Low Molecular Weight Heparin Novo (LHN-1) Does Not Cross the Placenta During the Second Trimester of Pregnancy

Abstract

SummaryUnfractionated heparin (UF-H) has been the drug of choice for the treatment of thromboembolic disorders during pregnancy. Low molecular weight heparin (LMW-H) preparations may present some advantages over UF-H. They have longer half-lives and a better bioavailability after subcutaneous (s. c.) injection and may cause less bleeding. It has not yet been established whether LMW-H Novo (LHN-1) crosses the placenta. 17 women admitted for abortion during the second trimester of pregnancy (induced by application of prostaglandine PGE2 gel at a concentration of 0.25 mg/ml into the cervix) were given s. c. 35 anti-Xa units per kg of body weight of LHN-1 (Novo). 10 patients not receiving LHN- 1 and their fetuses served as a control group. 7 women in whom the time interval between injection of LHN-1 and expulsion of the fetus was less than 3 h or more than 7 h were excluded from further study. In one fetus blood collection failed. Anti-Xa and anti-IIa levels increased approximately ten-fold in women receiving LHN-1 [anti-Xa units/ml from 0.02 ± 0.01 (mean ± SD) to 0.17 ± 0.01, p <0.001; anti-IIa units/ml from less than 0.01 ± 0.01 to 0.07 ± 0.03], but remained below the detection limit in their fetuses as well as in the women and fetuses of the control group.We conclude that LHN-1 at these doses does not cross the placenta during the second trimester of pregnancy to suggest that LHN-1 may be a safe alternative to heparin in the management of the thromboembolic complications during pregnancy.

Absence of Transplacental Passage of the Low Molecular Weight Heparin Enoxaparin

“…The fact that several LMWHs do not cross the placental barrier is well established [3,5,16,17]. But because of the differences among LMWHs, the clinical characteristics of a given LMWH or even of a given dose cannot be extrapolated to another or generalized to the whole LMWH family [18].…”

“…system during pregnancy and compression of the iliac vein and the inferior vena cava lead to an increased thrombotic potential, which is most likely to occur around term and the immediate postpartum period [3,4]. Additional risk factors, such as history of VTE, thrombophilia, antithrombin III deficiency, protein S or C deficiency, lupus anticoagulant and anticardiolipin antibody syndrome, obesity and immobilization increase the likelihood for VTE [2,5].…”

“…This agent is also used in women suffering from autoimmune etiology abortions. UH does not cross the placental barrier [3] and it is considered to be safe for the fetus, even in long-term administration [3,5]. However, UH may be associated with maternal bleeding, thrombocytopenia and osteoporosis [5].…”

New developments in the treatment of deep venous thrombosis

“…This is best ac complished with heparin or LMWH. A review of the published experience of the utilization of LMWH in obstetrics and gynaecology revealed that LMWH do not cross the placenta in any trimester and there is no evidence of any mutagenic and teratogenic effect of these drugs [86][87][88]. When long-term treatment is required, patients should be educated to administer heparin or LMWH by subcutaneous injections to themselves.…”

Fluctuations in anti-factor Xa levels with therapeutic enoxaparin anticoagulation in pregnancy

“…The advantages of using enoxaparin over unfractionated heparin include a more predictable dose response and a lower risk of heparin-induced thrombocytopenia and osteoporosis. 13,14 Similar to unfractionated heparin, studies have shown that enoxaparin does not cross the placenta in any trimester, [15][16][17] and is primarily cleared by the kidneys. Maternal physiological increases in plasma volume and glomerular filtration rate alter enoxaparin drug levels and may lead to lower anti-factor Xa activity.…”