How can the Simplified Pulmonary Embolism Severity Index (sPESI) be used to manage patients presenting with a pulmonary embolism?

The Bottom Line:  The Pulmonary Embolism Severity Index is a validated tool for predicting 30-day mortality in patients presenting at the hospital with PE.  The Simplified PESI (sPESI) predicts 30-day mortality with accuracy similar to the PESI And can assist in deciding whether inpatient treatment is required or if the patient can safely be treated at home.

SummaryJiménez D, et al.  Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism.  Arch Intern Med. 2010 Aug 9;170(15):1383-9. doi: 10.1001/archinternmed.2010.199.
The simplified PESI predicts 30-day mortality risk with accuracy similar to PESI.  Investigators condensed the 11 PESI criteria to 7, each worth 1 point:  aged > 80 years old, history of cancer, history of chronic lung disease or heart failure (2 factors combined), pulse ≥ 110 beats per minute, systolic blood pressure (SBP) < 100 mm Hg, arterial oxygen saturation < 90%.    A score = 0 is low-risk and a score ≥ 1 is high-risk.

For information on the original PESI:
Aujesky D, et al.  Derivation and validation of a prognostic model for pulmonary embolism.  Am J Respir Crit Care Med. 2005 Oct 15;172(8):1041-6. Epub 2005 Jul 14.
Investigators applied point values for 11 factors to categorize 30-day mortality rate for 10,354 patients in the derivation cohort.   Rates of 30-day mortality based on total score, ranged from Class I (very low risk) to Class V (very high risk).  View the 11 factors with the DynaMed PESI Calculator (From the Calculators menu, select Clinical Criteria.)

For complete summary and to see results from validation cohort studies, see Clinical Prediction of Pulmonary Embolism in DynaMed.

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How effective are the new oral anticoagulants at preventing recurrence of venous thromboembolism?

Bottom line:  Compared to LMWH The new oral anticoagulants (NOACs) are safe and effective for treatment of thromboembolism.  Rivaroxaban and apixiban have lower bleeding risk compared to warfarin therapy.

Summary:  Lana A. Castellucci, et al.  Clinical and safety outcomes associated with treatment of acute venous thromboembolism: A systematic review and meta-analysis.  JAMA. 2014 Sep 17;312(11):1122-35.
This systematic review compares 45 RCTs for efficacy and safety of anticoagulant treatments for 44,989 patients with acute venous thromboembolism.  Treatments included unfractionated heparin, (UFH) plus vitamin K antagonist, fondaparinux plus vitamin K antagonist, low-molecular-weight heparin (LMWH) plus dabigatran, LMWH plus edoxaban, LMWH plus vitamin K antagonist, rivaroxaban, apixaban, and LMWH alone.
RESULTS:  See Table 5 (p. 1130) Meta-analysis (including indirect comparisons)
Recurrent VTE:  No significant differences among treatments except for risk significantly decreased with LMWH alone compared to UFH plus vitamin K antagonist (hazard ratio 0.7, 95% CI 0.5-0.95).
Risk of major bleeding:  Decreased with apixaban compared to UFH plus vitamin K antagonist, fondaparinux plus vitamin K antagonist, LMWH plus dabigatran, LMWH plus edoxaban, and LMWH plus vitamin K antagonist.  Decreased risk with rivaroxaban compared to UFH plus vitamin K antagonist and LMWH plus vitamin K antagonist.

What is the predictive value of blood pressure differential in predicting aortic dissection in patients with chest pain?

Bottom line:  Presence of chest pain with blood pressure differential and/or pulse differential should raise clinical suspicion of aortic dissection.  There is evidence that the presence of pressure difference >20mmHg is a strong predictor of dissection, but absence of pressure differential should not exclude a diagnosis of aortic dissection.
Klompas M. Does this patient have an acute thoracic aortic dissection? JAMA. 2002 May 1;287(17):2262-72.
Summary:  Systematic review of English-language articles reporting studies of accuracy of physical exam, history, or chest x-ray in detecting thoracic aortic dissection.   RESULTS:  21 studies (N=1848) met inclusion criteria.  31% of patients with aortic dissection had pulse deficit or pressure differential with a pooled positive LR of 5.7.  Combination of blood pressure differential and other findings–such as focal neurological deficit, history of hypertension, widened mediastinum (See Table 50-9 for complete list of findings) can increase positive LR (Positive LR=66.0 for combination of 3 findings.)

What blood pressure differential is considered significant?

The review reports that most of the studies only look at loss or diminished pulses rather than the measured difference in pressure.  They did identify many older case series that refer to differences in systolic pressure between arms of 20 mm Hg or 30 mm Hg as significant, but they did not offer evidence of the cutoffs.  The review does cite one  prospective, observational study on predictive value of blood pressure differential of greater than 20 mm Hg. Von Kodolitsch Y, Schwartz AG, Nienaber CA. Clinical prediction of acute aortic dissection. Arch Intern Med. 2000;160(19):2977–2982.
Population: 250 patients with acute chest pain, back pain, or both; absence of an established differential diagnosis of the pain syndrome; and clinical suspicion of acute aortic dissection.  Presence of pressure differential >20 mmHg had an odds ratio of 75.05 (95% CI, 10.16-554.6) for an acute aortic dissection.

What are the mechanisms for coagulopathy and thrombophilia in patients with cirrhosis?

From Cirrhosis and its complications.  In:  Harrison’s Internal Medicine, 18th ed.

Under Major Complications, toward the bottom of the page.

Explains that patients with cirrhosis experience a decrease in production of clotting factors and diminished clearance of anticoagulants.  Portal hypertension may result in hypersplenism which is associated with thrombocytopenia.  Also, diminished vitamin K absorption (as in patients with chronic cholestatic syndrome or decreased hepatic mass) can interfere with production of some of the vitamin k-dependent clotting factors.

Regarding hypercoagulability, most studies seem to address portal vein thrombosis rather than a risk for any thrombosis.

Tripodi A, et al.  Hypercoagulability in cirrhosis: causes and consequences.  Journal of Thrombosis and Haemostasis, 2011; 9: 1713–1723.

This review identifies three case-control studies that look at the risk of VTE in hospitalized patients:  1) 625 cases with VTE & severe liver disease v. 625 controls – reduced risk of VTE in patients with severe liver disease; 2)  6500 cases VTE v. 10,000 controls – non-significant risk of VTE (RR 1.65) in patients with chronic liver disease.  The third study aimed to assess risk of VTE in patients with cirrhosis; 963 patients with cirrhosis v. 12,405 hospitalized patients without cirrhosis.  Incidence of DVT/PE in cases was 1.8% v. 0.9% in controls.  In multivariate analysis, the presence of cirrhosis was not associated with an increased risk in DVT/PE (OR, 0.87).  The article does discuss mechanisms for hypercoagulability that has been observed in plasma taken from cirrhotic patients.

In patients with acute pulmonary embolism, does elevated plasma lactate indicate an increased mortality risk?

Bottom line:   An elevated plasma lactate is associated with an increased risk for 30-day mortality in patients presenting with acute pulmonary embolism.

Summary:  Vanni S, et al.  Prognostic value of plasma lactate levels among patients with
acute pulmonary embolism: the Thrombo-Embolism Lactate Outcome Study.  Ann Emergency Med.  2013; 61(3): 330-338.

This study identified consecutive adult patients presenting to a level III teaching hospital ED with clinical suspicion of PE and life expectancy > 3 months.  270 patients with confirmed PE (by spiral CT or by lung scan) were enrolled.  Plasma lactate and troponin were collected at presentation.  RESULTS:  Hazard ration for all-cause death in patients with lactate ≥ 2 mmol/L was 11.67 (95% CI, 3.32–41.03).  Figure 3 shows the proportions of deaths by lactate level and Figure 4 shows the relationship between  lactate ≥ 2 mmol/L and outcomes up to 30-days after presentation.

Which chest x-ray findings are associated with a diagnosis of pulmonary embolism?

Bottom line:  While no individual CXR finding is diagnostic, some findings (when present, see below) do increase risk for PE.  Absence of abnormal findings are not helpful.

Summary:  Worsley DF, et al.  Chest radiographic findings in patients with acute pulmonary embolism: observations from the PIOPED Study.  Radiology. 1993 Oct;189(1):133-6.
The Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) included 1,063 patients with suspected PE.  PE was confirmed in 383 patients and excluded in 680 patients.  RESULTS:  In patients with confirmed PE, 78% had an abnormal chest x-ray.  Table 1 (p. 134) summarizes the sensitivities and specificities of various x-ray findings.

Finding Sensitivity Specificity
Enlarged central artery 20% 80%
Enlarged hilum 7% 94%
Enlarged mediastinum 5% 95%
Pulmonary edema 10% 80%

Elliott CG, et al.  Chest radiographs in acute pulmonary embolism. Results from the International Cooperative Pulmonary Embolism Registry. Chest 2000; 118:33 – 38.
This observational study included 2,454 consecutive patients with a diagnosis of pulmonary embolism at 52 hospitals 1994-1996.  Chest x-rays were available for 2,322 (95%) patients.  RESULTS:  78% of the x-rays were abnormal.  Most common abnormal findings in these x-rays included cardiac enlargement (27%), pleural effusion (23%), elevated hemidiaphragm (20%), PA enlargement (19%), and atelectasis (18%).  For 1,084 patients who also received echocardiogram, the chest x-ray finding of cardiomegaly had sensitivity of 0.48 and specificity of 0.63 for right ventricular hypokinesis found on the echocardiogram and associated with acute pulmonary embolism.  Likewise in these patients, the x-ray finding of PA enlargement had sensitivity of 0.38 and specificity of 0.76 for the same finding on echocardiogram.

How effective is aspirin at preventing recurrence of VTE or PE?

Bottom lineAspirin may decrease risk for recurrent symptomatic VTE in patients with first unprovoked VTE who have completed initial anticoagulation therapy.

SummaryPulmonary embolism, Treatment section, Antiplatelet therapy.  In:  DynaMed.
DynaMed summarizes results of two RCTs evaluating effectiveness of ASA in patients with first-ever unprovoked VTE who had completed anticoagulant therapy

WARFASA Trial (N Engl J Med 2012 May 24;366(21):1959), N=205, 100 mg daily ASA v. placebo for 2 years.  RESULTS:  Benefit for patient in preventing VTE (NNT=22) and symptomatic DVT (NNT=16).  No difference in rates of nonfatal PE, nonfatal major bleeding, or minor bleeding.

ASPIRE Trial (N Engl J Med 2012 Nov 22;367(21):1979), N=822, 100 mg daily ASA v. placebo for 2-4 years.  RESULTS:  Trial terminated before planned enrollment due to slow accrual of patients.  VTE recurrence 4.8%/year for ASA v. 6.5%/year for placebo (p=0.06); PE episode 3.3%/year for ASA v. 3.8%/year for placebo (p=0.06).

What is the incidence and physiopathology of CNS vasculitis following infectious meningitis?

Bottom line:  CNS vasculitis is a potentially lethal complication of infectious meningitis with limited therapeutic management.  Possible mechanisms of arterial narrowing in meningitis include subarachnoid inflammatory exudate affecting large vessels at the base of the brain and invasion of the vessel walls by inflammatory cells causing dilatation and edema.

SummaryChow FC, et al.  Cerebrovascular disease in central nervous system infections.  Seminars in Neurology.  2011; 31(3): 286-306.
This review discusses the physiopathology of vasculitis in the setting of infectious meningitis (pp. 287-288) and cites a case series (Kastenbauer.  Brain.  2003; 126: 1015-1025) of 87 patients with bacterial meningitis.  The authors reported that eight patients (9.2%) developed intracranial hemorrhage associated with vasculitis.

How do CTA and MRA compare for diagnosing mesenteric ischemia?

Bottom Line: When mesenteric ischemia is suspected, both CT angiography and MR angiography are suitable for the workup depending on circumstances.

American College of Radiology (ACR) Appropriateness Criteria for imaging of mesenteric ischemia.  2012.  IN:  DynaMed Acute Mesenteric Ischemia article, Guidelines section.

CTA has higher spatial resolution and faster acquisition times than MRA, allowing greater accuracy in assessment of the peripheral visceral branches and the inferior mesenteric artery. CTA also allows investigation of other causes of abdominal pain.  CTA exposes the patient to higher radiation levels than MRA.
A small diagnostic cohort study of 31 patients (age 16-73) with suspected acute mesenteric ischemia (AMI)  had multidetector CTA.  Reference standard was “surgical, clinical, or histopathologic findings.  RESULTS:    16 patients had AMI; sensitivity=100%; specificity=100%.

MRA eliminates exposure to radiation and iodinated contrast agents, making it the technique of choice for children and patients with azotemia.  It has a high sensitivity for severe stenosis or occlusions located in the celiac axis and the superior mesenteric artery, but is less sensitive in detecting  embolism, nonocclusive mesenteric ischemia, and mesenteric ischemia in the inferior mesenteric artery (as MRA only depicts 25% of the inferior mesenteric artery.)

How does the Wells score affect pre-test probability of a venous thromboembolism and how does it figure into management?

ICSI Healthcare guideline venous thromboembolism diagnosis & treatment, 2013.
Clinical prediction of pulmonary embolism.  In:  DynaMed.  Modified Wells criteria:
+3 Clinical Signs of DVT (leg swelling and pain with palpation of deep veins)
+3 Alternative Dx less likely than PE
+1.5 Heart rate > 100
+1.5 Immobilization previous 4 days 1.5
+1.5 Previous DVT/PE
+1 Hemoptysis 1
+1 Malignancy (on treatment for last 6 mo)

ICSI guideline indicates PE more likely if score > 4.  If score > 6, high risk for PE (Positive LR=17.0, see JAMA review below.)

ICSI guideline also includes algorithm for assessing risk for DVT (p. 1) using the following criteria:
+1 Active cancer (treatment ongoing or within previous 6 months or palliative)
+1 Paralysis, paresis or recent plaster immobilization of lower extremity
+1 Recently bedridden > 3 days or major surgery within 4 weeks
+1 Localized tenderness along the distribution of the deep venous system
+1 Entire leg swollen
+1 Calf swollen by more than 3 cm when compared to asymptomatic leg (measured 10 cm below tibial tuberosity)
+1 Pitting edema (greater in the symptomatic leg)
+1 Collateral superficial veins (non-varicose)
-2 Alternative diagnosis as likely or greater than that of DVT
High DVT Risk = 3+
Moderate DVT Risk = 1-2
Low DVT Risk ≤ 0
JAMA. 2003 Dec 3;290(21):2849-58. Does this patient have pulmonary embolism?  Chunilal SD, et al.
Systematic review to assess the accuracy of pretest probability evaluation in predicting pulmonary embolism.  Includes studies enrolling consecutive, unselected patients; where participating physicians estimated pretest probability of PE and were blinded to the results of diagnostic testing; and that used validated diagnostic methods to confirm or exclude pulmonary embolismon.  RESULTS:  Sixteen studies involving 8306 patients were included analysis.  Table summarizes the likelihood ratios of various clinical prediction rules.  Positive likelihood ratio for having more than 6 points (high probability) is 17.0.