Venous and arterial thromboembolism in severe sepsis

Robert L. Levine; Jacques R. LeClerc; Joan E. Bailey; Matthew J. Monberg; Samiha Sarwat

doi:10.1160/TH08-01-0004

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 99(05): 892-898
DOI: 10.1160/TH08-01-0004

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Venous and arterial thromboembolism in severe sepsis

Authors

Robert L. Levine

¹Department of Neurosurgery, University of Texas School of Medicine at Houston, Houston, Texas, USA
Jacques R. LeClerc

²Retired employee and current shareholder/beneficiary of Eli Lilly & Co., 2404 Sunny Slope, Bridgewater, New Jersey, USA
Joan E. Bailey

³Eli Lilly and Company, Lilly Corporate Center, Drop Code 6072, Indianapolis, Indiana, USA
Matthew J. Monberg

⁴Eli Lilly and Company, Drop Code 6831, Indianapolis, Indiana, USA
Samiha Sarwat

⁵Eli Lilly and Company, Lilly Corporate Center, Drop Code 6025, Indianapolis, Indiana, USA

Abstract

Summary

The burden of thromboembolism (TE) in severe sepsis is largely unknown. We assessed the prevalence of venous and arterial TE in patients with severe sepsis over a four-week period. We performed a retrospective analysis of a pooled database of three randomized, placebo-controlled trials of two novel pharmacological agents for the treatment of severe sepsis, drotrecogin alfa (activated) (DrotAA)and secretory phospholipase A2 inhibitor (sPLA₂I). The study was conducted at intensive care units of the participating institutions. A total of 2,649 patients with known or suspected infection and sepsis-associated acute organ dysfunction were enrolled in the three trials and were assigned to treatment groups (DrotAA=850; sPLA₂I =578; placebo=1221). The database was queried for venous and arterial TE, using investigator reports of serious adverse events. Eighty-four of 2,649 patients (3.2%; 95% confidence interval, 2.5% to 3.9%) developed at least one thromboembolic event over 28 days. Nearly threequarters of episodes were atheroembolic (n=62); 25% involved the deep venous system (n=25). Ischemic stroke (n=30) and venous thromboembolism (n=25) each occurred in about 1% of patients. Ischemic stroke and acute coronary syndrome had a higher peak incidence during the first five days compared to venous TE onset, which was more constant over the 28-day period. Subgroup analysis by pooled treatment groups yielded TE rates of 2.0% (DrotAA), 3.5% (placebo), and 4.0% (sPLA₂I), respectively. Clinically manifest TE occurred in about 3% of severe sepsis patients treated in the intensive care unit over a 28-day period. Arterial TE may be more common than previously recognized. More accurate estimates of TE prevalence and relationship to sepsis await future studies.

Keywords

Sepsis - thromboembolism - stroke - venous thrombosis - pulmonary embolism - drotrecogin alfa (activated)

Full Text

References

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