Thrombophilia in Pregnancy - Skin & Allergy News

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VIEWPOINT
A Professional Opinion Article
Thrombophilia in Pregnancy:
Stop Overscreening and
Overtreating!
Graham Gaylord Ashmead, MD
Venous thromboembolism (VTE) and
adverse pregnancy outcomes (APO) are
potential complications of pregnancy.
The risk of VTE in pregnancy is 1.8%
and with recurrent VTE can be 11.1%. 1,2 Normal
pregnancy is a hypercoagulable state evolved to
protect from hemorrhage at delivery. Thrombophilias
in pregnancy are associated with VTE
(20% to 40%) and APO, 2 but routine screening is
not the answer.
Thrombophilias are too common and costly
to screen asymptomatic patients. The most
common inherited thrombophilias in white
women in the United States are factor V Leiden
(8%) and prothrombin G20210A mutation
(3%). Less frequent are deficiencies of anticoagulants
protein C, protein S, and antithrombin
III. Thrombophilia charges can be more
than those for a delivery; however, what about
positive testing in 10% of the population?
What about treatment risks? What about
patient and physician anxiety?
First trimester pregnancy loss does not benefit
from thrombophilia screening. Second or
third trimester loss does not differ in patients
with factor V Leiden deficiency. Late fetal loss is
associated with homozygosity for mutation of
methylenetetrahydrofolate reductase (MTHFR)
gene but only in the absence of folic acid supplementation.
Known thrombophilias are not
associated with 75% of isolated and 50% of
familial thrombosis. 3
For some thrombophilias, there is no need to
screen everyone as most are being treated.
Hyperhomocysteinemia or MTHFR mutations
occur in 10% of the healthy US population. Therapy
is folate (4 mg/day), vitamin B 12
(250 mcg/day),
Graham Gaylord Ashmead, MD, is Vice Chair and Chief,
Division of Maternal Fetal Medicine, Department of Obstetrics
and Gynecology, Winthrop University Hospital, Mineola, NY.
and vitamin B 6
(25 mg/day) supplementation.
Folate in cereals and prenatal vitamins makes
pregnancy screening unnecessary.
Indiscriminate pregnancy screening can
cause problems. I saw an asymptomatic patient
on baby aspirin expecting heparin because of a
protein S deficiency. Protein S deficiency has an
incidence of 0.5%. 4 The risk of pregnant patients
with known protein S deficiency having a VTE
TABLE 1. A simplified treatment list for recurrent VTE
in pregnancy with thrombophilia with suggested
adjusted dose therapy prophylaxis intensity. 1
Disorder
Compound heterozygote of factor V Leiden
and Prothrombin G20210A
Factor V Leiden homozygote
Antithrombin III deficiency
Prothrombin G20210A homozygote
Antiphospholipid antibodies
Risk of VTE
150-fold
49- to 80-fold
25- to 50-fold
16-fold
5.3-fold
TABLE 2. A simplified treatment list for recurrent VTE
in pregnancy with thrombophilia with suggested
low-dose therapy prophylaxis intensity. 1
Disorder
Protein C deficiency
Factor V Leiden heterozygote
Prothrombin G20210A heterozygote
Protein S deficiency
Hyperhomocysteinemia
Risk of VTE
3- to 15-fold
3- to 9-fold
2- to 9-fold
2-fold
2.5- to 4-fold
The Female Patient | VOL 33 AUGUST 2008 31

VIEWPOINT
Thrombophilia in Pregnancy
TABLE 3. How can we stop overscreening for
thrombophilia?
• Asymptomatic patients should not be routinely screened.
• Screen patients with:
• A history of VTE
• Unexplained fetal loss greater than 12 weeks
• Severe preeclampsia or HELLP syndrome, especially preterm
• Severe fetal growth restriction, especially preterm
• Family history of thrombosis
• Start with a limited screening for:
• Factor V Leiden mutation
• Prothrombin G20210A mutation
• Functional protein S and C deficiencies (lower S levels in
pregnancy)
• AT-III deficiency
• Lupus anticoagulant
• Homocysteine level (if not on folate)
• Anticardiolipin antibodies
• Most asymptomatic pregnant patients with thrombophilia (no VTE or
APO) do not require treatment.
• Asymptomatic patients can benefit from UFH or LMWH throughout
pregnancy when the patient presents:
• AT-III deficiency
• Homozygotes or compound heterozygotes for the factor V Leiden
or prothrombin G20210A mutations
• For asymptomatic pregnant thrombophilia patients, use short-term
UFH or LMWH for risk factors (ie, multiple family members with VTE).
• Treat appropriately, using the consensus report. 1
in pregnancy is 22%, but as protein S activity
normally falls during pregnancy, the ‘cutoff’ is
lower (20% to 35% 2 ): the patient was normal.
Treatments for thrombophilia have risks,
whether it is aspirin (bleeding) or heparin (bruising,
bleeding, thrombocytopenia, heparin
allergy and rash, osteopenia, inability to receive
regional anesthesia at delivery, and bleeding at
delivery). 1-4 Such risks are unnecessary.
Patients with a history of VTE and thrombophilia
should receive prophylaxis with low
molecular weight heparin (LMWH) or unfractionated
heparin (UFH), specific to the risk of
VTE (Tables 1 and 2). Prophylaxis with LMWH
or UFH may be considered antepartum and
six weeks postpartum. Pregestational full
anticoagulation should be maintained during
pregnancy.
Antifactor-Xa levels can be monitored by
LMWH with a peak target range (drawn 3 to 4
hours after subcutaneous administration) of
0.5 to 1.0 IU/mL in therapeutic settings, twice
daily. Trough levels (12 hours) should be 0.2 to
0.4 IU/mL for therapeutic LMWH.
Substitute LMWH with UFH at 36 week’s gestation
or prior to delivery. Anticoagulation
problems with delivery or regional anesthesia
are unlikely to occur 12 hours from prophylactic
or 24 hours from therapeutic LMWH. Discontinue
UFH in labor or 6 to 8 hours prior to
cesarean delivery (skip morning dose for AM
cesarean), and restart anticoagulation 12 hours
after delivery or removing epidural catheter.
One LMWH regimen for VTE is enoxaparin
sodium 40 mg (4000 IU) QD for prophylaxis and
1 mg/kg (100 IU) BID for therapy. Prophylactic
UFH can be 5000, 7500 or 10,000 units subcutaneously
BID in the first, second, and third trimesters.
Because LMWH and UFH do not cross
the placenta, they are safe for breast feeding.
Consider calcium (1200 mg/day) and Vitamin D
(800 IU) and check platelet counts. Treatment
regimens are in a 2007 consensus report. 1
Eliminating superfluous screening, while
treating appropriately, should restore balance
in pregnancy thrombophilia management
(Table 3).
The author reports no actual or potential conflicts
of interest in relation to this article.
REFERENCES
1. Duhl AJ, Paidas MJ, Ural SH, et al. Antithrombotic therapy
and pregnancy: consensus report and recommendations
for prevention and treatment of venous thromboembolism
and adverse pregnancy outcomes. Am J Obstet Gynecol.
2007;197(5):457.e1-21.
2. James AH, Grotequt CA, Brancazio LR, Brown H. Thromboembolism
in pregnancy: recurrence and its prevention.
Semin Perinatol. 2007;31(3):167-175.
3. American College of Obstetricians and Gynecologists.
ACOG Practice Bulletin. Management of recurrent early
pregnancy loss. Number 24, February 2001. Int J Gynaecol
Obstet. 2002;78(2):179-190.
4. Auerbach RD, Lockwood CJ. Clotting Disorders. In: James
DK, Steer PJ, Weiner CP, Gonik B, eds. High Risk Pregnancy:
Management Options. 3 rd ed. London: Saunders; 2006:
925-937.
32 The Female Patient | VOL 33 AUGUST 2008 www.femalepatient.com