Hydroxyethyl starch enhances fibrinolysis in human plasma by diminishing α2-antiplasmin-plasmin interactions

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Abstract

Hydroxyethyl starch (HES) solutions are effective volume expanders but are also associated with poorly understood coagulopathy. Enhanced fibrinolysis following dilution with HES has been demonstrated. This investigation sought to identify the interactions of HES with critical fibrinolytic/antifibrinolytic enzymes. Normal plasma or plasmas deficient in factor XIII, thrombin activatable fibrinolysis inhibitor or α2-antiplasmin were either not diluted or were diluted 20% with 0.9% NaCl, 5% human albumin, high-molecular-weight HES (HES 450) or low-molecular-weight HES (HES 130). Plasma was activated with celite and exposed to 75 IU/ml tissue-type plasminogen activator. Coagulation growth/disintegration kinetics were determined with thrombelastography. Compared with undiluted plasma, diluted plasma had a significant decrease in the clot lysis time and the time to maximum rate of lysis in all plasma types except in α2-antiplasmin-deficient plasma. The hierarchy of the decrease in clot lysis time and time to maximum rate of lysis was HES 450 = HES 130 > 5% human albumin = 0.9% NaCl. In conclusion, HES dilution enhances fibrinolysis by diminishing α2-antiplasmin-plasmin interactions. Further laboratory and clinical investigation is warranted to better define the mechanisms by which HES enhances clot disintegration and to find new therapeutic roles for HES to either prevent or treat thrombosis.

Original languageEnglish (US)
Pages (from-to)647-656
Number of pages10
JournalBlood Coagulation and Fibrinolysis
Volume18
Issue number7
DOIs
StatePublished - Oct 2007
Externally publishedYes

Fingerprint

Antifibrinolytic Agents
Fibrinolysin
Fibrinolysis
Starch
Fibrin Clot Lysis Time
Albumins
Carboxypeptidase B2
Molecular Weight
Diatomaceous Earth
Thrombelastography
Factor XIII
Tissue Plasminogen Activator
Thrombosis

Keywords

  • α-antiplasmin
  • Coagulation
  • Factor XIII
  • Fibrinolysis
  • Measurement techniques: thrombelastography
  • Thrombin activatable fibrinolysis inhibitor
  • Tissue-type plasminogen activator

ASJC Scopus subject areas

  • Hematology

Cite this

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title = "Hydroxyethyl starch enhances fibrinolysis in human plasma by diminishing α2-antiplasmin-plasmin interactions",
abstract = "Hydroxyethyl starch (HES) solutions are effective volume expanders but are also associated with poorly understood coagulopathy. Enhanced fibrinolysis following dilution with HES has been demonstrated. This investigation sought to identify the interactions of HES with critical fibrinolytic/antifibrinolytic enzymes. Normal plasma or plasmas deficient in factor XIII, thrombin activatable fibrinolysis inhibitor or α2-antiplasmin were either not diluted or were diluted 20{\%} with 0.9{\%} NaCl, 5{\%} human albumin, high-molecular-weight HES (HES 450) or low-molecular-weight HES (HES 130). Plasma was activated with celite and exposed to 75 IU/ml tissue-type plasminogen activator. Coagulation growth/disintegration kinetics were determined with thrombelastography. Compared with undiluted plasma, diluted plasma had a significant decrease in the clot lysis time and the time to maximum rate of lysis in all plasma types except in α2-antiplasmin-deficient plasma. The hierarchy of the decrease in clot lysis time and time to maximum rate of lysis was HES 450 = HES 130 > 5{\%} human albumin = 0.9{\%} NaCl. In conclusion, HES dilution enhances fibrinolysis by diminishing α2-antiplasmin-plasmin interactions. Further laboratory and clinical investigation is warranted to better define the mechanisms by which HES enhances clot disintegration and to find new therapeutic roles for HES to either prevent or treat thrombosis.",
keywords = "α-antiplasmin, Coagulation, Factor XIII, Fibrinolysis, Measurement techniques: thrombelastography, Thrombin activatable fibrinolysis inhibitor, Tissue-type plasminogen activator",
author = "Nielsen, {Vance G}",
year = "2007",
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language = "English (US)",
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pages = "647--656",
journal = "Blood Coagulation and Fibrinolysis",
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T1 - Hydroxyethyl starch enhances fibrinolysis in human plasma by diminishing α2-antiplasmin-plasmin interactions

AU - Nielsen, Vance G

PY - 2007/10

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N2 - Hydroxyethyl starch (HES) solutions are effective volume expanders but are also associated with poorly understood coagulopathy. Enhanced fibrinolysis following dilution with HES has been demonstrated. This investigation sought to identify the interactions of HES with critical fibrinolytic/antifibrinolytic enzymes. Normal plasma or plasmas deficient in factor XIII, thrombin activatable fibrinolysis inhibitor or α2-antiplasmin were either not diluted or were diluted 20% with 0.9% NaCl, 5% human albumin, high-molecular-weight HES (HES 450) or low-molecular-weight HES (HES 130). Plasma was activated with celite and exposed to 75 IU/ml tissue-type plasminogen activator. Coagulation growth/disintegration kinetics were determined with thrombelastography. Compared with undiluted plasma, diluted plasma had a significant decrease in the clot lysis time and the time to maximum rate of lysis in all plasma types except in α2-antiplasmin-deficient plasma. The hierarchy of the decrease in clot lysis time and time to maximum rate of lysis was HES 450 = HES 130 > 5% human albumin = 0.9% NaCl. In conclusion, HES dilution enhances fibrinolysis by diminishing α2-antiplasmin-plasmin interactions. Further laboratory and clinical investigation is warranted to better define the mechanisms by which HES enhances clot disintegration and to find new therapeutic roles for HES to either prevent or treat thrombosis.

AB - Hydroxyethyl starch (HES) solutions are effective volume expanders but are also associated with poorly understood coagulopathy. Enhanced fibrinolysis following dilution with HES has been demonstrated. This investigation sought to identify the interactions of HES with critical fibrinolytic/antifibrinolytic enzymes. Normal plasma or plasmas deficient in factor XIII, thrombin activatable fibrinolysis inhibitor or α2-antiplasmin were either not diluted or were diluted 20% with 0.9% NaCl, 5% human albumin, high-molecular-weight HES (HES 450) or low-molecular-weight HES (HES 130). Plasma was activated with celite and exposed to 75 IU/ml tissue-type plasminogen activator. Coagulation growth/disintegration kinetics were determined with thrombelastography. Compared with undiluted plasma, diluted plasma had a significant decrease in the clot lysis time and the time to maximum rate of lysis in all plasma types except in α2-antiplasmin-deficient plasma. The hierarchy of the decrease in clot lysis time and time to maximum rate of lysis was HES 450 = HES 130 > 5% human albumin = 0.9% NaCl. In conclusion, HES dilution enhances fibrinolysis by diminishing α2-antiplasmin-plasmin interactions. Further laboratory and clinical investigation is warranted to better define the mechanisms by which HES enhances clot disintegration and to find new therapeutic roles for HES to either prevent or treat thrombosis.

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KW - Thrombin activatable fibrinolysis inhibitor

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