A 78-year old man with a history of mild dementia is hospitalized due to severe shortness of breath, pleuritic chest pain and mild fever for five hours. Today, in the morning, he woke up and could not breathe normally. He is afebrile, his heart rate is 105 bpm and his respiratory rate is 19 breaths per minute. His blood pressure is 140/93 mm Hg. Two days ago, he stopped going for his daily morning walk due to right leg pain. He also complains that his right leg has been burning for a couple of days. Four weeks ago, he underwent right hemicolectomy for a tumor in the ascending colon. His laboratory studies after surgery showed no abnormalities and he was discharged with appropriate instructions. He has no family history of cardiac or pulmonary disease. He quit smoking ten years ago and drinks two glasses of wine every Sunday, when his younger brother visits him. His BMI is 24. He has no other medical problems and takes no medications except from over the counter vitamins that "protect his neurons."
Which of the following drug would be the most appropriate, chronic therapeutic approach to prevent any recurrence of the current condition?
Show Answer
The correct answer is: E. Rivaroxaban
The sudden onset of dyspnea and shortness of breath after a few days of right leg aching and burning sensation (symptoms of deep vein thrombosis (DVT) indicates potentially pulmonary embolism (PE). The modified Wells Score for this patient is 10 (Signs of DVT=+3, PE is most likely diagnosis=+3, HR>100 =+1.5, Surgery in last month=+1.5, malignancy=+1) and as such the probability of PE is high. Acute management of his condition requires immediate anticoagulation, which can be provided either through unfractionated heparin (Answer A), low molecular weight heparin (LMWH), subcutaneous fondaparinux, or direct oral anticoagulants. However, to reduce the risk for future recurrent DVT, the addition of a direct oral anticoagulant (e.g. rivaroxaban, apixaban) is required as prophylaxis. Rivaroxaban is a factor Xa inhibitor and is approved for chronic prevention of DVT and PE. It requires no international normalized ratio (INR) monitoring and has better bioavailability than vitamin K antagonists.
Warfarin and LMWH would also be appropriate for prophylaxis. However, warfarin (Answer C) would be less appropriate than rivaroxaban in this patient with a history of mild dementia and daily vitamin use, which might interfere with the dietary restrictions that are applied with the use of warfarin. In addition, the patient has normal renal and hepatic function, so the use of rivaroxaban is not contraindicated. LMWH is not offered in the answers listed.
Aminocaproic acid (Answer B) can be used after severe bleeding due to the use of anticoagulants or antifibrinolytics. It is not indicated for chronic prophylaxis of DVT or PE. Fresh Frozen Plasma (Answer D) is used for acute reversal of warfarin overdose. It can also be used in disseminated intravascular coagulation (DIC) or severe cirrhotic coagulopathy, as it contains all coagulation factors of plasma.
Educational Objective
Rivaroxaban can be used in the acute management and chronic prophylaxis of pulmonary embolism. Patients who cannot follow dietary restrictions (e.g. people with dementia, taking multiple vitamins or frequent travelers) or who cannot undergo frequent INR monitoring are considered inappropriate candidates for coumarins. Rivaroxaban constitutes an acceptable therapeutic option for those patients.
References
EINSTEIN-PE Investiagors, Buller HR, Prins MH, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012;366:1287-97.
Young AM, Marshall A, Thirlwall J, et al. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol 2018;36:2017-23.
Hepburn-Brown M, Darvall J, Hammerschlag G. Acute pulmonary embolism: a concise review of diagnosis and management. Intern Med J 2019;49:15-27.
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