title: Colloids decrease clot propagation and strength: role of factor XIII-fibrin polymer and thrombin-fibrinogen interactions.
abstract: Colloid-mediated hypocoagulability is clinically important, but the mechanisms responsible for coagulopathy have been incompletely defined. Thus, my goal was to elucidate how colloids decrease plasma coagulation function. Plasma was diluted 0% or 40% with 0.9% NaCl, three different hydroxyethyl starches (HES, mean molecular weight 450, 220 or 130 kDa), or 5% human albumin. Samples (n=6 per condition) were activated with celite, and diluted samples had either no additions or addition of fibrinogen (FI), thrombin (FIIa) or activated Factor XIII (FXIIIa) to restore protein function to prediluted values. Thrombelastographic variables measured included clot propagation (angle, alpha), and clot strength (amplitude, A; or shear elastic modulus, G). Dilution with 0.9% NaCl significantly decreased alpha, A and G-values compared to undiluted samples. Supplementation with FI, but not FIIa or FXIIIa, resulted in 0.9% NaCl-diluted thrombelastographic variable values not different from those of undiluted samples. FI supplementation of HES 450, HES 220, HES 130 and albumin-diluted samples only partially restored alpha, A and G-values compared to undiluted samples. FIIa addition only improved clot propagation and strength in albumin-diluted samples. FXIIIa supplementation improved propagation in samples diluted with HES 450, HES 220 and albumin, and clot strength improved in HES 450 and albumin-diluted plasma. Considered as a whole, these data support compromise of FIIa-FI and FXIIIa--fibrin polymer interactions as the mechanisms by which colloids compromise plasma coagulation. Investigation to determine if clinical enhancement of FXIII activity and/or FI concentration (e.g. fresh-frozen plasma, cryoprecipitate) can attenuate colloid-mediated decreases in hemostasis is warranted.
authors.affiliation: Department of Anesthesiology, The University of Alabama at Birmingham, Birmingham, AL 35249-6810, USA. vnielsen@uab.edu
authors.forename: V G
authors.initials: VG
authors.lastname: Nielsen
mesh_terms: D000418:Albumins / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D003102:Colloids / Q000494:pharmacology*; D005176:Factor XIII / Q000737:chemistry* / Q000378:metabolism; D005337:Fibrin / Q000737:chemistry* / Q000378:metabolism; D005340:Fibrinogen / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D010952:Plasma Substitutes / Q000494:pharmacology; D011516:Prothrombin / Q000737:chemistry; D012965:Sodium Chloride / Q000494:pharmacology; D013916:Thrombelastography / Q000187:drug effects / Q000379:methods; D013917:Thrombin / Q000737:chemistry* / Q000378:metabolism; D013925:Thromboplastin / Q000494:pharmacology
chemical_list: D000418:Albumins; D003102:Colloids; D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes; D012965:Sodium Chloride; D011516:Prothrombin; D005337:Fibrin; D005340:Fibrinogen; C025337:Factor IIa; D005176:Factor XIII; D013925:Thromboplastin; D013917:Thrombin