The molecular-weight dependence of the rate-enhancing effect of heparin on the inhibition of thrombin, factor Xa, factor IXa, factor XIa, factor XIIa and kallikrein by antithrombin

Holmer, E.; Kurachi, Kotoku; Söderström, Gunilla

doi:10.1042/bj1930395

Cited by 271 publications

(135 citation statements)

References 27 publications

(22 reference statements)

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“…F Xa inactivationrequires the binding of heparin with AT III [28,29], thus this assay detects only heparin on the surface which is bioactive in forming complexes with both AT III and F X,. The results of this in vitro assay are summarized in Table II.…”

Section: Discussion 41 Estimation Of Surface-boundmentioning

confidence: 99%

Heparin-containing block copolymers

Vulić

Okano²,

Gaag

et al. 1993

J Mater Sci: Mater Med

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Newly synthesized heparin-containing block copolymers, consisting of a hydrophobic block of polystyrene (PS), a hydrophilic spacer-block of poly(ethylene oxide) (PEO) and covalently bonded heparin (Hep) as bioactive block, were coated either onto glass, poly (dimethylsiioxane), polyurethane or PS substrates. Coated surfaces were characterized by determination of the surface-bound heparin activity, adsorption of AT III, plasma recalcification time assays, adhesion of platelets and by an ex vivo rabbit A-A shunt model.It was demonstrated that heparin was available at the surface of all heparin-bound surfaces to interact with AT III and thrombin and to prevent the formation of clots. The maximum immobilized heparin activity was found to be 5.5 x 10 -3 U cm -2. Coated surfaces showed a significant prolongation of the plasma reclacification times as compared to control surfaces, due to surface-immobilized heparin. The platelet adhesion demonstrated that platelets reacted only minimally with the heparin-containing block copolymers in the test system and that the heparin-containing block copolymers seemed to passify the surface as compared to control surfaces. In the ex vivo A-A shunt experiments, which were carried out under low flow and low shear conditions, the heparin-containing block copolymers exhibited prolonged occlusion times, indicating the ability of the heparin-containing block copolymers to reduce thrombus formation at the surface.

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Section: Discussion 41 Estimation Of Surface-boundmentioning

confidence: 99%

Heparin-containing block copolymers

Vulić

Okano²,

Gaag

et al. 1993

J Mater Sci: Mater Med

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“…In 1965, Egeberg described a family with reduced levels of the antithrombin and recurrent episodes of venous thrombosis [7]. Antithrombin covalently binds and inactivates thrombin and factors Xa, IXa, Xia, and XIIa [8]. Antithrombin deficiency is rare (0.2%), but it can be as high as 0.5-7.5% in patients presenting with venous thromboembolism.…”

Section: Group 1 Thrombophiliamentioning

confidence: 99%

Thrombophilia – How Far and How Much to Investigate?

et al. 2012

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Thrombohemorrhagic balance is maintained by complicated interactions between the coagulation and fibrinolytic system, platelets, and the vessel wall. Dr. Virchow provided approach for investigating and managing thrombotic disorders. He proposed stasis, vascular injury, and hypercoagulability as causes for thrombosis. In 1965, antithrombin deficiency was described. After two decades, protein C and protein S deficiencies, mutations of factor V Leiden, and factor II were described. If we distinguish patients at high risk and low risk of thrombosis, we can optimize therapeutic decisions. There is currently no evidence to say that laboratory abnormality should influence intensity of anticoagulation. In this article we reviewed the risk factors and need for thrombophilia screening in patients. Screening general population for thrombophilia is not justified or recommended at this time.

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“…For the heparin -antithrombin complex to create a bridge to thrombin, it takes a chain of at least 18 saccharides, while for factor Xa inactivation, just one pentasaccharide molecule is needed (Bjork and Lindahl, 1982;Olson and Shore, 1982;Turpie, 1998). Needless to say, dekaoctosaccharide (19 monomers) or a bigger molecule is present in all UFH preparations, but only in 25 to 50% of all LMWH's (Holmer et al, 1981;Lindahl et al, 1984;Holmer et al, 1986). For this reason LMWH's are more or less Xa-selective inhibitors, while the anticoagulant activity of UFH is approximately the same for both factors (anti IIa : anti Xa ~ 1 : 1) (Hirsh, 1991).…”

Section: Anticoagulation Properties Of Lmwh'smentioning

confidence: 99%

Heparin and its derivatives in the treatment of arterial thrombosis: a review

Dvořák¹,

Vlašín²,

Dvorakova³

et al. 2010

Vet. Med. - Czech

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Arterial occlusion due to thrombosis caused by ruptured atherosclerotic plaques (Baba et al., 1975) has been recognized as a major cause of morbidity and mortality in western populations. Thrombosis may occur in various sections of arterial circulation, peripheral arteries of the limbs, coronary arteries, brain arteries, or both major and minor vessels within the abdominal cavity. The ultimate consequence is varying degrees of organ failure, mostly of ischemic origin. Arterial thrombosis represents a continuous problem, debilitating patients and decreasing their quality of life. Moreover, along with chronic heart failure, it can significantly decrease patient life expectancy. Arterial thrombosis results in ischemia, with serious systemic consequences, such as metabolic breakdown. The major goal of treatment remains fast and efficient recanalization -surgical, interventional or thrombolytic. To be able to prevent acute reocclusion with severe consequences (rhabdomyolysis, compartment syndrome, excessive tissue necrosis leading to limb amputation, etc.), several adjunctive treatment regimens have been advocated. Among others, thrombin inhibitors and platelet inhibitors have been widely used for both prophylaxis and adjunctive treatment. Direct thrombin inhibitors and antithrombin stimulators have been recognized as typical antithrombotic drugs. Direct (antithrombin-independent) thrombin inhibitors can be divided into two main categories: monovalent, active site inhibitors (argatroban, efegatran, inovastan, melagatran) and bivalent (hirudin, hirugen, hirulog, bivalirudin), while antithrombin stimulators represent standard (unfractionated) heparin (UFH) and its depolymerizing products -low molecular weight heparins (LMWH's). Recently, a clear change in the main use of heparin, as well as low-molecular weight heparins has been advocated representing a shift from treatment and prophylaxis of deep vein thrombosis to prophylaxis of thromboembolic disease following vascular, cardiovascular or orthopedic surgery, treatment of unstable angina and prevention of acute myocardial infarction. The main effect of heparins lies in their anticoagulant activity. Heparins are involved in different pathways of the coagulation cascade with anticoagulant, antithrombotic, profibrinolytic, anti-aggregative, as well as anti-inflammatory effects. Moreover, there is a little doubt about their anti-proliferative and anti-ischemic activity (Penka and Bulikova, 2006). Unlike standard heparin, low-molecular weight heparins do not affect the patient's general coagulation profile. Obviously, the difference in molecular weight results in different pharmacokinetic and pharmacodynamic properties of the agents.Key words: coagulation; arterial thrombosis; standard heparin; low-molecular weight heparins List of abbreviations ABI = axillary/...index, t-PA = tissue-type plasminogen activator, ADP = adenosin diphosphate, AG = angiography, AMI = acute myocardial infarction, APSAC = acylated plasminogen streptokinase activator complex, APTT = acti...

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The molecular-weight dependence of the rate-enhancing effect of heparin on the inhibition of thrombin, factor Xa, factor IXa, factor XIa, factor XIIa and kallikrein by antithrombin

Cited by 271 publications

References 27 publications

Heparin-containing block copolymers

Heparin-containing block copolymers

Thrombophilia – How Far and How Much to Investigate?

Heparin and its derivatives in the treatment of arterial thrombosis: a review

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