Different effects of enoxaparin and unfractionated heparin on extrinsic blood coagulation during haemodialysis: a prospective study.
BACKGROUND
Heparin inhibits prothrombotic tissue factor (TF) and releases its inhibitor, tissue factor pathway inhibitor (TFPI), from the endothelium, but repeated administration of heparin depletes vascular stores of TFPI. We studied the anticoagulant effects of unfractionated heparin (UFH) vs low-molecular-weight enoxaparin-used for thrice-weekly maintenance haemodialysis (HD)-on plasma levels of total TF and TFPI and on those of an activated coagulation marker prothrombin fragment 1+2 (PF 1+2).


METHODS
Twenty-five patients dialysed using a single injection of enoxaparin (at a mean dose of 0.68 mg/kg) were randomly assigned to either receive UFH administered as a mean bolus of 42.1 IU/kg and continuous infusion of 57.8 IU/kg (n=12) or to be maintained on enoxaparin (n=13), and were followed prospectively for 12 weeks. Plasma immunoreactive TF, TFPI and PF 1+2 were measured at the start and after 10 and 180 min of HD, and compared with values in 15 healthy controls.


RESULTS
Pre-dialysis TF, TFPI and PF 1+2 were higher than normal (all P<0.0001). TF and PF 1+2 did not change, while TFPI levels, compared with baseline, increased at each interval in enoxaparin-anticoagulated HD patients (all P<0.0001). TFPI increments correlated inversely with pre-dialysis TFPI (both P<0.0007). In patients switched to UFH, TF levels remained unchanged compared with pre-randomization values, TFPI increased at each interval of HD sessions (all P<0.035) and PF 1+2 increased pre-dialysis (P=0.015). The over-dialysis effects of UFH resembled those of enoxaparin. In contrast, baseline TFPI and its 10-min rise correlated inversely with the UFH loading dose (both P<0.040). Pre-dialysis PF 1+2 was inversely associated with TFPI increments (both P<0.034), and directly with pre-dialysis TFPI (P=0.018) and the UFH loading dose (P=0.045).


CONCLUSIONS
Depletion of heparin-releasable stores of TFPI is an untoward effect of repeated anticoagulation during maintenance HD therapy. The traditional UFH regimen is more prothrombotic than single enoxaparin injections, with high loading doses of UFH being involved in TFPI exhaustion and subsequent hypercoagulability.
Naumnik
Beata
B
Department of Nephrology and Internal Medicine, Medical Academy, Bialystok, Poland.
Borawski
Jacek
J
Myśliwiec
Michał
M
D000368:Aged; D000925:Anticoagulants / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D017984:Enoxaparin / Q000494:pharmacology*; D005260:Female; D005343:Fibrinolytic Agents / Q000097:blood; D005500:Follow-Up Studies; D006490:Hemostatics / Q000097:blood; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy*; D008074:Lipoproteins / Q000097:blood / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood / Q000187:drug effects; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood / Q000187:drug effects; D011516:Prothrombin / Q000032:analysis / Q000187:drug effects; D006435:Renal Dialysis; D013925:Thromboplastin / Q000032:analysis / Q000187:drug effects; D013997:Time Factors
D000925:Anticoagulants; D017984:Enoxaparin; D005343:Fibrinolytic Agents; D006490:Hemostatics; D008074:Lipoproteins; D010446:Peptide Fragments; D011498:Protein Precursors; C051928:lipoprotein-associated coagulation inhibitor; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D011516:Prothrombin; D006493:Heparin; D013925:Thromboplastin