Prophylaxis for venous thromboembolic disease in pregnancy and the early postnatal period.
BACKGROUND
Venous thromboembolic disease (TED), although rare, is a major cause of maternal mortality and morbidity, hence methods of prophylaxis are often used for women at risk. This may include women delivered by caesarean section, those with a personal or family history of TED and women with inherited or acquired thrombophilias (conditions that predispose people to thrombosis). Many methods of prophylaxis carry a risk of side effects, and as the risk of TED is low, it is possible that the benefits of thromboprophylaxis may be outweighed by harm. Current guidelines for clinical practice are based on expert opinion only, rather than high quality evidence from randomised trials.


OBJECTIVE
To determine the effects of thromboprophylaxis in women who are pregnant or have recently delivered and are at increased risk of TED on the incidence of venous TED and side effects of treatment.


METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (May 2009).


METHODS
Randomised trials comparing one method of thromboprophylaxis with placebo or no treatment, and randomised trials comparing two (or more) methods of thromboprophylaxis.


METHODS
Two review authors extracted data independently and resolved any discrepancies by discussion.


RESULTS
Sixteen trials met the inclusion criteria but only 13 trials, involving 1774 women, examining a range of methods of thromboprophylaxis, contributed data for the outcomes of interest. Four of them compared methods of antenatal prophylaxis: low molecular weight heparin (LMWH) versus unfractionated heparin (UFH) (two studies), and heparin versus no treatment (two studies). Eight studies assessed postnatal prophylaxis after caesarean section; one compared hydroxyethyl starch with unfractionated heparin; four compared heparin with placebo; and the other three compared UFH with LMWH. One study examined prophylaxis in the postnatal period.The small number of statistically significant findings in this review are largely derived from trials which are not of high methodological quality. It was not possible to assess the effects of any of these interventions on most outcomes, and especially on rare outcomes such as death, TED and osteoporosis, because of small sample sizes and the small number of trials making the same comparisons.There was some evidence of side effects associated with thromboprophylaxis.


CONCLUSIONS
There is insufficient evidence on which to base recommendations for thromboprophylaxis during pregnancy and the early postnatal period. Large scale randomised trials of currently-used interventions should be conducted.
Tooher
Rebecca
R
Paediatric Trials Unit, Children,Youth and Women's Health Service, Adelaide, South Australia, Australia, 5006.
Gates
Simon
S
Dowswell
Therese
T
Davis
Lucy-Jane
LJ
D005260:Female; D006801:Humans; D049590:Postpartum Period; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D020246:Venous Thrombosis / Q000517:prevention & control*
Postgrad Med J. 2000 Jun;76(896):354-6
10824050
Cochrane Database Syst Rev. 2003;(2):CD003580
12804477
BJOG. 2001 Jan;108(1):56-60
11213005
Thromb Haemost. 1990 Apr 12;63(2):319-20
2141957
J Thromb Haemost. 2003 Oct;1(10):2073-4
14521585
Clin Hemorheol Microcirc. 2007;37(3):211-8
17726250
J Thromb Haemost. 2005 Feb;3(2):227-9
15670024
J Thromb Haemost. 2009 Jan;7(1):58-64
19036070
N Engl J Med. 2000 Nov 16;343(20):1439-44
11078768
Obstet Gynecol. 2002 Sep;100(3):408-13
12220757
Haemostasis. 1993 Nov-Dec;23(6):314-20
8034237
Br Med J (Clin Res Ed). 1988 May 28;296(6635):1505-6
3134089
Br Med J. 1977 Jun 18;1(6076):1564-5
871666
Br J Haematol. 2005 Oct;131(1):80-90
16173967
Thromb Haemost. 2002 Feb;87(2):182-6
11858475
Ann Med Interne (Paris). 1996 Sep;147 Suppl 1:44
8992939
Obstet Gynecol. 1999 Oct;94(4):595-9
10511366
Thromb Res. 1999 Nov 15;96(4):275-82
10593430
Eur J Obstet Gynecol Reprod Biol. 1975;5(5):273-6
1053520
Obstet Gynecol Clin North Am. 1997 Sep;24(3):499-521
9266575
Acta Obstet Gynecol Scand. 1998 Feb;77(2):170-3
9512321
Cochrane Database Syst Rev. 2009 Jan 21;(1):CD004734
19160241
Eur J Obstet Gynecol Reprod Biol. 2002 Feb 10;101(1):6-14
11803092
Lancet. 2000 Apr 15;355(9212):1295-302
10776741
Thromb Haemost. 2007 Jul;98(1):163-71
17598009
Cochrane Database Syst Rev. 2008 Oct 08;(4):CD006681
18843725
Am J Obstet Gynecol. 2004 Oct;191(4):1296-303
15507957
Worldviews Evid Based Nurs. 2004;1(3):198-9
17163898
Anaesth Intensive Care. 1987 May;15(2):163-7
2440337
J Obstet Gynaecol. 2008 Apr;28(3):280-4
18569468
Ann Intern Med. 1996 Dec 15;125(12):955-60
8967705
J Thromb Haemost. 2008 Apr;6(4):632-7
18248600
Clin Exp Obstet Gynecol. 2007;34(3):143-5
17937086
J Thromb Haemost. 2007 Aug;5(8):1600-6
17663731
South Med J. 2003 Feb;96(2):146-8
12630638
Br J Obstet Gynaecol. 1983 Dec;90(12):1124-8
6360198
Am J Med. 1980 Jan;68(1):122-40
6985765
Br J Haematol. 2006 Nov;135(3):386-91
16984390
Cochrane Database Syst Rev. 2008 Oct 08;(4):CD005259
18843687
Blood Coagul Fibrinolysis. 1998 Jun;9(4):343-50
9690805
Obstet Gynecol. 1990 Dec;76(6):1055-60
2234713
Cochrane Database Syst Rev. 2008 Oct 08;(4):CD005258
18843686
Cochrane Database Syst Rev. 2009 Jul 08;(3):CD003747
19588346
Baillieres Clin Obstet Gynaecol. 1997 Sep;11(3):523-43
9488790
Obstet Gynecol. 1999 Nov;94(5 Pt 1):730-4
10546719
Rev Med Suisse Romande. 1981 Nov;101(11):925-34
7034116
Hum Reprod. 1997 Jul;12(7):1567-72
9262298
Fertil Steril. 2005 Mar;83(3):684-90
15749498
Scott Med J. 1996 Jun;41(3):83-6
8807703
Int J Gynaecol Obstet. 2005 Sep;90(3):203-7
15964002
Chest. 2008 Jun;133(6 Suppl):844S-886S
18574280
Am J Obstet Gynecol. 1996 May;174(5):1584-9
9065133
Baillieres Clin Obstet Gynaecol. 1997 Sep;11(3):489-509
9488788
Br J Obstet Gynaecol. 1986 Apr;93(4):348-52
3964611
Br J Obstet Gynaecol. 1998 Jul;105(7):795-7
9692422
Am J Reprod Immunol. 1996 Apr;35(4):402-7
8739461
Cochrane Database Syst Rev. 2000;(2):CD000492
10796208
Z Geburtshilfe Perinatol. 1994 Aug;198(4):120-5
7975797
BMJ. 1997 Jan 25;314(7076):253-7
9022487
Thromb Haemost. 2001 Dec;86(6):1374-8
11776302
Ann Intern Med. 2005 Nov 15;143(10):697-706
16287790
J Obstet Gynaecol Can. 2004 Aug;26(8):729-34
15307977
J Obstet Gynaecol Res. 2007 Aug;33(4):423-30
17688607
Fertil Steril. 2005 Sep;84(3):770-3
16169422
Am J Obstet Gynecol. 2006 Oct;195(4):1109-13
17000242
Obstet Gynecol. 1994 Aug;84(2):240-4
8041538
Z Geburtshilfe Perinatol. 1991 Jan-Feb;195(1):10-5
1711261
BJOG. 2001 Aug;108(8):835-9
11510709
Cochrane Database Syst Rev. 2005 Apr 18;(2):CD002859
15846641
J Thromb Haemost. 2003 Oct;1(10):2070-2
14521584