Comparison of the injection of low‐molecular weight heparin in the arterial vs. venous blood line for preventing extracorporeal circuit clotting during hemodialysis

SummaryThe clinical benefits of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) have been shown in many trials. However, the mode of action of heparin has not been fully elucidated. Thus, we wanted to study the effects of UFH and LMWH in vivo by measuring coagulation activation markers in blood obtained directly from a vascular injury site. In a double-blind, randomized, 3-way, cross-over study 18 healthy volunteers were given UFH (150 U/kg s.c.) and 2 doses of LMWH [35 U/kg s.c. (low dose, Id), 75 U/kg s.c. (high dose, hd)]. Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT) and fibrinopeptide A (FPA) were measured in bleeding time blood and in venous blood before and after drug application. In addition, the effects of UFH and LMWH on in vitro coagulation tests were studied. Compared to base line, UFH and both IdLMWH and hdLMWH caused significant reductions of F1+2, TAT and FPA in bleeding time blood at 2 h. A marked effect of UFH and of hdLMWH was also seen at 5 h. The inhibition of FPA generation was more pronounced after hdLMWH compared to IdLMWH. In venous blood, UFH and LMWH caused reductions of F1+2, but not of TAT and FPA. In vitro, UFH predominantly affected the anti-IIa assays (activated partial thromboplastin time, thrombin time) and LMWH mainly the anti-Xa test system. Using a technique that investigates the activated coagulation system in vivo, a time- and dose dependent inhibitory effect of heparin on coagulation activation was detectable. Therefore, in our experimental setting a preferential inhibition of a particular portion of the coagulation system by one of the two heparin preparations was not detectable.

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Studies on the Neutralizing Effects of Protamine on Unfractionated and Low Molecular Weight Heparin (Fragmin®) at the Site of Activation of the Coagulation System in Man

Thrombosis and Haemostasis ◽

10.1055/s-0038-1653794 ◽

1995 ◽

Vol 73 (03) ◽

pp. 439-443 ◽

Cited By ~ 81

Author(s):

Michael Wolzt ◽

Ansgar Weltermann ◽

Malgorzata Nieszpaur-Los ◽

Barbara Schneider ◽

Anita Fassolt ◽

...

Keyword(s):

Molecular Weight ◽

Low Molecular Weight Heparin ◽

Venous Blood ◽

Coagulation System ◽

Low Molecular Weight ◽

High Dose ◽

Thrombin Time ◽

Double Blind ◽

Shed Blood ◽

Complete Reversal

SummaryIn a double-blind, randomized, cross-over study the neutralizing action of protamine towards unfractionated heparin (UFH, 150 U/kg i.v.) and a low molecular weight heparin (LMWH, Fragmin®, 100 anti-Xa U/kg i.v.) was investigated in 15 healthy subjects in vitro by measuring activated partial thromboplastin time (APTT), thrombin time (TT) and anti factor Xa activity (anti-Xa) in venous blood and in vivo by determination of prothrombin fragment 1.2 (f1.2) and thrombin-antithrombin III complexes (TAT) in venous blood and in shed blood. UFH and LMWH caused a prolongation of APTT and TT, an increase in anti-Xa and significantly inhibited f1.2 and TAT formation in shed blood, whereas only a minimal effect on TAT and f1.2 formation in venous blood was noted. Administration of 1 mg protamine/100 U UFH resulted in a near complete reversal of APTT, TT and anti-Xa, whereas lower doses (0.25 and 0.5 mg) were less effective. The effects of UFH on f1.2 and TAT generation in shed blood were partially (60-70%) neutralized only by the high dose (1.0 mg). Application of 1 mg protamine/100 anti-Xa U LMWH caused a near complete reversal of both APTT and TT but had only a weak effect on anti-Xa. In shed blood, the effect of LMWH on TAT and f1.2 formation was reversed by protamine only by 14% and 23% respectively. Our data do not support the concept that to reduce the incidence of protamine’s potential clinical side effects, the administration of a lower dose of protamine than 1 mg protamine/100 U UFH is justified. Furthermore, a significant residual impairment of hemostasis is still detectable after administration of the recommended dose of protamine to neutralize the anticoagulant effects of a LMWH preparation.

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Extracorporeal circuit heparinization in selective low density lipoprotein apheresis: Changes in patient hemostasis and low molecular weight heparin benefit

Journal of Clinical Apheresis ◽

10.1002/jca.2920080302 ◽

1993 ◽

Vol 8 (3) ◽

pp. 141-146

Author(s):

Jean-Louis Lorenzini ◽

Fabienne Dutrillaux ◽

Christiane Mousson ◽

Bernard Lassale ◽

Marc Maynadié ◽

...

Keyword(s):

Molecular Weight ◽

Low Molecular Weight Heparin ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Low Molecular Weight ◽

Low Density ◽

Extracorporeal Circuit ◽

Lipoprotein Apheresis

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A Comparative Study of the Anticoagulant and Antithrombotic Effects of Unfractionated Heparin and a Low Molecular Weight Heparin (Fraxiparine®) in an Experimental Model of Human Venous Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649928 ◽

1995 ◽

Vol 74 (05) ◽

pp. 1286-1292 ◽

Cited By ~ 13

Author(s):

Armelle Diquélou ◽

Dominique Dupouy ◽

Roger Cariou ◽

Kjell S Sakariassen ◽

Bernard Boneu ◽

...

Keyword(s):

Molecular Weight ◽

Venous Thrombosis ◽

Unfractionated Heparin ◽

Low Molecular Weight Heparin ◽

Thrombus Formation ◽

Anticoagulant Activity ◽

Venous Blood ◽

Low Molecular Weight ◽

Venous Blood Flow ◽

Antithrombotic Effects

summaryWe have compared the anticoagulant and the antithrombotic effects of unfractionated heparin(Calciparine®)and low molecular weight heparin(Fraxiparine®)in an experimental human venous thrombosis model.One single subcutaneous injection of Calciparine® or Fraxiparine® was administered to healthy male volunteers at one month intervalin a randomised and cross-over design.Ten subjects received doses used in man for preventing venous thrombosis(5,000 IU and 3,075 IU,respectively),and seven other subjects received curative doses (12,500 IU and 6,150 IU, respectively).Thrombus formation was measured 3 h and 8 h after drug administration.Non-anticoagulated humanblood was drawn for 5 min directly from an antecubital vein over confluent cultured endothelial cells positioned in a parallel-plate perfusion chamber.The cells were previously stimulated for 4 h with lipopolysaccharides(10 µg/ml) and interleukin 1β(50 U/ml),resulting in optimal expression of biological active tissue factor.The wall shear rate at the cell surface was 50 s-1 and mimicked venous blood flow conditions.Immunologically quantified fibrin deposition on the stimulated cells was reduced only by curative doses of Calciparine® and Fraxiparine® at 3 h(3.4 ± 0.8 versus 1.0 ± 0.2 µg/cm2 and 2.6 ± 0.8 versus 1.0 ± 0.1 µg/cm2, respectively,p ≤0.05).The influence of Calciparine® and Fraxiparine® on the formation of thrombin and fibrin was determined by measuring the plasma levels of thrombin-antithrombin III complexes and fibrinopeptide A (FPA) in blood samples collected distally to the perfusion chamber.The generation of these markers was significantly inhibited (50-83%) by both prophylactic and curative doses of Calciparine® and Fraxiparine®(p ≤0.05).However, Fraxiparine® still significantly inhibited the thrombin and fibrin generation at 8 h (p ≤0.05), whereas Calciparine® did not.The antithrombotic effects of both heparins were correlated with their plasma activities as measured by the antifactor Xa or the antithrombin assays.Thus,it appears in this model that Calciparine® and Fraxiparine® produce comparable antithrombotic effects at clinically comparable doses. However Fraxiparine® has a longer-lasting anticoagulant activity than Calciparine®. These results are ingood agreement with clinical observations in man,and thus in favour of our model of human venous thrombogenesis for further studies of antithrombotic molecules.

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