Pharmacokinetic of a very low molecular weight heparin in chronic renal failure.

The pharmacokinetic characteristics of a low molecular weight heparin (LMWH) (Cy 222; mean mw: 2500 daltons) are studied in 24 patients with 3 degrees of chronic renal failure (CRF) stage I (creatinine clearance between 50 and 30 ml/mn), stage 2 (creatine clearance between 30 and 10 ml/mn), stage 3 (creatinine clearance below 10 ml/mn). Patients with CRF have significantly higher values of anti Xa activity at 3 hours (p less than 0.05), 5 hours (p less than 0.

[Parameters of hemostasis during treatments associating fractionated heparin administered subcutaneously to standard and fractionated heparin administered intravenously in the chronic hemodialysis patient].

The hemorrhagic risk of an association of fractioned heparin (Fraxiparine) injected intravenously at the dose of 7500 AXaICU or of unfractionned heparin (UFH) injected intravenously at the usual dose used for a priming dose for hemodialysis (3750 +/- 1280 IU + 1000 IU after 2 hours of dialysis) to the subcutaneous administration of a thrombo-embolism preventive dose of Fraxiparine (7500 AXaICU) was evaluated on the modifications of the following hemostasis parameters: thrombin time, Activated Partial Thrombin Time (APTT), prothrombin time, anti Xa activity in 13 uremic patients on hemodialysis. The association of intravenous and subcutaneous Fraxiparine prevents efficiently the clotting of the extracorporeal circulation without inducing a detectable antithrombinic activity. In contrast, the association of I.

Pharmacodynamics of CY 216 in healthy volunteers: inter-individual variations.

The pharmacodynamic parameters of a low molecular weight heparin (LMWH, CY 216) and their inter-individual variations were investigated. In a cross over study 100 anti-factor Xa IC U/kg were injected, one week apart, to 12 healthy volunteers by intravenous (IV) or subcutaneous (SC) route. The pharmacological effects were followed by performing activated partial thromboplastin time (APTT), thrombin clotting time (TCT) and a chromogenic anti-factor Xa assay.

[Prevention of deep venous thrombosis of the leg by a very low molecular weight heparin fraction (CY 222) in patients with hemiplegia following cerebral infarction: a randomized pilot study (30 patients)].

The effectiveness and safety of a very low molecular weight heparin fraction were evaluated in the prevention of deep-vein thrombosis in patients confined to bed due to hemiplegia consecutive to a recent cerebral infarction. CY 222 was administered within 48 hours of the stroke by one single daily subcutaneous injection of 0.6 ml (= 15,000 U AXa IC) during 14 days.

Unfractionated heparin and CY 216: pharmacokinetics and bioavailabilities of the antifactor Xa and IIa effects after intravenous and subcutaneous injection in the rabbit.

This report compares the pharmacokinetics and the bioavailabilities of the antifactor Xa and of the antifactor IIa activities generated by intravenous (IV) and subcutaneous (SC) injections of increasing doses of unfractionated heparin (UH) and of a low molecular weight heparin (CY 216). Rabbits were injected with 500, 1,000, 2,500, and 5,000 antifactor Xa u/kg of both heparins and their biological activities were followed at various time intervals. After IV injection the clearance of the antifactor Xa activities was independent of the dose and the clearance of UH was significantly higher than that of CY 216; after SC injection the bioavailability estimated from the antifactor Xa effect was consistently over 100% for CY 216 while that of UH increased from 27% at the lowest dose to 93% at the highest dose.

Low-molecular-weight heparin Fraxiparin in chronic hemodialysis. A dose-finding study.

A two-step dose-ranging study was undertaken with CY216 (Fraxiparin) in 8 patients on 7 sessions each. The different doses were administered each time as a single bolus injection at the start of hemodialysis without heparinized priming nor further administration during the 4-hour session. In the first step, the clinical efficacy of 4 different doses of Fraxiparin was compared with that of standard heparin on the percentage of sessions free of clot formation in the extracorporeal circulation (ECC).

[Plasma exchange with very low molecular weight heparin CY 222. Biological profile and therapeutic value].

In a clinical, between-patient study we investigated the effects of a VLMW Heparin fragment (CY 222) versus standard heparin (SH) in plasma exchanges (n = 10) on coagulation factors (CF). Fibrinogen (FGN), II, V, VIIF + X, IX, XI, XII, VIIIc, VIIIRag, VIIIvwf and ATIII, ProtC, ProtS, Plasminogen (PGN), Activated Thromboplastin time (APTT), Prothrombin time (PT), Thrombin time (TT), anti factor Xa (Axa), DDimer, Platelet count. Heparin was administered as a bolus and by infusion during the session, CY 222 as a bolus dose only; 1 to 1.

[Comparative study of heparin and a very low molecular-weight heparin in hemodialysis in chronic renal insufficiency].

In the course of dialysis sessions, we have compared the antithrombotic effect of two heparinization regimens: low molecular weight heparin (CY 222, mean molecular weight: 2,500, Institute Choay, France): 90 anti-Xa units/kg bodyweight as a bolus injection followed by a continuous infusion of 1,000 anti-Xa units/hour (regimen 1); or 300 anti-Xa units/kg as a bolus injection (regimen 3), with a standard heparinization regimen (100 IU/kg regimen 2). Eight patients received the 3 regimens successively. Factor IIa and factor Xa inactivation was measured by a method that uses chromogenic substrates.

Comparative study on the effects of a low molecular weight heparin (CY 216) and standard heparin in low dosage on experimental venous thrombosis.

In a venous thrombosis model in the rat obtained by ligation of the inferior vena cava, the effects of standard heparin and CY 216, a low molecular weight heparin fraction, are compared. At a dosage of less than 2 mg/kg b.w.

[Low molecular weight heparin (CY 222) levels during hemodialysis sessions. Comparison of various chromogenic and chronometric methods. Problem of standardization].

Current evaluation of biological activity of low molecular weight heparins (LMWH) is dependent solely on technics determining Xa inhibition. Comparison of these technics was carried out during 2 studies of the use of CY 222 during hemodialysis. In the first study, 66 plasma samples from 11 patients treated with 200 or 250 U A Xa IC kg/i.

[Anticoagulation in hemodialysis sessions with a low molecular weight heparin (CY 222, Choay). Dosage studies in chronic hemodialysis. Its use in patients at high risk of hemorrhage].

Efficacy of CY 222 for providing anticoagulation during hemodialysis was evaluated in three successive trials by rating quality of blood restitution (degree of coagulum formation in extracorporeal circulation) and by assay of fibrinopeptide A. Its safety was assessed by measurement of manual compression time necessary to ensure hemostasis of puncture points at end of session. Details of the first preliminary study were: 60 sessions in 11 chronic uremia patients; CY 222: 75, 150 and 300 A-Xa IC U/kg + 1,000 A-Xa IC U/h, then 150 and 300 A-Xa IC U/kg without continuous injection, compared with standard heparin (SH) at the usual dosage for each patient (60 +/- 13 IU/kg).

In vivo neutralization of low-molecular weight heparin fraction CY 216 by protamine.

The neutralization in vivo of a low molecular weight heparin by protamine was investigated. Large doses and excessive doses of intravenously administered CY 216 were studied. An intravenous injection of protamine given 10 minutes after the administration of CY 216 did not cause the studied biologic parameters to return to normal levels, but merely attenuated them, whatever the protamine dosage tested.