EUH Dressler Conference: What is the pathophysiology of disseminated intravascular coagulation (DIC)?

The Bottom Line: DIC is a systemic pathophysiologic process and not a single disease entity. The massive tissue factor stimulus results in excess intravascular thrombin, which overcomes the anticoagulant systems and leads to thrombosis. Because of consumption of coagulation factors and platelets, DIC also has a hemorrhagic phase. Treatment of the bleeding patient with DIC is supportive with the use of blood components. Some conditions associated with acute DIC include septic shock, exsanguinating trauma, burns, or acute promyelocytic leukemia.

Reference: Boral BM, Williams DJ, Boral LI. Disseminated intravascular coagulation. American Journal of Clinical Pathology. 2016 Dec; 146(6): 670-680. doi: 10.1093/ajcp/aqw195.

Summary:  DIC is relatively uncommon in the general hospitalized patient but accounts for 9% to 19% of ICU admissions and has a high mortality rate of 45% to 78%. The clinical course of DIC ranges from asymptomatic to life threatening. It is caused by excessive activation of coagulation so that the anticoagulation system is overwhelmed, secondary to a wide variety of clinical conditions. The pathogenesis involves the generation of high levels of thrombin, potentially leading to microvascular thrombosis, as well as the consumption of coagulation factors and the increased generation of plasmin, which could generate a hemorrhagic diathesis. Bleeding is related to several factors, including the consumption of factors, platelets, and fibrinogen, as well as the generation of D-dimers. Typical laboratory tests performed to evaluate DIC include PT, aPTT, platelet count, fibrinogen, and D-dimer.

Posted in Background question, EUH

EUH Dressler Conference: Can blood pressure index (BPI) be a predictor of right ventricular dysfunction in PE?

The Bottom Line: A recent study found the ratio of systolic to diastolic blood pressure ≤1.7 to be a strong indicator of right ventricle dysfunction. In his review of the article, Pallin (2017) notes that the results should not change current practice and must be considered preliminary, since there was no external validation. If validated in other populations, this simple bedside measure may help decide whether to manage patients with PE in the outpatient setting.

Reference: Ates H, Ates I, Kundi H, et al. A novel clinical index for the assessment of RVD in acute pulmonary embolism: Blood pressure index. American Journal of Emergency Medicine. 2017 April 12; S0735-6757(17)30283-8. doi: 10.1016/j.ajem.2017.04.019. [Epub ahead of print].

Pallin DJ. New bedside predictor of right ventricular dysfunction in acute pulmonary emobolism. NEJM Journal Watch. 2017 May 8.

Summary:  The study enrolled 539 patients with acute PE diagnosed by computed tomography. Of these, 74% had right ventricular dysfunction, which was diagnosed by tricuspid annular plane systolic excursion ≤17 mm on echocardiography. The mortality rate was 9.5% in patients with right ventricular dysfunction and 1.4% in those without. BPI ≤1.7 had a 100% positive predictive value and 42% negative predictive value for right ventricular dysfunction. For mortality, BPI ≤1.4 had a 98.5% positive predictive value and an 11.9% negative predictive value (Pallin 2017).

Posted in Diagnosis, EUH

EUH Resident Report: Are there cases of amoxicillin-induced aseptic meningitis?

The Bottom Line: Yes. According to Turk et al (2016), amoxicillin-induced aseptic meningitis (AIAM) is an extremely rare adverse reaction with only 12 reported cases.

References: Moris G, Garcia-Monco JC. The challenge of drug-induced aseptic meningtitis revisited. JAMA Internal Medicine. 2014 Sept; 174(9): 1511-1512. doi:10.1001/jamainternmed.2014.2918.

Turk VE, Simic I, Makar-Asperger K, Radacic-Aumiler M. Amoxicillin-induced aseptic meningitis: case report and review of published cases. International Journal of Clinical Pharmacology and Therapeutics. 2016 Sept; 54(9): 716-718. doi: 10.5414/CP202645. *NOTE: This article is not available through Emory subscriptions. Click here to request via Interlibrary Loan.

Summary: In speaking to the more general drug-induced antiseptic meningtitis (DIAM), Moris and Garcia-Monco (2014) find that aside from the classical NSAIDs and antibiotics, lamotrigine and a number of monoclonal antibodies stand out as new drugs associated with DIAM. The clinical profiles do not allow for a distinction between drugs, and the CSF profile, often with neutrophilic pleocytosis, may cause confusion with infectious meningitis. Many patients with DIAM have an underlying disorder, particularly SLE, which may also cause meningitis. Meningitis can be associated with a variety of other systemic disorders. A rapid onset and resolution of the signs and symptoms (1-5 days) with consistent CSF findings, together with a lack of systemic activity, suggest DIAM.

Posted in Diagnosis, EUH

EUH Resident Report: What are the guidelines for prophylaxis for dental procedures in patients with congenital heart disease?

The Bottom Line: Infective endocarditis (IE) prophylaxis for dental procedures should be recommended only for patients with underlying cardiac conditions associated with the highest risk of adverse outcome from IE. For patients with these underlying cardiac conditions, prophylaxis is recommended for all dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa. Prophylaxis is not recommended based solely on an increased lifetime risk of acquisition of IE (AHA, 2007).

References: American Heart Association. Prevention of infective endocarditis. Guidelines from the American Heart Association. Circulation. 2007.

European Society of Cardiology. Infective endocarditis (Guidelines on prevention, diagnosis, and treatment of): ESC clinical practice guidelines. 2015.

Summary: Recommendations for prophylaxis of IE in the highest-risk patients according to the type of at-risk procedure (Table 5, ESC, 2015).



TOE = transoesophageal echocardiography.

aClass of recommendation.

bLevel of evidence.

cFor management when infections are present, please refer to Section 3.5.3.

Posted in Applying evidence, EUH, Therapy

EUH Krakow Conference: Are there instances of pancreatic ductal leaks into pleural effusions?

The Bottom Line: Yes. Pancreatic ductal leaks, or pancreatic duct disruption, are often  complications of acute pancreatitis (AP) or chronic pancreatitis (CP). However, no published cases were identified regarding ductal leaks into pleural effusions as result of trauma.

References: King JC, Reber HA, Shiraga S, Hines OJ. Pancreatic-pleural fistual is best managed by operative care. Surgery. 2010 Jan; 147(1): 154-159. doi:10.1016/j.surg.2009.03.024.

Ross A, Waxman I, Prachand VN. Endoscopic and minimally invasive therapy for complications of acute and chronic pancreatitis. In Shakelford’s Surgery of the Alimentary Tract (7th ed). 2013:1168-1178.

Summary: Virtually every case of AP involves some form of duct leak, which may or may not persist. Persistent leaks in the setting of acute pancreatitis can lead to pancreatic ascites and high amylase pleural effusions, pancreaticobiliary fistula, as well as the disconnected duct syndrome. In patients with CP, leaks are invariably associated with a downstream calculus or stricture. Endoscopy plays a significant role in the management of duct leaks in each of these clinical scenarios.

Also, pancreatic-pleural fistula is an uncommon complication of chronic pancreatitis occurring as a result of disruption of the main pancreatic duct and tracking of pancreatic fluid through the retroperitoneum into 1 or both thoracic cavities. In a review of cases from 1970 to 2008, King et al (2010) found that a majority of patients recover from pancreatic–pleural fistula without sequelae (81%). Attempts at prolonged periods of medical therapy tend to delay the resolution of the fistula compared with patients who undergo definitive operative intervention early in the course of treatment.

Posted in Background question, EUH

EUH Krakow Conference: What causes elevated amylase in pleural effusions?

The Bottom Line: The pleural fluid amylase is elevated in patients with pleural effusions secondary to esophageal perforation, pancreatic disease, or malignant disease (Broaddus and Light, 2016).

References: Broaddus VC, and Light RW. Pleural Effusion. In Murray and Nadal’s Textbook of Respiratory Medicine (6th ed). 2016:79.

Villena V, Perez V, Pozo F, et al. Amylase levels in pleural effusions: a consecutive unselected series of 841 patients. Chest. 2002 Feb;121(2):470-474.

Summary: There’s an association between high amylase levels in pleural fluid and a neoplastic cause of the effusion. A very high amylase level strongly suggests a malignant etiology. Also, high levels of amylase in effusions secondary to pancreatitis are widely known. The mechanism seems to be associated with an increase in microvascular permeability. Exceedingly high levels have been reported in pancreatic pseudocysts (Villena et al, 2002). In approximately 10% of malignant effusions, the pleural fluid amylase level is mildly elevated. The site of the primary tumor in such patients is usually not the pancreas. Malignancy can be differentiated from pancreatic disease with amylase isoenzymes because the amylase with malignant effusions is primarily of the salivary type (Broaddus and Light, 2016)).


Posted in Background question, Diagnosis, EUH

EUH Krakow Conference: What are the indications for leukopheresis?

The Bottom Line: The primary indication for leukopheresis is leukostatis, which is seen most frequently in CML and acute leukemia patients, especially AML. Leukopheresis is also occasionally performed in ALL and CLL.

Reference: Ganzel C, Becker J, Mintz PD, et al. Hyperleukocytosis, leukostasis and leukapheresis: Practice management. Blood Reviews. 2012 May; 26(3):117-122. doi:10.1016/j.blre.2012.01.003.

Summary: The goal of leukapheresis is to reduce the peripheral WBC count. This can decrease the acute symptoms of leukostasis, prevent the development of leukostasis in patients with hyperleukocytosis and avoid or reduce the severity of tumor lysis syndrome and DIC. There are some reports of it as a chronic treatment for CLL and CML. Additionally, leukopheresis is a unique indication for management of a new diagnosis of CML during pregnancy, in order to prevent the exposure of the fetus to cytotoxic drugs and to imatinib.

Posted in EUH, Therapy