coagulatory potencies expressed in Prothrombin Times (PTs), revealed the snail juice of 0.80 mL volume had the least time for clot formation (PT=10.02 seconds), and indicated its hemostatic property. This PT was lesser compared to that of the standard, liquid plastin (PT= 11.0-12.5 seconds). As volumes of the three juices were increased from 0.8 to 1.0 mL, their PTs correspondingly decreased (p< 0.05). The snail juice of 0.9 mL volume had the least PT of 8.52 seconds. The plantain stem juice of 0.9 mL volume was next to the snail juice in order of ranking with a PT of 10.79 seconds, and lastly the cassava leaf juice of 1.0 mL volume with a PT of 14.42 seconds. Comparatively, the PTs for the plantain stem and snail juices were the same as the PT for the liquid plastin (PT=11.0 to 12.5 seconds, p<0.050), and all the three juices had PTs within the range considered for substances to be hemostatic (≤ 20.0 seconds). This demonstrated an increased in hemostasis as volumes of the juices were increased, and therefore the plantain stem, cassava leaf and snail juices possess hemostatic property. A blend of the plantain stem and snail juices (1:1) revealed a lesser PT of 18.20 seconds compared to the PT of ≤ 20.0 seconds considered for hemostatic substances. Thus the plantain stem, cassava leaf and snail juices, and the blend of the plantain stem and snail juices (1:1) investigated in the present research work demonstrated hemostasis, and possess hemostatic property. This scientific evidence supports the use of plantain stem, cassava leaf and snail juices as hemostatic substances.

The inhibitory effect of non-steroidal anti-inflammatory agents on aggregation of red cells in vitro.

Abstract Aggregation of red cells of rat in saline suspension was induced by gelatin, high molecular weight dextran and fibrinogen. Except chloroquine, non-steroidal anti-inflammatory agents (NAIA) inhibited macromolecule-induced red cell aggregation in vitro. Glucocorticoids failed to inhibit red cell aggregation even in large concentrations. Of many drugs examined, only the NAIA and certain antihistamines, having experimental anti-inflammatory effects proved to be effective inhibitors of gelatin-induced red cell aggregation, in vitro.

Fibrinogen and high molecular weight fibrinogen during and after normal pregnancy

<h2>Abstract</h2> <i>Introduction</i>: Pregnancy has recently been described as a generalized intravascular inflammatory response to the conceptus. Total fibrinogen concentrations increase during pregnancy. The percentage high molecular weight fibrinogen (HMW-Fg) of the concentration total fibrinogen is known to increase during acute-phase conditions like inflammation. Therefore, we investigated whether the percentage high molecular weight fibrinogen increases during normal pregnancy. <i>Materials and Methods</i>: Eighteen healthy nulliparous women with uncomplicated pregnancies with normal course and outcome participated in this study. Five blood samples were drawn from every woman in the gestational age periods 9 to 16, 17 to 24, 25 to 33 and 34 to 42 weeks and at 12 to 20 weeks after delivery. Total fibrinogen concentrations were determined according to Clauss and the percentage high molecular weight fibrinogen was assessed by SDS-electrophoresis and densitometry after isolation of fibrinogen by precipitation. One-way analysis of variance (ANOVA) was used to evaluate differences between gestational age periods and correlation coefficients were calculated by Pearson's method. <i>Results</i>: Total fibrinogen concentrations increased with advancing gestational age and decreased after delivery. The percentage high molecular weight fibrinogen of the total fibrinogen remained unaltered during and after pregnancy. <i>Conclusions</i>: During normal pregnancy, there is an increase of total fibrinogen concentrations with advancing gestational age, without a rise in percentage high molecular weight fibrinogen. After delivery, the total fibrinogen returns to baseline concentrations.

Fibrinogen and high molecular weight fibrinogen during and after normal pregnancy

Introduction: Pregnancy has recently been described as a generalized intravascular inflammatory response to the conceptus. Total fibrinogen concentrations increase during pregnancy. The percentage high molecular weight fibrinogen (HMW-Fg) of the concentration total fibrinogen is known to increase during acute-phase conditions like inflammation. Therefore, we investigated whether the percentage high molecular weight fibrinogen increases during normal pregnancy. Materials and Methods: Eighteen healthy nulliparous women with uncomplicated pregnancies with normal course and outcome participated in this study. Five blood samples were drawn from every woman in the gestational age periods 9 to 16, 17 to 24, 25 to 33 and 34 to 42 weeks and at 12 to 20 weeks after delivery. Total fibrinogen concentrations were determined according to Clauss and the percentage high molecular weight fibrinogen was assessed by SDS-electrophoresis and densitometry after isolation of fibrinogen by precipitation. One-way analysis of variance (ANOVA) was used to evaluate differences between gestational age periods and correlation coefficients were calculated by Pearson's method. Results: Total fibrinogen concentrations increased with advancing gestational age and decreased after delivery. The percentage high molecular weight fibrinogen of the total fibrinogen remained unaltered during and after pregnancy. Conclusions: During normal pregnancy, there is an increase of total fibrinogen concentrations with advancing gestational age, without a rise in percentage high molecular weight fibrinogen. After delivery, the total fibrinogen returns to baseline concentrations.

Increased high molecular weight fibrinogen in pre-eclampsia

Introduction: The major coagulation protein fibrinogen (Fg) is a heterogeneous protein with three main fractions: high molecular weight fibrinogen (HMW-Fg), low molecular weight fibrinogen (LMW-Fg) and low molecular weight′ fibrinogen. The clottability of high molecular weight fibrinogen is highest as compared to the other fractions. Pre-eclampsia is associated with a state of hypercoagulability, and with an increase of fibrinogen concentration. The aim of the present study was to examine if the increased total fibrinogen plasma concentration in patients with pre-eclampsia is associated with a change in distribution of the main fibrinogen fractions. Material and Methods: Plasma was collected from 14 patients with pre-eclampsia and from 14 healthy pregnant matched controls. Total fibrinogen concentrations were determined according to Clauss. The percentage high molecular weight fibrinogen was assessed by SDS-electrophoresis and densitometry after isolation of fibrinogen by precipitation. The study groups were compared by the Mann–Whitney U-test. Results: The median (range) total fibrinogen concentration in the pre-eclampsia group was 5.04 (3.25–6.51) g/l and in the control group 4.19 (3.61–5.38) g/l ( p<0.05). The median (range) percentage high molecular weight fibrinogen was 76.5 (69.6–84.0)% and 73.0 (69.0–78.9)% in the pre-eclampsia and control group, respectively ( p<0.05). Conclusions: In pre-eclampsia, the concentration of total fibrinogen is increased and the percentage high molecular weight fibrinogen is also slightly higher than in normal pregnancy. These results may be a reflection of the exaggerated inflammatory response, and subsequent endothelial activation, which are currently believed to be the key pathophysiological mechanisms in pre-eclampsia.

Relationship Between Fibrinogen Protein and Fibrinogen Function in Postmyocardial Infarction Patients

The present study investigates the association between increases in the concentration and function of plasma fibrinogen in two groups of patients with chronic ischemic heart disease (11 with recurrent ischemic events and 19 free of these episodes) and in 34 healthy controls. The fibrinogen function index (fibrinogen function per unit of fibrinogen protein) (FgFI) was used as a measure of the fibrinogen clotting potential. The prothrombin fragment 1+2 (F1+2) and thrombin–antithrombin (TAT) were used as procoagulant markers. Plasma sialic acid (SA) was also evaluated as an inflammatory marker. No differences were found between FgFI (1.06±0.13 vs. 1.02±0.13), F1+2 (1.2±0.5 vs. 1.1±0.4 nmol/l) and TAT (2.5±1.3 vs. 2.5±0.7 μg/ml) in postinfarction patients without recurrent coronary ischemic events and the control group. However, postinfarction patients who suffered recurrent coronary ischemic events had significantly higher FgFI than patients without these symptoms (1.19±0.09 vs. 1.06±0.13), P<.01) and than the control group (1.19±0.09 vs. 1.02±0.13, P<.001). Moreover, the F1+2 (1.4±0.5 vs. 1.1±0.4 nmol/l, P<.05) and TAT (3.6±3.3 vs. 2.5±0.7 μg/ml, P<.05) were significantly higher in patients who suffered recurrent coronary ischemic events than in the control group. However, F1+2 and TAT were not different between patients with and without these symptoms. The fibrinogen protein (Fg-protein) concentration and high molecular weight fibrinogen (HMW-Fg) levels were significantly higher in both postinfarction patient groups than in the control group and in postinfarction patients with recurrent coronary ischemic events than in postinfarction patients without these symptoms. The plasma SA levels were significantly increased in postinfarction patients with and without recurrent coronary ischemia as compared with the control group. A positive correlation was found between fibrinogen and SA levels ( r=.5, P<.01). In conclusion, our study indicates that the procoagulant factors, among which we include fibrinogen, F1+2 and TAT play a very active role in recurrent ischemic events in postmyocardial infarction patients. High plasma concentrations of both fibrinogen and SA suggests that fibrinogen becomes elevated as a consequence of inflammatory processes. The FgFI as an indicator of clotting potential of fibrinogen appears to be associated with ischemic events in chronic coronary artery disease.

Fibrinogen Fractions in the Third Trimester of Pregnancy and in Puerperium

The concentration of fibrinogen, its fractions, and the concentration of C-reactive protein were determined in 45 healthy pregnant women before and after vaginal (27) or caesarean section 18 delivery. The control group consisted of 33 blood donors. In pregnancy, increased concentration of total fibrinogen and its fractions and a normal concentration of C-reactive protein were noted. Three days after vaginal delivery the concentration of total and high molecular weight fibrinogen fraction decreased slightly and the ratio of high to low molecular weight fibrinogen increased. After caesarean section both total and high molecular weight fibrinogen and the ratio of high to low molecular weight fibrinogen increased. The C-reactive protein concentration increased after either type of delivery. The degree of augmentation, however, was ten times as strong after caesarean section. In all women at the end of puerperium the concentrations of the compounds studied returned to normal values. The results suggest that the mechanisms leading to the increase of fibrinogen during pregnancy and after delivery are different. The increase of all fibrinogen fractions in pregnancy may depend first of all on hormones, whereas the increased proportion of high molecular weight to low molecular weight fibrinogen after delivery depends on the acute phase reaction. The degree of this reaction depends on the type of delivery.

Elevated High Molecular Weight Fibrinogen in Plasma Is Predictive of Coronary Ischemic Events after Acute Myocardial Infarction

This study investigates the association between the concentration and function of plasma fibrinogen molecules measured at the time of hospital admission in patients with acute myocardial infarction (AMI), with reference to the risk of new coronary ischemic events during a three-day follow-up period of. Before starting fibrinolytic and anticoagulant treatment plasma fibrinogen, high molecular weight fibrinogen (HMW-fibrinogen), fibrin formation rate (FbFR) and phosphorous content in fibrinogen were determined in 90 AMI patients. During a three-day follow-up period 12 patients suffered new ischemic events. The 12 patients with coronary ischemia had higher concentrations of plasma fibrinogen (312+/-23 vs. 270+/-73 mg/dl, p<0.05) and HMW-fibrinogen (246+/-35 vs. 189+/-23 mg/dl, p<0.001) and a higher FbFR (65+/-30 vs. 40+/-25, p<0.001) than patients without these events. No association was found between the phosphorous content in fibrinogen and new coronary ischemic events. We conclude that after myocardial infarction an elevated plasma level of HMW-fibrinogen and a high FbFR value at the time of hospital admission are associated with new coronary ischemic events during a three-day follow-up period.

Postoperative Plasma Interleukin-6 in Patients with Renal Cancer Correlates with C-reactive Protein but Not with Total Fibrinogen or with High Molecular Weight Fibrinogen Fraction

The concentration of fibrinogen (Fb) and its fractions, the levels of interleukin-6 (Il-6), C-reactive protein (CRP), and immunoglobulin G (IgG) were determined in 38 patients operated on because of renal cancer. The increased Fb and Il-6 concentrations were found in approximately one-half of the patients with malignancy. The relations among the high molecular weight (HMW) and two low molecular weight (LMW and LMW′) fibrinogen fractions in these patients before surgery did not differ from the corresponding relations in normal subjects. The levels of all (except IgG) compounds studied increased after surgery and the peak of Il-6 was observed on the first postoperative day but that of CRP on the third day. The concentrations of total Fb and of its HMW fraction were the highest also on the third postoperative day and this was in contrast with the decline of low molecular weight fractions at the same time. These variations of estimated variables can be regarded as being relevant to the acute phase response. We have noted a correlation between the maximal concentrations of Il-6 and CRP, but not between the corresponding concentrations of Il-6 and total Fb or HMW Fb; this may suggest that the concentration of Fb is also under the control of a factor other than Il-6.

Fibrinogen Heterogeneity in Homozygous Plasminogen Deficiency Type I: Further Evidence that Plasmin Is not Involved in Formation of LMW- and LMW’-Fibrinogen

Human plasma fibrinogen is heterogeneous in SDS-polyacrylamide gel electrophoresis and other methods for separation of proteins by molecular size. A high molecular weight fraction (HMW-fibrinogen, 340 kD) contributes approximately 50% of total fibrinogen antigen. Low molecular weight fibrinogen (LMW-fibrinogen, 300 kD) adds another 40%. The residual amount is LMW'-fibrinogen with a molecular weight of 280 kD, and a small amount of very high molecular weight fibrinogen (Fib420), the product of alternative splicing of the A alpha-chain genetic information, resulting in an extended A alpha-chain C-terminus. Fibrinogen was detected by specific immunostaining of nonreduced SDS-PAGE gel immunoblots with antibodies against fibrinopeptide A. Using densitometric scans of the immunoblots we found a ratio of HMW-, LMW- and LMW'-fibrinogen in a patient with homozygous plasminogen deficiency that was similar to the ratio found in immunoblots of plasma from healthy blood donors. Treatment with plasminogen concentrate resulted in a slight decrease of the proportion of HMW-fibrinogen, followed by an increase to 78%. The LMW'-fibrinogen band gained intensity initially, increasing to 11.9% of fibrinogen antigen 6 h after starting plasminogen infusion, but then dropped to levels below detection limit of the immunoblotting assay. LMW-fibrinogen remained constant during the initial 72 h of plasminogen treatment, then dropping to values in the range of 22-25% afterwards. The proportion of HMW-, LMW-, and LMW'-fibrinogen again reached the initial levels two weeks after starting treatment with plasminogen concentrate. We conclude that plasminogen is not involved in the limited proteolysis leading to formation of LMW-fibrinogen and LMW'-fibrinogen in the absence of a generalized fibrinolytic condition. Fibrinolytic activation may lead to the formation of fibrinogen degradation product X, which appears in a similar position as LMW'-fibrinogen in SDS-PAGE.

Increase of high molecular weight fibrinogen after surgery for renal cancer.

Increase of high molecular weight fibrinogen after surgery for renal cancer.

Biochemistry and measurement of fibrinogen.

Fibrinogen is a large heterogeneous family of closely related molecules consisting of three pairs of non-identical polypeptide chains: two A alpha-, two B beta- and two gamma-chains, held together by disulphide bridges. The heterogeneity of fibrinogen is due to heterogeneities in all three chains. Four main types of assay are used to determine fibrinogen:clotting rate (Clauss), clottable protein, precipitation and immunological assays. Heterogeneities may differ from person to person and may affect the apparent fibrinogen concentrations in different assays. A further complicating factor was, until recently, the lack of an international fibrinogen standard. The ratio of Clauss:enzyme immunoassay (EIA) for high + low molecular weight fibrinogen decreases during therapy for acute myocardial infarction and increases again after thrombolytic therapy to above normal values. Furthermore, high molecular weight fibrinogen tends to clot more easily than low molecular weight fibrinogen. This suggests that high molecular weight fibrinogen might be associated with increased thrombotic risk. Fibrinogen assessed by a functional assay (Clauss) alone is strongly associated with ischaemic heart disease. Although not proven, it is conceivable that a fibrinogen with a Clauss:EIA ratio of > 1 has an even stronger association in epidemiological studies.

Fragmentation pattern of fibrinogen during thrombolysis in acute myocardial infarction with fibrin-specific plasmionogen activators — Detection of high molecular weight fibrinogen split products

Fragmentation pattern of fibrinogen during thrombolysis in acute myocardial infarction with fibrin-specific plasmionogen activators — Detection of high molecular weight fibrinogen split products

Fragmentation pattern of fibrinogen during thrombolysis in acute myocardial infarction with fibrin-specific plasminogen activators — Detection of high-molecular weight fibrinogen degradation products

In thrombolysis in acute myocardial infarction, the fibrin-specific plasminogen activators are infused in non-physiologically high doses. Only limited fibrin-specific in nature, this may give rise to extensive fibrinogen degradation. In a series of 65 patients — 24 rt-PA, 41 pro-urokinase — we investigated, whether fibrinogen degradation follows a similar fragmentation pattern as known from thrombolysis with streptokinase. During thrombolysis, fibrinogen levels were stable (3.2 ± 1.7 before and 3.1 ± 1.3 g/l at 2 hours), whereas plasminogen and α 2-antiplasmin levels decreased from 96.1 ± 23.8 to 59.3 ± 25.6 and 93.4 ± 26.9 to 31.9 ± 32.4%, respectively. Simultaneously low molecular weight fibrinogen — and fibrin degradation products increased from 0.55 ± 0.42 to 3.31 ± 5.69 mg/l and from 0.61 ± 0.83 to 6.58 ± 6.78 mg/I respectively. Moreover high molecular weight fibrin degradation products (250–300,000 D) were detected in the plasmas of 14 pts (8 pro-urokinase, 6 rt-PA) with means of SDS-PAGE (Polyacrylamide-gradient 6–12%, 250 V, 30 mA, silver staining). Furthermore generation of high molecular weight degradation products was correlated to consumption of the plasminogen and α 2-antiplasmin. Thus the fibrinogen fragmentation pattern of all plasminogen activators is similar and is correlated to the extent of systemic lytic state.

The stimulatory capacity of soluble fibrin prepared from high and low molecular weight fibrinogen on plasminogen activation

The stimulatory capacity of soluble fibrin prepared from high and low molecular weight fibrinogen on plasminogen activation

The stimulatory capacity of soluble fibrin prepared from high and low molecular weight fibrinogen on plasminogen activation

High molecular weight, low molecular weight and very low molecular weight fibrinogen were purified from human plasma, and converted partially or completely to fibrin by the action of thrombin or batroxobin. The stimulatory effects of these fibrin(ogen) preparations on plasminogen activation by tissue plasminogen activator were studied. When only 3-30% of the fibrinogen molecules were converted to fibrin, the high molecular weight fibrin had a greater stimulatory effect on plasminogen activation than equal amounts of low and very low molecular weight fibrin. In completely converted fibrin preparations, the plasminogen activating capacity of high molecular weight fibrin was either equal to (thrombin treated preparations) or greater than (batroxobin-treated preparations) that of very low molecular weight fibrin. These findings suggest that degradation of the A alpha-chain of fibrin does not per se increase its plasminogen activating capacity.

Decreased high-molecular weight fibrinogen and impaired alpha-chain polymerization in full-term newborns.

Some properties of fibrinogen from 30 newborn and 30 normal adult plasmas obtained under the same conditions have been studied. The results show that the high-molecular weight fibrinogen (HMW-Fg) was decreased by nearly 25% in newborn plasma as compared to normal adult values. The kinetics of fibrin gel formation was decreased in newborn as compared with normal adult plasmas (gelation rates 2.2 +/- 1 vs. 5.6 +/- 0.5 x 10(-4) OD/s, lag time 128 +/- 25 vs. 72 +/- 3 s). The release rates of fibrinopeptide A (FPAp +/- FPA) and fibrinopeptide B (FPB) were decreased in newborn fibrinogen (FPAp + FPA 10.8 and FPB 1.2 x 10(-3) s-1) as compared to normal adult fibrinogen (FPAp + FPA 11.8 and FPB 1.7 x 10(-3) s-1). Analysis by SDS-PAGE of the reduced, highly cross-linked fibrin from the newborns showed that only 23% of the alpha-chain participates in the formation of alpha-chain polymers. The results suggest that the retarded release rate of fibrinopeptides and the decrease in the HMW fibrinogen concentration are causes of the prolonged kinetics of fibrin gel formation in newborns.

Abnormal fibrinogens IJmuiden (B beta Arg14----Cys) and Nijmegen (B beta Arg44----Cys) form disulfide-linked fibrinogen-albumin complexes.

The molecular defects in two congenital abnormal fibrinogens, IJmuiden and Nijmegen, were determined by sequence analysis of genomic DNA amplified by the polymerase chain reaction. Both fibrinogens were heterozygous, IJmuiden having a B beta Arg14----Cys substitution and Nijmegen having a B beta Arg44----Cys substitution. Clotting induced by thrombin or Reptilase was impaired in both fibrinogens, indicating defective fibrin polymerization. Immunoblot analysis of both purified fibrinogens demonstrated that some of the abnormal molecules were linked by disulfide bonds to albumin. In addition, abnormal high molecular weight fibrinogen complexes with Mrs between 600,000 and 700,000 were present. Fibrinogen-albumin and high molecular weight complexes were also detected in the patients' plasmas. Quantitative analysis demonstrated that of the total plasma fibrinogen in the IJmuiden patient, 20% was linked to albumin and 10% was present as high molecular weight complexes. In plasma Nijmegen, 13% was linked to albumin and 15% was present as high molecular weight complexes. These results demonstrate that the additional abnormal cysteine in fibrinogens IJmuiden and Nijmegen resulted in the formation of disulfide-linked complexes with other proteins, predominantly albumin. We also found that a significant fraction of the abnormal fibrinogen molecules contained free sulfhydryl groups. These findings complicate interpretation of functional studies of these altered fibrinogens.