Biotech Values

[DewDiligence]

Another abstract on antithrombin in sepsis:

[The reason I keep posting about these sepsis studies is that antithrombin treatment for sepsis has had mixed results, and it still isn’t clear whether AT therapy offers a bona fide treatment benefit for sepsis. GTCB evidently thinks that it does, however, because sepsis is on the company’s short list of possible acquired-deficiency indications for partner LEO to take into the clinic next year.]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_...

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Int J Infect Dis. 2005 Nov 10; [Epub ahead of print]

Decreased protein C, protein S, and antithrombin levels are predictive of poor outcome in Gram-negative sepsis caused by Burkholderia pseudomallei.

Larosa SP, Opal SM, Utterback B, Yan SC, Helterbrand J, Simpson AJ, Chaowagul W, White NJ, Fisher CJ Jr.

Division of Infectious Disease, Rhode Island Hospital, Gerry House 113, 593 Eddy Street, Providence, Rhode Island 02903, USA.

BACKGROUND: Acute septicemic melioidosis is associated with systemic release of endotoxin and the proinflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin-1, and interleukin-6. Excessive release of these cytokines may lead to endothelial injury, depletion of naturally occurring endothelial modulators, microvascular thrombosis, organ failure, and death.

METHOD: Plasma samples drawn at baseline and after initial antimicrobial therapy in 30 patients with suspected acute severe melioidosis were assayed for D-dimer levels, protein C and protein S antigen levels, and antithrombin functional activities.

RESULTS: Both baseline and continued deficiencies of protein C, protein S, and antithrombin were statistically associated with a poor outcome by logistic regression. Baseline D-dimer levels were significantly higher in fatal cases than survivors and correlated inversely with protein C and antithrombin, suggesting both increased fibrin deposition and fibrinolysis.

CONCLUSION: The inflammatory response to systemic Burkholderia pseudomallei infection leads to depletion of the natural endothelial modulators protein C, protein S, and antithrombin. Both baseline and continued deficiency of these endothelial modulators is predictive of poor outcome in melioidosis.
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