FIBRIN FORMATION AND DISSOLUTION

SummaryIncreased fibrinopeptide A (FPA) levels have been reported in various non-thrombotic disorders, including cancer, acute myocardial infarction, liver cirrhosis and collagen vascular diseases. To investigate the significance of these findings, the present study combined the radioimmunoassay of FPA with that of fibrinogen/fibrin degradation fragment E (FgE) in the aforementioned disorders and compared the results with those observed in healthy subjects as well as in patients with thromboembolism and overt disseminated intravascular coagulation (DIC). Mean FPA and FgE in malignancy were 6.3 and 305 ng/ml, in myocardial infarction 5.6 and 98 ng/ml, in liver cirrhosis 2.7 and 132 ng/ml and in collagen vascular diseases 5.6 and 142 ng/ml. All these values were significantly higher than in healthy controls (mean FPA 1.6 ng/ml, mean FgE 49 ng/ml) but significantly lower than in thromboembolism (mean FPA 10.7 ng/ml, mean FgE 639 ng/ ml) and DIC (mean FPA 22.0 ng/ml, mean FgE 1041 ng/ml). The overall correlation between FPA and FgE was highly significant. Elowever, different disorders showed peculiar patterns in FPA, FgE and fibrinogen levels. In malignancy, a definite increase of FPA, FgE and plasma fibrinogen levels was observed. This finding probably indicates a compensated state of (intra- or extravascular) fibrin formation and lysis. Acute myocardial infarction was characterized by a high FPA to FgE ratio, which is interpreted to reflect acute thrombin generation and fibrin formation. FPA in cirrhosis was only marginally elevated with most single values within the normal range, indicating that intravascular coagulation was infrequent and unimportant in quantitative terms.

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Fibrin Formation: The Role of the Fibrinogen-Fibrin Monomer Complex

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648007 ◽

1976 ◽

Vol 36 (01) ◽

pp. 037-048 ◽

Cited By ~ 49

Author(s):

Eric P. Brass ◽

Walter B. Forman ◽

Robert V. Edwards ◽

Olgierd Lindan

Keyword(s):

Particle Size ◽

Induction Period ◽

Fibrin Clot ◽

Clot Formation ◽

Appreciable Amount ◽

Buffer System ◽

Homeostatic Mechanism ◽

Fibrin Formation ◽

Fibrin Monomer

SummaryThe process of fibrin formation using highly purified fibrinogen and thrombin was studied using laser fluctuation spectroscopy, a method that rapidly determines particle size in a solution. Two periods in fibrin clot formation were noted: an induction period during which no fibrin polymerization occurred and a period of rapid increase in particle size. Direct measurement of fibrin monomer polymerization and fibrinopeptide release showed no evidence of an induction period. These observations were best explained by a kinetic model for fibrin clot formation incorporating a reversible fibrinogen-fibrin monomer complex. In this model, the complex serves as a buffer system during the earliest phase of fibrin formation. This prevents the accumulation of free polymerizable fibrin monomer until an appreciable amount of fibrinogen has reacted with thrombin, at which point the fibrin monomer level rises rapidly and polymerization proceeds. Clinically, the complex may be a homeostatic mechanism preventing pathological clotting during periods of elevated fibrinogen.

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A 3.5-Second Phenomenon in Haemostasis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649086 ◽

1973 ◽

Vol 30 (02) ◽

pp. 363-370

Author(s):

D Thilo ◽

E Böhm

Keyword(s):

Bleeding Time ◽

Rat Skin ◽

Fibrin Formation ◽

Bleeding Area ◽

Platelet Thrombus ◽

Platelet Aggregates ◽

Primary Platelet ◽

System Mechanism

SummaryExperiments with injury of the abdominal rat skin were carried out to examine the haemostatic system mechanism in vivo after zero to 30 seconds bleeding time. In the bleeding area only a few platelet aggregates could be found with no primary platelet thrombus. After 3.5 second bleeding time the first fibrin strands have been observed at the site of injury. The hypothesis is put forward that there is a very fast reacting haemostatic mechanism which results in the fibrin formation already at 3.5 seconds.

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The Intravascular Generation of Fibrinogen Derivatives and the Blood Vessel Wall in Venous Thrombosis and Disseminated Intravascular Coagulation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651902 ◽

1977 ◽

Vol 38 (04) ◽

pp. 0831-0849 ◽

Cited By ~ 1

Author(s):

Gwendolyn J. Stewart

Keyword(s):

Blood Vessel ◽

Venous Thrombosis ◽

Vessel Wall ◽

Fluid Phase ◽

Primary Site ◽

Blood Vessel Wall ◽

Fibrin Deposition ◽

Tissue Destruction ◽

Fibrin Formation ◽

Rich Material

SummaryBoth deep venous thrombosis and DIC are intermediate mechanisms of disease – both are a consequence of the deposition of fibrin-rich material in blood vessels some distance from the primary site of tissue destruction. The great difference in the sites of fibrin deposition may depend on the extent and site of activation of the clotting mechanism. DIC likely occurs in the fluid phase of the blood as a consequence of massive fibrin formation while thrombosis results from limited fibrin formation at the interface between blood and vessel wall. Leukocytes may be essential for attaching thrombi to the vessel wall in many places.

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The Anticoagulant Effect of Heparinoid Org 10172 During Haemodialysis: An Objective Assessment

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661535 ◽

1986 ◽

Vol 55 (02) ◽

pp. 271-275 ◽

Cited By ~ 22

Author(s):

Helen Ireland ◽

D A Lane ◽

Angela Flynn ◽

E Anastassiades ◽

J R Curtis

Keyword(s):

Renal Failure ◽

Bolus Dose ◽

Bolus Injection ◽

Objective Assessment ◽

Factor Xa ◽

Fibrin Clot ◽

Natural Origin ◽

Fibrin Formation ◽

Single Bolus Injection

SummaryThe heparinoid of natural origin Org 10172 has anti-factor Xa activity but minimal anti-thrombin activity, and little effect upon broad spectrum assays such as the KCCT in vitro. Its anticoagulant effects have been compared to those of commercial heparin in 7 patients undergoing haemodialysis for chronic renal failure. Commercial heparin was administered in a dose (5,000 iu bolus + 1,500 iu/hour continuous iv infusion) previously shown to inhibit fibrin formation during haemodialysis. This produced mean anti-factor Xa levels in plasma between 0.7-1.0 iu/ml and largely suppressed fibrin formation for 5 h dialysis measured as mean FPA levels in plasma. Administration of Org 10172 as a bolus of 1,350 anti-factor Xa u or 2,000-2,400 anti-factor Xa u produced plasma anti-factor Xa levels of less than 0.5 u/ml and allowed fibrin clot and FPA generation during dialysis. Org 10172 administered as a bolus dose of 4,000-4,800 anti-factor Xa u produced mean anti-factor Xa levels of greater than 0.5 u/ml, allowed dialysis of 6 patients for 5 h and appreciably suppressed FPA generation during dialysis, with little effect on the KCCT.It is concluded that the anti-factor Xa activity of Org 10172 may reflect its ability to inhibit fibrin during dialysis and that single bolus injection of Org 10172 may be a useful alternative method of achieving anticoagulation.

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Fibrin Clot Formation and Lysis in Plasma

Methods and Protocols ◽

10.3390/mps3040067 ◽

2020 ◽

Vol 3 (4) ◽

pp. 67

Author(s):

Julie Brogaard Larsen ◽

Anne-Mette Hvas

Keyword(s):

Fibrinolytic Activity ◽

Research Laboratory ◽

Ex Vivo ◽

Fibrin Clot ◽

Clot Formation ◽

Coagulation Assays ◽

Fibrin Formation ◽

Over Time ◽

Routine Coagulation

Disturbance in the balance between fibrin formation and fibrinolysis can lead to either bleeding or thrombosis; however, our current routine coagulation assays are not sensitive to altered fibrinolysis. The clot formation and lysis assay is a dynamic plasma-based analysis that assesses the patient’s capacity for fibrin formation and fibrinolysis by adding an activator of coagulation as well as fibrinolysis to plasma and measuring ex vivo fibrin clot formation and breakdown over time. This assay provides detailed information on the fibrinolytic activity but is currently used for research only, as the assay is prone to inter-laboratory variation and as it demands experienced laboratory technicians as well as specialized personnel to validate and interpret the results. Here, we describe a protocol for the clot formation and lysis assay used at our research laboratory.

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Coexisting macrophage-associated fibrin formation and tumor cell urokinase in squamous cell and adenocarcinoma of the lung tissues

Cancer ◽

10.1002/1097-0142(19910901)68:5<1061::aid-cncr2820680525>3.0.co;2-d ◽

1991 ◽

Vol 68 (5) ◽

pp. 1061-1067 ◽

Cited By ~ 33

Author(s):

Deborah L. Ornstein ◽

Leo R. Zacharski ◽

Vincent A. Memoli ◽

Walter Kisiel ◽

Bohdan J. Kudryk ◽

...

Keyword(s):

Tumor Cell ◽

Squamous Cell ◽

Adenocarcinoma Of The Lung ◽

Fibrin Formation

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Tyrosine Kinase Inhibitor Sunitinib Delays Platelet-Induced Coagulation: Additive Effects of Aspirin

Thrombosis and Haemostasis ◽

10.1055/s-0041-1730312 ◽

2021 ◽

Author(s):

Delia I. Fernández ◽

Alicia Veninga ◽

Bibian M. E. Tullemans ◽

Constance C. F. M. J. Baaten ◽

Linsey J. F. Peters ◽

...

Keyword(s):

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitor ◽

Cancer Patients ◽

Kinase Inhibitor ◽

Synergistic Effects ◽

Thrombus Formation ◽

Type I ◽

Glycoprotein Vi ◽

Fibrin Formation ◽

Increased Risk

Abstract Background Sunitinib is a multitarget tyrosine kinase inhibitor (TKI) used for cancer treatment. In platelets, sunitinib affects collagen-induced activation under noncoagulating conditions. We investigated (1) the effects of sunitinib on thrombus formation induced by other TK-dependent receptors, and (2) the effects under coagulating conditions. Cardiovascular disease is a comorbidity in cancer patients, resulting in possible aspirin treatment. Sunitinib and aspirin are associated with increased bleeding risk, and therefore we also investigated (3) the synergistic effects of these compounds on thrombus and fibrin formation. Methods Blood or isolated platelets from healthy volunteers or cancer patients were incubated with sunitinib and/or aspirin or vehicle. Platelet activation was determined by TK phosphorylation, flow cytometry, changes in [Ca2+]i, aggregometry, and whole blood perfusion over multiple surfaces, including collagen with(out) tissue factor (TF) was performed. Results Sunitinib reduced thrombus formation and phosphatidylserine (PS) exposure under flow on collagen type I and III. Also, sunitinib inhibited glycoprotein VI-induced TK phosphorylation and Ca2+ elevation. Upon TF-triggered coagulation, sunitinib decreased PS exposure and fibrin formation. In blood from cancer patients more pronounced effects of sunitinib were observed in lung and pancreatic as compared to neuroglioblastoma and other cancer types. Compared to sunitinib alone, sunitinib plus aspirin further reduced platelet aggregation, thrombus formation, and PS exposure on collagen under flow with(out) coagulation. Conclusion Sunitinib suppresses collagen-induced procoagulant activity and delays fibrin formation, which was aggravated by aspirin. Therefore, we urge for awareness of the combined antiplatelet effects of TKIs with aspirin, as this may result in increased risk of bleeding.

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