Low Molecular Weight Heparin as Thromboprophylaxis in Familial Thrombophilia during the Whole Period of Pregnancy

Boda, Zoltán; Pajor, László; Rovó, László; Tornai, István; Paragh, György; Blaskó, György; K, Rák

doi:10.1055/s-0038-1650538

Cited by 19 publications

(10 citation statements)

References 2 publications

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“…Of these, LMWH was used for thromboprophylaxis in 1321 pregnancies. [24][25][26]28,[33][34][35][38][39][40][41][44][45][46]53,56,57,59,61,63,66,67,69,70,75,77,78,84,98,99 LMWH was administered because patients had thromboembolic risk factors (eg, previous VTE or thrombophilia). In 27 pregnancies, thromboprophylactic doses of LMWH were administered following initial treatment of VTE with UFH.…”

Section: Lmwh For Thromboprophylaxismentioning

confidence: 99%

Low-molecular-weight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy: a systematic review of safety and efficacy

Greer

Nelson‐Piercy

2005

Blood

741

422

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To assess the safety and efficacy of lowmolecular-weight heparins (LMWHs) for thromboprophylaxis and treatment of venous thromboembolism (VTE) in pregnancy, a systematic review of studies to the end of 2003 was undertaken. Data on VTE recurrence and side effects were extracted and cumulative incidences of VTE and adverse effects calculated. Of 81 reports identified, 64 reporting 2777 pregnancies were included. In 15 studies (174 patients) the indication for LMWH was treatment of acute VTE, and in 61 studies (2603 pregnancies) it was thromboprophylaxis or adverse pregnancy outcome. There were no maternal deaths. VTE and arterial thrombosis (associated with antiphospholipid syndrome) were reported in 0.86% (95% confidence interval [CI], 0.55%-1.28%) and 0.50% (95% CI, 0.28%-0.84%) of pregnancies, respectively. Significant bleeding, generally associated with primary obstetric causes, occurred in 1.98% (95% CI, 1.50%-2.57%), allergic skin reactions in 1.80% (95% CI, 1.34%-2.37%), heparin-induced thrombocytopenia in 0%, thrombocytopenia (unrelated to LMWH) in 0.11% (95% CI, 0.02%-0.32%), and osteoporotic fracture in 0.04% (95% CI, < 0.01%-0.20%) of pregnancies. Overall, live births were reported in 94.7% of pregnancies, including 85.4% in those receiving LMWH for recurrent pregnancy loss. LMWH is both safe and effective to prevent or treat VTE in pregnancy. IntroductionPulmonary embolism (PE) remains the leading cause of direct maternal death in the United Kingdom 1 and venous thromboembolism (VTE) in pregnancy is an important cause of morbidity, not only in pregnancy but also in the long term. 2 Effective primary prevention and acute management of VTE in pregnancy are therefore important to reduce maternal mortality and morbidity. Coumarins cross the placenta and their use in pregnancy is associated with significant fetal and maternal risks, related particularly to teratogenesis and hemorrhage. 3 For many years, unfractionated heparin (UFH) was the standard anticoagulant used in pregnancy. 4 Low-molecular-weight heparins (LMWHs) have replaced UFH for the prevention and management of acute VTE without pregnancy. 5,6 In the United Kingdom, Europe, and Australasia, LMWHs are now also widely used for the prevention and treatment of VTE in pregnancy. 7,8 The advantages of LMWHs over UFH include an enhanced ratio of anti-Xa (antithrombotic) to anti-IIa (anticoagulant), resulting in a reduced risk of bleeding; stable and predictable pharmacokinetics with increased bioavailability and half-life, allowing less frequent fixed or weight-based dosing without the need for monitoring; subcutaneous administration 8 ; and less activation of platelets, with less binding to platelet factor 4 substantially reducing the risk of heparin-induced thrombocytopenia (HIT). 9,10 A major concern with the widespread use of UFH in pregnancy has been the 2% risk of symptomatic heparininduced osteoporotic fracture in pregnancy. 9 LMWHs are associated with a lower risk of this devastating complication. [11][12][13] Peer-reviewed international guid...

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Section: Lmwh For Thromboprophylaxismentioning

confidence: 99%

Low-molecular-weight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy: a systematic review of safety and efficacy

Greer

Nelson‐Piercy

2005

Blood

741

422

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“…(4-12 nedelja), dok se znacajne razlikc u stavovima "or prevention for pregnant women being at extremely high risk ofdeveloping thrombosis (with the prothetic mitral value atrialfibrilationt srecu u odnosu na prevenciju tokom trudnoce [28][29][30]. (4-12 nedelja), dok se znacajne razlikc u stavovima "or prevention for pregnant women being at extremely high risk ofdeveloping thrombosis (with the prothetic mitral value atrialfibrilationt srecu u odnosu na prevenciju tokom trudnoce [28][29][30].…”

Section: Postpartalna Projilaksamentioning

confidence: 99%

Treatment of pregnancy related venous thromboembolism

2009

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Prophylactic antithrombotic regimen during subsequent pregnancies should also be individualized. The use of low molecular weight heparins is becoming more widespread. They have reliable pharmacokinetics, require less frequent injections than unfractionated heparin and carry a lower risk of treatment complications. LMW heparins are safe and effective and they are replacing UFH as the anticoagulant of choice during pregnancy. Both UFH and LMWH are not secreted into breast milk and can be safely given to nursing mothers. Warfarin does not induce an anticoagulant effect in the breast-fed infant, so it can be safely used in women who require postpartum anticoagulant therapy.

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“…This dearth of information and lack of published dosing protocols are frustrating. Due to inherent difficulties conducting prospective, randomized, controlled studies in pregnant patients, clinical experience with LMWHs in pregnancy is largely documented as abstracts, letters, [13][14][15][16][17][18][19][20][21][22][23] case reports, [24][25][26][27][28][29][30][31][32][33][34] case series (or experience reports), [35][36][37][38][39]45 and retrospective studies. [40][41][42][43] A few prospective studies 44,[46][47][48][49][50][51][52] were performed, most of which were nonrandomized and/or uncontrolled.…”

Section: Studies Of Low-molecular-weight Heparin Therapy In Pregnancymentioning

confidence: 99%

“…Forty citations were identified; abstracts were 1015 [35][36][37][38][39]45 ; 11 case reports [24][25][26][27][28][29][30][31][32][33][34] ; and 11 letters to the editor. [13][14][15][16][17][18][19][20][21][22][23] According to the U.S. Preventive Services Task Force rating scale, 53 only 2 studies qualified as level I, 50, 52 3 were level II-1, 47-49 3 were level II-2, 39, 46, 51 4 were level II-3, 35, 38, 43, 45 9 were level III, 16,19,22,36,37,[40][41][42]44 and the remaining 19 were classified as other (i.e. below level III).…”

Section: Study Designsmentioning

confidence: 99%

Low‐Molecular‐Weight Heparins in Pregnancy

Ensom

Stephenson

1999

Pharmacotherapy

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We conducted a systematic review, with MEDLINE and Cochrane Library data base searches and bibliographic reviews, of English-language reports describing therapy with low-molecular-weight heparin (LMWH) in pregnancy. Altogether 40 citations, excluding abstracts, were identified. When the quality of evidence was categorized according to the method outlined by the U.S. Preventive Services Task Force, 2 articles were level I, 3 were level II-1, 3 were level II-2, 4 were level II-3, 9 were level III, and the remaining 19 were classified as other (i.e., below level III). Of the 728 pregnant women and 1 postpartum woman described in the 40 citations, 340 (47%) received dalteparin, 192 (26%) enoxaparin, 108 (15%) certoparin, 54 (7%) nadroparin, 30 (4%) other LMWH, and 6 (< 1%) unspecified. The indication for LMWH in most patients (606 pregnancies, 83%) was for thromboprophylaxis. Daily doses ranged from 2500-22,000 U for dalteparin, 20 mg (2000 U)-80 mg (8000 U) for enoxaparin, 3000 U for certoparin, and 2050-15,000 U for nadroparin. Regimens included fixed dosages, increasing dosages as pregnancy progressed, dosages based on body weight, and dosages titrated according to anti-Xa levels. Duration of therapy ranged from a single dose to 476 days. Maternal anti-Xa levels were reported for 255 pregnancies. Target anti-Xa levels ranged from 0.1-0.6 U/ml and measured values from 0.0-0.7 U/ml. Major maternal findings were 18 local and generalized skin reactions, 27 bleeding complications, 9 thromboembolic events, 8 deep vein thromboses, 1 bilateral renal vein thrombosis, 4 pulmonary emboli, 1 hepatic infarction, 4 cases of thrombophlebitis, 12 cases of preeclampsia, 1 placental abruption, and 2 osteoporotic vertebral fractures. A major fetal finding was lack of anti-Xa activity in fetal or cord blood. Published experience suggests that LMWHs are generally safe and effective when administered for thromboprophylaxis during pregnancy. Until prospective, randomized, controlled trials comparing them with unfractionated heparin are performed, their benefits in pregnancy will remain inconclusive.

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Low Molecular Weight Heparin as Thromboprophylaxis in Familial Thrombophilia during the Whole Period of Pregnancy

Cited by 19 publications

References 2 publications

Low-molecular-weight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy: a systematic review of safety and efficacy

Low-molecular-weight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy: a systematic review of safety and efficacy

Treatment of pregnancy related venous thromboembolism

Low‐Molecular‐Weight Heparins in Pregnancy

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