Heparin and the formation of white thrombi

Best, C. H.; Cowan, C.; Maclean, D. L.

doi:10.1113/jphysiol.1938.sp003580

Cited by 79 publications

(14 citation statements)

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“…The relation of the migration of platelets to strands of fibrin already formed can only be hypothesized (13 The lack of the increase in thickness of the fibrin strands upon retraction of the clot is consistent with the observations of other workers in this field (7,13). They believe that after coagulation, the platelets which either acted as foci for laying the fibrin network or migrated to the fibrin strands, become attached (14,61) to the fibrin and then begin to fuse together (viscous metamorphosis [50,62,63] ).9 As this fusion of the platelets continues, the fibrin network is drawn together to give the phenomena of clot retraction. Since the fibrin strands are not involved in this process, their sizes remain unchanged.…”

Section: Discussionsupporting

confidence: 74%

Effects of Thrombin and Platelet Concentrations and of Clot Retraction on Fibrin Strand Widths 12

Greene¹,

McConaughy²

1955

J. Clin. Invest.

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Stubel in 1914 (1) first noted with an ultramicroscope that the fibrin strands produced from hemophilic blood are thicker than from normal blood. He attributed the thicker strands to the slower rate of clotting in hemophilic blood. Later in the same year Howell (2) performing similar kinds of experiments reported an experiment in which cat's plasma was clotted with thrombin: "A large amount of thrombin caused very rapid clotting with the production of small but distinct needles, while with a small amount of thrombin the clotting was slow and the needles were relatively large." In 1947, Ferry and Morrison (3) reported a similar microscopic observation in which decreasing thrombin concentration produced larger fibrin strands. They observed this at pH 6.0 since at pH 7.0 the strands were too fine to be seen. Morrison and Scudder (4) working at pH 6.4 believed there was no change in the thickness of the fibrin strands with varying thrombin concentrations. This was based on electron microscope photographs. A light scattering method for the determination of the average fibrin strand width has been reported previously from this laboratory (5). With this technique it is now possible to examine the effect of thrombin concentration on fibrin strand width in more detail.Although numerous papers have been written on the relation of platelets to clot retraction 8 (7,

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Section: Discussionsupporting

confidence: 74%

Effects of Thrombin and Platelet Concentrations and of Clot Retraction on Fibrin Strand Widths 12

Greene¹,

McConaughy²

1955

J. Clin. Invest.

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“…Howell [1][2][3][4], It was later devel oped as an antithrombotic medication by the Toronto University Research team headed by C.H. Best [3,[5][6][7][8] building on those initial findings. UFH has found widespread use for the prevention and treatment of thromboem bolism but is still a mysterious compound, a 'challenging enigma' with poorly understood properties [9,10].…”

Section: Introductionmentioning

confidence: 99%

Low-Molecular-Weight Heparins: An Overview of their Pharmacodynamics, Pharmacokinetics and Metabolism in Humans

Frydman¹

1996

Pathophysiol Haemos Thromb

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Low-molecular-weight heparins (LMWHs) comprise a group in the class of antithrombotic medications, a class headed by unfractionated heparin (UFH). The LMWHs, with mean molecular weights of 4.0-6.0 kD, differ in their individual manufacturing processes, the distribution of their fragment molecular weights, their in vitro potency (anti-Xa, antithrombin and anticoagulant activities) and, consequently, in their biodynamic patterns, recommended dose regimen, and efficacy/safety ratio. Their drug disposition profiles have been evaluated using two significant markers of their pharmacodynamic activity, namely anti-Xa and anti-IIa activities. Since they are mainly administered subcutaneously, then compared to UFH, they are almost completely absorbed (F > 90%) and, in contrast to UFH, those for which data are available in the literature exhibit linear pharmacokinetics with proportionality between anti-Xa (and anti-IIa in some cases) plasma concentration and dose, and stationary distribution volume and clearance processes when the dosage is increased. Their distribution volume is close to the blood volume, they are partially metabolized by desulphatation and depolymerization, but urinary excretion of anti-Xa activity for enoxaparin, dalteparin and nadroparin, all given at doses for prevention of venous thrombosis, is between 5 and 10% of the injected dose. However, these LMWHs differ in the extent of their non-renal clearance, resulting in different apparent elimination half-life values and relative apparent bioavailability. When considering certain at-risk situations, using doses for preventing thromboembolism, the LMWHs do not significantly cross the placenta of pregnant women and their excretion profiles are only slightly altered in severe (endogenous creatinine clearance less than 15 ml/min) renal disease patients when given at doses recommended for prevention of venous thromboembolism. Because of the differences among LMWHs, the clinical profile of a given LMWH cannot be extrapolated to another one or generalized to the whole LMWH family.

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“…Very early studies using this model provided evidence that anticoagulants like heparin and hirudin inhibit thrombus development in AV shunts. Today, AV shunt thrombosis models are often used to evaluate the antithrombotic potential of new compounds in different species including rabbits (136), rats (137), pigs (138), dogs and cats (139), and non-human primates (140).…”

Section: Modifications Of the Methodsmentioning

confidence: 99%

In Vivo Models for the Evaluation of Antithrombotics and Thrombolytics

Mousa

2010

Anticoagulants, Antiplatelets, and Thrombolytics

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The development and application of animal models of thrombosis have played a crucial role in the discovery and validation of novel drug targets and the selection of new agents for clinical evaluation, and have informed dosing and safety information for clinical trials. These models also provide valuable information about the mechanisms of action/interaction of new antithrombotic agents. Small and large animal models of thrombosis and their role in the discovery and development of novel agents are described. Methods and major issues regarding the use of animal models of thrombosis, such as positive controls, appropriate pharmacodynamic markers of activity, safety evaluation, species specificity, and pharmacokinetics, are highlighted. Finally, the use of genetic models of thrombosis/hemostasis and how these models have aided in the development of therapies that are presently being evaluated clinically are presented.

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Heparin and the formation of white thrombi

Cited by 79 publications

References 0 publications

Effects of Thrombin and Platelet Concentrations and of Clot Retraction on Fibrin Strand Widths 12

Effects of Thrombin and Platelet Concentrations and of Clot Retraction on Fibrin Strand Widths 12

Low-Molecular-Weight Heparins: An Overview of their Pharmacodynamics, Pharmacokinetics and Metabolism in Humans

In Vivo Models for the Evaluation of Antithrombotics and Thrombolytics

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