Deep vein thrombosis and pulmonary embolism in pregnancy

Military Maternity Hospital28 September 2015

D.Kahtan Sbeqi

INTRODUCTIONPregnancy and the puerperium are

well-established risk factors for venous thromboembolism (VTE)

incidence of VTE ranging from 4 to 50 times higher in pregnant versus non-pregnant women

it an absolute incidence rate of 1 in 500 to 2000 pregnancies (0.025 to 0.10 percent)

more common postpartum than antepartum

DVT is far more common in the left than the right leg

PATHOGENESIS AND RISK FACTORSVirchow's triad :venous stasis, endothelial injury, and a hypercoagulable stateStasis :pregnancy-associated changes in venous

capacitance and compression of large veins by the gravid uterus

Endothelial injury:Delivery is associated with vascular

injury and changes at the uteroplacental surface

Forceps, vacuum extraction, or surgical delivery can exaggerate vascular intimal injury

Hypercoagulability:associated with progressive

increases in several coagulation factors, such as factors I, II, VII, VIII, IX, and X, along with a decrease in protein S

A progressive increase in resistance to activated protein C

Activity of the fibrinolytic inhibitors is increased during pregnancy

risk factors included cesarean section, premature delivery, or history of cardiac disease. Multiple births

The risk of deep vein thrombosis (DVT) is approximately twice as high after cesarean delivery than vaginal birth

In addition, DVT is far more common in the left than the right leg

increased venous stasis in the left leg related to compression of the left iliac vein by the right iliac artery, coupled with compression of the inferior vena cava by the gravid uterus itself

INHERITED THROMBOPHILIACommon inherited hypercoagulable stateFactor V Leiden mutationProthrombin gene mutationProtein S deficiency Protein C deficiencyAntithrombin deficiencyDysfibrinogenemiaACQUIRED THROMBOPHILIAinclude a prior thrombotic event, recent major

surgery, presence of a central venous catheter, trauma, immobilization, malignancy, pregnancy, the use of oral contraceptives or heparin, myeloproliferative disorders, and antiphospholipid syndrome (APS)

DIAGNOSIS :Clinical examinationLaboratory studies: D-dimer,low specificity, high

sensitivity Radiographic evaluation:  Deep vein thrombosis:Doppler ultrasound: less sensitive for calf vein

thrombosis (which is less common in the pregnant population) and pelvic vein thrombosis

Magnetic resonance imaging (MRI):The safety of MRI during pregnancy has not been proven

Ascending contrast venography:gold standard for the diagnosis of lower extremity DV, gold standard for the diagnosis of lower extremity DVT:delivered radiation to the fetus is small (<500 mcGy)

We recommend compression venous color Doppler ultrasound as the initial test in pregnant women with suspected DVT

Pulmonary embolism  negative examinations for DVT are not definitive because

fewer than 30 percent of unselected patients with PE have radiographic evidence of DVT at the time of presentation

CT angiography is the non-invasive study of choice for the diagnosis of pulmonary embolism in the non-pregnant population

the chest X-ray (CXR) is normal, V/Q scanning is more accurate

Because of the superior accuracy of V/Q scanning and lower maternal breast irradiation, there has been a movement away from CT angiography toward V/Q scanning as the diagnostic test of choice in the workup of pulmonary embolism in pregnancy in women with a negative CXR. In those patients with an abnormal CXR, CT angiography remains the test of choice.

The estimated fetal radiation exposure from the combination of a chest radiograph, V/Q scanning, and pulmonary arteriography is less than 0.5 mSv (50 mrad)

Deep vein thrombosis and pulmonary embolism in pregnancy: treatment

When there is a high clinical suspicion for acute PE, empiric anticoagulant therapy is indicated prior to the diagnostic evaluation. Anticoagulant therapy is discontinued if VTE is excluded

When there is suspicion for DVT alone (no clinical evidence or suspicion of acute PE), anticoagulant therapy is generally withheld until VTE is confirmed, assuming that diagnostic evaluation can be performed in a timely fashion

SC LMWH is preferred over IV UFH or SC UFH in most patients because it is easier to use and it appears to be more efficacious with a better safety profile.

In contrast, IV UFH is preferred in patients who have a markedly elevated risk of bleeding or persistent hypotension due to PE

short half-life and near complete reversal with protamine make it the most desirable anticoagulant if it needs to be discontinued due to bleeding or to perform a procedure

Dosing LMWH :initial doses of SC LMWH

include dalteparin 200 units/kg once daily, tinzaparin 175 units/kg once daily, or enoxaparin 1 mg/kg every 12 hours

The dose is then titrated to an anti-Xa level of 0.6 to 1.0 IU/mL for twice daily administration, or 1 to 2 IU/mL for once daily administration

IV UFH :Initial dosing of IV UFH consists of an IV UFH bolus of 80 units/kg, followed by a continuous infusion of 18 units/kg per hour

The infusion is titrated every six hours to achieve a therapeutic activated partial thromboplastin time (aPTT)

SC UFH — A reasonable initial dose of SC UFH is 17,500 units every 12 hours

Labor and deliveryTreatment with SC LMWH or SC UFH should be

discontinued 24 to 36 hours prior to delivery if the delivery time is predictable (induction of labor, planned cesarean section)

patients may benefit from having their SC LMWH or SC UFH switched to IV UFH, which can be discontinued 4 to 6 hours prior to delivery

Neuraxial anesthesia should not be administered to an anticoagulated patient

In cases in which preterm delivery is anticipated (eg, triplets, preterm rupture of membranes, significant cervical dilation, preeclampsia, growth restriction), it is common to discontinue SC LMWH or SC UFH at 36 weeks of gestation. IV UFH is then used instead

After deliveryA heparin regimen (SC LMWH, IV UFH, or SC

UFH) should be restarted 12 hours after a cesarean delivery or 6 hours after a vaginal birth

If warfarin therapy is chosen, the patient should receive both warfarin and heparin for at least five days

The heparin should not be stopped until the (INR) has been within therapeutic range (usually 2 to 3) for two consecutive days

Length of therapy — Anticoagulant therapy generally continues for at least six weeks postpartum

a total duration of anticoagulant therapy of at least six months for women whose only risk factors for VTE were transient (eg, pregnancy)

Deep vein thrombosis and pulmonary embolism in pregnancy: Prevention

Thromboprophylaxis can be pharmacologic (ie, anticoagulation) or mechanical (eg, graduated compression stockings)

The indications for thromboprophylaxis differ for antepartum and postpartum women

Antepartum :The 2008 American College of Chest Physicians (ACCP) guidelinesSingle prior episode of VTE plus a

higher risk thrombophiliaMultiple prior episodes of VTEAntithrombin deficiency

In contrast, the benefits, risks, and burdens of thromboprophylaxis should be carefully weighed: Single prior episode of VTE that was related to

pregnancy or estrogen use (eg, contraceptives)

Single prior episode of idiopathic VTESingle prior episode of VTE in a patient with

thrombophilia that is not considered higher risk

Higher risk thrombophilias :antithrombin deficiency, persistent antiphospholipid antibodies, compound heterozygosity for the prothrombin and factor V Leiden mutations, homozygosity for the prothrombin mutation, and homozygosity for the factor V Leiden mutation

Postpartum :There is generally a lower threshold for initiating thromboprophylaxis during the postpartum period, compared with during pregnancyPostpartum thromboprophylaxis is

indicated for women who have had one or more episodes of VTE

who have any type of thrombophilia, even those that are not considered higher risk

Cesarean section :thromboprophylaxis is NOT recommended for women whose only risk factors for VTE are the pregnancy and CS

Thromboprophylaxis may be warranted for women who have risk factors for VTE in addition to the pregnancy and CSThe ACCP guidelines for VTE and pregnancy

suggest the following for women who have undergone cesarean section

Women who have only one additional risk factor for VTE should receive either thromboprophylaxis, graduated compression stockings, or a pneumatic compression device while in the hospital following delivery

Women who have multiple additional risk factors for VTE should receive thromboprophylaxis plus graduated compression stockings and/or pneumatic compression devices while in the hospital following delivery

REGIMENS Low molecular weight heparininclude dalteparin 5000 units once

daily, dalteparin 5000 units every 12 hours, tinzaparin 4500 units once daily, enoxaparin 40 mg once daily, or enoxaparin 40 mg every 12 hours.

Unfractionated heparinFixed dose: SC UFH 5000 units every 12

hoursWarfarin :It should be initiated at the

same time or after heparin is started because warfarin alone is associated with an increased incidence of VTE

Choosing a regimen LMWH-based regimens are generally

preferred for antepartum thromboprophylaxis for several reasons

LMWH is effective and safe in pregnant women

DURATION :Antepartum thromboprophylaxis should be continued through the pregnancyIt is generally discontinued 24 to 36 hours

prior to deliveryThe optimal duration of postpartum

thromboprophylaxis is uncertain. Several clinical practice guidelines suggest four to six weeks on the basis of clinical experience

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