scholarly journals Laboratory Control of Fibrinolytic Therapy

1977 ◽  
Author(s):  
W. Theiss ◽  
A. Wirtzfeld ◽  
E. Sauer ◽  
L. Lutilsky ◽  
A. Kriessmann
Keyword(s):  
Detailed Analysis ◽  
Oral Anticoagulation ◽  
Laboratory Tests ◽  
Degradation Products ◽  
Fibrinolytic Therapy ◽  
Fibrinogen Concentration ◽  
Thrombin Time ◽  
Routine Monitoring ◽  
Clinical Control ◽  
Clinical Conditions

Under fibrinolytic therapy, the levels of fibrinogen and of fibrin(ogen)degradation products (FDP) grossly influence most of the laboratory tests usually performed for clinical control of fibrinolytic treatment. Although these interferences are basically known, there is a lack of more detailed analysis under true clinical conditions. Therefore, fibrinogen determination according to Clauss (1957), thrombin time, and thromboplastin time were used for routine monitoring of 29 patients undergoing therapy with streptokinase for up to 6 days, and the results of these tests were correlated with true clottable fibrinogen as determined according to Ratnoff and Menzie (1961) and with FDP as determined according to Merskey et al. (1966).Fibrinogen determination by the Clauss method yielded poor results; for immediate clinical control, however, they were sufficient, when values above 80 mg/dl were obtained (r=0.60 when compared to actual fibrinogen concentration). Values below 80 mg/dl were completely unreliable and more closely reflected FDP (r=0.63) than actual fibrinogen levels (r<0.20). The Clauss assay is entirely insufficient, when exact fibrinogen determinations are required as for rheological or pharmacological considerations. Quite in contrast, fibrinogen levels measured according to Ratnoff and Menzie were independent of FDP levels.After bilogarithmic transformation, the thrombin time closely correlated to the FDP level (r=0.86); it thus is a valuable test for quickly estimating FDP. Since FDP also greatly influence thromboplastin time determinations (r=0.79), they must duely be considered, when overlapping oral anticoagulation is planned towards the end of fibrinolytic therapy.

A Rapid Method for the Semiquantitative Determination of Fibrinogen and Fibrinogen Degradation Products (FDP) in Defibrination Syndrome

1971 ◽  
Vol 25 (03) ◽  
pp. 555-565 ◽  
Author(s):  
G Sas ◽  
J Jákó ◽  
J Domán ◽  
C László ◽  
J Pádár
Keyword(s):  
Degradation Products ◽  
Substantial Reduction ◽  
Experimental System ◽  
Fibrinogen Concentration ◽  
Thrombin Time ◽  
Clotting Time ◽  
Fibrinogen Degradation Products ◽  
Linear Plot ◽  
Fibrinogen Content

Summary1. It was found that effects of deliberate changes in fibrinogen concentration and in the amount of FDP added to the experimental system (containing pure fibrinogen solution and saline- or serumdiluted plasma) could be approximated with satisfactory accuracy by a linear plot of the logarithm of clotting times versus the inverse of fibrinogen concentration.By increasing FDP activity the slope of the obtained lines becomes proportionately steeper. The constants, which interrelate clotting time, fibrinogen concentration and FDP activity, are to be derived experimentally. The obtained formula is expressed also nomographically.2. Apart from the presence of some very rare anticoagulants, an elongation of thrombin time observed under strictly specified conditions points to a substantial reduction of fibrinogen concentration and/or an interplay of fibrinogen degradation products.If a definite amount of fibrinogen (Fibrinogen sec. Warner Chilcott) is admixed to a pathological plasma, thrombin time in the latter will decrease in a specifiable manner. By entering the original and corrected thrombin time values in the reported nomogram the fibrinogen content and FDP activity of the pathological plasma can be calculated.3. The described procedure for fibrinogen and FDP assay is suitable first of all in acute defibrination syndrome and at the thrombolytic therapy. Its agreement with the results obtained by immunodiffusion was satisfactory as regards the fibrinogen in plasmas of different fibrinogen concentration.

Fibrinogen Bastia (γ 318 Asp → Tyr) a Novel Abnormal Fibrinogen Characterized by Defective Fibrin Polymerization

1999 ◽  
Vol 82 (12) ◽  
pp. 1639-1643 ◽  
Author(s):  
Karim Chabane Lounes ◽  
Claudine Soria ◽  
Antoine Valognes ◽  
Marie France Turchini ◽  
Jaap Koopman ◽  
...  
Keyword(s):  
Calcium Ions ◽  
Clinical Symptoms ◽  
Degradation Products ◽  
Base Substitution ◽  
Chain Gene ◽  
Fibrinogen Concentration ◽  
Clotting Time ◽  
Terminal Part ◽  
Fibrin Polymerization ◽  
Chain Sequence

SummaryA new congenital dysfibrinogen, Fibrinogen Bastia, was discovered in a 20-year-old woman with no clinical symptoms. The plasma thrombin-clotting time was severely prolonged. The functional plasma fibrinogen concentration was low (0.2 mg/ml), whereas the immunological concentration was normal (2.9 mg/ml). Purified fibrinogen Bastia displayed a markedly prolonged thrombin-clotting time related to a delayed thrombin-induced fibrin polymerization. Both the thrombin-clotting time and the fibrin polymerization were partially corrected by the addition of calcium ions. The anomaly of fibrinogen Bastia was found to be located in the γ-chain since by SDS-PAGE performed according to the method of Laemmli two γ-chains were detected, one normal and one with an apparently lower molecular weight. Furthermore, analysis of plasmin degradation products demonstrated that calcium ions only partially protect fibrinogen Bastia γ-chain against plasmin digestion, suggesting that the anomaly is located in the C-terminal part of the γ-chain. Sequence analysis of PCR-amplified genomic DNA fragments of the propositus demonstrated a single base substitution (G → T) in the exon VIII of the γ chain gene, resulting in the amino acid substitution 318 Asp (GAC) → Tyr (TAC). The PCR clones were recloned and 50% of them contained the mutation, indicating that the patient was heterozygous. These data indicate that residue Asp 318 is important for normal fibrin polymerization and the protective effect of calcium ions against plasmin degradation of the C-terminal part of the γ-chain.

The Measurement of Heparin

1973 ◽  
Vol 30 (03) ◽  
pp. 471-479 ◽  
Author(s):  
K. W. E Denson ◽  
John Bonnar
Keyword(s):  
Degradation Products ◽  
Factor Xa ◽  
Assay Method ◽  
Thrombin Time ◽  
Fibrinogen Degradation Products ◽  
Low Levels

SummaryA method for the measurement of heparin utilising the potentiating effect of heparin on the action of anti-factor Xa is described. The effect on the assay of platelet contamination of plasma, the presence of fibrinogen degradation products and low levels of anti-factor Xa have been studied. The assay method has been compared with the calcium thrombin time method and a group of obstetrical patients have been studied using both methods.

EFFECTS OF NICKEL CHLORIDE ON INDICES OF HEMOCOAGULATION AND LIPID PEROXIDATION IN RATS

2019 ◽  
pp. 83-90
Author(s):  
Э.М. Гаглоева ◽  
В.Б. Брин ◽  
С.В. Скупневский ◽  
Н.В. Боциева ◽  
Т.В. Молдован
Keyword(s):  
Lipid Peroxidation ◽  
Antioxidant Enzymes ◽  
Platelet Aggregation ◽  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Nickel Chloride ◽  
Activated Partial Thromboplastin Time ◽  
Fibrinogen Concentration ◽  
Thrombin Time ◽  
Hemostasis System

Цель исследования - изучить состояние системы гемостаза при хронической интоксикации хлоридом никеля, исследовать взаимосвязь показателей гемокоагуляции с процессами липопероксидации у крыс в эксперименте. Методика. Опыты проводили на крысах-самцах Вистар (n=50, 230-250 г). Раствор NiCl2 (5 мг/кг) вводили внутрижелудочно ежедневно в течение 2 нед, 1 и 2 мес. По завершении эксперимента исследовали состояние тромбоцитарного и коагуляционного звеньев гемостаза, антикоагулянтную и фибринолитическую активность крови, а также определяли активность процессов перекисного окисления липидов и антиоксидантных ферментов. Результаты. Установлено, что через 2 нед и 1 мес интоксикации у крыс отмечались гиперкоагуляционные изменения показателей свертывающей системы крови: повышение агрегационной активности тромбоцитов, увеличение концентрации фибриногена, снижение активированного частичного тромбопластинового времени (АЧТВ) и протромбинового времени. В этот период регистрировалось увеличение антитромбиновой и фибринолитической активности крови. Через 2 мес наблюдалось подавление активности клеточного звена гемостаза - тромбоцитопения, ослабление степени АДФ-индуцируемой агрегации тромбоцитов. Выявлялась тенденция к уменьшению концентрации фибриногена. На фоне снижения АЧТВ и тромбинового времени отмечалось увеличение протромбинового времени. В то же время регистрировалось угнетение противосвертывающего звена системы гемостаза (снижалась активность антитромбина III), наблюдалось истощение резервных возможностей фибринолитического звена (замедление фXIIа-зависимого эуглобулинового лизиса) и увеличение содержания растворимых фибрин мономерных комплексов, что свидетельствует о наличии тромбинемии. Через 2 нед, один и два месяца интоксикации у животных выявлялись корреляционные связи между основными показателями системы гемостаза и активностью процессов перекисного окисления липидов и антиоксидантных ферментов. Заключение. Полученные данные подтверждают наличие взаимосвязи активности процессов липопероксидации и системы гемостаза, в том числе при хронической никелевой интоксикации. Результаты исследования позволяют рекомендовать применение антиоксидантов для разработки способов коррекции гемостатических сдвигов при воздействии на организм тяжелых металлов. The aim. To study the state of the hemostasis system in chronic nickel intoxication and to investigate the relationship between hemocoagulation indices and lipoperoxidation processes in rats. Methods. Experiments were carried out on male Wistar rats (n=50, 230-250 g). A solution of nickel chloride (5 mg/kg) was administered daily intragastrically for two weeks, one and two months. At the end of the experiments, indices of platelet and coagulation hemostasis systems, anticoagulant and fibrinolytic activity of blood plasma, and activities of lipid peroxidation and antioxidant enzymes were studied. Results. Hypercoagulative changes in indices of the coagulation system were observed in rats after two weeks and one month of intoxication, including increased platelet aggregation and fibrinogen concentration and shortened activated partial thromboplastin time and prothrombin time. During the same period, increased antithrombin and fibrinolytic activities were observed. The depressed activity of the cellular component of hemostasis evident as thrombocytopenia and impaired ADP-induced platelet aggregation was detected after two months of intoxication. A tendency to decrease in fibrinogen concentration was observed. The shortened activated partial thromboplastin time and thrombin time were associated with prolonged prothrombin time. At the same time, inhibition of the anticoagulant component of hemostasis (decreased antithrombin III activity), exhaustion of the fibrinolysis system reserve (delayed fXIIa-dependent euglobulin lysis), and a significant increase in soluble fibrin monomeric complexes indicative of thrombinemia were observed. After two weeks, one and two months of nickel intoxication, a correlation was found between the major indices of the hemostasis system and the activities of lipid peroxidation and antioxidant enzymes. Conclusion. The study confirmed a relationship between the lipid peroxidation activity and the hemostasis system, specifically in chronic nickel intoxication. This result allows to recommend the use of antioxidants in developing methods for correction of hemostatic induced affected by heavy metals.

Identification of Crosslinked Fibrin Degradation Products in Plasma of Patients During Fibrinolytic Therapy Using a Heat Extraction/SDS-Polyacrylamide Gradient Gel Electrophoretic Technique

1979 ◽  
Author(s):  
C.W. Francis ◽  
V. J. Marder ◽  
S.E. Martin
Keyword(s):  
Degradation Products ◽  
Fibrinolytic Therapy ◽  
Heat Extraction ◽  
Molecular Weights ◽  
Fibrin Degradation Products ◽  
Normal Plasma ◽  
Electrophoretic Technique ◽  
Gradient Gel Electrophoresis ◽  
Derivatives Of

To quantitate plasmic degradation products of crosslinked fibrin in plasma, a technique has been developed which employs heat precipitation, SDS-polyacrylamide gradient gel electrophoresis of the dissolved, reduced heat precipitate, and quantitation by densitometrie analysis of γ-γ derivatives identified in the stained get. When studied with this sensitive electrophoretic technique, plasmic digests of purified crosslinked fibrin were found to contain a heterogeneous group of γ-γ chain derivatives with molecular weights between 76,000 and 100,000 daltons. In samples of normal plasma to which digests of crosslinked fibrin had been added, this heat extraction/ge1 electrophoretic technigue allowed the detection of γ-γ derivatives with a sensitivity of 20 µg/ml. Derivatives of γ-γ chains with molecular weights of 82,000 and 86,000 daltons have been identified in the plasma of patients with DIC and during fibrinolytic therapy but were not found in normal plasma or in normal plasma treated in vitro with urokinase. This quantitative assay can be performed in 24 hours and appears to be of value in judging the efficacy of thrombolytic therapy.

scholarly journals A novel missense mutation in the FGB g. 3354 T>A (p. Y41N), Fibrinogen Caracas VIII

2011 ◽  
Vol 105 (04) ◽  
pp. 627-634 ◽  
Author(s):  
Héctor Rojas ◽  
Michael Meyer ◽  
Oscar Castillo ◽  
Arlette De Sáez Ruiz ◽  
John Weisel ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Fibrin Clot ◽  
Polymerization Process ◽  
Confocal Laser ◽  
Fibrinogen Concentration ◽  
Thrombin Time ◽  
Normal Range ◽  
Amino Terminal ◽  
Fibrin Network ◽  
Β Chain

SummaryA novel dysfibrinogenaemia with a replacement of Tyr by Asn at Bβ41 has been discovered (fibrinogen Caracas VIII). An asymptomatic 39-year-old male was diagnosed as having dysfibrinogenaemia due to a mildly prolonged thrombin time (+ 5.8 seconds); his fibrinogen concentration was in the low normal range, both by Clauss and gravimetric determination, 1.9 g/l and 2.1 g/l, respectively. The plasma polymerization process was slightly impaired, characterised by a mildly prolonged lag time and a slightly increased final turbidity. Permeation through the patients´ clots was dramatically increased, with the Darcy constant around four times greater than that of the control (22 ± 2 x10–9 cm2 compared to 6 ± 0.5 x10–9 cm2 in controls). The plasma fibrin structure of the patient, by scanning electron microscopy, featured a mesh composed of thick fibres (148 ± 50 nm vs. 120 ± 31 nm in controls, p<0.05) and larger pores than those of the control fibrin clot. The viscoelastic properties of the clot from the patient were also altered, as the storage modulus (G‘, 310 ± 30) was much lower than in the control (831 ± 111) (p ≤0.005). The interaction of the fibrin clot with a monolayer of human microvascular endothelial cells, by confocal laser microscopy, revealed that the patients´ fibrin network had less interaction with the cells. These results demonstrate the significance of the amino terminal end of the β chain of fibrin in the polymerisation process and its consequences on the clot organisation on the surface of endothelial cells.

scholarly journals Specific identification of fibrin polymers, fibrinogen degradation products, and crosslinked fibrin degradation products in plasma and serum with a new sensitive technique

Blood ◽  
1985 ◽  
Vol 65 (3) ◽  
pp. 589-597
Author(s):  
DG Connaghan ◽  
CW Francis ◽  
DA Lane ◽  
VJ Marder
Keyword(s):  
Degradation Products ◽  
Sodium Dodecyl ◽  
Fibrinolytic Therapy ◽  
Electrophoretic Patterns ◽  
Fibrin Degradation Products ◽  
Low Concentrations ◽  
Combined Action ◽  
Derivatives Of ◽  
Normal Controls ◽  
Immunological Identification

A new method is described for identifying low concentrations of circulating derivatives of fibrinogen and fibrin, even when present in heterogeneous mixtures. This technique is applicable to plasma and serum and uses electrophoresis in 2% agarose in the presence of sodium dodecyl sulfate (SDS) followed by immunological identification of separated derivatives, using radiolabeled antifibrinogen antiserum and autoradiography. Unique electrophoretic patterns distinguish plasmic derivatives of crosslinked fibrin from those of fibrinogen and also identify crosslinked fibrin polymers produced by the combined action of thrombin and factor XIII on fibrinogen. The assay is sensitive to a concentration of 0.1 micrograms/mL of fibrinogen in serum or plasma. Fibrin polymers, plasmic degradation products of fibrinogen, and plasmic degradation products of crosslinked fibrin were detected in the plasma or serum of a patient with disseminated intravascular coagulation. Plasmic derivatives of both fibrinogen and crosslinked fibrin appeared in serum in the course of fibrinolytic therapy for pulmonary embolism, whereas during acute myocardial infarction a marked increase in the proportion of fibrin polymers in plasma was found in comparison with normal controls. Thus, the procedure can distinguish between the simultaneous processes of fibrin polymer formation, fibrinogenolysis, and fibrinolysis, and is sufficiently sensitive to detect relevant quantities of derivatives in pathologic conditions.

scholarly journals Coagulation and Bleeding Disorders: Review and Update

2000 ◽  
Vol 46 (8) ◽  
pp. 1260-1269 ◽  
Author(s):  
Douglas A Triplett
Keyword(s):  
Laboratory Tests ◽  
Platelet Adhesion ◽  
Vascular Wall ◽  
Activated Partial Thromboplastin Time ◽  
Thrombin Time ◽  
Bleeding Disorders ◽  
Coagulation Proteins ◽  
Hereditary Disorders ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Hemostasis is initiated by injury to the vascular wall, leading to the deposition of platelets adhering to components of the subendothelium. Platelet adhesion requires the presence of von Willebrand factor and platelet receptors (IIb/IIIa and Ib/IX). Additional platelets are recruited to the site of injury by release of platelet granular contents, including ADP. The “platelet plug” is stabilized by interaction with fibrinogen. In this review, I consider laboratory tests used to evaluate coagulation, including prothrombin time, activated partial thromboplastin time, thrombin time, and platelet count. I discuss hereditary disorders of platelets and/or coagulation proteins that lead to clinical bleeding as well as acquired disorders, including disseminated intravascular coagulation and acquired circulating anticoagulants.

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