Use of Anticoagulants During Pregnancy and Postpartum

20/05/2021 Use of anticoagulants during pregnancy and postpartum - UpToDate
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Use of anticoagulants during pregnancy and postpartum

Author: Kenneth A Bauer, MD
Section Editors: Lawrence LK Leung, MD, Charles J Lockwood, MD, MHCM
Deputy Editors: Jennifer S Tirnauer, MD, Vanessa A Barss, MD, FACOG
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Apr 2021. | This topic last updated: Aug 19, 2020.
INTRODUCTION
Some pregnant women require anticoagulation during pregnancy and/or in the postpartum period, including women at high
risk of deep vein thrombosis and women with prosthetic heart valves, atrial fibrillation, cerebral venous sinus thrombosis, left
ventricular dysfunction, and some women with fetal loss.
Use of anticoagulants during pregnancy is challenging due to the potential teratogenic effects and dosing complexities of the
various agents, and the management of anticoagulation around the time of labor. In addition, women receiving chronic
anticoagulation who are contemplating pregnancy need counseling regarding how to avoid the potential teratogenic effects of
warfarin.
This topic review describes our approach to the clinical issues of anticoagulant use in women during attempted conception,
pregnancy, and postpartum. Our practices are largely consistent with guidelines from societies such as the American Society of
Hematology (ASH), American College of Chest Physicians (ACCP), the American College of Obstetricians and Gynecologists
(ACOG), and the European Society of Cardiology (ESC), with the acknowledgement that most of the data on which
recommendations are based are not from randomized trials. (See 'Society guideline links' below.)
Indications for anticoagulation during pregnancy are discussed in disease-specific topic reviews:
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● DVT and PE, treatment – (See "Deep vein thrombosis and pulmonary embolism in pregnancy: Treatment".)
● DVT and PE, prevention – (See "Deep vein thrombosis and pulmonary embolism in pregnancy: Prevention".)
● Inherited thrombophilia – (See "Inherited thrombophilias in pregnancy".)
● Sickle cell disease – (See "Pregnancy in women with sickle cell disease", section on 'VTE prophylaxis during antepartum
hospitalization'.)
● Atrial fibrillation – (See "Supraventricular arrhythmias during pregnancy", section on 'Anticoagulation'.)
● Prosthetic heart valve – (See "Management of antithrombotic therapy for a prosthetic heart valve during pregnancy".)
● APS – (See "Antiphospholipid syndrome: Pregnancy implications and management in pregnant women".)
General issues related to anticoagulants are discussed separately. (See "Heparin and LMW heparin: Dosing and adverse effects"
and "Warfarin and other VKAs: Dosing and adverse effects" and "Direct oral anticoagulants (DOACs) and parenteral direct-acting
anticoagulants: Dosing and adverse effects".)
CHOICE OF ANTICOAGULANT
Overview of anticoagulant choice — In contrast to anticoagulation of nonpregnant women, the choice of anticoagulant
during pregnancy needs to take into account fetal safety and maternal peripartum issues (eg, unpredictable onset of labor, use
of neuraxial anesthesia for management of labor pain).
● Heparins – Heparins are used for most pregnant women because they do not cross the placenta and do not result in fetal
anticoagulation.
• Low molecular weight (LMW) heparins – We recommend a LMW heparin rather than unfractionated heparin for all
but the final weeks of the pregnancy, because they are effective and easier to administer than unfractionated heparin
[1,2]. LMW heparins produce a more predictable anticoagulant response than unfractionated heparin and do not
require routine monitoring [3-5]. The incidence of developing heparin-induced thrombocytopenia (HIT) is also less with
LMW heparin than unfractionated heparin. (See "Clinical presentation and diagnosis of heparin-induced
thrombocytopenia", section on 'Incidence and risk factors'.)

• Unfractionated heparin – Unfractionated heparin is a reasonable alternative to a LMW heparin when cost or need for
rapid reversal is important (eg, for delivery or perioperatively). Unfractionated heparin is preferred over LMW heparin in
patients with severe renal insufficiency (eg, creatinine clearance <30 mL/min) because LMW heparin clearance is almost
exclusively renal, while elimination of unfractionated heparin is renal and hepatic.
● Fondaparinux, argatroban, danaparoid – There is less information on the fetal effects of fondaparinux, argatroban, or
danaparoid (not available in the United States), but available evidence suggests that they are reasonable options for
pregnant women who require anticoagulation and cannot take any type of heparin (eg, due to HIT). For pregnant women
with a history of HIT (or active HIT) who require an anticoagulant, fondaparinux is preferred, as discussed separately.
Argatroban is most likely to cross the placenta. (See "Clinical presentation and diagnosis of heparin-induced
thrombocytopenia", section on 'Terminology and HIT variants'.)
● Avoidance of warfarin – Warfarin is generally avoided during pregnancy because it crosses the placenta, is a teratogen, and
causes fetal anticoagulation throughout the pregnancy. Exposure during early pregnancy can result in embryopathy, while
exposure later in pregnancy can cause fetal bleeding, including intracranial hemorrhage.
An exception is a woman considered to be at especially high risk for thrombosis or thromboembolism (eg, due to a
mechanical heart valve). In such patients, warfarin use during pregnancy is a potential option; the choice of anticoagulant
in this setting is based upon careful consideration of maternal and fetal risks in discussion with the patient, as discussed in
more detail separately. (See "Management of antithrombotic therapy for a prosthetic heart valve during pregnancy".)
● Avoidance of direct oral anticoagulants – The oral direct thrombin inhibitor dabigatran and oral direct factor Xa inhibitors
rivaroxaban, apixaban, and edoxaban are not used during pregnancy because of absence of information on efficacy and
fetal safety.
Women receiving chronic anticoagulation who are contemplating pregnancy need counseling regarding how to avoid the
teratogenic effects of oral anticoagulants. (See 'Women on warfarin' below and 'Women on direct thrombin inhibitors or factor
Xa inhibitors' below.)

LMW heparins — A LMW heparin is the preferred anticoagulant for most pregnant women [6]. This is largely because available
evidence has shown these agents to be effective and safe for the fetus. LMW heparins do not cross the placenta and do not
cause fetal anticoagulation [1,2].
A systematic review of studies of the use of LMW heparin for prevention or treatment of venous thromboembolism (VTE) in
pregnancy concluded that LMW heparin was both safe and effective (64 studies, 2777 pregnancies) [7]. Rates of venous and
arterial thrombosis were 0.8 and 0.5 percent, respectively, and rates of significant bleeding (2 percent), skin reactions (1.8
percent), and osteoporotic fractures (0.04 percent) were acceptably low. There were no maternal deaths and no cases of
heparin-induced thrombocytopenia.
Unfractionated heparin — Unfractionated heparin is an acceptable and less expensive alternative to LMW heparin. It may be
more appropriate than LMW heparin during stages of the pregnancy when rapid temporal control of anticoagulation is required
(eg, near the time of delivery, if surgery is required). (See 'Switch to unfractionated heparin' below.)
Unfractionated heparin is also preferred over LMW heparin in patients with severe renal insufficiency because LMW heparin
metabolism is exclusively renal, while metabolism of unfractionated heparin is renal and hepatic.
Unfractionated heparin does not cross the placenta, and available evidence has not indicated any harmful effects on the fetus
[8-10].
Alternatives to heparin — Non-heparin anticoagulants are generally not used during pregnancy unless there is a
contraindication to heparins (eg, heparin-induced thrombocytopenia) or an inability to use injections.
● Danaparoid – Danaparoid is a low molecular weight heparinoid (heparan derivative) that is available in many countries (eg,
Canada, Japan, Europe, Australia) but not the United States. It does not cross the placenta. (See "Heparin and LMW heparin:
Dosing and adverse effects", section on 'Danaparoid'.)
High quality data regarding the use of danaparoid in pregnancy are lacking; this agent generally is reserved for pregnant
women with heparin-induced thrombocytopenia (HIT) during or immediately preceding pregnancy [11-14]. (See 'HIT during
or immediately preceding pregnancy' below.)

● Fondaparinux – Fondaparinux is a synthetic pentasaccharide based on the active moiety of heparin. Experience with
fondaparinux during pregnancy is extremely limited, and data regarding placental passage are mixed. As an example, a
series of 13 women treated with fondaparinux during 15 pregnancies reported uncomplicated deliveries of healthy babies
in 10 cases [15]. Of the remaining five pregnancies, three ended in miscarriage, one had an elective termination due to fetal
anomalies, and one was associated with recurrent VTE, possibly due to underdosing. One of the adverse outcomes may
have been related to a delay in delivery due to lack of experience with fondaparinux management, which emphasizes the
importance of having a clear delivery plan. Another series reported the use of fondaparinux during 12 pregnancies in 10
women who had hypersensitivity reactions to LMW heparin [16]. Outcomes were good; there was no major increased
bleeding or fetal abnormalities. The American College of Chest Physicians (ACCP) suggests limiting the use of fondaparinux
during pregnancy to women with severe reactions to heparin (eg, HIT) who are unable to receive danaparoid [14]. (See
"Fondaparinux: Dosing and adverse effects" and 'HIT during or immediately preceding pregnancy' below.)
● Argatroban – Argatroban is a parenteral direct thrombin inhibitor reserved for those with severe reactions to heparins (eg,
HIT) who cannot receive danaparoid or fondaparinux (eg, due to lack of availability or allergic reactions) [17-19]. Argatroban
requires continuous intravenous administration and is monitored by the activated partial thromboplastin time (aPTT).
Argatroban is likely to cross the placenta due to its small size, although this has not been well studied [19]. (See "Direct oral
anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects", section on 'Argatroban'.)
Anticoagulants that are generally avoided during pregnancy
● Warfarin – Warfarin is generally avoided in pregnant women, except in those considered especially high risk (eg, due to a
mechanical heart valve). (See "Management of antithrombotic therapy for a prosthetic heart valve during pregnancy".)
Warfarin and other vitamin K antagonists freely cross the placenta and are teratogenic, with the highest risk occurring with
administration between weeks 6 and 12 of gestation; these agents can also cause fetal bleeding at any stage of pregnancy
[8,9,20,21].
Warfarin has also been reported to be associated with early miscarriage [22], although the incidence is unknown, and it is
unclear whether the increased rate of early miscarriages is due to the use of warfarin or to the underlying conditions for
which warfarin was administered. Warfarin has been used during the second trimester of pregnancy when organogenesis

has been mostly completed, but the risk of fetal bleeding is a disadvantage compared with other agents. (See 'Warfarin
teratogenicity' below and "Management of antithrombotic therapy for a prosthetic heart valve during pregnancy".)
● Oral direct thrombin inhibitors and factor Xa inhibitors – Oral direct thrombin inhibitors (eg, dabigatran) and factor Xa
inhibitors (eg, rivaroxaban, apixaban, edoxaban), collectively referred to as direct oral anticoagulants (DOACs), should not
be used during pregnancy due to increased reproductive risks in animal studies and insufficient human safety and efficacy
data [14,23,24]. DOACs also should not be administered to women who are breastfeeding [23]. (See 'Breastfeeding' below.)
In a 2016 series of 137 DOAC-exposed pregnancies from case reports and pharmacovigilance sources for which outcomes
were available, there were 67 live births and 31 miscarriages (49 and 23 percent, respectively), which is comparable to the
general population [25]. There were no instances of fetal bleeding; however, there were three anatomical abnormalities that
might be interpreted as embryopathy (eg, facial dimorphism, limb deformity, cardiac defect). This frequency is similar to
population estimates, but conclusions are difficult to draw because outcomes were unavailable for an additional 96 DOAC-
exposed pregnancies.
WHEN TO START LMW HEPARIN
Switching from oral anticoagulants to LMW heparin — Women receiving chronic oral anticoagulation who are contemplating
pregnancy need counseling regarding avoidance of the potential teratogenic effects of warfarin. (See 'Women on warfarin'
below.)
Women receiving direct thrombin inhibitors (eg, dabigatran) or factor Xa inhibitors (eg, apixaban, edoxaban, rivaroxaban)
should plan to switch to low molecular weight (LMW) heparin when they become pregnant. (See 'Women on direct thrombin
inhibitors or factor Xa inhibitors' below.)
The management of anticoagulation around the time of conception is discussed below and in disease-specific topics. (See
'Specific scenarios' below and "Supraventricular arrhythmias during pregnancy", section on 'Anticoagulation' and "Management
of risks of prosthetic valves during pregnancy", section on 'Preconception evaluation and counseling'.)

Initiating LMW heparin — For women who are not receiving chronic anticoagulation but require anticoagulation during
pregnancy (eg, for thromboprophylaxis), anticoagulation is initiated when pregnancy is established rather than before
conception. For these women, LMW heparin is generally started in the first trimester after pregnancy is confirmed by a positive
pregnancy test, as long as there is no vaginal bleeding.
ADMINISTRATION DURING PREGNANCY
Low molecular weight (LMW) and unfractionated heparin are usually administered subcutaneously, although unfractionated
heparin can also be administered intravenously to achieve a more constant level of anticoagulation or during times when rapid
discontinuation is advantageous (eg, delivery, surgery). (See 'Switch to unfractionated heparin' below.)
Injections are usually well tolerated. Ice applied to the proposed injection site for 20 minutes prior to the injection can help to
minimize bruising, although this generally is not necessary.
Baseline laboratory testing — We obtain a baseline platelet count in all patients. The risk of heparin-induced
thrombocytopenia (HIT) is very low in pregnancy, and monitoring of the platelet count is generally not required. However, it is
reasonable to check hematologic parameters including hemoglobin, hematocrit, and platelet count after approximately three to
four weeks of therapy. If the platelet count is stable, it does not need to be repeated because subsequent development of HIT is
unlikely, although there may be opportunities for additional monitoring if other laboratory testing is obtained. A platelet count
should always be checked if thrombosis occurs during treatment with any form of heparin. (See 'Suspected heparin-induced
thrombocytopenia' below.)
We also obtain a baseline serum creatinine level in all patients. Patients with diminished renal function may require more
intensive monitoring or use of unfractionated rather than LMW heparin. (See 'Choice of anticoagulant' above.)
Preservative-free vials — The multi-dose vials of LMW and unfractionated heparin contain benzyl alcohol and/or other
preservatives. Alcohols can have adverse fetal effects and are contraindicated in pregnancy, although the concentration of
alcohol in maternal blood from the preservative and a correlation of specific levels of benzyl alcohol with fetal harm have not

been well characterized. Prefilled, single dose syringes are generally preservative-free. Confirmation of the absence of
preservatives from the product label is advised.
Dosing and laboratory monitoring — Anticoagulants such as LMW heparin can be administered at different doses depending
upon the risk of thromboembolism and desired degree of anticoagulation. The appropriate dosing level is discussed in topic
reviews that describe the indications for anticoagulation. (See "Inherited thrombophilias in pregnancy" and "Deep vein
thrombosis and pulmonary embolism in pregnancy: Prevention".)
We use the following terminology to describe heparin anticoagulation dosing:
● Prophylactic dose anticoagulation refers to the use of low doses of anticoagulants, which aims to reduce the risk of
thromboembolism while minimizing bleeding complications.
● Intermediate dose anticoagulation refers to the adjustment of prophylactic dose anticoagulation with weight gain during
pregnancy. (See 'Prophylactic and intermediate dose' below.)
● Therapeutic dose anticoagulation refers to the use of anticoagulants at doses typically reserved for treatment of
thromboembolic disease. Therapeutic dosing is used when lower dosing is thought to be insufficient for thromboembolism
prophylaxis in some patients at very high risk of thromboembolism. Despite the nomenclature, therapeutic dosing may be
used prophylactically (ie, to prevent thromboembolism in the setting of severe thrombophilias, mechanical heart valves and
other high risk situations). For LMW heparin, therapeutic dosing is based on weight and, in rare cases, using anti-factor Xa
levels. For unfractionated heparin, therapeutic dosing is titrated to keep the activated partial thromboplastin time in the
therapeutic range (eg, 1.5 to 2.5 times baseline). (See 'Therapeutic dose' below.)
Dosing regimens for prophylactic and therapeutic LMW and unfractionated heparin are summarized in the table ( table 1) and
below. (See 'Prophylactic and intermediate dose' below and 'Therapeutic dose' below.)
There is no exact formula for converting between LMW and unfractionated heparin. A reasonable approach is as follows:
● Converting from prophylactic dose LMW to unfractionated heparin – Use the doses of unfractionated heparin listed below
by trimester. (See 'Unfractionated heparin' below.)

● Converting from therapeutic dose LMW to unfractionated heparin in a pregnant woman deemed to be at high risk for
ongoing or recurrent thrombosis (eg, a woman presenting with acute pulmonary emboli in the third trimester) – A rough
calculation for the initial dose of unfractionated heparin in a woman receiving enoxaparin 1 mg/kg every 12 hours would be
to use 250 units of unfractionated heparin per kg of body weight, given subcutaneously every 12 hours (sample calculation
for a 100 kg woman: 250 units/kg x 100 kg = 25,000 units subcutaneously every 12 hours) [26]. Clinicians should note that
this dosing has not been validated in pregnancy; clinical judgment should be used. Subsequent dosing must be adjusted
according to an aPTT obtained six hours after administration, as described below. (See 'Unfractionated heparin' below.)
Dosing of heparins in pregnancy is altered because pregnancy-associated weight gain and metabolism affect the
pharmacokinetics of these agents; higher doses are necessary compared with nonpregnant women due to alterations in a
variety of factors (eg, metabolism, plasma volume, renal clearance) [24]. In a study of LMW heparin pharmacokinetics in 24
women at 12, 24, and 36 weeks of gestation and six weeks postpartum, peak anti-factor Xa activity levels during pregnancy
were lower than in nonpregnant (postpartum) women and occurred later after injection (four versus two hours) [27].
Dosing postpartum is discussed below and in separate topic reviews. (See 'Postpartum and breastfeeding' below and "Cesarean
delivery: Preoperative planning and patient preparation", section on 'Thromboembolism prophylaxis' and "Deep vein
thrombosis and pulmonary embolism in pregnancy: Treatment", section on 'After delivery'.)
Prophylactic and intermediate dose
LMW heparin — Prophylactic dose LMW heparin uses a fixed dose of anticoagulant (eg, dalteparin 5000 units
subcutaneously every 24 hours; enoxaparin 40 mg subcutaneously every 24 hours) with adjustment for extremes of body
weight ( table 1).
Due to concerns that standard prophylactic dose LMW heparin may not adequately prevent VTE in women at intermediate risk,
we often increase LMW heparin dosing as the pregnancy progresses and the patient's weight increases, up to a maximum dose
of enoxaparin 1 mg/kg once daily (ie, "intermediate dosing") ( table 1). The frequency of dose increases is individualized
depending on the interval between office visits. This use of increased dosing is based on findings from pharmacokinetic studies
that suggested a greater dose requirement in most women after 20 weeks of gestation [28]. Intermediate dosing provides a

higher dose than standard prophylactic regimens of LMW heparin, but with only a single daily injection, which is better
tolerated than twice daily injections.
Support for our approach comes from a retrospective study that found a high incidence of VTE in high-risk pregnant women
who were treated with standard prophylactic dose LMW heparin [29]. This study included 34 women (44 pregnancies) at
intermediate risk of VTE who received prophylactic dose LMW heparin for six weeks postpartum, and 57 women (82
pregnancies) at high risk of VTE who received both antepartum and postpartum prophylactic dose LMW heparin. All VTE events
occurred in the high-risk patients (postpartum VTE incidence 7.0 percent, 95% CI 2.9–16.7; antepartum incidence 1.8 percent,
95% CI 0.4–9.2). These results suggested that low-dose LMW heparin prophylaxis may not be sufficient in high-risk patients.
Monitoring of prophylactic or intermediate dose LMW heparin is not required.
Unfractionated heparin — Unfractionated heparin is given subcutaneously every 12 hours, with increasing doses as the
pregnancy progresses, from 5000 to 7500 units in the first trimester, to 7500 to 10,000 units in the second trimester, to 10,000
units in the third trimester (reduce if the activated partial thromboplastin time [aPTT] is elevated) [24,30]. Some clinicians use
5000 units subcutaneously every 12 hours throughout the pregnancy, but studies have suggested that this dose is probably
insufficient in some patients based on plasma heparin levels [31-35].
Monitoring of prophylactic dose unfractionated heparin is generally not performed, although the aPTT can be measured if there
are concerns about bleeding or thrombosis.
Therapeutic dose
LMW heparin — Therapeutic doses of LMW heparin based on body weight are usually administered every 12 hours by
subcutaneous injection ( table 1). Our preference is enoxaparin 1 mg/kg every 12 hours or dalteparin 100 units/kg every 12
hours; we do not employ once daily regimens (enoxaparin 1.5 mg/kg or dalteparin 200 units/kg once daily) because we wish to
avoid higher peak and lower trough levels.
We do not monitor laboratory values (eg, anti-factor Xa activity levels) in most pregnant women treated with therapeutic-dose
LMW heparin in routine clinical practice, consistent with a 2018 American Society of Hematology (ASH) guideline [6]; however,
some experts do recommend such monitoring (see "Deep vein thrombosis and pulmonary embolism in pregnancy: Treatment",
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section on 'LMWH'). An exception is extremes of body weight. As an example, we occasionally monitor anti-factor Xa activity
levels (and use the results to make dose adjustments if needed) for women >100 kg and especially for those >150 kg.
If monitoring is done, peak anti-factor Xa activity levels are measured four to six hours after dosing, and the dose is titrated to
maintain a target peak anti-factor Xa activity of approximately 0.6 to 1.2 units/mL [24]. Data supporting the need for laboratory
monitoring of therapeutic dose LMW heparin are sparse [27,36,37]. (See "Clinical use of coagulation tests", section on
'Monitoring heparins'.)
Unfractionated heparin — Therapeutic dose unfractionated heparin is administered every 12 hours by subcutaneous

injection and titrated based on the aPTT. In some patients, the volume of medication in the injection may become unacceptably
high; this can be avoided by using more concentrated heparin solutions (eg, 20,000 units/mL). Heparin can be administered
intravenously if the need for rapid discontinuation is likely (eg, imminent labor, surgery).
Unfractionated heparin is monitored using the aPTT, measured six hours after injection. The dose should be adjusted to
maintain the aPTT at 1.5 to 2.5 times the mean of the control value or the patient's baseline aPTT value. We monitor the aPTT
daily until the proper dose is achieved and every one to two weeks once it is in the therapeutic range.
Intravenous heparin dosing and heparin dose monitoring in individuals with a baseline prolonged aPTT (eg, those with
antiphospholipid syndrome) are discussed separately. (See "Heparin and LMW heparin: Dosing and adverse effects", section on
'Prolonged baseline aPTT'.)
PREVENTION OF THROMBOSIS AND BLEEDING
Anticoagulants are administered to patients at increased risk of thromboembolic disease, and this risk, although mitigated by
therapy, persists and may increase during pregnancy. Pregnant women should thus be aware of the signs and symptoms of
thromboembolism (eg, leg swelling, pleuritic chest pain, central nervous system symptoms) and have instructions to contact
their clinician should these occur. (See "Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis" and
"Cerebrovascular disorders complicating pregnancy".)

Concerns about excess bleeding in a patient receiving low molecular weight (LMW) or unfractionated heparin apply only to the
mother, since heparins do not cross the placenta. Patients should be educated about the signs and symptoms of bleeding and
instructed to contact their provider in the event of a bleed.
Other than appropriate dosing and monitoring, strategies to decrease the risk of bleeding include the following:
● Convert from subcutaneous LMW heparin to unfractionated heparin prior to delivery, and from subcutaneous
unfractionated heparin to intravenous unfractionated heparin prior to anticipated delivery in those who require more
continuous anticoagulation. Discontinue heparin at the onset of labor. Maximum control of anticoagulation can be achieved
if the timing of delivery is planned (scheduled cesarean or induction of labor). (See 'Switch to unfractionated heparin'
below.)
● If preterm labor develops in a patient receiving heparin, protamine sulfate has been used to reverse maternal
heparinization. However, it is best to avoid administration of protamine antepartum unless hemorrhage cannot be
controlled using routine supportive measures. (See "Heparin and LMW heparin: Dosing and adverse effects", section on
'Reversal' and "Heparin and LMW heparin: Dosing and adverse effects", section on 'Bleeding'.)
● Place or remove a neuraxial needle or catheter only after the patient is no longer anticoagulated. (See 'Neuraxial
anesthesia' below.)
MANAGEMENT OF COMPLICATIONS
Treatment of bleeding on heparin — Protamine sulfate can be used to rapidly reverse the effects of unfractionated heparin in
patients with serious or severe bleeding unrelated to pregnancy; patients at risk of severe bleeding because of imminent
vaginal or cesarean delivery; or patients at risk of serious or severe bleeding due to antepartum complications (eg, placental
abruption, placenta previa, expanding subchorionic hematoma). Repeated small doses of protamine may be required because
of ongoing absorption of heparin from subcutaneous tissue. (See "Heparin and LMW heparin: Dosing and adverse effects",
section on 'Reversal'.)

Low molecular weight (LMW) heparin may not be completely reversed by protamine, but protamine may reduce bleeding and
should be used if bleeding is severe. (See "Heparin and LMW heparin: Dosing and adverse effects", section on 'Reversal'.)
Minor bleeding that is easily visible (eg, spotting) does not require pharmacologic reversal of anticoagulation. If bleeding
persists, one option is to withhold anticoagulation, if possible, until the bleeding stops and then resume the anticoagulant. Such
decisions depend on the degree and site of bleeding and the indication for anticoagulation, and are made on a case-by-case
basis by the hematologist and obstetrician.
Patients with bleeding who require VTE prophylaxis can be managed with mechanical means or vena cava filters if needed;
these interventions are discussed separately. (See "Prevention of venous thromboembolic disease in acutely ill hospitalized
medical adults", section on 'Mechanical methods of thromboprophylaxis' and "Deep vein thrombosis and pulmonary embolism
in pregnancy: Treatment", section on 'Inferior vena cava filters'.)
Suspected heparin-induced thrombocytopenia — Heparin-induced thrombocytopenia (HIT) is an adverse reaction to heparin

in which an antibody to platelets is induced by the drug. Unlike other drug-induced thrombocytopenias, the HIT antibody
causes platelet activation that can result in life-threatening arterial and venous thrombosis. (See "Clinical presentation and
diagnosis of heparin-induced thrombocytopenia" and 'HIT during or immediately preceding pregnancy' below.)
HIT can occur in any patient receiving any amount of heparin; however, the incidence in pregnant women is very low. This was
illustrated in a meta-analysis of 2777 pregnancies during which LMW heparin was administered; no instances of HIT were
reported [7]. LMW heparin appears less likely to precipitate HIT compared with unfractionated heparin in some populations (eg,
surgical patients); this has not been studied in pregnancy [3].
Any patient who develops thrombocytopenia while receiving heparin should have a clinical evaluation for HIT that includes
platelet count and clinical assessment for thrombosis and/or skin changes. Those with a high clinical suspicion for HIT should
have immediate discontinuation of heparin, institution of an alternative anticoagulant, and laboratory testing for HIT (heparin-
PF4 antibody testing). (See "Clinical presentation and diagnosis of heparin-induced thrombocytopenia", section on 'Evaluation'
and 'HIT during or immediately preceding pregnancy' below.)

Of note, a modest decrease in platelet count is expected during pregnancy and should not prompt laboratory testing for HIT.
(See "Thrombocytopenia in pregnancy", section on 'Gestational thrombocytopenia (GT)'.)
In addition to evaluation for HIT, pregnant patients with a drop in platelet count that is greater than expected should be
evaluated for other potential causes of thrombocytopenia besides HIT. (See "Thrombocytopenia in pregnancy".)
Bone loss — Prolonged use of unfractionated heparin (ie, more than a few weeks) is associated with decreases in bone mineral
density (BMD). Women taking unfractionated heparin for more than a few weeks should have adequate intake of calcium and
vitamin D, and regular weight bearing exercise (eg, walking) should be encouraged. (See "Prevention of osteoporosis", section
on 'Minimizing bone loss'.)
It is unclear whether bone loss may be reduced or prevented by using LMW heparin instead of unfractionated heparin. A study
that randomly assigned 44 pregnant women to receive either dalteparin (target anti-Xa greater than 0.20 international units/mL
three hours after injection) or unfractionated heparin (mean dose 17,250 units/day) found that mean BMD in the lumbosacral
spine was significantly lower with unfractionated heparin at one week to three years postpartum; those who received LMW
heparin had similar BMD to postpartum women who were not exposed to any form of heparin [38]. Other studies have found
no difference in the effect of LMW versus unfractionated heparin on BMD [39]. (See "Drugs that affect bone metabolism",
section on 'Anticoagulants'.)
LABOR AND DELIVERY
Anticoagulation during labor should be avoided except in the highest risk settings (eg, reduced cardiopulmonary reserve and
recent pulmonary embolus).
Switch to unfractionated heparin — With limited exceptions (eg, for patients with mechanical heart valves), most obstetricians
replace therapeutic-dose low molecular weight (LMW) heparin with unfractionated heparin at 36 to 37 weeks of gestation. This
minimizes the risk that labor will begin or delivery will be required within 24 hours of the last dose of LMW heparin and thus
increases the chance of being able to receive neuraxial anesthesia [24]. (See 'Neuraxial anesthesia' below.)

LMW heparin is replaced with unfractionated heparin earlier than 36 to 37 weeks if there is a threatened preterm birth or if
there are obstetrical complications likely to warrant preterm delivery.
Some obstetricians extend LMW heparin therapy to 38 to 39 weeks on a case-by-case basis in patients they believe to be at very
low risk of delivering while receiving LMW heparin (ie, those with no risk factors for spontaneous preterm birth, no history of
pregnancy complications that could warrant early delivery, and no signs/symptoms of imminent labor). In such patients, LMW
heparin is continued until 24 hours before scheduled cesarean delivery, induction of labor, or anticipated spontaneous vaginal
delivery at full term.
Subcutaneous LMW or unfractionated heparin is discontinued for most patients when spontaneous labor begins, or 12 to 24
hours before planned induction of labor or cesarean delivery (12 hours for prophylactic dose; 24 hours for higher doses),
consistent with an American College of Obstetricians and Gynecologists (ACOG) practice bulletin and an American Society of
Hematology (ASH) guideline from 2018 [6,24].
As noted above, some patients have a strong need for ongoing anticoagulation (eg, prosthetic heart valve, atrial fibrillation with
thrombus, pulmonary embolism within a few weeks prior to delivery), and in these individuals, a period of 24 or 36 hours
without anticoagulation may be undesirable. Details of management in these settings are presented separately. (See
"Management of antithrombotic therapy for a prosthetic heart valve during pregnancy", section on 'Peripartum management'
and "Deep vein thrombosis and pulmonary embolism in pregnancy: Treatment", section on 'Labor and delivery'.)
Women who are anticoagulated with heparin until the onset of labor and deliver vaginally generally do not have greater blood
loss than non-anticoagulated women. However, cesarean delivery in patients on heparin may be accompanied by increased
wound complications or greater blood loss than would otherwise be anticipated in a woman not receiving an anticoagulant [40-
42].
The dosing and aPTT monitoring for prophylactic-dose and therapeutic-dose unfractionated heparin is described above. (See
'Dosing and laboratory monitoring' above.)
Neuraxial anesthesia — Neuraxial anesthesia techniques (ie, spinal, epidural or combined spinal epidural) should not be
performed if a patient is anticoagulated, due to the risk of spinal or epidural hematoma. Therefore, anticoagulation is

discontinued before labor so women can receive neuraxial analgesia or anesthesia, which is performed for >95 percent of
cesarean deliveries and >60 percent of women undergoing labor and vaginal delivery in the United States [43]. Examples of the
interval between anticoagulant discontinuation and neuraxial anesthesia/analgesia include the following ( table 2):
● Prophylactic dose LMW heparin – After at least 12 hours have elapsed since the last dose.
● Intermediate and therapeutic dose LMW heparin – After at least 24 hours have elapsed since the last dose.
● Prophylactic and therapeutic dose unfractionated heparin – Once the aPTT has normalized following discontinuation
(timing of aPTT testing depends on dose and route of administration; eg, in patients on therapeutic doses of unfractionated
heparin, the aPTT is usually normal 6 hours after stopping intravenous administration, but can take 24 hours after stopping
subcutaneous administration).
It is possible that in the future, thromboelastography (TEG) may be used to determine when neuraxial anesthesia can be
initiated following discontinuation of LMW heparin, but more data are needed before this approach can be used [44]. We do not
administer a reversal agent (eg, protamine) unless there is excessive or unexpected bleeding due to the anticoagulant.
Further details, and timing of anticoagulant resumption after catheter removal, are discussed in detail separately. (See
"Neuraxial anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet medication".)
POSTPARTUM AND BREASTFEEDING
Resuming or initiating anticoagulation postpartum — Anticoagulation is reinstituted following delivery in most patients who
were receiving an anticoagulant during pregnancy; a possible exception is patients who received anticoagulation to prevent
miscarriage or fetal loss.
● Acute VTE (therapeutic dosing) – For women with acute venous thromboembolism (VTE) who are still in the active
treatment period (ie, first three months) or who have other indications requiring continuous anticoagulation (eg, high-risk
thrombophilia), either unfractionated heparin or low molecular weight (LMW) heparin can be given alone at therapeutic
doses, or one of these anticoagulants should be administered during the initiation of warfarin and continued for a

minimum of five days and an additional one to two days after an appropriate International Normalized Ratio (INR) has been
obtained. (See "Deep vein thrombosis and pulmonary embolism in pregnancy: Treatment", section on 'After delivery'.)
Women with an acute VTE are at the highest risk for VTE recurrence, progression, or complications, and the risk-benefit
calculation favors initiation of heparin as early as safely possible.
The ideal time to start anticoagulation after delivery is based on clinical judgment, as comparative data are very limited.
Unfractionated heparin or LMW heparin are generally resumed four to six hours after vaginal delivery or 6 to 12 hours after
cesarean delivery, unless there was significant postpartum bleeding or traumatic neuraxial catheter placement.
A retrospective study reported that bleeding rates were lower when more time elapsed following delivery (≥9.25 hours for
vaginal and ≥15.1 hours for cesarean) [45]. However, bleeding rates in a matched control group not receiving
anticoagulation were not provided, co-interventions may have differed among groups, and the confidence intervals were
wide and overlapping. Major factors to consider in deciding when to restart anticoagulation include the underlying
indication for anticoagulation (such as acute treatment of VTE versus prophylaxis) and other risk factors for bleeding. (See
"Neuraxial anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet medication".)
Women can be transitioned to warfarin, fondaparinux, or danaparoid (not available in the United States-), or, if not
breastfeeding, to a direct oral anticoagulant (DOAC) if appropriate [24]. (See 'Breastfeeding' below and "Direct oral
anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects", section on 'Transitioning
between anticoagulants' and "Warfarin and other VKAs: Dosing and adverse effects", section on 'Transitioning between
anticoagulants/bridging'.)
Resumption of anticoagulation for women with mechanical heart valves is discussed separately. (See "Management of
antithrombotic therapy for a prosthetic heart valve during pregnancy", section on 'Postpartum management'.)
● VTE prophylaxis – Additional patients who were not receiving anticoagulation during pregnancy may initiate it postpartum
for VTE prevention (eg, some women with thrombophilia due to inherited or acquired defects or prior VTE who did not
receive anticoagulation during pregnancy). These indications are discussed separately. (See "Inherited thrombophilias in
pregnancy", section on 'Prevention of VTE' and "Deep vein thrombosis and pulmonary embolism in pregnancy: Prevention".)

For these women, the urgency of starting heparin is less than for those with acute VTE (or VTE within the prior three
months). We initiate prophylactic doses of unfractionated heparin or LMW heparin 6 to 12 hours after vaginal delivery and
12 to 24 hours after cesarean delivery. In a review of 95 women treated with postpartum anticoagulation, mostly at
prophylactic doses, we found very few cases of bleeding, with the exception of two incisional hematomas in women
undergoing cesarean delivery who received enoxaparin within 24 hours following delivery [46]. If oral anticoagulation is
chosen for continued postpartum thromboprophylaxis, warfarin can be started immediately after delivery; unfractionated
or LMW heparin can be discontinued when a therapeutic INR has been obtained in women who are not at very high risk for
thrombotic complications.
● Prophylactic anticoagulation for women who undergo cesarean delivery is discussed separately. (See "Cesarean delivery:
Preoperative planning and patient preparation", section on 'Thromboembolism prophylaxis'.)
Duration of postpartum anticoagulation — The duration of postpartum anticoagulation depends upon the underlying reason
for anticoagulation.
● Women receiving anticoagulation for VTE prophylaxis during pregnancy should continue to receive anticoagulation for at
least six weeks postpartum, due to the continued high risk of VTE in the early postpartum period. (See "Inherited
thrombophilias in pregnancy" and "Deep vein thrombosis and pulmonary embolism in pregnancy: Prevention", section on
'Duration'.)
● The duration of anticoagulation for women who have had a VTE during pregnancy is discussed separately. (See "Deep vein
thrombosis and pulmonary embolism in pregnancy: Treatment".)
Breastfeeding — Many anticoagulants can be used during breastfeeding because they do not accumulate in breast milk. The
2018 American Society of Hematology (ASH) guidelines recommend continuation of the following anticoagulants during
breastfeeding [6]:
● LMW heparin
● Unfractionated heparin
● Fondaparinux

● Warfarin or other vitamin K antagonists

● Danaparoid (not available in the United States)
Continuation of low-dose aspirin for vascular indications is also suggested [14].
The 2012 American College of Chest Physicians (ACCP) guidelines agreed with the above list with the exception of fondaparinux,
for which there was considered to be insufficient evidence at the time the 2012 guideline was published [14].
In contrast to the agents listed above, we do not use the following during breastfeeding, consistent with the 2018 ASH and 2012
ACCP guidelines [6,13]:
● Oral direct thrombin inhibitors (eg, dabigatran)

● Oral direct factor Xa inhibitors (eg, rivaroxaban, apixaban, edoxaban)
If anticoagulation is required during breastfeeding, another agent should be selected.
Birth control in women with increased VTE risk — Contraceptive options in women with inherited thrombophilias are
discussed separately. (See "Contraception: Counseling for women with inherited thrombophilias".)
SPECIFIC SCENARIOS
HIT during or immediately preceding pregnancy — A prior episode of heparin-induced thrombocytopenia (HIT) that has been
adequately treated is not an indication for anticoagulation during pregnancy. However, if a pregnant patient with a history of
HIT requires anticoagulation for another reason, or if a patient develops HIT immediately prior to or during pregnancy, an
anticoagulant other than heparin should be used. All sources of heparin (including heparin flushes) should be avoided.
The 2012 American College of Chest Physicians (ACCP) guidelines recommend danaparoid as the preferred alternative to
heparin for pregnant patients; this agent is not available in the United States [14]. For patients who cannot receive danaparoid,
argatroban or fondaparinux can be used. We generally use fondaparinux because of the ease of administration during

pregnancy. Other aspects of the management of HIT are discussed separately. (See "Management of heparin-induced
thrombocytopenia".)
The use of danaparoid, outside of the United States, in women with HIT is supported by review of outcomes of 91 pregnancies
in 83 women with HIT who were treated with danaparoid; some of the patients also had antiphospholipid syndrome [47].
Maternal adverse events included two post-cesarean deaths in the setting of placenta previa and placental abruption (one from
pulmonary embolus and one from bleeding in which the patient refused transfusion); three major bleeds; three
thromboembolic events; and 10 rashes. There were seven early miscarriages, one therapeutic termination, and one neonatal
death associated with a lupus anticoagulant and placental infarction [48]. Of note, HIT is associated with a high baseline
mortality, even with treatment. The live birth rate in this review was 90 percent, which compares favorably with women treated
with aspirin or heparin during pregnancy [47].
We screen for HIT in pregnant patients receiving unfractionated or low molecular weight (LMW) heparin by checking platelet
counts before initiating heparin therapy and periodically thereafter. (See 'Suspected heparin-induced thrombocytopenia' above.)
Thromboembolism during pregnancy — If a new thromboembolic event is suspected during pregnancy, this should be
evaluated immediately. Diagnosis and management of venous thromboembolism (VTE) during pregnancy is discussed
separately. (See "Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis" and "Deep vein thrombosis
and pulmonary embolism in pregnancy: Treatment".)
Cesarean delivery — Cesarean delivery increases the risk of VTE, especially when performed urgently or in an emergency.
Prevention of VTE in women undergoing cesarean delivery is reviewed separately. (See "Cesarean delivery: Preoperative
planning and patient preparation", section on 'Thromboembolism prophylaxis'.)
Women on warfarin — Warfarin and other vitamin K antagonists cross the placenta; these agents can be teratogenic and can
cause fetal bleeding, including hemorrhagic fetal death. Thus, warfarin use is generally avoided during pregnancy, or, rarely,
restricted to the second and early third trimester. For women at exceptionally high thromboembolic risk (eg, women with
mechanical heart valves) the benefits and risks (including fetal risks) of warfarin use are weighed during each phase of
pregnancy (eg, first trimester versus later trimesters) and an alternative anticoagulant is used as delivery approaches, as
discussed in detail separately. (See "Management of antithrombotic therapy for a prosthetic heart valve during pregnancy".)

Warfarin-associated bleeding — The management of excessive anticoagulation and/or bleeding in a pregnant woman on

warfarin depends on the original indication for warfarin therapy, the degree and site of bleeding, and the International
Normalized Ratio (INR). Thus, management decisions are made on a case-by-case basis in consultation with the hematologist
and other specialists (eg, cardiologist, neurologist, obstetrician). Available agents for reversal (eg, fresh frozen plasma [FFP],
unactivated prothrombin complex concentrates [PCCs], vitamin K) and their use in specific situations are discussed separately
(See "Management of warfarin-associated bleeding or supratherapeutic INR" and "Reversal of anticoagulation in intracranial
hemorrhage".)
In the setting of preterm labor and/or unplanned delivery in a woman on warfarin, it is important to remember that the fetus is
anticoagulated. (See 'Delivery' below.)
Warfarin teratogenicity — Warfarin is a teratogen. The precise incidence of warfarin embryopathy is unknown, with
different series reporting widely ranging incidences; the best overall estimate of the risk is less than 10 percent. The teratogenic
effect appears to be dose-related rather than correlating with maternal INR; doses less than 5 mg/day appear to provide the
highest margin of safety but teratogenicity at these doses has been reported [49-51].
The risk of teratogenicity is greatest for fetuses exposed to warfarin between the sixth and 12th weeks of gestation [31], but
toxicity before or after this period is still possible [52-55]. As an example, the following findings were noted in report of 72
pregnancies in women with prosthetic cardiac valves who were treated with warfarin [20]:
● Virtually no embryopathic events occurred in the 23 pregnancies in which warfarin was discontinued by the sixth week of
gestation and not restarted until after the 12th week.
● Warfarin embryopathy occurred in 25 percent of the 12 pregnancies in which warfarin was not stopped until after the
seventh week.
● Embryopathy occurred in 30 percent of the 37 pregnancies in which warfarin was continued throughout the entire
pregnancy.
The most common developmental abnormalities affect bone and cartilage; these simulate chondromalacia punctata, with
stippled epiphyses and nasal and limb hypoplasia [31]. The mechanism of this type of warfarin teratogenicity has not been
established, but may be related to the drug's interference with the post-translational modification of calcium-binding proteins
that are important for the normal growth and development of bony structures [21]. (See "Vitamin K and the synthesis and
function of gamma-carboxyglutamic acid".)
Less well-documented are reports of central nervous system abnormalities (eg, optic atrophy, microcephaly, mental retardation,
spasticity, and hypotonia) associated with warfarin use at any stage during pregnancy [8,56-59]. This complication may be
related to fetal anticoagulation leading to cerebral hemorrhage.
Attempted conception/first trimester — Women taking warfarin prior to conception should have a clear plan to switch to
another anticoagulant (eg, LMW heparin) during attempted conception or immediately upon becoming pregnant, to avoid
teratogenic effects of the drug during the first trimester. Though the DOACs have not been shown to be teratogenic, women
taking these anticoagulants should be switched to LMW heparin prior to conception; in women who unintentionally become
pregnant while on a DOAC, the DOAC should be discontinued immediately and LMW heparin commenced [23].
The optimal timing for changing to LMW heparin is unclear, and it is necessary to balance the importance of avoiding warfarin
or a DOAC during early pregnancy/organogenesis with the inconvenience of using LMW heparin for an undefined period until
conception occurs. The two major options are to change to LMW heparin during attempted conception, or to wait until
pregnancy is confirmed before changing from warfarin to LMW heparin, as long as the switch can be made before six weeks of
pregnancy (ie, ≤14 days after the missed first day of expected menses).
In women receiving warfarin, the 2012 ACCP guidelines made a weak suggestion in favor of performing frequent pregnancy
tests and substituting treatment with LMW heparin as soon as pregnancy is achieved, rather than changing to LMW heparin
while attempting pregnancy [14]. (See 'Society guideline links' below.)
We believe that this is a reasonable option for a woman who meets all of the following criteria:
● She has regular monthly menstrual cycles.
● She agrees to have a blood pregnancy test within the first seven days of the missed first day of expected menses. This can
be facilitated by having a standing order at a laboratory or giving her laboratory requisitions in advance.

● She can be switched to a LMW heparin preparation promptly if the pregnancy test is positive, and will have a second blood
pregnancy test if the first test is negative and menses have not begun within 10 days of the missed first day of expected
menses. This can be facilitated by having a prescription for LMW heparin readily available or filled in advance.
● She understands the increased risk and types of embryopathy if she continues to take her long-term vitamin K antagonist
during or after the sixth week of pregnancy (ie, ≥14 days after the missed first day of expected menses). (See 'Warfarin
teratogenicity' above.)
Women who do not meet all of the above criteria; those who prefer to minimize the possible increased risk of early miscarriage
associated with warfarin therapy or any possible risk of a DOAC; and those who place less value on avoiding risks,
inconveniences, and costs of LMW heparin of uncertain duration should be switched to LMW heparin during attempted
conception. An exception is a woman with a mechanical heart valve, for whom warfarin generally is continued during attempted
conception, as discussed separately. (See "Management of risks of prosthetic valves during pregnancy", section on 'Counseling
regarding anticoagulant therapy'.)
If a woman becomes pregnant while taking warfarin, LMW heparin should be substituted as soon as possible. Prompt obstetric
consultation should be obtained to establish the gestational age of the fetus and to provide appropriate counseling regarding
any potential teratogenic risk to the fetus.
Delivery — The risk of fetal hemorrhage related to warfarin use is thought to be greatest during and immediately after
delivery [20,49,58-62]. If warfarin is used during pregnancy, it should be discontinued after 34 to 36 weeks of gestation, and an
alternative anticoagulant substituted if appropriate. (See 'Switch to unfractionated heparin' above.)
If preterm delivery occurs in a patient receiving warfarin, cesarean delivery should be considered to reduce the risk of fetal
bleeding [31]. Vitamin K and fresh frozen plasma should be administered to the neonate if preterm delivery occurs in a patient
receiving warfarin.
The immaturity of fetal enzyme systems and the relatively low concentration of vitamin K-dependent clotting factors render the
fetus more sensitive than the mother to the anticoagulant effects of warfarin [8,56,57]. Importantly, fetal levels of coagulation

factors do not correlate with maternal levels, and infusion of fresh frozen plasma into the mother does not reliably reverse fetal
anticoagulation.
Women on direct thrombin inhibitors or factor Xa inhibitors — Direct thrombin inhibitors and factor Xa inhibitors are not
used during pregnancy. A woman taking one of these agents who plans to become pregnant should be monitored very closely
as described for women taking warfarin. (See 'Attempted conception/first trimester' above.)
If a woman taking one of these agents becomes pregnant, she should switch immediately to LMW heparin.
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided
separately. (See "Society guideline links: Anticoagulation in pregnancy".)
SUMMARY AND RECOMMENDATIONS
● For most patients who require anticoagulation during pregnancy (except for patients with mechanical heart valves),
heparins are safer than other anticoagulants. For such patients, we recommend low molecular weight (LMW) heparin rather
than unfractionated heparin for all but the final weeks of the pregnancy (Grade 1B). This is based on the ease of
administration of LMW heparin compared with unfractionated heparin. Unfractionated heparin is a reasonable alternative
when cost or need for rapid reversal is important, and it is the preferred agent for patients with severe renal insufficiency
(eg, creatinine clearance ≤30 mL/min) and for all patients in preparation for labor and delivery. (See 'Choice of
anticoagulant' above.)
The choice of anticoagulant in pregnant women with mechanical heart valves is discussed separately. (See "Management of
antithrombotic therapy for a prosthetic heart valve during pregnancy".)
● LMW heparin can be administered at different doses depending upon the risk of thromboembolism and desired degree of
anticoagulation. The general terms "therapeutic dose" and "prophylactic dose" are used to convey the intensity of
anticoagulation and vary depending upon the agent used ( table 1). It is important to use preservative-free preparations.
We obtain a baseline creatinine level and platelet count prior to initiating LMW or unfractionated heparin, and monitor
platelet counts during heparin administration. (See 'Administration during pregnancy' above.)
Choice of the appropriate dosing level is discussed in separate topic reviews on indications for anticoagulation:
• Inherited thrombophilia – (See "Inherited thrombophilias in pregnancy", section on 'Prevention of VTE'.)

• Prior venous thromboembolism – (See "Deep vein thrombosis and pulmonary embolism in pregnancy: Prevention",
section on 'Indications'.)
● Bleeding is a risk with any anticoagulant. Management of bleeding depends on the degree and site of bleeding, and the
original indication for anticoagulation, and decisions regarding discontinuation and reversal of anticoagulants are made on
a case-by-case basis in consultation with a hematologist and other specialists. (See 'Prevention of thrombosis and bleeding'
above and 'Treatment of bleeding on heparin' above.)
● Heparin-induced thrombocytopenia (HIT) is an adverse reaction to heparin; the incidence of HIT during pregnancy is very
low. We monitor for HIT by assessing the patient's platelet count periodically during LMW or unfractionated heparin
administration. Patients with suspected HIT should have an immediate assessment of clinical parameters (eg, platelet
count, presence of thrombosis or skin changes); for those considered to a high likelihood of HIT, an alternate anticoagulant
should be substituted and laboratory testing for HIT should be obtained. (See 'Suspected heparin-induced
thrombocytopenia' above and 'HIT during or immediately preceding pregnancy' above.)
● Anticoagulation during labor should be avoided; most obstetricians replace therapeutic dose LMW heparin with
unfractionated heparin at 36 to 37 weeks of gestation to reduce the risk of bleeding associated with delivery. An exception
is women with mechanical heart valves, for whom the switch to unfractionated heparin generally is made later. (See 'Switch
to unfractionated heparin' above.)
● A catheter for neuraxial anesthesia cannot be inserted if a patient is anticoagulated. The length of time without
anticoagulation prior to neuraxial anesthesia depends upon the agent and dose used. (See 'Neuraxial anesthesia' above.)

● Anticoagulation is reinstituted following delivery in most patients who were receiving an anticoagulant during pregnancy;
additional patients may initiate anticoagulation postpartum for venous thromboembolism (VTE) prophylaxis.
Unfractionated or LMW heparin can be resumed at prophylactic doses as early as four to six hours after vaginal delivery
and 6 to 12 hours after cesarean delivery unless there was significant bleeding, although for most patients we wait 6 to 12
hours after vaginal delivery and 12 to 24 hours after cesarean. Many anticoagulants (eg, heparins, warfarin) can be used
during breastfeeding because they do not accumulate in breast milk. (See 'Postpartum and breastfeeding' above.)
● Women receiving chronic anticoagulation who are contemplating pregnancy need counseling regarding avoidance of the
potential teratogenic effects of oral anticoagulants (eg, warfarin). Warfarin, oral direct thrombin inhibitors, and factor Xa
inhibitors should not be continued during the first trimester, and a switch should be made to LMW heparin either before
attempted conception or immediately upon confirmation of pregnancy. (See 'Women on warfarin' above and 'Women on
direct thrombin inhibitors or factor Xa inhibitors' above and 'When to start LMW heparin' above.)
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47. Magnani HN. An analysis of clinical outcomes of 91 pregnancies in 83 women treated with danaparoid (Orgaran). Thromb
Res 2010; 125:297.
48. van Besien K, Hoffman R, Golichowski A. Pregnancy associated with lupus anticoagulant and heparin induced
thrombocytopenia: management with a low molecular weight heparinoid. Thromb Res 1991; 62:23.
49. Cotrufo M, De Feo M, De Santo LS, et al. Risk of warfarin during pregnancy with mechanical valve prostheses. Obstet
Gynecol 2002; 99:35.
50. Vitale N, De Feo M, De Santo LS, et al. Dose-dependent fetal complications of warfarin in pregnant women with mechanical
heart valves. J Am Coll Cardiol 1999; 33:1637.
51. Basu S, Aggarwal P, Kakani N, Kumar A. Low-dose maternal warfarin intake resulting in fetal warfarin syndrome: In search
for a safe anticoagulant regimen during pregnancy. Birth Defects Res A Clin Mol Teratol 2016; 106:142.
52. Stevenson RE, Burton OM, Ferlauto GJ, Taylor HA. Hazards of oral anticoagulants during pregnancy. JAMA 1980; 243:1549.
53. Chong MK, Harvey D, de Swiet M. Follow-up study of children whose mothers were treated with warfarin during pregnancy.
Br J Obstet Gynaecol 1984; 91:1070.
54. Whitfield MF. Chondrodysplasia punctata after warfarin in early pregnancy. Case report and summary of the literature. Arch
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57. Beeley L. Adverse effects of drugs in later pregnancy. Clin Obstet Gynaecol 1986; 13:197.
58. Ginsberg JS, Chan WS, Bates SM, Kaatz S. Anticoagulation of pregnant women with mechanical heart valves. Arch Intern
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61. Sbarouni E, Oakley CM. Outcome of pregnancy in women with valve prostheses. Br Heart J 1994; 71:196.
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1993; 45:17.
Topic 1342 Version 50.0

GRAPHICS
Use of heparins during pregnancy
Heparin Dose level Dose
LMW heparin Prophylactic* Enoxaparin 40 mg SC once daily
Dalteparin 5000 units SC once daily

¶
Intermediate Enoxaparin 40 mg SC once daily, increase as pregnancy progresses to 1 mg/kg once daily
Dalteparin 5000 units SC once daily, increase as pregnancy progresses to 100 units/kg once daily
Therapeutic Enoxaparin 1 mg/kg SC every 12 hours
Dalteparin 100 units/kg SC every 12 hours
Unfractionated heparin Prophylactic 5000 units SC every 12 hours
Intermediate ¶ First trimester: 5000 to 7500 units SC every 12 hours
Second trimester: 7500 to 10,000 units SC every 12 hours
Third trimester: 10,000 units SC every 12 hours
Therapeutic Can be given as a continuous IV infusion or an SC dose every 12 hours. Titrated to keep the aPTT in the
therapeutic range.
Doses apply to pregnant women receiving heparin for venous thromboembolism prophylaxis. Therapeutic-dose level refers to doses used both for prophylaxis in individuals
at especially high risk and for treatment of venous thromboembolism. This dosing table should not be used in women with prosthetic heart valves. Refer to the UpToDate
topic on anticoagulant use in pregnancy for details of administration and monitoring. Refer to UpToDate topics on specific pregnant patient populations for other dosing
recommendations (eg, prosthetic heart valve, atrial fibrillation, treatment of deep vein thrombosis or pulmonary embolism).
LMW: low molecular weight; SC: subcutaneously; IV: intravenous; aPTT: activated partial thromboplastin time; ACCP: American College of Clinical Pharmacy; ACOG: American College of
Obstetricians and Gynecologists.
* Prophylactic dosing may require modifications for extremes of body weight.
¶ Our "intermediate" dose level differs from that used in society guidelines (eg, ACCP, ACOG). Some clinicians prefer to use a different "intermediate" dose level such as enoxaparin 40
mg SC every 12 hours; however, this entails a significant increase in the number of injections over the course of the pregnancy.
Graphic 91838 Version 9.0

Timing of neuraxial anesthesia during antithrombotic therapy
Interval from last dose to Interval from

Anticoagulant Notes
placement/removal placement/removal to next dose
Warfarin 4 to 5 days and verify normal INR; no Continue regular neurologic evaluation
monitoring needed for single dose within until 24 hours after removal. If dosed with
24 hours of placement catheter in place, check INR daily and
remove when INR <1.5; if INR 1.5 to 3.0,
remove catheter with caution, monitor
neurologic status until INR stabilized; if
INR >3, hold/reduce warfarin dose. Use of
other antihemostatic medications that do
not influence INR may increase risk of
bleeding complications.
Heparin (unfractionated) When heparin given for >4 days, check

platelets (risk of HIT) prior to insertion or
removal.
Intravenous 4 to 6 hours and verify normal aPTT 1 hour Bloody/difficult needle placement may
increase bleeding risk with subsequent IV
heparin; use with caution.
Subcutaneous low dose 4 to 6 hours or verify normal aPTT 1 hour

thromboprophylaxis (5000 units
subcutaneously twice per day or three
times per day)
Subcutaneous higher dose 12 hours and verify normal aPTT

thromboprophylaxis (7500 to 10,000
units subcutaneously twice per day,
total daily dose ≤20,000 units)
Subcutaneous therapeutic (individual 24 hours and verify normal aPTT

dose >10,000 units subcutaneously or
total daily dose >20,000 units
subcutaenously)
Low molecular weight heparin (LMWH) Delay LMWH 24 hours after traumatic Anti-Xa level is not predictive of the risk of
placement bleeding.
Do not use with antiplatelet or oral
anticoagulant medications as this
increases risk of spinal hematoma.
Assess platelet count prior to NA for
patients who have received LMWH >4
days; SOAP consensus statement and

European guidelines do not recommend
platelet count.
Therapeutic (subcutaneous) ≥24 hours, anti-factor Xa level may be ≥4 hours after catheter removal Do not use therapeutic dosing with
Enoxaparin 1 mg/kg every 12 helpful* catheter in place.
hours
Enoxaparin 1.5 mg/kg daily
Dalteparin 100 to 120 units/kg
every 12 hours
Dalteparin 200 units/kg daily
Tinzaparin 175 units/kg daily
Nadroparin 86 units/kg every 12
hours
Nadroparin 171 units/kg daily
Prophylactic (subcutaneous) ≥12 hours First postoperative dose ≥12 hours after Do not maintain epidural catheter with
Enoxaparin 30 mg every 12 hours neuraxial procedure; subsequent dose twice daily dosing.
Enoxaparin 40 mg daily ≥24 hours after the first dose Epidural catheter may be maintained with
Dalteparin 2500 to 5000 units For twice daily dosing: Remove catheter once daily dosing, without administration
daily >4 hours prior to first postoperative dose of any other antihemostatic drugs.
Tinzaparin 3500 units daily For single daily dose during continuous
Tinzaparin 50 to 75 units/kg daily epidural: Remove catheter 12 hours prior
Nadroparin 2850 units daily to next dose of LMWH, and subsequent
Nadroparin 38 units/kg daily dose should be >4 hours after removal
Anti-factor Xa inhibitors
Fondaparinux ASRA: not addressed 6 hours Do not administer with catheter in place.
European guidelines: 36 to 42 hours Remove catheter prior to first (European guidelines allow epidural
postoperative dose catheter with prophylactic dosing.)
Limited clinical experience.
Direct oral factor Xa inhibitors
Rivaroxaban 3 days or measure rivaroxaban specific 6 hours If unanticipated administration of

anti Xa level* Remove catheter prior to first rivaroxaban occurs with catheter in place,
postoperative dose withhold further doses and wait 22 to 26
hours to remove catheter, or measure
rivaroxaban specific anti-Xa level.
European guidelines: NA procedure or
catheter removal should occur ≥22 to 26
hours after last dose.
FDA: Delay first dose 24 hours after
traumatic puncture.
Apixaban 3 days or measure apixaban specific anti 6 hours If unanticipated administration of

Xa level* apixaban occurs with catheter in place,

Remove catheter prior to first withhold further doses and wait 26 to 30
postoperative dose hours to remove catheter, or measure
rivaroxaban specific anti-Xa level.*
FDA: Delay first dose ≥5 hours after
epidural catheter removal; Delay first
postoperative dose 48 hours after
traumatic puncture.
Edoxaban 3 days or measure edoxaban specific anti 6 hours If unanticipated administration of

Xa level* Remove catheter prior to first edoxaban occurs with catheter in place,
hours to remove catheter, or measure
edoxaban specific anti-Xa level.*
Betrixaban 3 days or measure betrixaban specific anti 5 hours Do not perform NA for patients with CrCl
Xa level* Remove catheter prior to first <30 mL/minute.
postoperative dose FDA: Delay first postoperative dose 72
hours after traumatic puncture.
Thrombin inhibitors
Dabigatran CrCl <30 mL/minute: avoid NA 6 hours If unanticipated administration of

CrCl 30 to 49 mL/minute: 5 days Remove catheter prior to first dabigatran occurs with catheter in place,
CrCl 50 to 79 mL/minute: 4 days
hours to remove catheter, or measure dTT
CrCl ≥80 mL/minute: 3 days or ecarin clotting time*.
Renal function unknown: 5 days May be reversed with idarucizumab if
necessary.
Argatroban Avoid neuraxial techniques
Hirudin derivatives (desirudin, Avoid neuraxial techniques

bivalirudin)
Antiplatelet medication
Platelet P2Y12 receptor blockers
Clopidogrel 5 to 7 days Without loading dose: immediate Neuraxial catheters can be maintained for
With loading dose: 6 hours 1 or 2 days if no loading dose will be
administered.
Prasugrel 7 to 10 days Without loading dose: immediate Neuraxial catheters should not be
With loading dose: 6 hours maintained after administration of
prasugrel.
Ticlopidine 10 days Without loading dose: immediate Neuraxial catheters can be maintained for
With loading dose: 6 hours 1 or 2 days if no loading dose will be
administered.
Ticagrelor 5 to 7 days Without loading dose: immediate Neuraxial catheters should not be
maintained after administration of
With loading dose: 6 hours ticagrelor.
Cangrelor 3 hours 8 hours

Remove catheter prior to first
postoperative dose
Platelet GP IIb/IIIa inhibitors Contraindicated for 4 weeks after surgery;

monitor neurologic status if given after
neuraxial technique.
Tirofiban 4 to 8 hours
Eptifibatide 4 to 8 hours
Abciximab 24 to 48 hours
Cilostazol 2 days 6 hours

Remove catheter ≥6 hours prior to first
postoperative dose
Dipyridamole 24 hours Remove catheter ≥6 hours prior to first

postoperative dose
Aspirin May continue dosage May continue dosage Affects platelet function for the life of the
platelet (up to 7 days). Avoid neuraxial
techniques on aspirin if early
postoperative use of other anti-
hemostatic drugs (including heparin) is
anticipated.
NSAIDs (nonsteroidal antiinflammatory May continue dosage May continue dosage Effect on platelet function normalizes
drugs) within 3 days. Avoid neuraxial techniques
on NSAIDs if early postoperative use of
other anti-hemostatic drugs (including
heparin) is anticipated. COX-2 inhibitors
(celecoxib) have minimal effect on platelet
function.
Herbal medications (garlic, ginkgo, May continue dosage May continue dosage Concurrent use with other anti-
ginseng) hemostatic drugs may increase bleeding
risk.
Recommendations in this table reflect those that appear in the guidelines of the ASRA fourth edition [1], unless otherwise specified.
INR: international normalized ration; PT: prothrombin time; aPTT: activated partial thromboplastin time; HIT: heparin-induced thrombocytopenia; IV: intravenous; NA: neuraxial
anesthesia; ASRA: American Society of Regional Anesthesia and Pain Medicine; FDA: US Food and Drug Administration; CrCl: creatine clearance; P2Y12: purinergic receptor P2Y.
* Safe levels other than zero have not been determined.
Data from:
1. Horlocker TT, Vandermeuelen E, Kopp SL, et al. Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy: American Society of Regional Anesthesia and Pain
Medicine Evidence-Based Guidelines (Fourth Edition). Reg Anesth Pain Med 2018; 43:263.
2. Gogarten W, Vandermuelen E, Van Aken H, et al. Regional anaesthesia and antithrombotic agents: recommendations of the European Society of Anaesthesiology. Eur J Anaesthesiol 2010;
27:999.
Graphic 87862 Version 7.0

Contributor Disclosures
Kenneth A Bauer, MD Consultant/Advisory Boards: BMS [Anticoagulation]; Takeda [Anticoagulation Reversal]. Lawrence LK Leung,
MD Nothing to disclose Charles J Lockwood, MD, MHCM Nothing to disclose Jennifer S Tirnauer, MD Nothing to disclose Vanessa A Barss,
MD, FACOG Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a
multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content
is required of all authors and must conform to UpToDate standards of evidence.
Conflict of interest policy

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20/05/2021 Use of anticoagulants during pregnancy and postpartum - UpToDate

Official reprint from UpToDate®

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Anticoagulants that are generally avoided during pregnancy

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WHEN TO START LMW HEPARIN

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ADMINISTRATION DURING PREGNANCY

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We use the following terminology to describe heparin anticoagulation dosing:

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Prophylactic and intermediate dose

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Monitoring of prophylactic or intermediate dose LMW heparin is not required.

Unfractionated heparin — Therapeutic dose unfractionated heparin is administered every 12 hours by subcutaneous

PREVENTION OF THROMBOSIS AND BLEEDING

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Suspected heparin-induced thrombocytopenia — Heparin-induced thrombocytopenia (HIT) is an adverse reaction to heparin

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LABOR AND DELIVERY

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POSTPARTUM AND BREASTFEEDING

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● Warfarin or other vitamin K antagonists

Continuation of low-dose aspirin for vascular indications is also suggested [14].

● Oral direct thrombin inhibitors (eg, dabigatran)

If anticoagulation is required during breastfeeding, another agent should be selected.

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Warfarin-associated bleeding — The management of excessive anticoagulation and/or bleeding in a pregnant woman on

● She has regular monthly menstrual cycles.

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SOCIETY GUIDELINE LINKS

SUMMARY AND RECOMMENDATIONS

• Inherited thrombophilia – (See "Inherited thrombophilias in pregnancy", section on 'Prevention of VTE'.)

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Use of heparins during pregnancy

Heparin Dose level Dose

LMW heparin Prophylactic* Enoxaparin 40 mg SC once daily

Dalteparin 5000 units SC once daily

Therapeutic Enoxaparin 1 mg/kg SC every 12 hours

Dalteparin 100 units/kg SC every 12 hours

Unfractionated heparin Prophylactic 5000 units SC every 12 hours

Intermediate ¶ First trimester: 5000 to 7500 units SC every 12 hours