Coetzee, E. J.

Pillans, P. I.

University of Queensland eSpace

SAMT DEEL 69 12 APRIL 1986 469
~v1edisyne in die Praktyk/Drugs in Practice
Anticoagulation during pregnancy
Anticoagulation therapy during pregnancy is essential in
thrombo-embolic disease and for prophylaxis in patients with
prosthetic heart valves. Any agent used to achieve this intro-
duces a certain risk to mother and fetus. There is a definite,
although low, incidence of teratogenesis associated with the
use of warfarin in the first trimester of pregnancy. I-4 Exposure
at 6 - 9 weeks' gestation is reported to carry an approximately
8% incidence of warfarin embryopathy (the fetal warfarin syn-
drome), characterized by nasal hypoplasia and stippled
epiphyses.] Warfarin administration during the second and
third trimesters of pregnancy has been associated with an
increased incidence of central nervous system defects such as
microcephaly and mental retardation, and eye defects including
blindness, optic atrophy and microphthalmia.5-7 Late third-
trimester exposure carries with it a clear danger of prenatal,
perinatal or postnatal haemorrhage. In a series of 418 pregnant
women treated with coumarin derivatives, one-sixth of the
pregnancies resulted in abnormal liveborn infants, one-sixth
ended in abortion or stillbirth, and two-thirds had a normal
outcome.]
Heparin, on the other hand, is strongly polar and has certain
advantages in pregnancy since it does not cross the placenta.
However, although heparin is not known to be teratogenic its
administration to pregnant women has been associated with an
increased incidence of prematurity and stillbirth. Furthermore,
significant maternal complications may occur, such as painful
haematomas at injection sites and bone demineralization or
osteopenia. Of particular concern is possible heparin-induced
osteopenia in patients who receive more than 15000 U daily
for more than 6 months, and which has been associated with
complications such as multiple vertebral compression
fractures. 8- 11 Even asymptomatic patients receiving prolonged
subcutaneous heparin therapy have been shown to develop a
degree of bone demineralization. 12
Streptokinase has been used successfully to treat deep-vein
thrombosis in 12 pregnant patients,IJ and there are several
other case reports of streptokinase use in pregnancy.14-16
Although little streptokinase crosses the placenta,17 pregnancy
is considered a minor contraindication to the use of thrombo-
lytic therapy and subsequent delivery within 10 days a major
contraindication. 18 At present there is insufficient experience
documented to recommend the use of thrombolytic agents in
pregnancy except under exceptional circumstances.
The most widely followed recommendations for anticoagu-
lation in pregnancy are those of Hirsch er al.: 19 intravenous
heparin during the first trimester followed by warfarin between
13 and 36 weeks, and reverting to heparin for the last weeks of
pregnancy. It has been questioned whether oral anticoagulants
should be used even after the first trimester20 and some
authors prefer subcutaneous, self-administered heparin
throughout pregnancy:,21 It is not established whether sub-
cutaneous heparin is as efficacious as warfarin, and because of
the real risk of heparin-induced maternal osteopenia and the
apparently low incidence of abnormalities induced by warfarin
during the second and third trimester it would seem prudent
to follow the recommendations of Hirsch er al. 19
Because of the risks of anticoagulation therapy, venography
is advisable to confirm the diagnosis in pregnant women
considered to have deep-vein thrombosis. With adequate
shielding of the uterus the direct radiation dose is small and
venography of the femoral and more distal veins can be
performed.4
Patients with prosthetic heart valves should be on effective
contraception and need to be warned of the dangers of oral
anticoagulants during the first trimester should they become
pregnant. Those patients who require anticoagulation and who
strongly desire to become pregnant should ideally attend a
pre-conception clinic, be taking warfarin at the time of con-
ception, and then be converted to heparin therapy as soon as
pregnancy is diagnosed, following the protocol outlined by
Hirsch er al. 19
Not infrequently cardiac patients conceive inadvertently and
present to their doctor only after 4-6 weeks, having continued
to take warfarin. The most susceptible period of exposure for
the development of warfarin embryopathy is the 6th - 9th
week of pregnancy and it is therefore important to change to
heparin for the remainder of the first trimester. However,
patients should be advised of the potential risks to the fetus of
exposure to warfarin and perhaps be offered the option of
therapeutic abortion.
P. I. Pillans
E. J. Coetzee
1. Abott A, Silbert JR, Weaver JB. Chondrodysplasia punctata and maternal
warfarin treatment. Br Med J 1977; 1: 1639-1640.
2. Peltifor JM, Benson R. Congenital malformations associated with the
administration of oral anticoagulants during pregnancy. J Pediaer 1975; 86:
459-462.
3. Pauli RM, Hall JG, Wilson KM. Risks of anticoagulation during pregnancy.
Am Hear! J 1980; 100: 761-762.
4. De Swiet' M. Medical Disorders in ObsleCric Practice. London: Blackwell
Scientific Publications, 1984: 98-115.
5. Hall JG, Pauli RM, Wilson KM. Maternal and fetal sequelae of anti-
coagulation during pregnancy. AmJ Med 1980; 68: 122-140.
6. Holzgreve W, Carey JC, Hall BD. Warfarin-induced fetal abnormalities.
Lancee 1976; ii: 914-915.
7. Briggs GG, Bodendorfer TW, Freeman RK, Sunner JY. Drugs in Pregnancy
and Lacta/ion. Baltimore: Williams & Wilkins, 1983: 89-90.
8. Griffith GC, Nichols G, Asher JD, Hanagan B. Heparin osreoporosis.
JAMA 1965; 193: 91-94.
9. Jaffee MD, Willis PW. Multiple fractures associated with long-term sodium
heparin therapy.JAMA 1965; 193: 152-154.
10. Avioli LV. Heparin-induced osteopenia: an appraisal. Adv Exp Med Bioi
1975; 52: 375-387.
11. Wise PH, Hall AJ. Heparin induced osteopenia in pregnancy. Br Med J
1980; 281: 110-111.
12. De Swiet M, Dorrington Ward P, Fidler J et al. Prolonged heparin therapy
in pregnancy causes bone demineralisation (heparin-induced Osteopenia). Br
J Obseee Gynaecol 1983; 90: 1129-1134.
13. Pfeifer GW. The use of thrombolytic therapy in obstetrics and gynaecology.
Auseralas Ann Med 1970; 19: suppl. 28-31.
14. McTaggart OR, Engram TG. Massive pulmonary embolism during preg-
nancy treated with streptokinase. Med J AI/se 1977; 1: 18-20.
15. Amias AG. Streptokinase, cerebral vascular disease - and triplets. Br Med J
1977; 1: 1414-1415.
16. Hall RJC, Young C, Sulton GC, Cambell S. Treatment of acute massive
pulmonary embolism by streptokinase during labour and delivery. Br Med J
1972; 4: 647-649.
17. Pfeifer GW. Distribution and placental transfer of 131 1 streptokinase. Auseralas
Ann Med 1970; 19: suppl. 17-18.
18. National Institute of Health Consensus Conference. Thrombolytic therapy
in treatment. Br MedJ 1980; 280: 1585-1587.
19. Hirsch J, Cade JF, O'Sullivan EF. Clinical experience with anticoagulant
therapy during pregnancy. BrMedJ 1970; 1: 270-273.
20. Leading Article. Venous thrombo-embolism and anti-coagulants in preg-
nancy. Br MedJ 1975; 2: 421-422.
21. Berkowitz RL, Coustan OR, Mochizuki TK. Handbook for Prescribing
Medications During Pregnancy. Boston: Little, Brown, 1981: 62-65.


Anticoagulation during pregnancy

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Anticoagulation during pregnancy

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