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Thursday, December 13, 2012

Mama Knows Best: Thrombolytic Therapy for MPE in the Pregnant Patient

My residency program director once made the following statement:

"Pregnancy is the worst STD that anyone can get."

At the time, I laughed when he said this, and I asked him to clarify this somewhat startling observation. We then had a brief discussion and came to the conclusion that pregnancy is associated with many comorbidities that otherwise would not typically occur in the non-pregnant patient. These include conditions of pregnancy that we commonly think of such as morning sickness and acid reflux disease. Diseases that are concerning for us clinicians practicing in the emergency department that pregnant patients may present with include diabetic ketoacidosis, preeclampsia and eclampsia, and thromboembolism.

This led me to wonder about the treatment of life-threatening thromboembolism, particularly massive pulmonary embolism (MPE), in the pregnant patient. We are familiar with the fact that pregnancy in and of it itself is a hypercoaguable state that puts patients at increased risk of thromboembolism. One of the worst-case scenarios I can envision is a young pregnant patient at 32 weeks' gestation presenting to the emergency department after a syncopal episode with the classical picture of MPE: acute dyspnea, sudden chest pain, and signs of hemodynamic instability with a blood pressure of 83/46 mmHg, respiratory rate of 33 bpm, heart rate of 120 bpm, and 80% oxygen saturation upon room air. EKG reveals sinus tachycardia and evidence of right ventricular strain. An emergent transthoracic 2D echocardiogram is performed, which reveals a grossly enlarged right ventricle with severe tricuspid regurgitation and impaired right ventricular function. A VQ scan is highly suspicious for MPE, and a CT scan of the thorax shows a large saddle embolus that extends from the right to the left pulmonary arteries, confirming the diagnosis of MPE.

The ED attending physician orders alteplase 100 mg IV to be infused over 2 hours for this patient. Upon seeing this order, you state something to the following effect:

"You want to use THAT in HER?? That's preposterous!!"

But is it?

We are aware that one of the relative contraindications of thrombolytic therapy is indeed pregnancy. You are faced with the fact that you now have two lives at stake here (mother and baby) in the setting of an MPE, with the caveat that the risk associated with the administration of thrombolytic therapy is bleeding that could be potentially life-threatening. So what is the best option here?

Much of the literature that exists regarding the use of thrombolytic therapy for the treatment of MPE in pregnancy originates primarily from case reports. In many of these studies, thrombolytic therapy has been shown to be successful in rapidly lysing pulmonary emboli with minimal maternal and/or fetal complications. The risk of maternal hemorrhage has been determined to be approximately 8%, occurring from the genitourinary tract and not secondary to intracranial hemorrhage. Any of the bleeding complications experienced by pregnant patients in these case reports were mostly associated with the administration of streptokinase, and there has been no reported evidence of maternal death. Fetal deaths and preterm deliveries that reportedly occurred in pregnant patients treated with thrombolytic therapy for MPE were secondary to the course of the disease itself and not deemed to be associated with treatment. In addition, an interesting case series demonstrated that both patients and their offspring did not have long-term complications associated with therapy at a two-year follow up period.

In terms of the choice of thrombolytic agent, it seems that alteplase would be the most ideal agent to use in this setting for now. Unlike urokinase, alteplase does not cross the placenta (although it is not clear whether this has any implications in inducing coagulopathy of the fetus). In addition, the "claim-to-fame" for alteplase when compared to streptokinase is the idea that the proposed incidence of immunogenic reactions is minimized (which has been previously discussed here). Perhaps there may be some interest in investigating the use of tenecteplase in pregnancy first, and then for the treatment of MPE in the setting of pregnancy, due to the fact that it can be given as an IV bolus with the added potential benefit of possessing a lower risk of bleeding compared to alteplase.

Although MPE is a difficult situation to manage, and even more so in the setting of pregnancy, there is no evidence to support the withholding of thrombolytic therapy in these patients. With two lives to potentially care for in this scenario, a rapid turnaround time can be expected with the administration of thrombolytic therapy that can salvage both the mother and baby. And as the saying goes, "Mama knows best."

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