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At least 775 records · Page 43Linked to original sources
PubMed1988

Method for the determination of functional (clottable) fibrinogen by the new family of ACL coagulometers.

A new family of coagulometers ACL 100, 200 and 300 (Instrumentation Laboratory, IL) has recently been introduced, in addition to the existing ACL 810. This paper presents a technique to determine clottable fibrinogen using the ACL method based on the measurement of the light scattered from the reaction mixture during a PT test. This technique was found to compare well with the present most commonly used methods.

Afibrinogenemia↗
PubMed1993

Evidence that plasma fibrinogen and platelet membrane GPIIb-IIIa are involved in the adhesion of platelets to an artificial surface exposed to plasma.

We investigated the molecular mechanism(s) by which platelets adhere to an artificial surface exposed to plasma, using polystyrene microtiter plates pretreated with plasma. Washed platelets labelled with 51Cr were incubated with the plates under static conditions. Prostaglandin E1(PGE1) was added to the platelets to prevent platelet-platelet interactions. Adhesion required the presence of a divalent cation such as Mg++ or Ca++. Polyclonal anti-fibrinogen antibody inhibited adhesion by 70%. Polyclonal antibodies against fibronectin, vitronectin, von Willebrand's Factor, and the Fc portion of human IgG, had no effect on adhesion. Platelets adhered normally to a surface pretreated with plasma from a patient with severe von Willebrand's disease. No platelet adhesion occurred when the surface was pretreated with an afibrinogenemic plasma. Monoclonal antibodies against platelet membrane GPIIb-IIIa, potent inhibitors of ADP-induced fibrinogen binding to platelets, completely inhibited adhesion. Monoclonal antibodies against the GPIb alpha subunit and GPIc(VLA alpha 5) showed no inhibitory effects on adhesion. Platelets from a patient with Glanzmann's thrombasthenia (type I) did not adhere to the surface pretreated with normal plasma. These results suggest that plasma fibrinogen adsorbed onto the surface and that platelet membrane glycoprotein(GP)IIb-IIIa were responsible for adhesion in an activation-independent manner.

Adsorption↗
PubMed1994

Inhibitory effects of TFPI variants on thrombin and factor Xa generation in fibrinogen-deficient human plasma.

Using a fast kinetic centrifugal analyzer, the inhibitory effects of glycosylated and unglycosylated full-length and truncated forms of TFPI on protease generation were studied in fibrinogen-deficient human plasma after extrinsic (EA) or intrinsic (IA) activation of coagulation. When the assay system was supplemented with increasing amounts of the TFPI variants the generation of both thrombin and factor Xa was inhibited in a concentration-dependent manner. Clear differences in the effectiveness of the TFPI variants were found. After EA, the unglycosylated full-length TFPI was most effective followed by the glycosylated full-length form. The C-terminal truncated TFPI showed the lowest inhibitory activity in this system. However, its efficiency increased several fold when coagulation was activated via the intrinsic pathway. Comparing the IC50 values after IA, the truncated TFPI was more effective than the unglycosylated full-length form and nearly as effective as the glycosylated full-length TFPI. After both EA and IA the thrombin generation inhibition by TFPI variants was more pronounced than the inhibition of factor Xa generation. The results show that chemical modifications of the TFPI structure can result in changes of TFPI's inhibitory properties to activated clotting factors leading to differences in protease generation inhibition.

Afibrinogenemia↗
PubMed1994

Screening of dysfibrinogenaemia using the fibrinogen function versus antigen concentration ratio.

The diagnosis of inherited and acquired dysfibrinogenaemia is usually suspected in patients with otherwise unexplained prolonged thrombin time or other tests with thrombin-like enzymes (1). Confirmation of the diagnosis requires discordant results from the investigation of functional fibrinogen and its antigen concentration. However, the issue of the difference between the two results required to confirm dysfibrinogenaemia has rarely been addressed. A difference of at least 0.5 g/l between functional fibrinogen using the method of Clauss and heat precipitation method according to Schulz has been suggested as a prerequisite (1). In the case of acquired dysfibrinogenaemia with an underlying liver disease the discordance should reach at least 1.0 g/l (2). Rodgers and Garr (3) suggested to establish a ratio between fibrinogen function and antigen concentration. In that study plasma from healthy blood donors was investigated using the Clauss method and radial immunodiffusion. We applied this approach to randomly selected patients at the time of admission to a University Hospital Department. Since fibrinogen is one of the major acute phase proteins, the determination of the C-reactive protein (CRP) was included for comparison.

Adult↗
PubMed1995

Fibrinogen Guarenas I: partial characterization of a new dysfibrinogenemia with an altered rate of fibrinopeptide release and an impaired polymerization.

A congenitally abnormal fibrinogen was isolated from the blood of a young woman with a severe bleeding diathesis. Coagulation tests showed a prolonged Thrombin and Reptilase time partially corrected by Ca2+. Polymerization of thrombin induced preformed fibrin monomers was severely impaired. Thrombin caused the release of fibrinopeptides with normal retention times on HPLC. However, the rate of release was abnormally slow and the total amount of fibrinopeptide A (FpA) released reached only approximately 50% of the theoretical maximum. The rate and quantity of FpA release was normal when Reptilase was used. Transmission Electron Microscopy (TEM) of Thrombin induced clots showed an altered clot structure characterized by a reduced mean fiber diameter. The mother has a polymerization defect similar to the propositus, her fibrinopeptide release is unaffected however. The father has a minor fibrinopeptide release defect suggesting the presence of two populations of fibrinogen. This study supports the idea that the fibrinogen isolated from the propositus has two defects inherited as separate genetic traits. This fibrinogen has been named Fibrinogen Guarenas I.

Adolescent↗
PubMed1984

Effect of cobaltous chloride on aggregation of platelets from normal and afibrinogenaemic human blood.

The aggregation of normal human platelets in vitro induced by ADP was severely inhibited after preincubation of platelet-rich plasma (PRP) with CoCl2. Platelets from a patient with congenital afibrinogenaemia did not aggregate until fibrinogen was added. This recovered response was also inhibited by CoCl2. The impairment of aggregation seemed to be due to the action of cobalt on surrounding fibrinogen and not to a direct action on the platelets themselves. These results illustrate another aspect of the potential toxicity resulting from the use of cobaltous salts in treating the anaemia of renal failure, in which bleeding disorders have been reported.

Adenosine Diphosphate↗
PubMed1996

The structure-function relationship of hereditary dysfibrinogens.

Fibrinogen is a 340-kDa multi-subunit glycoprotein present in plasma and tissues of all classes of vertebrates. Fibrinogen exerts a variety of physiologically important functions, and most of them, if not all, are assigned to certain structures of fibrin including double-stranded fibrin protofibrils and highly crosslinked fibrin networks. Fibrin formation is indeed a series of highly ordered molecular interactions. The mechanisms underlying these molecular interactions have been extensively studied in the last 40 years, but there still remain many enigmas. In this mini-review, the structure-function relationships of hereditary dysfibrinogens are discussed.

Afibrinogenemia↗
PubMed2006

In vitro fibrin clot formation and fibrinolysis using heterozygous plasma fibrinogen from gammaAsn319, Asp320 deletion dysfibrinogen, Otsu I.

INTRODUCTION: We have reported a heterozygous dysfibrinogenemia, fibrinogen Otsu I, caused by the deletion of gammaAsn319 and gammaAsp320, which was originally identified in the dysfibrinogen Vlissingen/Frankfurt IV (V/FIV) associated with thrombosis. Unlike the V/FIV family, the Otsu propositus showed no thrombotic tendencies. To analyze the relationship between thrombosis and the heterozygous plasma variant fibrinogen, we used purified plasma fibrinogen from the Otsu patient and compared it with a normal control. MATERIALS AND METHODS: Thrombin-induced fibrin clot formation and clot structure were observed by fibrin polymerization and scanning electron microscopy, respectively. For in vitro observation of fibrinolysis, plasmin generation and clot lysis assays were performed by the addition of tissue type plasminogen activation (tPA) and plasminogen. RESULTS AND CONCLUSIONS: Polymerization of Otsu was markedly impaired, while fibrin fibers were much thicker and the density of the bundles of fibrin fibers was less and porous compared with normal. Lysis of the Otsu clot was not significantly different from normal when a tPA and plasminogen mixture was overlaid onto the clots. For Otsu, the penetration of the tPA/plasminogen mixture into the clot was much faster than normal and the protection against plasmin cleavage was impaired; however, tPA-induced plasmin activation of the Otsu fibrin was slower than that of normal fibrin, resulting in a clot lysis of Otsu similar to normal.

Afibrinogenemia↗
PubMed2006

Fibrinogen Guarenas, an abnormal fibrinogen with an Aalpha-chain truncation due to a nonsense mutation at Aalpha 467 Glu (GAA)-->stop (TAA).

Fibrinogen Guarenas is a dysfibrinogenemia with a nonsense mutation at G4731T that causes an Aalpha-chain truncation at Ser 466. This abnormal fibrinogen is associated with a bleeding diathesis, severe in the proposita and mild in one brother, even though the fibrinogen levels in plasma are normal. All other family members are asymptomatic. Fibrinogens from the proposita and one family member, the mother of the proposita, both heterozygous for the mutation, were studied. Turbidity curves of fibrin polymerization showed that the lateral association of protofibrils was impaired and the maximum rate of polymerization was slightly diminished. The binding of albumin to fibrinogen was increased compared to control due to the presence of a free sulfhydryl group because of the missing disulphide bridge between Aalpha-Cys 442-472 in the mutated molecules. The abnormal fibrinogen formed much less alpha-polymer, and gamma-dimer formation was delayed compared to the control. Plasminogen activation by t-PA in the presence of fibrin was decreased. When Guarenas clots were perfused with fibrinolytic enzymes, clot degradation was retarded. Clot structure studied by confocal 3D microscopy showed that the fibrin network was dense, made up of thin and highly branched fibers, which accounted for the decreased flow rates by buffer permeation and increased rigidity of the fibrin clots, measured using a torsion pendulum. It seems that the increased clot rigidity, decreased porosity, hypofibrinolysis and t-PA induced fibrinolysis, by itself are not necessarily associated with thrombotic disorders in dysfibrinogenemia.

Afibrinogenemia↗
PubMed2005

Pharmacokinetic properties of a pasteurised fibrinogen concentrate.

The main pharmacokinetic characteristics of a plasma-derived, pasteurised fibrinogen concentrate were assessed in an open, multicentre, non-controlled study in five patients with congenital afibrinogenaemia or severe congenital hypofibrinogenaemia. Plasma samples were assayed for fibrinogen content in laboratories of the participating clinical centres (CCs) and additionally in a central laboratory at Aventis Behring (ABL). The values of the pharmacokinetic variables, using the fibrinogen determination at ABL, yielded a somewhat shorter terminal half-life compared with that determined at the CCs, with median (range) values of 2.7 days (2.5-3.7 days) versus 3.6 days (3.0-5.3 days), respectively. Fibrinogen clearance rate was clearly lower at the ABL with values of 0.91 ml/h/kg (0.84-1.22 ml/h/kg) compared with 1.65 ml/h/kg (0.82-2.55 ml/h/kg) at the CCs. The distribution volume at steady state (V-ss) of 89 ml/kg (81-116 ml/kg) was also smaller at the ABL than at the CCs (101 ml/kg [84-139 ml/kg]). Response, in vivo recovery and area under the curve did not differ noticeably between the laboratories. The normalisation or near normalisation of pre-infusion pathological coagulation tests indicated a good haemostatic efficacy of the tested fibrinogen concentrate, which was also generally well tolerated and not associated with any serious adverse reactions.

Adult↗