Dilutional Coagulopathy in Patients Undergoing Elective Surgery
The purpose of the present study is to perform a comprehensive description of haemostasis parameters before and after haemodilution with Hydroxyethyl starch (HES) following acute bleeding during elective surgery. Moreover the study aims to test the in vivo haemostatic potential of fibrinogen concentrate in dilutional coagulopathy caused by HES in a clinical, prospective, placebo-controlled randomised setup.
We hypothesise; a) A coagulopathy is induced following in vivo haemodilution; b) the coagulopathy is improved or partially improved by fibrinogen.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Diagnostic
|Official Title:||Fibrinogen vs Placebo for Improvement of Clot Strength|
- Dynamic whole blood clot formation. [ Time Frame: 60 minutes ] [ Designated as safety issue: No ]
- A) Single coagulation factor activities B) Platelet function C) Whole blood clot stability. D) Thrombin generation. [ Time Frame: 60 minutes ] [ Designated as safety issue: No ]
|Study Start Date:||June 2007|
|Study Completion Date:||April 2008|
|Primary Completion Date:||April 2008 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
Other Name: Active drug
Active Comparator: Fibrinogen
Other Name: Active drug
Background Hydroxyethyl starch (HES) is a group of artificial colloid solutions widely used for plasma expansion and volume resuscitation. HES consist of branched chains of hydroxylated glucose molecules defined by average molecular weight, degree of hydroxyethylation, and C2/C6 ratio. Several clinical reports and in vitro experiments have documented an impaired coagulation system induced by haemodilution with HES and other colloid plasma expanders. The exact mechanisms responsible for HES induced coagulopahty are not fully understood although reduced levels of von Willebrand factor (vWF), acquired platelet dysfunction, reduced factor VIII levels, and dysfunctional fibrinogen polymerization seems to reflect an important aspect of the pathogenesis.
Experimental laboratory studies performed in our centre and verified by several other research groups have shown successful reversal of the colloid plasma expander induced coagulopathy by fibrinogen concentrate.10-13 So far, the present knowledge are based on laboratory experiments and animal studies. Hence, it appears desirable to perform a comprehensive description of haemostasis parameters following HES induced dilutional coagulopathy in an acute clinical bleeding situation.
Materials and Methods
Study design: Clinical, prospective, double-blind, randomised, place-controlled trial. Blood samples:
Primary end point:
Dynamic whole blood clot formation
Secondary end points:
A) Single coagulation factor activities B) Platelet function C) Whole blood clot stability. D) Thrombin generation
Serious surgical and traumatic bleedings are common and associated with a high mortality rate. The present study can significantly contribute to our overall understanding of the mechanisms involved in HES induced dilutional coagulopathy.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00493272
|Aarhus University Hospital, Department of Anaesthesiology|
|DK-8200 Aarhus N, Denmark|
|Principal Investigator:||Else Tønnesen, MD, Prof||Aarhus University Hospital, Department of Anaesthesiology|