Thromboelastography, whole-blood haemostasis and recurrent miscarriage

Rai, Raj; Tuddenham, Edward G. D.; Backos, M.; Jivraj, Shehnaaz; Elgaddal, S; Choy, S.; Cork, B.A.; Regan, Lesley

doi:10.1093/humrep/deg494

Cited by 79 publications

(57 citation statements)

References 14 publications

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“…15 Previous studies have postulated that TEG changes may correlate with obstetric morbidity. Elevated prepregnancy MA has been associated with an increased risk of miscarriage, 22 and strong correlations have also been shown between MA and low platelet counts in patients with severe preeclampsia. 23,24 However, there is limited data comparing changes in coagulation following fluid preloading in pregnant patients.…”

Section: Discussionmentioning

confidence: 99%

The effect of colloid and crystalloid preloading on thromboelastography prior to Cesarean delivery

Butwick

Carvalho

2007

Can J Anesth/J Can Anesth

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Purpose: Fluid preloading with colloids reduces hypotension after spinal anesthesia for Cesarean delivery more effectively than crystalloids. However, the effects of fluid preloading regimens on coagulation in pregnant patients remain unresolved. The aim of this study was to compare the effects on coagulation of fluid preloading with 6% hydroxyethyl starch (HES) and lactated Ringer's (LR) solution using thromboelastography (TEG) with kaolin-activated whole blood in healthy pregnant patients prior to spinal anesthesia for Cesarean delivery. Methods:After obtaining Ethics committee approval, 30 parturients were prospectively randomized prior to spinal anesthesia for elective Cesarean delivery to receive fluid preloading with either 1500 mL LR or 500 mL 6% HES over 30 min. Thromboelastography was performed immediately prior to and after fluid preloading. Standard TEG parameters were analyzed in terms of r time (min), k time (min), α angle (degrees) and maximum amplitude (mm).Results: Group HES had statistically significant longer reaction times (r) and clot formation times (k) after fluid loading compared to baseline values (P < 0.05 respectively), although these post-fluid loading TEG parameters remained within a normal reference range. No significant differences in TEG values were seen after preloading within the LR group. Conclusion:Fluid preloading with 500 mL 6% HES in healthy parturients produced mild coagulation effects, as measured with TEG, prior to spinal anesthesia for Cesarean delivery. No significant effects on coagulation with TEG were observed following preloading with 1500 mL LR.

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Section: Discussionmentioning

confidence: 99%

The effect of colloid and crystalloid preloading on thromboelastography prior to Cesarean delivery

Butwick

Carvalho

2007

Can J Anesth/J Can Anesth

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“…Furthermore, the prepregnancy MA was predictive of future pregnancy outcome, being signifi cantly higher among those women with recurrent miscarriage whose next pregnancy ended in a further miscarriage as opposed to a live birth. Once pregnancy is confi rmed, serial TEG testing during the fi rst trimester can identify increases in the MA that precede the clinical evidence of impending miscarriage by several weeks [ 31 ]. Our pilot studies suggest that variable doses of aspirin can normalize the raised MA levels in early pregnancy and improve the live birth rate.…”

Section: Thromboelastographymentioning

confidence: 79%

Pregnancy Morbidity Associated with Thrombophilias: Recurrent Miscarriage

Rai

Regan

2015

Disorders of Thrombosis and Hemostasis in Pregnancy

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Miscarriage, the loss of a pregnancy before viability, is the commonest complication of pregnancy. The term therefore includes all pregnancy losses from the time of conception, which is shortly after ovulation, until 24 weeks of gestation [ 1 ]. Although 15 % of clinically recognized pregnancies miscarry, total reproductive losses are closer to 50 %. The vast majority of miscarriages occur early in pregnancy, before 10 weeks gestation. The incidence of late-or secondtrimester pregnancy loss, between 10 and 24 weeks of gestation, is no more than 2 % [ 2 ]. Components of the haemostatic pathways play a key role in the establishment and maintenance of pregnancy. Pregnancy itself is a hypercoaguable state. An exaggerated haemostatic response is associated with an increased risk not only for recurrent miscarriage but for adverse pregnancy outcome at all gestational stages. Antiphospholipid antibodies (aPL) are the most important treatable cause for recurrent miscarriage. Recent advances have allowed us to escape from the restrictive concept of pregnancy loss being purely related to thrombosis to now emphasising the role of these antibodies in decidualisation of the endometrium and in trophoblast biology. Concurrently emphasis is now placed on the potential for the non-anticoagulant effects of heparin to improve pregnancy in those with a thrombophilic defect. KeywordsRecurrent miscarriage • Obstetric antiphospholipid syndrome • Heritable thrombophilias • Thromboelastography

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“…16,17 The use of LMWH was supported by some studies in which a basal prothrombotic state outside of pregnancy was measured in women with previous recurrent miscarriage and without known thrombophilia. [24][25][26] In addition, heparin and LMWH have other biological properties that could be critical for implantation and placentation. [27][28][29][30][31][32][33][34][35] It is possible that to be beneficial, heparins may require administration at the time of the initial implantation.…”

Section: Discussionmentioning

confidence: 99%

Enoxaparin for prevention of unexplained recurrent miscarriage: a multicenter randomized double-blind placebo-controlled trial

Pasquier

Martin

Bohec

et al. 2015

Blood

105

102

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Key Points• The use of low-molecularweight heparin did not improve live-birth rates in nonthrombophilic women with consecutive recurrent miscarriage.• Prophylactic doses of lowmolecular-weight heparin should no longer be prescribed in this clinical setting.It is common practice in many centers to offer antithrombotic medications to women with unexplained recurrent miscarriage, in the presence or absence of inherited thrombophilia. Although no benefit of aspirin vs placebo has been clearly demonstrated, a doubleblind placebo-controlled trial on the effect of low-molecular-weight heparin is lacking. We enrolled 258 pregnant women with a history of unexplained recurrent miscarriage ( ‡2 consecutive miscarriages before 15 weeks' gestation) and a negative thrombophilia workup. They were randomly assigned to receive one daily subcutaneous injection of enoxaparin 40 mg or placebo until 35 weeks' gestation. We included 256 women (mean age 32 years, ‡3 miscarriages: 72%; mean gestational age 39 days of amenorrhea) in the intention-to-treat analysis; 66.6% of 138 who received enoxaparin had a live birth vs 72.9% of 118 who received placebo. The absolute difference was 26% (95% CI, 217.1 to 5.1), excluding a 10% increase in the rate of live-birth on enoxaparin (P 5 .34). In this first randomized, double-blind, placebo-controlled trial, enoxaparin (40 mg once daily) did not improve the chance of a live birth in nonthrombophilic women with unexplained recurrent miscarriage. This trial is registered at www.ClinicalTrials.gov as #NCT00740545 and the French

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Thromboelastography, whole-blood haemostasis and recurrent miscarriage

Abstract: Thromboelastography identifies a subgroup of women with recurrent miscarriage to be in a prothrombotic state outside of pregnancy. Women in such a state are at increased risk of miscarriage in future untreated pregnancies.

Cited by 79 publications

References 14 publications

The effect of colloid and crystalloid preloading on thromboelastography prior to Cesarean delivery

The effect of colloid and crystalloid preloading on thromboelastography prior to Cesarean delivery

Pregnancy Morbidity Associated with Thrombophilias: Recurrent Miscarriage

Enoxaparin for prevention of unexplained recurrent miscarriage: a multicenter randomized double-blind placebo-controlled trial

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