Postinjury hyperfibrinogenemia compromises efficacy of heparin-based venous thromboembolism prophylaxis. Shock 2014 Jan;41(1):33-9
Date
12/20/2013Pubmed ID
24351527Pubmed Central ID
PMC3902785DOI
10.1097/SHK.0000000000000067Scopus ID
2-s2.0-84891599456 (requires institutional sign-in at Scopus site) 39 CitationsAbstract
BACKGROUND: Venous thromboembolism (VTE) prophylaxis remains debated following trauma, and recommendations have not been established. Although hyperfibrinogenemia is a marker of proinflammatory states, it also contributes to thrombus formation. Postinjury hyperfibrinogenemia is common, but the effect of hyperfibrinogenemia on VTE prophylaxis has not been fully elucidated. Therefore, we hypothesized that heparin is less effective for VTE prophylaxis following severe injury due to hyperfibrinogenemia.
METHODS: In vitro studies evaluated thromboelastography (TEG) parameters in 10 healthy volunteers after the addition of fibrinogen concentrate and heparin. Data from a recent randomized controlled trial, conducted at an academic level I trauma center surgical intensive care unit, were reviewed. Critically injured patients were randomized to standard VTE prophylaxis (5,000 U low-molecular-weight heparin daily) or TEG-guided prophylaxis (up to 10,000 U low-molecular-weight heparin daily) and were followed up for 5 days. Analysis was performed to evaluate the relationship between fibrinogen levels, measures of anticoagulation, and TEG parameters.
RESULTS: In vitro studies revealed increased fibrinogen reversed the effects of heparin as measured by TEG. Fifty patients were enrolled in the clinical study with 25 in each arm. Thromboelastography parameters, fibrinogen, platelet count, and anti-Xa levels did not differ between groups despite treatment provided. Fibrinogen levels increased over the 5-day study period (597 ± 24.0 to 689.3 ± 25.0), as well as clot strength (9.8 ± 0.4 to 14.5 ± 0.6), which had a significant correlation coefficient (P < 0.01). Moreover, there was a moderate inverse correlation between fibrinogen level and the effect of heparin (RF), which was significant on study days 1 and 3, implicating hyperfibrinogenemia in heparin resistance.
CONCLUSIONS: Hypercoagulability and heparin resistance are common following trauma. The preclinical and clinical relationships between fibrinogen levels and hypercoagulability implicate hyperfibrinogenemia as a potential factor in heparin resistance.
Author List
Harr JN, Moore EE, Chin TL, Ghasabyan A, Gonzalez E, Wohlauer MV, Sauaia A, Banerjee A, Silliman CCMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Aged
Anticoagulants
Blood Coagulation
Dose-Response Relationship, Drug
Female
Fibrinogen
Heparin, Low-Molecular-Weight
Humans
Injury Severity Score
Male
Middle Aged
Thrombelastography
Treatment Outcome
Venous Thromboembolism
Wounds and Injuries
Young Adult
