Chris J. Hong and David Chelmow
History of present illness
A 38-year-old gravida 0 woman presents to the emergency department complaining of chest pain, difficulty breathing, and a blood-tinged cough that started suddenly several hours ago. She describes the pain as sharp, right sided, and worse with deep breaths. She denies any fevers, chills, nausea, vomiting, or pain radiating to her arms or jaw.
She returned last week to the United States after a month- long trip to South Korea. She has no significant past medical or surgical history. Family history is unremarkable. Her current medications include a multivitamin and a daily com- bined oral contraceptive pill containing 35μg of ethinyl estra- diol and 0.25 mg norgestimate, which she began taking 6 months ago. She denies any tobacco, alcohol, or illicit drug use.
Physical examination
General appearance: Woman with mild dyspnea and seeming uncomfortable
Vital signs:
Temperature: 37.3°C Pulse: 104 beats/min
Blood pressure: 122/76 mmHg Respiratory rate: 22 breaths/min Oxygen saturation: 93% on room air BMI: 37 kg/m2
HEENT: Unremarkable Neck: Supple, no masses
Cardiovascular: Tachycardic, regular rhythm, no murmurs, gallops, or rubs
Pulmonary: Increased respiratory effort, clear to auscultation bilaterally, no wheezes, rales, or rhonchi Abdominal: Obese, bowel sounds active, nontender to deep palpation, no hepatosplenomegaly
Extremities: No swelling or tenderness, no visible cords Laboratory studies:
Urine pregnancy test: Negative
CBC and basic metabolic profile: Within normal limits Imaging:
Twelve-lead ECG: Sinus tachycardia, no ischemic changes Chest x-ray: Unremarkable
What is the differential diagnosis?
The most likely differential diagnosis for the sudden-onset chest pain and shortness of breath in a 38-year-old woman on oral contraceptive pills includes pulmonary embolism, acute coronary syndrome/myocardial infarction (ACS/MI), Mallory–Weiss tear, and pneumothorax. ACS/MI is unlikely given the patient’s age, negative medical and family history, and lack of ECGfindings. Pneumothorax is unlikely given the patient’s unremarkable chest x-ray, and a Mallory–Weiss tear is unlikely in the absence of vomiting.
How would you manage this patient?
This patient’s history and physical examination are most con- sistent with a pulmonary embolism (PE), and as such, further diagnostic evaluation was required. She was placed on a car- diac monitor and 2 L oxygen, which improved her oxygen saturation to 98%. A computed tomography pulmonary angio- gram (CTPA or“spiral CT”) was performed (Fig. 12.1).
The patient has a large pulmonary embolus. Given the large size of the clot and her symptoms, she was admitted to the hospital and started on low-molecular-weight heparin and warfarin. The heparin was continued until she was therapeut- ically anticoagulated on warfarin. Oral contraceptive pills were immediately discontinued. Prior to initiating anticoagulation,
Acute Care and Emergency Gynecology, ed. David Chelmow, Christine R. Isaacs and Ashley Carroll. Published by Cambridge University Press.
© Cambridge University Press 2015.
Fig. 12.1CT of the chest from a 38-year-old female with saddle embolism.
(Image provided by Kathyrn Olsen, MD.)
blood was drawn to test for Protein S and C deficiencies, factor V Leiden mutation, antiphospholipid antibody, antithrombin III deficiency, prothrombin gene mutations, and lupus anti- coagulant. All tests were negative. As the clot likely stemmed from her combined oral contraceptive use in conjunction with her obesity and recent immobility, a three-month course of anticoagulation was chosen. She was counseled on weight reduction and the need to avoid prolonged immobility.
A levonorgestrel intrauterine device (IUD) was placed for contraception.
Venous thromboembolism
Risk factors for venous thromboembolism (VTE) include combined hormonal contraceptive use, age greater than 65 years, personal history of VTE, pregnancy and the puerperium, obesity, recent surgery, prolonged travel, and thrombophilia.
The risk of VTE is increased up to fourfold among combined hormonal contraceptive users (3–9/10 000 woman-years) when compared with nonusers who are not pregnant and not taking hormones (1–5/10 000 woman-years). However, the risk of VTE with combined hormonal contraceptive use is still lower than the risk of VTE during pregnancy (5–20/10 000 woman- years) and the postpartum period (40–65/10 000 woman-years).
Third-generation combined oral contraceptives were previ- ously thought to carry significant risk compared to second- generation combined oral contraceptives, but recent studies are conflicting [1]. Twenty percent of patients with VTE have no identifiable risk factors at the time of presentation. This patient’s risk factors for VTE include combined hormonal contraceptive use, recent immobilization, and obesity.
Patients suspected of having a PE can have their pretest probability for VTE determined by validated assessment tools such as the Wells Criteria and be stratified into low, moderate, and high probability groups. Pulmonary Embolism Rule-out Criteria (PERC) rules may be applied to patients with low pretest probabilities to clinically exclude the presence of PE; a negative test gives a probability of less than 2% for the presence of PE. This patient is PERC positive due to estrogen use, tachycardia, oxygen saturation less than 94%, and hemoptysis.
Therefore, she requires diagnostic evaluation for PE [3].
Confirmatory tests for VTE include D-dimer testing, CTPA, Ventilation/Perfusion (V/Q) scans, and lower extrem- ity Doppler testing. Use of D-dimer testing should be restricted to excluding VTE in patients with a low pretest probability.
D-dimer testing was not performed for this patient as she was already at high probability for PE. CTPA is the diagnostic modality of choice with sensitivity and specificity ranging from 83 to 100% and 86 to 100% respectively. V/Q scans are second- line imaging studies, typically used for patients with a contra- indication to CTPA such as allergy to contrast, kidney failure, or inability to obtain intravenous access. Pulmonary angiog- raphy was once considered the gold standard to diagnose PE, but is rarely used today due to the invasiveness of the test and the availability of CTPA. Lower extremity Doppler studies can
play a role in the evaluation of VTE. A patient with a positive Doppler study for deep vein thrombosis (DVT) and pulmon- ary symptoms can be presumed to have PE and can be man- aged accordingly. However, a negative study does not rule out PE. Here, CTPA confirmed the presence of PE.
Usual treatment for VTE includes anticoagulation with unfractionated or low-molecular-weight heparin and warfarin.
Thrombolytics may be considered in patients with extensive DVTs involving the iliac and femoral veins as well as in patients with massive PEs. Inferior vena cava (IVC)filters may be placed in patients with contraindications to medical management or in patients with recurrent DVTs [2]. As this patient was hemody- namically stable, she was treated with low-molecular-weight heparin while initiating warfarin to therapeutic doses. An IVC filter was not indicated given this was herfirst VTE event.
Once VTE is confirmed, further evaluation for underlying coagulopathy may be performed. As some parts of the labora- tory evaluation are altered by anticoagulation, laboratory studies should be drawn prior to initiation of such therapy.
The evaluation typically includes Protein S and C deficiencies, factor V Leiden mutation, antiphospholipid antibody, anti- thrombin III deficiency, prothrombin gene mutations, and lupus anticoagulant. The presence of an underlying hyper- coagulable state may require long-term anticoagulation. Rou- tine screening for these disorders is not recommended prior to starting combined hormonal contraception due to the rarity of the conditions and the high cost of screening. A thrombophilia workup was ordered and found negative in this patient. As the VTE likely stemmed from her combined oral contraceptive use in conjunction with her obesity and recent immobility, a three-month treatment course of anticoagulation was recommended. She was counseled on modifiable risk factors including weight reduction and the need to avoid prolonged immobility.
Combined hormonal contraceptives are contraindicated in patients with a history of a VTE. However, due to the overall increased risk of VTE during pregnancy, effective contracep- tion is advised in this patient. Although combined hormonal contraceptive use is associated with up to a fourfold increase in risk of VTE in a nonpregnant female, that absolute risk of VTE is still lower than women in the pregnant and puerperium state. As in other patients, long-acting reversible contraception (LARC) methods are preferred. Recommendations for contra- ceptive management in a patient with VTE are outlined by the Centers for Disease Control and Prevention (CDC) in their “US medical eligibility criteria for contraceptive use, 2010” [3]. These guidelines recommend the discontinuation of combined hormonal contraceptives in any patient with acute VTE or history of VTE regardless of current anticoagu- lation therapy or predisposing factors. In patients with DVT or PE, progestin-only contraceptive pills, depot medroxyproges- terone acetate injections, etonogestrel implants, and levonor- gestrel or copper IUDs are all acceptable alternatives, and are category 2 (advantages of the method generally outweigh the theoretical or proven risks). This patient was instructed to Case 12: A 38-year-old woman with sudden-onset shortness of breath
discontinue combined oral contraceptives and she chose to initiate the levonorgestrel IUD, which may also help prevent heavy menstrual bleeding while the patient is anticoagulated.
Key teaching points
The diagnostic evaluation and management of venous thromboembolism (VTE) in a female taking combined hormonal contraceptives is the same as patients with VTE from any other cause. Risk factors for VTE include combined hormonal contraceptive use, age greater than 65 years, personal history of VTE, pregnancy and
puerperium, obesity, recent surgery, prolonged travel, and thrombophilia.
Twenty percent of patients with VTE have no identifiable risk factors at presentation.
Patients diagnosed with VTE are typically evaluated for: Protein S and C deficiencies, factor V Leiden, antiphospholipid antibody, antithrombin III deficiency, prothrombin gene mutations, and lupus anticoagulant.
Patients who have VTE while taking combined hormonal contraceptives should discontinue use. Alternative safe methods include progestin-only contraceptive pills, depot medroxyprogesterone acetate injections, etonogestrel implants, and the levonorgestrel and copper intrauterine devices (IUDs).
Although combined hormonal contraceptive use is associated with up to a fourfold increased risk of VTE, this absolute risk of VTE is still lower than that of women in the pregnant and puerperium state.
References
1. American College of Obstetricians and Gynecologists. Risk of venous thromboembolism among users of drospirenone-containing oral contraceptive pills.
Committee Opinion No. 540.
Obstet Gynecol2012;120:
1239–42.
2. Fesmire FM, Brown MD, Espinosa JA, et al. Critical issues in the evaluation and management of adult patients presenting to the emergency
department with suspected pulmonary
embolism. American College of Emergency Physicians.Ann Emerg Med 2011;57:628–52.
3. Centers for Disease Control and Prevention. US medical eligibility criteria for contraceptive use, 2010.
MMWR2010;59:1–86.