Effects of nadroparin, enoxaparin, and unfractionated heparin on endogenous formation of factor Xa and IIa and on thrombelastometry profiles in cord versus adult blood.

BACKGROUND

To date, only few pharmacokinetic studies on low-molecular-weight heparins (LMWHs) in neonates exist not allowing to formally assess pharmacodynamics of LMWHs in neonates.

OBJECTIVE

To evaluate the anticoagulant effects of the two LMWHs nadroparin and enoxaparin on endogenous formation of FXa or FIIa in cord versus adult platelet-poor plasma (PPP) and on thrombelastometry profiles in cord versus adult whole blood (WB). Unfractionated heparin (UH) was the reference antithrombotic drug.

METHODS

The effects of nadroparin, enoxaparin, or UH on endogenous formation of FXa or FIIa was investigated in tissue factor-activated PPP using a subsampling technique and chromogenic substrates. The anticoagulant efficacy of these drugs was also investigated in WB triggered by the physiological relevant activator collagen/endogenous thrombin using thrombelastometry.

RESULTS

The major findings are (i) nadroparin is as efficient as enoxaparin concerning inhibition of the endogenous formation of FXa and FIIa, (ii) cord PPP and WB are significantly more susceptible to the addition of LMWHs or UH than adult PPP or WB, and (iii) compared by equivalent anti-FXa activity, the anticoagulant action of UH is markedly higher than that of the LMWHs in PPP and WB of neonatal or adult origin.

CONCLUSIONS

Administration of LMWHs in neonates has to be performed carefully to avoid bleeding side effects due to their high anticoagulant efficacy in cord PPP and WB.