Miniati et al40 have shown that using PE pretest probabilities of 10%, 50%, and 90%, the posttest probabilities with a positive echocardiogram (echo) were 38%, 85%, and 98%. With a negative echo, posttest probabilities were 5%, 33%, and 81%, respectively. The value of transthoracic echo in the diagnosis of PE results were taken from this prospective study in unselected patients.40 Because of the poor sensitivity, echocardiography should not be used as a routine test to screen patients for suspected PE.
Magnetic Resonance Imaging. In pregnant women and in patients with kidney disease, MRI has been used to detect PE. However, the PIOPED III study found that many of the participating centers had difficulty obtaining adequate quality MR angiography (MRA) for suspected PE. The study therefore determined that this modality should be ordered only when there is appropriate expertise in both performing and reading the images, and in patients who have contraindications to standard tests.4
Considering the high risk of developing VTE in the cancer population, there should be a low threshold for diagnostic imaging (ie, CTA and duplex ultrasonography). The patient in this case would have benefited from a CTA to rule-out PE before he was discharged.
Treatment
The National Comprehensive Cancer Network2 (NCCN), American Society of Clinical Oncology3 (ASCO), European Society for Medical Oncology4 (ESMO), International Society on Thrombosis and Haemostasis42 and American College of Chest Physicians5 all have recently published evidence-based clinical practice guidelines for the treatment of established VTE in cancer patients. Once a diagnosis of VTE has been established, immediate treatment with a parenteral anticoagulant should be initiated. For the purpose of this article we shall discuss only the initial treatment of VTE in the emergency setting. The available treatment options are low molecular weight heparin (LMWH), unfractionated heparin (UFH), fondaparinux, warfarin, apixaban and rivaroxaban, and thrombolytic agents.
Low Molecular Weight Heparin. As recommended by the ASCO, NCCN, and ESMO guidelines, the preferred initial treatment for VTE in cancer patients is LMWH. This recommendation stems from the Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) trial,43 which showed a decreased incidence of recurrent VTE in patients treated with a LMWH versus a coumarin derivative. Recurrent VTE occurred in 17% of patients who received warfarin versus 9% of patients who received dalteparin after 6 months. Numerous other studies evaluating LMWH versus warfarin have shown superior efficacy with LMWH for the treatment of VTE in cancer patients.
Options for LMWH currently available include enoxaparin, dalteparin, and tinzaparin. Enoxaparin is dosed at 1 mg/kg subcutaneously every 12 hours or 1.5 mg/kg subcutaneously every 24 hours. A subgroup analysis of cancer patients with PE showed a higher VTE recurrence rate in those who received once-daily versus twice-daily dosing of enoxaparin in a trial conducted by Merli and colleagues.44 Therefore, it is the authors’ recommendation to utilize the twice-daily regimen of enoxaparin for the treatment of PE in cancer patients during the acute phase of treatment.
Dalteparin is dosed at 200 IU/kg subcutaneously every 24 hours for the first month, and then 150 IU/kg subcutaneously every 24 hours thereafter. Tinzaparin is dosed at 175 IU/kg subcutaneously every 24 hours.
Since the LMWH drugs are renally eliminated, they can accumulate in patients with renal impairment. Patients with renal impairment should be considered for dose reductions if applicable, anti-Xa monitoring, and carefully observed for bleeding. Limited data with both dalteparin and tinzaparin, though, suggest less accumulation in patients with severe renal impairment compared to enoxaparin.
Unfractionated Heparin. The UFH drugs are administered via an IV bolus dose of 80 units/kg, followed by a continuous infusion of 18 units/kg/h, titrated to a goal activated partial thromboplastin time. Although LMWHs are preferred, UFH should be considered in certain settings, such as in patients with renal failure, patients with questionable absorption via the subcutaneous route, or patients who are under consideration for systemic thrombolytic therapy.5 Hospitalized patients who are at high risk for bleeding or patients who may undergo invasive procedures are good candidates for UFH over LMWHs. This is due to the fact that UFH can be promptly discontinued and is reversible with protamine sulfate (versus the partial reversibility and longer half-life of LMWH).