Pulmonary Embolus in Pregnancy Case File
Eugene C. Toy, MD, Patti Jayne Ross, MD, Benton Baker III, MD, John C. Jennings, MD
CASE 15
A 19-year-old G1P0 woman at 20 weeks’ gestation complains of the acute onset of pleuritic chest pain and severe dyspnea. She denies a history of reactive airway disease or cough. She has no history of trauma. On examination, her temperature is 98°F (36.6°C), heart rate (HR) is 120 beats per minute (bpm), blood pressure (BP) is 130/70 mm Hg, and respiratory rate (RR) is 40 breaths per minute. The lung examination reveals clear lungs bilaterally. The heart examination shows tachycardia. The fetal heart tones are in the range of 140 to 150 bpm. The oxygen saturation level is 89%. Supplemental oxygen is given.
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ANSWER TO CASE 15:
Pulmonary Embolus in Pregnancy
Summary: A 19-year-old G1P0 woman at 20 weeks’ gestation complains of the acute onset of pleuritic chest pain and severe dyspnea. On examination, her HR is 120 bpm and RR is 40 breaths per minute. The lung examination reveals clear lungs bilaterally. The oxygen saturation is low.
- Test most likely to lead to the diagnosis: Spiral computed tomography or ventilation/ perfusion (V/ Q) imaging of the lungs.
- Concern: Pulmonary embolism.
ANALYSIS
Objectives
- Understand that pleuritic chest pain and severe dyspnea are common presenting symptoms of pulmonary embolism.
- Know that the pregnant woman is predisposed to deep venous thrombosis due to venous obstruction and a hypercoagulable state.
- Understand that the spiral computed tomography (CT) or V/Q imaging scan is an initial diagnostic test for pulmonary embolism.
Considerations
This 19-year-old woman at 20 weeks’ gestation complains of the acute onset of severe dyspnea and pleuritic chest pain. The physical examination confirms respiratory distress due to tachycardia and tachypnea. The lungs are clear on auscultation, and the patient does not complain of cough or fever, which rules out reactive airway disease or significant pneumonia. Clear lungs also speak against pulmonary edema. The patient has significant hypoxia with oxygen saturation of 89%, which translates to a partial pressure of 58 mm Hg (life-threatening). Thus, the most likely diagnosis is pulmonary embolism. Although many diagnostic tests should be considered in the initial evaluation of a patient with respiratory distress (such as arterial blood gas, chest radiograph, electrocardiograph), in this case, a CT pulmonary angiogram (CTPA), also referred to as spiral/ helical CT, or ventilation-perfusion (V/ Q) scan would likely lead to the diagnosis. The D-dimer assay may also be used in nonpregnant patients with a low pretest probability for pulmonary embolism (PE). The test has been shown to have a good negative predictive value, making it useful in ruling out pulmonary embolism if negative. However, since an elevated D-dimer level is normally found in pregnant patients, the assay would have limited value in this case.
If the imaging confirms pulmonary embolism, then the patient should receive anticoagulation to help stabilize the clot and decrease the likelihood of further venous thromboembolism. Pregnancy itself leads to an increased risk for thromboembolism by causing venous stasis and decreased outflow due to the mechanical effect of the uterus on the vena cava; additionally, the high estrogen levels induce a hypercoagulable state due to the increase in clotting factors, particularly fibrinogen.
APPROACH TO:
Respiratory Distress in Pregnancy
DEFINITIONS
DEEP VENOUS THROMBOSIS: Blood clot involving the deep veins of the lower extremity, rather than just the superficial involvement of the saphenous system.
PULMONARY EMBOLUS: Blood clot that is lodged in the pulmonary arterial circulation, usually arising from a thrombus of the lower extremity or pelvis.
HELICAL COMPUTED TOMOGRAPHY PULMONARY ANGIOGRAM: High-resolution imaging using intravenous (IV) contrast with multiple sections to allow for three-dimensional analysis and examination for vascular filling defects in the pulmonary vasculature.
MAGNETIC RESONANCE ANGIOGRAPHY: High-resolution magnetic resonance imaging using IV contrast to assess for vascular defects, typically not used in pregnancy due to the gadolinium.
VENTILATION-PERFUSION SCAN IMAGING PROCEDURE: Using a small amount of intravenous, radioactively tagged albumin, such as technetium, in conjunction with a ventilation imaging, with inhaled xenon or technetium, in an effort to find large ventilation-perfusion mismatches suggestive of pulmonary embolism.
DUPLEX ULTRASOUND FLOW STUDY: Ultrasound technique using both realtime sonography and Doppler flow to assess for deep venous thrombosis (DVT).
CLINICAL APPROACH
Respiratory distress is an acute emergency and necessitates rapid assessment and therapy. Oxygen is the most important substrate for the human body, and even 5 or 10 minutes of severe hypoxemia can lead to devastating consequences. Hence, a quick evaluation of the patient’s respiratory condition, including the respiratory rate and effort; use of accessory muscles, such as intercostal and supraclavicular muscles; anxiety; and cyanosis; may indicate mild or severe disease. (See Figure 15– 1 for one algorithm to evaluate dyspnea in pregnancy.) The highest priority is to identify impending respiratory failure, since this condition would require immediate intubation and mechanical ventilation. Pulse oximetry and arterial blood gas studies should be ordered while information is gathered during the history and physical. A cursory and targeted history directed at the pulmonary or cardiac organs, such as a history of reactive airway disease, exposure to anaphylactoid stimuli such as penicillin or bee sting, chest trauma, cardiac valvular disease, chest pain, or palpitations, are important. Meanwhile, the physical examination should be directed at the heart and lung evaluation. The heart should be assessed for cardiomegaly and valvular disorders. The lungs should be auscultated for wheezes, rhonchi, rales, or absent breath sounds. The abdomen, back, and skin should also be examined.
Figure 15–1. Algorithm for evaluation of dyspnea in pregnancy.
A pulse oximetry reading of <90% corresponds to an oxygen tension of <60 mm Hg. Supplemental oxygen should immediately be given. An arterial blood gas should be obtained to assess for hypoxemia, carbon dioxide retention, and acid– base status. These findings should be evaluated in the context of the physiological changes in pregnancy (see Table 15– 1). A chest radiograph should be performed rather expeditiously to differentiate cardiac versus pulmonary causes of hypoxemia. A large cardiac silhouette may indicate peripartum cardiomyopathy, which is treated by diuretic and inotropic therapy; pulmonary infiltrates may indicate pneumonia or pulmonary edema. A clear chest radiograph in the face of hypoxemia suggests pulmonary embolism, although early in the course of pneumonia, the chest x-ray may appear normal.
The diagnosis of pulmonary embolism may be made presumptively on the basis of high clinical suspicion, hypoxemia, and a clear chest x-ray. In some cases, intravenous heparin is initiated prophylactically while confirmatory testing is ordered. Diagnostic algorithms differ, but chest x-ray followed by either CTPA or V/Q scan has been shown to be an effective strategy in pregnant patients. Although controversial, CTPA and V/Q scan appear to provide comparable accuracy in diagnosis as well as similar levels of radiation. The choice of imaging modality will depend on physician preference, patient contraindications, and the speed at which the test can be obtained. Many institutions have CTPA more readily available compared to V/Q scan. If the patient presents with symptoms of concurrent DVT, compression ultrasonography of the proximal veins should be ordered first.
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Table 15-1 • NORMAL ARTERIAL BLOOD GAS CHANGES IN PREGNANCY
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Parameter
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Nonpregnant Value |
Pregnant Value |
Comment
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pH
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7.40
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7.45
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Respiratory alkalosis with partial metabolic compensation |
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PO2 (mm Hg)
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90–100
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95–105
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Increased tidal volume leads to increased minute ventilation and higher oxygen level |
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PCO2 (mm Hg)
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40
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28
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Higher tidal volume leads to increased minute ventilation and lower PCO2 |
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HCO3 (mEq/L)
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24
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19
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Renal excretion of bicarbonate to partially compensate for respiratory alkalosis, leads to lower serum bicarbonate, making the pregnant woman more prone to metabolic acidosis
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Once the diagnosis of acute thromboembolism is confirmed, the pregnant woman is usually placed on full intravenous anticoagulation therapy for 5 to 7 days. Later, the therapy is generally switched to subcutaneous therapy to maintain the aPTT at 1.5 to 2.5 times control (if unfractionated heparin is used) for at least 3 months after the acute event. Heparin, which is a potent thrombin inhibitor that blocks conversion of fibrinogen to fibrin, combines with antithrombin III to stabilize the clot and inhibit its propagation. Both unfractionated heparin and low molecular weight heparin (LMWH) are safe to use in pregnancy as they do not cross the placenta. LMWH has the advantages of fewer bleeding complications and freedom from aPTT monitoring to assess therapeutic anticoagulation. After 3 months, either full heparinization or “prophylactic heparinization” doses can be utilized for the remainder of the pregnancy and for 6 weeks postpartum. Warfarin is associated with teratogenicity and is rarely used in pregnancy.
Estrogen products, such as oral contraceptive agents, are relatively contraindicated in women diagnosed with pulmonary embolism. Prophylactic anticoagulation for future pregnancies is more controversial, but is often used. Although pregnancy itself may induce thrombosis, many experts advise obtaining tests for other causes of thrombosis such as protein S and protein C deficiency, prothrombin gene G20210A, antithrombin III activity, Factor V Leiden (FVL) mutation, hyperhomocysteinemia, and antiphospholipid antibodies. Aside from antiphospholipid syndrome, which is typically treated with aspirin and heparin during pregnancy, the remaining thrombophilias without prior history of VTE are usually not given anticoagulation during pregnancy. Specifically, heterozygous Factor V Leiden mutation in the absence of prior VTE is usually not given anticoagulation; however, homozygous FVL or a prior history of VTE confers a much higher thrombosis risk and generally requires anticoagulation.
Deep Venous Thrombosis
Deep venous thrombosis (DVT) occurs in slightly <1% of pregnancies. The pregnant state increases the risk fivefold due to the venous stasis with the large gravid uterus pressing on the vena cava and the hypercoagulable state due to the increase in clotting factors. Cesarean delivery further increases the risk of DVT. Although clots involving the superficial venous system pose virtually no danger and may be treated with analgesia, DVT is associated with pulmonary embolism in 40% of untreated cases. The risk of death is increased tenfold when pulmonary embolism is unrecognized and untreated. Therefore, early diagnosis and anticoagulation treatment are crucial.
Signs and symptoms of DVT include deep leg pain, linear cords palpated along the calf, and tenderness and swelling of the lower extremity. A 2-cm difference in leg circumferences is also highly suggestive. Unfortunately, none of these findings are very specific for DVT, and in fact, the examination is normal in half of patients with DVT. Hence, imaging tests are necessary for confirmation.
In pregnancy, the diagnostic test of choice is Doppler ultrasound imaging, which usually employs a 5- to 7.5-MHz Doppler transducer to measure venous blood flow with and without compression of the deep veins. This modality is nearly as sensitive and specific as the time-honored method of contrast venography.
Management of DVT is primarily anticoagulation with bed rest and extremity elevation. Anticoagulation therapy is the same as pulmonary embolism treatment with full intravenous doses for 5 to 7 days, followed by subcutaneous therapy for at least 3 months after the acute event. After 3 months, either full or prophylactic heparin doses can be utilized for the remainder of the pregnancy and for 6 weeks postpartum. Patients who have additional risk factors for thromboembolism outside of pregnancy may need long-term anticoagulation.
AMNIOTIC FLUID EMBOLISM
Another clinical scenario that can present similarly to pulmonary embolism is amniotic fluid embolism (AFE). This occurs when amniotic fluid enters the maternal circulation and subsequently causes obstruction and vasoconstriction of the pulmonary vessels due to fetal debris and vasoactive substances in the fluid. The patient may present with sudden dyspnea, hypoxia, hypotension, and coagulopathy. Fetal heart tones often become nonreassuring secondary to hypoperfusion. AFE most often occurs during labor or immediately postpartum. It is considered an exceedingly rare event, which is difficult to predict, but there are some risk factors associated with AFE: caesarian delivery, instrumental vaginal delivery, induction of labor, traumatic delivery, placental abruption, placenta accreta, advanced maternal age, and grandmuliparity. The rate of maternal mortality ranges from 20% to 60% and is typically due to cardiovascular collapse. Treatment is largely supportive with immediate delivery if there is rapid maternal or fetal decompensation.
MATERNAL MORTALITY
Recent studies on maternal death have shown a pregnancy-related mortality ratio of 16 per 100 000 live births in the United States, with a slight upward trend over the years. Ratios are higher in African-American women and tend to increase with maternal age. The most common overall etiology for maternal mortality is embolism of all types, followed by cardiovascular conditions and infection. Recent rates of mortality due to hemorrhage, hypertensive disorders, embolism, and anesthesia complications have declined, whereas cardiovascular conditions and infectious causes have increased. This suggests that the increasing number of pregnant women with comorbid health conditions may be playing a role in maternal adverse outcomes.
COMPREHENSION QUESTIONS
15.1 A 32-year-old woman pregnant at 29 weeks’ gestation is noted to have symptoms concerning for a pulmonary embolism. The evaluation included chest radiograph, arterial blood gas, EKG, and CT pulmonary angiogram. A diagnosis of pulmonary embolism is made. Which of the following is most likely to be present in this patient?
A. DyspneaB. Chest painC. PalpitationsD. HemoptysisE. Sudden death
15.2 A third-year medical student is assigned to perform a chart review of the cases of maternal mortality occurring in a hospital over the past 20 years. When the cases are collated, the student organizes the deaths by etiology. Which of the following is most likely to be the common underlying mechanism of death?
A. Uterine atonyB. Hypercoagulable stateC. Hypertensive diseaseD. SepsisE. Rupture of pregnancy through the fallopian tube
15.3 A 28-year-old otherwise healthy woman is found incidentally to have a factor V Leiden mutation (heterozygous). She is pregnant at 14 weeks’ gestation. Which of the following is the best management of this patient?
A. Aspirin therapyB. Expectant managementC. Coumadin (Warfarin) therapyD. Heparin therapy
15.4 A 29-year-old G1P0 woman at 14 weeks’ gestation is seen in the emergency room for possible diabetic ketoacidosis. The emergency room physician is evaluating the arterial blood gas which has been performed, and the findings are listed below. Based on these findings, which of the following is the most accurate statement? pH 7.45; PO2 103 mm Hg; PCO2 31 mm H g; HCO3 18 mEq/L
A. The markedly decreased bicarbonate level indicates that the patient likely has DKA.
B. The decreased PCO2 indicates that the patient is likely having a panic attack.
C. This arterial blood gas result is normal for pregnancy.
D. The elevated arterial pH reading likely indicates a metabolic alkylosis condition.
15.5 A 19-year-old G1P0 woman at 29 weeks’ gestation has reactive airway disease. She has received two nebulized albuterol inhalant treatments with still some wheezing. Her arterial blood gas findings are listed below. Based on these findings, which of the following is the most accurate statement? pH 7.40; PO2 94 mm H g; PCO2 35 mm Hg; HCO3 20 mEq/ L
A. The low PO2 level indicates significant exacerbation of the reactive airway disease.B. The PCO2 level indicates significant retained PCO2 and a worrisome respiratory failure.C. The arterial blood gas is normal in pregnancy.D. The serum bicarbonate level is elevated for pregnancy and indicates metabolic alkalosis.
15.6 A 27-year-old G1P0 is at 31 weeks’ gestation. She is seen by her physician for right leg pain and calf tenderness. A Doppler flow study indicates a deep venous thrombosis of the right lower extremity. Which of the following is a reason for the increased incidence of venous thromboembolism in pregnancy?
A. Venous stasisB. Decreased clotting factors levelsC. Elevated platelet countD. Endothelial damage
15.7 A 38-year-old G2P1 woman had been diagnosed with a deep venous thrombosis of the right leg when she was at 8 weeks’ gestational age. She has been on subcutaneous heparin therapy for 6 months. Which of the following is the most likely result of long-term heparin therapy?
A. OsteoporosisB. ThrombophiliaC. Fetal intracranial hemorrhageD. Diabetes mellitus
ANSWERS
15.1 A. Dyspnea is the most common symptom of pulmonary embolus, whereas tachypnea is the most common sign. Another common symptom is pleuritic chest pain. A person with a pulmonary embolus may also experience palpitations or feel like they are having an anxiety attack. Few patients will have hemoptysis. However, these symptoms are not nearly as common as dyspnea. Sudden death is uncommon, but is more likely in a massive embolus. Patients with a pre-existing heart or lung condition are at increased risk of mortality. When a patient presents with dyspnea, the clinician should prioritize the examination and assessment toward the possibility of significant hypoxia.
15.2 B. Embolism (both thrombotic and amniotic)is the most common cause of maternal mortality. Pregnant women are predisposed to deep venous thromboses due to the obstructive effects the growing uterus has on the great vessels (ie, vena cava) and the hypercoagulable state of pregnancy, which persists for about 6 weeks postpartum. Hemorrhage typically occurs postpartum, usually due to uterine atony. The readily available blood products decrease the likelihood of death. Hypertensive disease is not typically deadly at the time of diagnosis and can be medically managed before, during, and after pregnancy. Ectopic pregnancies are usually not deadly unless rupture occurs and the patient goes into shock. Though this can occur, it is less common than embolism. Patients usually present with early signs (ie, vaginal bleeding) and symptoms (ie, adnexal pain) of an ectopic pregnancy before rupture occurs. Sepsis can also send a patient into shock; however, there are usually signs and symptoms of a bacterial infection (ie, fever, chills, vomiting) that will prompt medical intervention before there is progression to shock.
15.3 B. A patient who is heterozygous for FVL mutation and never had a VTE episode is at low risk for developing VTE in pregnancy. Generally, these patients are expectantly managed and not given anticoagulation. However, if she had a prior DVT or pulmonary embolism, or was homozygous for FVL mutation, then heparin (usually low molecular weight) would be advisable.
15.4 C. This arterial blood gas is normal in a pregnant woman. Pregnancy induces a respiratory alkalosis with partial metabolic compensation. This is the reason the serum bicarbonate level is decreased as compared to the nonpregnant patient.
15.5 B. This arterial blood gas reveals a PCO2 of 35 mm H g, which is elevated. In the face of reactive airway disease, this retained PCO2 is worrisome, and may indicate respiratory failure. Initially, with asthma, hyperventilation should be associated with a decreased PCO2. When the PCO2 increases, fatigue, ineffective ventilation, or respiratory failure are possibilities.
15.6 A. Venous stasis is one of the main factors contributing to the hypercoagulable state in pregnancy. Venous stasis is present due to the uterus compressing the vena cava. Usually, the platelet count is slightly lower in the pregnant state. The lower limit of normal is 150 000/mm3 in the nonpregnant patient and 120 000/mm3 in the pregnant woman. There is an increased level of clotting factors in pregnancy, and this along with venous stasis are the two factors that increase the risk of DVT in a pregnant woman fivefold. Endothelial damage is part of Virchow’s triad (stasis, hypercoagulability, and endothelial damage) that contributes to thrombosis. It typically does not play a role during the pregnancy, but rather in the postpartum period when delivery, especially if surgical, may have caused some vascular damage.
15.7 A. The most common side effect of long-term heparin use in pregnancy is osteoporosis, usually not apparent unless on the agent for at least a month. The mechanism is thought to be overactive osteoclast activity as well as decreased osteoblast activity. Thrombocytopenia and bleeding episodes are other adverse effects. Heparin-induced thrombocytopenia occurs in < 0.5% of pregnant women on subcutaneous heparin, and is less common than in nonpregnant individuals. Thrombocytopenia usually is manifest within the first 10 days of heparin use. Both unfractionated heparin and LMWH are associated with thrombocytopenia. Although there is conflicting evidence, LMWH may have a lower incidence of osteoporosis.
CLINICAL PEARLS
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» The diagnosis of pulmonary embolism is suspected in a patient with dyspnea, a clear chest radiograph, and hypoxemia. It is confirmed with imaging tests such as ventilation-perfusion scan or CT pulmonary angiogram. » The most common presenting symptom of pulmonary embolism is dyspnea. » Amniotic fluid embolism may present during delivery with sudden hypoxia, hypotension, coagulopathy, and fetal distress. » The most common cause of maternal mortality is embolism (both thromboembolism and amniotic fluid embolism). » A PO2 of <80 mm Hg in a pregnant woman is abnormal. » The physical examination is not very useful in assessing for deep venous thrombosis (DVT). » Venous duplex Doppler sonography is an accurate method to diagnose DVT. » After a DVT or pulmonary embolus is diagnosed, anticoagulation is indicated for at least 3 months. » The most common locations for DVT after gynecologic surgery are the lower extremities and the pelvic veins. » Heterozygous Factor V Leiden mutation in the absence of prior VTE usually does not require anticoagulation during pregnancy. |
REFERENCES
American College of Obstetricians and Gynecologists. Prevention of deep vein thrombosis and pulmonary embolism. ACOG Practice Bulletin 84. Washington, DC; 2007.
American College of Obstetricians and Gynecologists. Thromboembolism in pregnancy. ACOG Practice Bulletin 123. Washington, DC; November 2011.
Castro LC, Ognyemi D. Common medical and surgical conditions complicating pregnancy. In: H acker NF, Gambone JC, Hobel CJ, eds. Essentials of Obstetrics and Gynecology. 5th ed. Philadelphia, PA: Saunders; 2009:191-218.
Clark SR. Amniotic fluid embolism. Obstetrics and Gynecology. 2014;123(2 Pt 1):337-348.
Creanga AA, Berg CJ, Syverson C, Seed K, Bruce FC, Callaghan WM. Pregnancy-related mortality in the United States, 2006-2010. Obstetrics and Gynecology. 2015;125(1):5-12.
Cunningham FG, Leveno KJ, Bloom SL, Hauth JC, Gilstrap LC III, Wenstrom KD. Pulmonary disorders. In: Williams Obstetrics. 22nd ed. New York, NY: McGraw-Hill; 2005:1055-1072.
Leung AN, Bull TM, Jaeschke R, et al. American Thoracic Society documents: an official American Thoracic Society/ Society of Thoracic Radiology Clinical Practice Guideline—evaluation of suspected pulmonary embolism in pregnancy. Radiology. 2012;262(2):635-646.
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