Peer Reviewed
A Diabetic Woman Presents With Acute Onset of Shortness of Breath
Author:
Ronald Rubin, MD—Series Editor
Citation:
Rubin R. A diabetic woman presents with acute onset of shortness of breath. Consultant. 2015;55(1):49-51.
A 34-year-old woman reports sudden onset of shortness of breath while walking and caring for her 4-week-old daughter. She has never previously experienced such symptoms.
History
The patient recently gave birth to her third child by vaginal delivery. She is a juvenile onset diabetic but does reasonably well on an insulin regimen and has not required any hospital admissions for the past decade. However, she does have microalbuminuria and a glomerular filtration rate (GFR) in the range of 40 cc/minute at her most recent evaluation.
Physical Examination
The patient recorded a blood pressure of 110/75 mm Hg, heart rate of 100 beats per minute, and respiration rate of 20 breaths per minute. She is afebrile and manifests normal breath sounds without wheezing or rales. The heart displays regular rhythm without murmurs or gallops. There is mild pitting edema of the right ankle.
Laboratory Tests
Ultrasonography revealed acute deep vein thrombosis of the right leg at the popliteal level. A spiral CT was deferred due to her renal insufficiency. Cardiac echocardiogram revealed right ventricular (RV)/pulmonary artery pressure of 40 mm Hg and mild RV dilation. A d-dimer assay is 2100 ng/mL and cardiac troponin is 0.63 ng/L (normal, >0.15 ng/L). Creatinine is 2.4 mg/dL compared to 2.0 mg/dL at last measurement.
Which of the following is the most appropriate therapy for the presented patient?
A. Initiate rivaroxaban
B. Initiate lovenox 75 mg subcutaneous twice daily
C. Administer tenecteplase 40 mg by IV bolus and a spiral CT immediately thereafter
D. Administer unfractionated heparin by bolus, followed by infusion to maintain activated partial thromboplastin time (PTT) of 2-2.5 times control
Answer and discussion on next page
Answer: D, administer unfractionated heparin by bolus, followed by infusion to maintain activated partial thromboplastin time (PTT) of 2-2.5 times control
The findings in this case are diagnostic of acute pulmonary embolism (PE). Although this disorder has a long history of diagnostic conundrums, paradigms, and techniques, this case has sufficient data to support the diagnosis.
Clinical Findings
The patient exhibited the classic symptom of new and unexplained dyspnea. There is no other obvious or even subtle cause. Furthermore, the risk of PE increases during the 6-week period after delivery. Her d-dimer value is very high, however, her postpartum state likely also contributed to the elevation.
An ultrasonography confirmed the presence of a deep venous thrombosis. Thus, a multidetector CT is not necessary for this patient; in fact, there is at least a theoretical contraindication of significant radiation exposure, as well as actual contrast exposure in a renal insufficiency patient.
Treatment
The issue here is how to manage the PE. The clinical findings demonstrate that the patient is hemodynamically stable. Her blood pressure is normal. RV testing and measurement of cardiac troponins reveal dysfunction and mild myocardial injury. Therefore, she can be considered at intermediate risk.1
The patient has experienced a significant PE, which fulfills the clinical criteria for acute RV dysfunction (abnormal cardiac echo) and even myocardial injury (troponin elevation), so what is an optimal acute therapeutic approach?
Patients that have been recently classified as an intermediate risk—although not nearly as ominous as PE patients with hemodynamic instability—have an increased chance for adverse early outcomes.2,3 The latter clearly require more aggressive acute interventions, such as fibrinolysis and embolectomy, but management of the former is less well-defined.
If standard anticoagulation is deemed appropriate, there are 3 treatment options:
• An ever growing list of new, “easier to use” anticoagulants that share the properties of oral administration, immediate onset of action, as well as a lack of requirement for dosing schemes or laboratory monitoring are available and ever increasing in popularity.4 Rivaroxaban (Answer A) is one of these agents.
Lovenox (Answer B) is a heparin derivative that, although parenteral, also has demonstrated outstanding efficacy using weight-based dosage and does not need monitoring. However, both agents require renal clearance and will accumulate to toxic and dangerous levels with increased hemorrhagic diathesis in the setting of renal dysfunction. Our index case has significant renal dysfunction, likely diabetic, and thus, these agents are strongly relatively contraindicated here.
Although some might try to titrate these agents, most certainly would not since the T½ becomes quite extended (days) and antidotes are very problematic; protamine has some efficacy for lovenox, but rivaroxaban has no antidote at all.4
• A good alternative is standard heparin, given in the usual fashion with partial thromboplastin time monitoring (Answer D)—the preferred answer here. Further, should there be hemodynamic deterioration, standard heparin can be quickly stopped and quickly be out of the system (T½ = 90 minutes) such that more aggressive medical (thrombolytics) or surgical (embolectomy) techniques can be used without added hemorrhagic risk.
• Regarding Answer C, use of thrombolytics acutely in an intermediate risk situation was decisively tested in a recent trial of 1000 patients.5 In patients given thrombolytic therapy as the initial maneuver, a non-significant death from any cause primary end point benefit was found. And, although a significant benefit in lack of hemodynamic decompensation (lytic 8 cases or 1.6% vs placebo 25 cases or 5%, P=0.002) was demonstrated, such hemodynamic decompensation could effectively be addressed in this small group as needed. Also, in the lytic group, all forms of hemorrhagic complications (major extra cranial bleeding, lytic 32 or 6.3% vs placebo 6 or 1.2%, P=<0.001; hemorrhagic stroke by day 7, lytic 10 or 2.0%, placebo 0, P=0.003) were egregiously and morbidly increased.5
These morbid, life-threatening, and permanently disabling risks more than outweigh any demonstrable benefit and early lytic therapy (Answer C) is excluded.
Of the 4 choices offered, Answer D is best.
Outcome of the Case
The patient was admitted to the ICU for monitoring and was treated with standard heparin with maintenance of PTT, 2 to 2.5 times control. Her hemodynamics never deteriorated and after 2 days her pulse rate and oxygen saturation normalized. Warfarin was initiated and standard heparin stopped when international normalized ratio (INR) reached 2.5.
At 3 months, she was asymptomatic with good exercise tolerance. At 6 months, a repeat echocardiogram showed normal RV anatomy and function. She remains on warfarin.
Take-Home Message
Natural history studies suggest that PE with RV dysfunction and myocardial injury have a prognosis somewhere between those patients without RV findings and those with hemodynamic instability. Labeled an intermediate risk, more aggressive acute intervention with thrombolytics seems to be a cause for more serious toxicity than benefit, and therefore standard anticoagulation regimens remain the optimal therapy.
When choosing which of the ever-growing list of efficacious anticoagulants to use, pay attention to the pharmacokinetics of these agents, particularly in regards to renal function.
Ronald Rubin, MD, is a professor of medicine at Temple University School of Medicine and chief of clinical hematology in the department of medicine at Temple University Hospital, both in Philadelphia, PA.
References:
- Agnelli G, Becattini C. Acute pulmonary embolism. N Engl J Med. 2010;363(3):266-274.
- Konstantinides S, Geibel A, Heusal G, et al. Heparin plus alteplase with heparin alone in patients with submassive pulmonary embolism. N Engl J Med. 2002;347(15):1143-1150.
- Jaff MR, McMurtry MS, Archer SL, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypotension. Circulation. 2011;123:1788-1830.
- Hunt BJ. Bleeding and coagulopathies in critical care. N Engl J Med. 2014;370(9):847-859.
- Meyer G, Vicant E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370(15):1402-1411.