Thromboprophylaxis following caesarean section--a comparison of the antithrombotic properties of three low molecular weight heparins--dalteparin, enoxaparin and tinzaparin.
Pharmacological thromboprophylaxis is increasingly being used after caesarean section to prevent venous thromboembolism. Although a variety of low molecular weight heparins (LMWH) have been used no comparative study exists on their effects on the haemostatic system in this situation. Furthermore, their antithrombotic effect may be mediated through effects other than their inhibitory effect on activated factor X. We compared the plasma anti-factor Xa activity, plasma concentration of tissue factor pathway inhibitor (TFPI) and the reduction in plasma thrombin-antithrombin (TAT) complex concentration in 30 women randomised to receive either dalteparin 5,000 IU anti-Xa once daily (n = 10), enoxaparin 4,000 IU anti-Xa once daily (n = 10) or tinzaparin 50 IU/kg anti-Xa (average dose 3,650 anti-Xa units) once daily (n = 10) following caesarean section. Sampling occurred at 0, 1, 3, 6, 12 and 24 h relative to time of dosing. All preparations produced an increase in mean anti-Xa assay (p < 0.0001), a reduction in mean TAT (p < 0.05) and an increase in mean TFPI concentration (p <0.05). Analysis of variance (ANOVA) revealed a significant difference between the LMWHs in terms of mean anti-factor Xa activity (p < 0.005) and reduction in plasma TAT concentration (p < 0.005). Post hoc analysis indicated that the anti-Xa values of the groups receiving enoxaparin and dalteparin were significantly higher than those of the group receiving tinzaparin (p < 0.05), but not significantly different from each other. Post hoc analysis of the reduction in plasma TAT concentration showed the reduction to be significantly less in the group receiving enoxaparin compared to the dalteparin and tinzaparin groups (p < 0.05), which did not differ significantly from each other. There was no significant difference between treatment groups with regard to plasma concentration of TFPI. These findings demonstrate that LMWHs differ in their effects on haemostatic parameters including thrombin generation as assessed by TAT. The increase in TFPI may be an additional mediator of LMWH's antithrombotic effects. Although these findings demonstrate that LMWHs differ in their haemostatic effects, this does not necessarily infer a clinical difference between these agents.
Ellison
J
J
Glasgow University Department of Obstetrics and Gynaecology, Glasgow Royal Infirmary, UK. J.Ellison@clinmed.gla.ac.uk
Thomson
A J
AJ
Conkie
J A
JA
McCall
F
F
Walker
D
D
Greer
A
A
D000293:Adolescent; D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D000990:Antithrombin III / Q000032:analysis; D002585:Cesarean Section; D017985:Dalteparin / Q000008:administration & dosage / Q000627:therapeutic use*; D017984:Enoxaparin / Q000008:administration & dosage / Q000627:therapeutic use*; D065427:Factor Xa Inhibitors; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008074:Lipoproteins / Q000032:analysis; D008423:Maternal Age; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology; D010298:Parity; D010447:Peptide Hydrolases / Q000032:analysis; D011183:Postoperative Complications / Q000517:prevention & control*; D011247:Pregnancy; D011248:Pregnancy Complications; D018566:Pregnancy, High-Risk; D011516:Prothrombin / Q000037:antagonists & inhibitors; D011644:Puerperal Disorders / Q000517:prevention & control*; D012306:Risk; D012307:Risk Factors; D016037:Single-Blind Method; D019851:Thrombophilia / Q000188:drug therapy; D013927:Thrombosis / Q000517:prevention & control*; D000078222:Tinzaparin
D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; D008074:Lipoproteins; C046193:antithrombin III-protease complex; C051928:lipoprotein-associated coagulation inhibitor; D000078222:Tinzaparin; D000990:Antithrombin III; D011516:Prothrombin; C025337:Factor IIa; D010447:Peptide Hydrolases; D017985:Dalteparin