Venous Thrombosis in Pregnancy

Vicky Tagalakis, MD MSCVicky Tagalakis, MD MSC

General Internal MedicineGeneral Internal Medicine

Academic RoundsAcademic Rounds

September 8, 2009September 8, 2009

Objectives

1.1. Facts about VTE in pregnancyFacts about VTE in pregnancy

2.2. VTE diagnostic modalities in pregnancyVTE diagnostic modalities in pregnancy

3.3. Treatment of VTE in pregnancyTreatment of VTE in pregnancy

4.4. Thrombophilia in pregnancy?Thrombophilia in pregnancy?

5.5. Thromboprophylaxis during pregnancy?Thromboprophylaxis during pregnancy?

VTE in pregnancy Pregnant women are at an increased risk for venous Pregnant women are at an increased risk for venous

thromboembolic disease (VTE)thromboembolic disease (VTE) 1 in 1000 pregnancies1 in 1000 pregnancies 2-4 fold increase compared to non-pregnant state2-4 fold increase compared to non-pregnant state Cesarian delivery > vaginal deliveryCesarian delivery > vaginal delivery 2/3 of DVT occur antepartum (equally distributed among all 2/3 of DVT occur antepartum (equally distributed among all

three trimesters)three trimesters) 43-60% of PE occur 4-6 weeks after delivery43-60% of PE occur 4-6 weeks after delivery Daily riskDaily risk of PE and DVT highest following delivery than of PE and DVT highest following delivery than

antepartumantepartum PE is the major non-obstetric cause of maternal mortalityPE is the major non-obstetric cause of maternal mortality

2/100 000 pregnancies2/100 000 pregnancies

Case scenario #1

34 year old woman 24 weeks pregnant who reports 34 year old woman 24 weeks pregnant who reports non-productive cough, SOBOE, and pleuritic non-productive cough, SOBOE, and pleuritic chest pain of 3 days duration. Sick 2 year old at chest pain of 3 days duration. Sick 2 year old at home. She has had 2 prior uncomplicated home. She has had 2 prior uncomplicated pregnancies. She has a history of a prior DVT post pregnancies. She has a history of a prior DVT post surgery for an ankle fracture repair.surgery for an ankle fracture repair.

90% of DVT during pregnancy occurs on 90% of DVT during pregnancy occurs on the left side.the left side.

A significant proportion of DVT in A significant proportion of DVT in pregnancy occurs in the pelvic veins and pregnancy occurs in the pelvic veins and therefore, may not be picked up by routine therefore, may not be picked up by routine testing.testing.

Ovarian vein thrombosis can also occur. Ovarian vein thrombosis can also occur.

DVT facts

Why is the risk greater in pregnancy?

PathopsysiologyPathopsysiology Increased venous capacity (estrogen)Increased venous capacity (estrogen) Increased plasma volumeIncreased plasma volume Compression of IVCCompression of IVC Increased levels of coagulation factors Increased levels of coagulation factors

(fibrinogen, factor VII)(fibrinogen, factor VII) Decreased levels of natural anticoagulants Decreased levels of natural anticoagulants

(protein S)(protein S) Acquired protein C resistanceAcquired protein C resistance

Independent risk factors of a higher VTE risk in pregnancy?

Bed restBed rest Multiparity Multiparity Advanced maternal age (>35 yo)Advanced maternal age (>35 yo) OverweightOverweight Personal or family history of VTEPersonal or family history of VTE PreeclampsiaPreeclampsia

Case scenario #1

34 year old woman 14 weeks pregnant who reports non-34 year old woman 14 weeks pregnant who reports non-productive cough, SOBOE, and pleuritic chest pain. Sick 2 year productive cough, SOBOE, and pleuritic chest pain. Sick 2 year old at home.She has a history of a prior DVT post surgery for an old at home.She has a history of a prior DVT post surgery for an ankle fracture repair.ankle fracture repair.

Physical examPhysical exam

BP 105/80, HR 95, OBP 105/80, HR 95, O22 Sat 91% on RA, T 37.8 Sat 91% on RA, T 37.8°°CC

Mild bilateral leg swellingMild bilateral leg swelling

Decreased a/e at basesDecreased a/e at bases

VTE presentation in pregnancy

Leg symptoms, chest pain, and dyspnea are Leg symptoms, chest pain, and dyspnea are common in pregnancy.common in pregnancy.

Swelling, tenderness, skin discoloration, warm to Swelling, tenderness, skin discoloration, warm to touch, unusual firmness/hardness, cord, pain on touch, unusual firmness/hardness, cord, pain on

dorsiflexiondorsiflexion Tachycardia may be a normal physiologic Tachycardia may be a normal physiologic

response.response. ABG and A-a gradient are often normal. ABG and A-a gradient are often normal.

Diagnosis of VTE in pregnancy: challenges

Clinical diagnosis by itself is unreliable.Clinical diagnosis by itself is unreliable. In symptomatic pregnant patients, DVT and PE are In symptomatic pregnant patients, DVT and PE are

less prevalent than in non-pregnant patients.less prevalent than in non-pregnant patients. Anticoagulant treatment is highly effective but carries Anticoagulant treatment is highly effective but carries

risks.risks. Untreated VTE can result in fatal and non fatal PE.Untreated VTE can result in fatal and non fatal PE. Hence, when VTE is suspected, it is essential to Hence, when VTE is suspected, it is essential to

diagnose it when present and exclude it when absent.diagnose it when present and exclude it when absent.

Diagnosis of VTE in pregnancy: challenges

The common diagnostic tests have not been studied The common diagnostic tests have not been studied in pregnant women, and hence not appropriately in pregnant women, and hence not appropriately validated for this populationvalidated for this population

D-dimer assays and DVT/PE clinical prediction rules D-dimer assays and DVT/PE clinical prediction rules have not been validated in the pregnant populationhave not been validated in the pregnant population

……..and what about the issue of both radiation ..and what about the issue of both radiation exposure to the fetus with diagnostic testing???exposure to the fetus with diagnostic testing???

Diagnosis of VTE in pregnancy: challenges

It is important to avoid ionizing radiation It is important to avoid ionizing radiation exposure whenever possible during exposure whenever possible during pregnancy, but the risks of undiagnosed PE pregnancy, but the risks of undiagnosed PE are much greater than any theoretical risk to are much greater than any theoretical risk to the fetus from diagnostic testingthe fetus from diagnostic testing

DVT and PE - Investigation

CUS, IPG, and venography can be done safely and with CUS, IPG, and venography can be done safely and with reliable results in pregnancy.reliable results in pregnancy.

Ventilation perfusion scans and pulmonary angiograms Ventilation perfusion scans and pulmonary angiograms can be done safely during pregnancy.can be done safely during pregnancy.

Pelvic vein ultrasound, CT scan and MRI are all tests that Pelvic vein ultrasound, CT scan and MRI are all tests that can be used to look for pelvic clot.can be used to look for pelvic clot.

CT angiography can be done in pregnancy (risk of CT angiography can be done in pregnancy (risk of congenital hypothyroidism in first trimester)congenital hypothyroidism in first trimester)

IVC filters can be placed in pregnancy.IVC filters can be placed in pregnancy.

Risk of radiologic procedures to the fetus Radiation exposure of up to 0.05 Gy (5 rad) in Radiation exposure of up to 0.05 Gy (5 rad) in

utero:utero: Oncogenicity Oncogenicity

Relative risks of 1.2-2.4Relative risks of 1.2-2.4 Absolute risk of malignancy (baseline) in fetus Absolute risk of malignancy (baseline) in fetus

is estimated to be 0.1%. is estimated to be 0.1%. TetratogenicityTetratogenicity

No increase in pregnancy loss, growth or No increase in pregnancy loss, growth or mental retardationmental retardation

CT angiography: 0.013- 0.0026 (rads)

Techniques to lower radiation exposure during

Circumferential screening of the abdomen and pelvis (CTPA)Circumferential screening of the abdomen and pelvis (CTPA) Duration of scanning reduced (CTPA)Duration of scanning reduced (CTPA) Half-dose (perfusion) techniques (VQ scan)Half-dose (perfusion) techniques (VQ scan) If perfusion is normal, then ventilation scan unnecessary (PE If perfusion is normal, then ventilation scan unnecessary (PE

excluded)excluded)

***Please note that even if a pregnant woman underwent a CXR, ***Please note that even if a pregnant woman underwent a CXR, followed by a VQ scan, then CTPA, and then pulmonary followed by a VQ scan, then CTPA, and then pulmonary angiogram, the combined fetal radiation dose would still be less angiogram, the combined fetal radiation dose would still be less than that obtained via background radiation during the nine than that obtained via background radiation during the nine months of pregnancy!months of pregnancy!

Case scenario #1

WBC 14 with neutrophilia.WBC 14 with neutrophilia.

Platelets are normal. Platelets are normal.

CXR: RLL atelectatic changesCXR: RLL atelectatic changes

ABG shows an increased aA gradient.ABG shows an increased aA gradient.

Fig. 2. Algorithm for clinically suspected pulmonary embolism in pregnancy. PE, pulmonary embolism; CT, computed tomography; PA, pulmonary angiography; HP, high probability; CUS, compression ultrasonography. *ND, non-diagnostic result. Non-diagnostic results are those that indicate an intermediate or low-probability of pulmonary embolism, or that do not indicate a high probability.

CTPA

Nijkeuter et al, JTH 2008

Scarsbrook et al, Clinical Radiology, 2007

Diagnosis of DVT: Algorithm

VTE Treatment

VTE treatment LMWH LMWH preferredpreferred based on better safety profile, based on better safety profile,

reliable pharmacokinetics, more practical, and as reliable pharmacokinetics, more practical, and as effective as UFHeffective as UFH

Largely based on studies in non-pregnant populationLargely based on studies in non-pregnant population

Widespread use over the last 10-15 years in pregnant women Widespread use over the last 10-15 years in pregnant women have shown that LMWHs are as effective and safer than UFH have shown that LMWHs are as effective and safer than UFH (less HIT and less osteoporosis than UFH)(less HIT and less osteoporosis than UFH)

Does not cross placenta!Does not cross placenta!

VTE treatments: other options UFHUFH

Initial IV UFH therapy followed by UFH bid sc dosing Initial IV UFH therapy followed by UFH bid sc dosing (adjusted weekly to achieve target PTT (60-80 sec) 6H after (adjusted weekly to achieve target PTT (60-80 sec) 6H after injection). Weekly surveillanceinjection). Weekly surveillance

VKAVKA Teratogenicity Teratogenicity (coumarin embryonopathy: nasal hypoplasia and/or stippled (coumarin embryonopathy: nasal hypoplasia and/or stippled

epiphyses); observed only duirng 6-12 weeks of gestation (Chan et al, studied 549 epiphyses); observed only duirng 6-12 weeks of gestation (Chan et al, studied 549 live births; VKA through out preg vs. UFH 6-12 weeks then VKA vs. UFH live births; VKA through out preg vs. UFH 6-12 weeks then VKA vs. UFH throughout pregnancy)throughout pregnancy)

CNS abnormalitiesCNS abnormalities during any trimester (corpus callosum agenesis; midline during any trimester (corpus callosum agenesis; midline cerebellar atrophy); very rare and questionable associationcerebellar atrophy); very rare and questionable association

Fetal hemorrhagic complicationsFetal hemorrhagic complications especially at delivery due to prolonged especially at delivery due to prolonged anticoagulant effect of warfarin as a result of fetal liver being immature and hence anticoagulant effect of warfarin as a result of fetal liver being immature and hence fetal levels of vit K dependent coag factors are low.fetal levels of vit K dependent coag factors are low.

?role in pregnant women with mechanical prosthetic valves at high risk for ?role in pregnant women with mechanical prosthetic valves at high risk for embolization (i.e. previous CVA)embolization (i.e. previous CVA)

VTE treatments: other options FondaparinuxFondaparinux

Anti Xa activity found in plasma umbilical cord of 6 women Anti Xa activity found in plasma umbilical cord of 6 women treated with fondaparinuxtreated with fondaparinux

For now, avoid general use and reserve for pregnant women For now, avoid general use and reserve for pregnant women with HIT or a history of HIT who cannot receive danaproidwith HIT or a history of HIT who cannot receive danaproid

Danaproid Danaproid In vitro data shows placenta crossing but…In vitro data shows placenta crossing but… No detectable anti Xa activity in plasma umbilical cord of the No detectable anti Xa activity in plasma umbilical cord of the

few women wolr-wide that have been treated with danaproid.few women wolr-wide that have been treated with danaproid.

DTIsDTIs No human data!No human data!

DVT and PE – Treatment

CHEST 2008 recommendations:CHEST 2008 recommendations: Treatment of acute DVT/PE in pregnancyTreatment of acute DVT/PE in pregnancy

Adjusted doseAdjusted dose LMWH thru pregnancy LMWH thru pregnancy

OR (but less preferred)OR (but less preferred)

weight-based intravenous UFH protocol for 5 weight-based intravenous UFH protocol for 5 days, then adjusted dose UFH (PTT mid-interval days, then adjusted dose UFH (PTT mid-interval of 60-80 secs; weekly surveillance).of 60-80 secs; weekly surveillance).

LMWH: adjust dose during pregnancy? LMWH requirements may alter as pregnancy progresses ( volume of LMWH requirements may alter as pregnancy progresses ( volume of

distribution of LMWH changes and GFR increases in second trimester)distribution of LMWH changes and GFR increases in second trimester)

Hence, some suggest that dose should change as weight changes Hence, some suggest that dose should change as weight changes (based on small studies that support dose escalation to achieve (based on small studies that support dose escalation to achieve “therapeutic anti Xa levels”)“therapeutic anti Xa levels”) Adjusted doseAdjusted dose LMWH thru pregnancy LMWH thru pregnancy

adjust as weight adjust as weight , or adjust to anti Xa level 0.5-1.2 U/ml (every 1-3 , or adjust to anti Xa level 0.5-1.2 U/ml (every 1-3 months blood test, 4 hrs after last dose) (bid vs qd dosing)months blood test, 4 hrs after last dose) (bid vs qd dosing)

Others have demonstrated that few women require dose adjustment Others have demonstrated that few women require dose adjustment when therapeutic LMWH doses are givenwhen therapeutic LMWH doses are given

Controversial; ACCP does not give any recommendations

At time of delivery D/C LMWH (or UFH sc) 24 hrs. prior to elective inductionD/C LMWH (or UFH sc) 24 hrs. prior to elective induction

If very high risk of recurrence (eg, PE or DVT within 2-4 weeks If very high risk of recurrence (eg, PE or DVT within 2-4 weeks of expected delivery), IV UFH can be initiated and d/c 4-6 hours of expected delivery), IV UFH can be initiated and d/c 4-6 hours prior to delivery; in addition, a temporary IVC filter can be prior to delivery; in addition, a temporary IVC filter can be insertedinserted

If spontaneous labour occurs while receiving If spontaneous labour occurs while receiving adjusted-dose SC adjusted-dose SC UFHUFH, monitor PTT and if prolonged give protamine , monitor PTT and if prolonged give protamine

If spontaneous labor occurs while If spontaneous labor occurs while receiving LMWHreceiving LMWH, , anticoagulant effect depends on timing of last dose. anticoagulant effect depends on timing of last dose.

Avoid epiduralAvoid epidural Protamine can be consideredProtamine can be considered

Postpartum management

Re-start anticoagulation within 8-12 hours of Re-start anticoagulation within 8-12 hours of delivery (consult with obstetrician)delivery (consult with obstetrician)

LMWH or coumadin for 6 weeks after deliveryLMWH or coumadin for 6 weeks after delivery

For a minimum total duration of 6 monthsFor a minimum total duration of 6 months

Fetal complications during pregnancy Heparins and LMWHHeparins and LMWH

Heparins and UFH do not cross placentaHeparins and UFH do not cross placenta Uteroplacental bleeding possible but very rareUteroplacental bleeding possible but very rare

WarfarinWarfarin Risk of embryopathy (nasal hypoplasia) (6-12 Risk of embryopathy (nasal hypoplasia) (6-12

weeks of gestation)weeks of gestation) CNS abnormalities in any trimesterCNS abnormalities in any trimester Anticoagulant effect in fetus (**at delivery)Anticoagulant effect in fetus (**at delivery)

Maternal complications of anticoagulant therapy BleedingBleeding

2% risk with UFH2% risk with UFH Very uncommon with LMWHVery uncommon with LMWH

Heparin induced osteoporosisHeparin induced osteoporosis 2.2% incidence of vertebral fracture with UFH (>1 2.2% incidence of vertebral fracture with UFH (>1

month) month) Uncommon with LMWHUncommon with LMWH

HIT HIT 3% risk with UFH3% risk with UFH suspect HIT if platelets <100 or 50% of baseline value 5-suspect HIT if platelets <100 or 50% of baseline value 5-

15 days after commencing UFH15 days after commencing UFH Uncommon with LMWHUncommon with LMWH

Nursing mother

Heparin and warfarinHeparin and warfarin not secreted into breast milk. not secreted into breast milk.

LMWHLMWH: small amounts may be secreted into breast milk but not : small amounts may be secreted into breast milk but not absorbed by infant and no anticoagulant effect in breast-fed absorbed by infant and no anticoagulant effect in breast-fed infantinfant

DanaproidDanaproid: case reports +/- passage into breast milk; no : case reports +/- passage into breast milk; no anticoagulant effect in infantanticoagulant effect in infant

Fondaparinux and DTIsFondaparinux and DTIs: unknown: unknown

Prevention of VTE during pregnancy How do we evaluate women with an How do we evaluate women with an

increased risk of VTE?increased risk of VTE?

Prior history of VTEPrior history of VTE

Thrombophilia without a prior history of Thrombophilia without a prior history of VTEVTE

Case scenario #2

28 year old woman who is 10 weeks pregnant is 28 year old woman who is 10 weeks pregnant is referred to you to assess the need for DVT referred to you to assess the need for DVT prophylaxis. She has a history of a prior DVT. She prophylaxis. She has a history of a prior DVT. She is currently not on any anticoagulants. She feels is currently not on any anticoagulants. She feels well otherwise.well otherwise.

Thromboprophylaxis during pregnancy and postpartum

How we manage pregnant women who have a high risk of VTE

Women with a history of VTE have a higher risk of recurrence with Women with a history of VTE have a higher risk of recurrence with subsequent pregnancy (1-13% risk of recurrence)subsequent pregnancy (1-13% risk of recurrence)

Risk dependent on Risk dependent on naturenature of VTE risk factor, presence or absence of of VTE risk factor, presence or absence of thrombophiliathrombophilia, and (, and (numbernumber of previous VTEs). of previous VTEs).

N=125 women with a single previous VTE who only received N=125 women with a single previous VTE who only received prophylaxis in ppp for 4-6 weeks (Brill-Edwards, NEJM 2000)prophylaxis in ppp for 4-6 weeks (Brill-Edwards, NEJM 2000)

3/125 had antepartum recurrence (2.4%, 95% CI 0.2-6.9%) and 3/125 had antepartum recurrence (2.4%, 95% CI 0.2-6.9%) and 3/125 had ppp VTE recurrence3/125 had ppp VTE recurrence

Post hoc analysis: women without thrombophilia and a VTE Post hoc analysis: women without thrombophilia and a VTE associated with a temporary risk factor were at low risk for associated with a temporary risk factor were at low risk for recurrence (0%)recurrence (0%)

Single prior VTE

1.1. VTE associated with VTE associated with transient risk factortransient risk factor: clinical : clinical surveillance and pp prophylaxis for 6 weekssurveillance and pp prophylaxis for 6 weeks

2.2. VTE associated with VTE associated with pregnancy or estrogen-relatedpregnancy or estrogen-related or or there are additional risk factors (eg. obesity) clinical there are additional risk factors (eg. obesity) clinical surveillance and pp prophylaxis for 6 weeks OR antenatal surveillance and pp prophylaxis for 6 weeks OR antenatal with pp prophylaxis for 6 weekswith pp prophylaxis for 6 weeks

LMWH (dalteparin 5000u q24 hrs or enoxaparin 40mg sc q24hrs)LMWH (dalteparin 5000u q24 hrs or enoxaparin 40mg sc q24hrs) Mini-dose UFH SC (5000 U SC bid) vs intermediate dose UFH Mini-dose UFH SC (5000 U SC bid) vs intermediate dose UFH

SC (10 000 sc bid)SC (10 000 sc bid)

Single prior VTE3.3. Idiopathic VTEIdiopathic VTE: antenatal and pp prophylaxis (4-6 weeks pp) : antenatal and pp prophylaxis (4-6 weeks pp)

OR clinical surveillance and pp prophylaxisOR clinical surveillance and pp prophylaxis Prophylactic dose LMWH Prophylactic dose LMWH Mini- or moderate-dose UFH SC Mini- or moderate-dose UFH SC

4.4. With thrombophiliaWith thrombophilia: antenatal and pp prophylaxis (4-6 : antenatal and pp prophylaxis (4-6 weeks pp) OR clinical surveillance and pp prophylaxisweeks pp) OR clinical surveillance and pp prophylaxis

Prophylactic dose LMWH (eg. dalteparin 5000u q12 Prophylactic dose LMWH (eg. dalteparin 5000u q12 hours)hours)

Mini- or moderate-dose UFH SCMini- or moderate-dose UFH SC

Single prior VTE

5.5. With “higher risk” thrombophiliaWith “higher risk” thrombophilia: antenatal and pp : antenatal and pp prophylaxis (4-6 weeks pp) prophylaxis (4-6 weeks pp)

Prophylactic dose LMWH (eg. dalteparin 5000u q12 Prophylactic dose LMWH (eg. dalteparin 5000u q12 hours)hours)

Mini- or moderate-dose UFH SCMini- or moderate-dose UFH SC

APLA, ATIII deficiency, compound heterozygote PT/FVL, APLA, ATIII deficiency, compound heterozygote PT/FVL, or homozygosity for FVL or PTor homozygosity for FVL or PT

Multiple episodes of VTE

(or those on long-term anticoagulation)(or those on long-term anticoagulation)

Prophylactic, vs. intermediate, vs. adjusted dose Prophylactic, vs. intermediate, vs. adjusted dose LMWH (or UFH)LMWH (or UFH)

PP prophylaxis for 6 weeks, consider long-term PP prophylaxis for 6 weeks, consider long-term anticoagulants, or resumption of long-term anticoagulants, or resumption of long-term anticoagulantsanticoagulants

For all women with prior DVT..

Consider compression stockings during Consider compression stockings during pregnancy and ppppregnancy and ppp reduce risk of PTSreduce risk of PTS

Do you adjust LMWH prophylaxis dosing in pregnancy?

The need to adjust according to anti-Xa levels is The need to adjust according to anti-Xa levels is very controversialvery controversial Appropriate “therapeutic range” for Appropriate “therapeutic range” for

prophylaxis is not known prophylaxis is not known It has not been shown that dose adjustment to It has not been shown that dose adjustment to

attain specific anti-Xa level increases safety or attain specific anti-Xa level increases safety or efficacy.efficacy.

Thrombophilia with no history of prior VTE

50% of gestational VTEs occur in women with an underlying 50% of gestational VTEs occur in women with an underlying thrombophilic disorderthrombophilic disorder

AT 3 deficient: OR = 8-13.1AT 3 deficient: OR = 8-13.1 FVL Homozygote: OR = 6.9-8.7FVL Homozygote: OR = 6.9-8.7 PT Homozygote: OR 1.8-9.5PT Homozygote: OR 1.8-9.5 Double FVL/PT mutations: OR=15Double FVL/PT mutations: OR=15

Antenatal and pp prophylaxis is recommended in women Antenatal and pp prophylaxis is recommended in women without a prior VTE and with any of the above disorders.without a prior VTE and with any of the above disorders.

For women without prior VTE and who have less For women without prior VTE and who have less thrombogenic thrombophilias, clinical surveillance and pp thrombogenic thrombophilias, clinical surveillance and pp prophylaxisprophylaxis

Antiphospholipid Antibodies

Lupus anticoagulant/non-specific inhibitorLupus anticoagulant/non-specific inhibitor Anticardiolipin antibodiesAnticardiolipin antibodies

Convincing evidence of an association with increased Convincing evidence of an association with increased risk of thrombosis and pregnancy loss (less so with risk of thrombosis and pregnancy loss (less so with preeclampsia, abruptio, IUGR)preeclampsia, abruptio, IUGR)

But how to manage during pregnancy…not clear?But how to manage during pregnancy…not clear? Prednisone not usefulPrednisone not useful ASA with LMWH (UFH) is likely the best ASA with LMWH (UFH) is likely the best

combination (outcomes: fetal loss, pregnancy combination (outcomes: fetal loss, pregnancy complications, VTE)complications, VTE)

Management of pregnant women with APLAs

Positive APLAs and hx of 2 or more early pregnancy losses or Positive APLAs and hx of 2 or more early pregnancy losses or one or more late pregnancy losses, IUGR, preeclampsia, or one or more late pregnancy losses, IUGR, preeclampsia, or abruptioabruptio Antepartum ASA plus prophylactic LMWHAntepartum ASA plus prophylactic LMWH Antepartum ASA plus minidose or moderate dose UFHAntepartum ASA plus minidose or moderate dose UFH

Positive APLAs and hx of VTE are usually receiving long-term Positive APLAs and hx of VTE are usually receiving long-term anticoagulation bc of high risk of recurrenceanticoagulation bc of high risk of recurrence Antepartum adjusted dose LMWH (or UFH) plus ASAAntepartum adjusted dose LMWH (or UFH) plus ASA Long-term oral anticoagulation postpartumLong-term oral anticoagulation postpartum

Positive APLAs and no hx of pregnancy complications or VTEPositive APLAs and no hx of pregnancy complications or VTE Clinical surveillanceClinical surveillance Minidose UFHMinidose UFH Prophylactic LMWHProphylactic LMWH

and/or asa?

Prevention of pregnancy complications in women with non-APLA thrombophilia? Data support weak associations between Data support weak associations between

thrombophilias (FVL, PT mutation) and adverse thrombophilias (FVL, PT mutation) and adverse pregnancy outcomes (early (recurrent) preg loss, pregnancy outcomes (early (recurrent) preg loss, preeclampsia, IUGR)preeclampsia, IUGR)

But, clinical studies with LMWH or UFH vs. placebo But, clinical studies with LMWH or UFH vs. placebo (no drug) in women with a history of adverse (no drug) in women with a history of adverse pregnancy outcomes and non-APLA thrombophilias do pregnancy outcomes and non-APLA thrombophilias do not show improved pregnancy outcomes.not show improved pregnancy outcomes.

C-section and the risk of VTE?

Risk 0.4/1000 (c-section) vs. 0.2/1000 (vaginal Risk 0.4/1000 (c-section) vs. 0.2/1000 (vaginal delivery)delivery)

Not standard of care to thromboprophylaxNot standard of care to thromboprophylax Thrombosis risk assessment to determine need for Thrombosis risk assessment to determine need for

prophylaxis (grade 2C)prophylaxis (grade 2C) If no additional thrombosis risk factor, no prophylaxisIf no additional thrombosis risk factor, no prophylaxis If additional risk factors (eg. prior VTE, lower limb If additional risk factors (eg. prior VTE, lower limb

paralysis, thrombophilia, extended surgery such as paralysis, thrombophilia, extended surgery such as hysterectomy, preeclampsia, obesity, increased age, hysterectomy, preeclampsia, obesity, increased age, heart failure), then…heart failure), then…

C-section and the risk of VTE?

Prophylaxis doses of LMWH or UFH +/- Prophylaxis doses of LMWH or UFH +/- stockings while in hospital following stockings while in hospital following delivery (grade 2C) and perhaps for 6 delivery (grade 2C) and perhaps for 6 weeks pp if important risk factors persist weeks pp if important risk factors persist (grade 2C). (grade 2C).