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

Ireland, H; Lane, David A.; Flynn, A; Anastassiades, E.; Curtis, J. Randall

doi:10.1055/s-0038-1661535

Cited by 34 publications

(17 citation statements)

References 7 publications

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“…All subjects had a normal coagulation screen (see details of tests below) and platelet aggregation studies were within the pattern we expect for the majority of healthy subjects of this age and sex. Platelet counts (in whole blood and in platelet rich plasma) were within the normal (Ireland et al, 1986;ten Cate et al, 1984ten Cate et al, , 1985Turpie et al, 1987) (also see Mikhailidis et al, 1984Mikhailidis et al, , 1985b for additional literature).…”

Section: Selection Ofsubjectsmentioning

confidence: 90%

Platelet activation following intravenous injection of a conventional heparin: absence of effect with a low molecular weight heparinoid (Org 10172).

Mikhailidis

Fonseca

Barradas

et al. 1987

Brit J Clinical Pharma

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1 The effects of an intravenous injection of a conventional high molecular weight heparin (HMWH) were compared with those of a low molecular weight heparinoid (Org 10172). A bolus injection of HMWH (5000 iu) was associated with: (a) a small but significant prolongation of bleeding time (BT); (b) a significant fall in PRP platelet count; (c) significantly enhanced platelet aggregation; and (d) significantly increased platelet thromboxane A2 (TXA2) release. These changes were not observed following the intravenous injection of Org 10172 (3200 anti Xa U). 2 These experiments were repeated following the oral administration of acetylsalicylic acid (ASA). HMWH again caused some enhancement of platelet aggregation despite the ASA-mediated inhibition of platelet aggregation and TXA2 release. Administration of Org 10172 to subjects taking ASA did not alter any of the platelet function indices. 3 In additional control experiments the injection of 5000 iu of HMWH was associated with a significant fall in PRP but not whole blood platelet counts. This finding suggests that the fall in PRP platelet count is a methodological artefact. 4 The HMWH also induced a significantly greater increase in serum non-esterified fatty acid (NEFA) concentrations than Org 10172. 5 The present findings indicate that Org 10172 is a less potent stimulator of platelet aggregation and lipolysis than HMWH. 6 The minor prolongation of the BT after HMWH is not compatible with enhanced aggregation but may be a consequence of alterations in the activity of coagulation factors and vascular-platelet interactions or of ongoing platelet activation accompanied by granule depletion. 7 The different effects of the two anticoagulants assessed suggests a therapeutic advantage in favour of Org 10172, especially in patients with hyperactive platelets.Keywords heparin low molecular weight heparinoid platelet count platelet aggregation thromboxane A2 non-esterified fatty acids

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Section: Selection Ofsubjectsmentioning

confidence: 90%

Platelet activation following intravenous injection of a conventional heparin: absence of effect with a low molecular weight heparinoid (Org 10172).

Mikhailidis

Fonseca

Barradas

et al. 1987

Brit J Clinical Pharma

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“…In view of the results reported by other authors using LMWH in hemodialysis, the advantage of Fraxiparin is its use as a single intravenous bolus injection at the start of the session whereas an additional continuous in fusion is usually recommended with UFH [3,16,[20][21][22][23]. This is due to a greater half-life of Fraxiparin as compared to standard heparin.…”

Section: Discussionmentioning

confidence: 99%

Low-Molecular-Weight Heparin Fraxiparin® in Chronic Hemodialysis

Morinière

Dieval²,

Bayrou³

et al. 1989

Blood Purif

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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). Safety was evaluated by the compression time for hemostasis at the puncture sites. The second step was a randomized comparison of 3 Fraxiparin dosages. In addition to the clinical assessment of efficacy, the following biological parameters were measured: fibrinopeptide A (FPA), anti-Xa (AXa) activity calibrated against Fraxiparin, thrombin time (TT), activated partial thromboplastin time, blood counts, hemoglobin, hematocrit, plasma creatinine and urea, and residual blood volume in the dialyzer. A ‘standard’ dosage of 10,000 AXa Institut Choay units of Fraxiparin was shown to prevent clot formation in the ECC. It resulted in a marked increase in TT, without any lengthening of the puncture site compression time. After 4 h, AXa and FPA levels in the venous line were related to the doses used (p < 0.05). After 48 h AXa activity was very low. Dialysance and tolerance were excellent. Thus, a single dose of Fraxiparin unrelated to body weight and not determined by the measurement of the whole-blood activated clotting time appeared to be a safe and effective means for preventing fibrin formation in 4-hour dialysis sessions.

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“…Full suppression of fibrinopeptide A generation requires anti-Xa levels of 0.7-1.0 U/nil [28]. At a regimen with anti-Xa levels in the range of 0.4-0.6 U/ml using a heparinoid.…”

Section: Discussionmentioning

confidence: 99%

Heparin versus Low Molecular Weight Heparin K 2165 in Chronic Hemodialysis Patients: A Randomized Cross-Over Study

Borm

Krediet

Sturk

et al. 1986

Pathophysiol Haemos Thromb

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Ten patients on chronic intermittent hemodialysis treatment received either unfractionated heparin or low molecular weight (LMW) heparin K 2165 in a single-blinded randomized cross-over study to assess: (1) effects on hemostasis and ex vivo platelet functions, and (2) effectiveness, i.e. prevention of fibrin formation in the extracorporeal circuit. The 20 dialysis treatments were without untoward side effects, for both drugs used. The variation in the plasma anti-Xa activities was significantly less during K 2165 treatment than during heparinization. No differences between the drugs were observed regarding the Ivy bleeding time, platelet count and platelet aggregation (spontaneous, and induced by ADP and collagen). Plasma platelet factor 4 levels did not increase under K 2165 to such an extent as under heparin. Both drugs did not influence the plasma levels of β-thromboglobulin, thromboxane B₂ and platelet serotonin content. K 2165 did not affect platelet adhesion to collagen, in contrast to heparin which substantially inhibited platelet adhesion. Under both treatments, 4 minor clots were observed in 4 artificial kidneys, despite plasma anti-Xa levels in between 0.19 and 0.46 U/ml. K 2165 may therefore be considered as effective an anticoagulant as heparin, with less effects on ex vivo platelet functions.

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

Cited by 34 publications

References 7 publications

Platelet activation following intravenous injection of a conventional heparin: absence of effect with a low molecular weight heparinoid (Org 10172).

Platelet activation following intravenous injection of a conventional heparin: absence of effect with a low molecular weight heparinoid (Org 10172).

Low-Molecular-Weight Heparin Fraxiparin® in Chronic Hemodialysis

Heparin versus Low Molecular Weight Heparin K 2165 in Chronic Hemodialysis Patients: A Randomized Cross-Over Study

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