Podcast production, editing and sound design by Anton Helman
Podcast content, written summary & blog post by Saly Halawa, Brit Long, edited by Anton Helman
Cite this podcast as: Helman, A. Swaminathan, A. Lang, E. Morgenstern J. Bhate, T. Long, B. EM Quick Hits 39 – Overdiagnosis, Lytics for Submassive PE, Pericardial Effusion, Hemophilia Treatment. Emergency Medicine Cases. June, 2022. https://emergencymedicinecases.com/em-quick-hits-june-2022/. Accessed [date].
Overdiagnosis in Emergency Medicine
Definition of overdiagnosis: Labelling a person with a disease or abnormal condition that would not have caused the person harm if left undiscovered. Individuals derive no clinical benefit from overdiagnosis and can experience physical, psychological, and financial harm
5 main causes of overdiagnosis
Over reliance on medical tests. A societal belief in prevention and early diagnosis, despite the general lack of evidence to support cancer screening to decrease mortality
Increasingly sensitive diagnostic tests, leading to findings of of questionable importance
Risk averse medical culture
Expanding disease definitions and thresholds/over-medicalization of disease
Pervasive financial incentives from industry
Common ED clinical scenarios
Subsegmental PE – with higher resolution CTs pulmonary emboli are more prevalent than ever, yet PE mortality has not changed in decades
CT angiogram for suspected subarachnoid hemorrhage – leads to detection of lesions that may not be causative but may result in follow-up burden without clinical benefit
Anaphylaxis – recent increase in the incidence of the diagnosis as many patients do not meet the disease threshold, leading to costly over-prescription of epinephrine auto-injectors.
Solutions to the overdiagnosis problem in EM
A collective understanding that in the pursuit of making a diagnosis in the ED diagnosis we should seek to balance our desire for a near zero miss rate with the downstream deleterious effects of overdiagnosis
Use shared decision making so that patients understand the problems of overdiagnosis
Aim to educate medical students, residents staff docs and each other about the downstream effects of overdiagnosis. The more we are collectively aware of the problems, the more likely we will be to address them.
An approach to the indications and dosing of systemic thrombolytics for patients with submassive pulmonary embolism
Despite murky evidence for IV thrombolytics in a wide spectrum of patients with submassive PE (more recently termed “intermediate risk” PE), we should risk stratify this group of PE patients and consider thrombolytics in those patients on the end of the submissive PE clinical spectrum that we anticipate might decompensate/develop shock (massive PE). For example, PE patients with soft BP, poor oxygen saturation, severe respiratory distress, very high elevated troponin, worrisome PoCUS findings for impending obstructive shock, large proximal clot burden on CTPA etc.The risk of death from PE needs to be weighed against the risk of death from bleeding.
Dr. Swaminathan’s approach to thrombolytics and interventional radiology in patients with submassive pulmonary embolism
HIGH risk for decompensation and LOW risk bleeding – consider alteplase 50 mg infusion over 1 hr and repeat at the end of the infusion if no clinical improvement
LOW risk for decompensation and HIGH risk for bleeding – consider holding off on thrombolytics and arranging for interventional radiology as catheter directed thrombolysis or embolectomy may be indicated
HIGH risk for decompensation and unlikely to remain stable while waiting for interventional radiology – consider systemic thrombolytics
HIGH risk for decompensation and HIGH risk for bleeding– in most cases thrombolytics are likely to portent more benefit than harm as these patients are more likely to die from PE than a bleed. Consider lower dose: alteplase 25mg over 1 hr, or a slower infusion over 2 or 6 hrs
MODERATE risk for decompensation and LOW risk for bleed– arrange for interventional radiology, but if delay to interventional radiology consider low dose thrombolytics – alteplase 25mg infused over 1hr, repeat dose if no clinical improvement
Update 2022:An open label randomized clinical trial of 94 patients with intermediate-high risk pulmonary embolisms found that the proportion of patients with an RV/LV ratio >0.9 (suggestive of RV dysfunction) at 3 months was lower in patients who underwent catheter directed thrombolysis plus anticoagulation compared to those who received anticoagulation monotherapy, but was not a statistically significant difference (95% CI 0.06-1.69). One case of nonfatal major gastrointestinal bleeding occurred in the catheter-directed thrombolysis group. Note – this study was prematurely stopped due to the COVID-19 pandemic and underpowered. Abstract
Igneri LA, Hammer JM. Systemic Thrombolytic Therapy for Massive and Submassive Pulmonary Embolism. J Pharm Pract. 2020 Feb;33(1):74-89. doi: 10.1177/0897190018767769. Epub 2018 Apr 19. PMID: 29673293.
Nguyen PC, Stevens H, Peter K, McFadyen JD. Submassive Pulmonary Embolism: Current Perspectives and Future Directions. J Clin Med. 2021;10(15):3383. Published 2021 Jul 30. doi:10.3390/jcm10153383
Murphy E, Lababidi A, Reddy R, Mendha T, Lebowitz D. The Role of Thrombolytic Therapy for Patients with a Submassive Pulmonary Embolism. Cureus. 2018;10(6):e2814. Published 2018 Jun 15. doi:10.7759/cureus.2814
Chatterjee S, Chakraborty A, Weinberg I, Kadakia M, Wilensky RL, Sardar P, Kumbhani DJ, Mukherjee D, Jaff MR, Giri J. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA. 2014 Jun 18;311(23):2414-21.
Konstantinides S, Geibel A, Heusel G, Heinrich F, Kasper W; Management Strategies and Prognosis of Pulmonary Embolism-3 Trial (MAPPET-3) Investigators. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med. 2002 Oct 10;347(15):1143-50.
Meyer G, et al; PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014 Apr 10;370(15):1402-11.
Nakamura S, Takano H, Kubota Y, Asai K, Shimizu W. Impact of the efficacy of thrombolytic therapy on the mortality of patients with acute submassive pulmonary embolism: a meta-analysis. J Thromb Haemost. 2014 Jul;12(7):1086-95.
Sharifi M, Bay C, Skrocki L, Rahimi F, Mehdipour M; “MOPETT” Investigators. Moderate pulmonary embolism treated with thrombolysis (from the “MOPETT” Trial). Am J Cardiol. 2013 Jan 15;111(2):273-7.
Step 3: Replace coagulation factors – see treatment below
Step 4: Speak with a hematologist
Treat based on history and suspected site/severity of bleeding. Do not wait for exam, imaging, or laboratory testing to administer factor replacement.
Major bleeds: major trauma, the airway, CNS, GI hemorrhage, bleeding in the chest, the retroperitoneum, epistaxis, and the eyes or orbits.
Raise factor to 100%
Minor bleeds: muscles, joints, oral mucosa, and hematuria.
Raise factor to 50%.
May use patient’s own factor replacement.
Each unit/kg of factor VIII replacement raises factor levels by 2%, and each unit/kg of factor IX replacement raises factor levels by 1%.
Major bleeds in a hemophilia A patient, give 50 units/kg to reach 100%. In hemophilia B, give 100 units/kg to reach 100%.
If concerned about bleeding and don’t know the patient’s baseline factor levels, assume the factor level is 0%. If there’s any doubt, give full factor replacement.
Other indications for factor replacement: fracture, sprain, or dislocation, heavy menstrual bleeding with moderate to severe anemia or volume loss, need for an invasive procedure or surgery.
If factor replacement not available, activated PCC or FEIBA can be used in hemophilia A (80-100 units/kg). Recombinant FVIIa can be used in both hemophilia A and B (90 mcg/kg IV), even if an inhibitor is present.
Inhibitors cause multiple problems: interfere with the patient’s own circulating factors; interfere with infused factor concentrates.
Difficult to diagnose in the ED unless the patient knows they have an inhibitor
Consider in patient with recurrent or breakthrough bleeds
Safest treatment for those with inhibitor in hemophilia A or B is recombinant factor VIIa at 90 mcg/kg
Non-bleeding complications: HIV, hepatitis B, hepatitis C.
If fever and long-term vascular access are present, consider line infection and infective endocarditis.
Other considerations: avoid intramuscular (IM) administration of medications.
Dr. Anton Helman is an Emergency Physician at North York General in Toronto. He is an Assistant Professor at the University of Toronto, Division of Emergency Medicine and the Education Innovation Lead at the Schwartz-Reisman Emergency Medicine Instititute. He is the founder, editor-in-chief and host of Emergency Medicine Cases.