MedPath

Dilutional Coagulopathy in Patients Undergoing Elective Surgery

Phase 1
Completed
Conditions
Blood Coagulation Disorder
Interventions
Registration Number
NCT00493272
Lead Sponsor
Christian Fenger-Eriksen
Brief Summary

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.

Detailed Description

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

Perspectives:

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
20
Inclusion Criteria
  • > 18 years
  • Indication for performing cystectomia
  • Written informed consent
Exclusion Criteria
  • Uses of acetyl-salicylic or non-steroid anti-inflammatory drugs 2 days prior to blood sampling.
  • Abnormal preoperative coagulations parameters (Platelets, PP, APTT, D- dimer, Fibrinogen, AT, TT)
  • Disseminated cancer and/or bone metastasis
  • Medical history of ischemic heart disease, claudicatio, or arteriosclerosis
  • Medical history of previous thrombo-embolic event
  • Renal failure defined as clinical relevant abnormal levels of creatinine
  • Liver failure defined as clinical relevant abnormal levels of ALAT
  • Hypersensibility to Voluven, Haemocomplettan or ingredients
  • Fertile women not using safe contraception

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboFibrinogenNacl
FibrinogenFibrinogenFibrinogen
Primary Outcome Measures
NameTimeMethod
Dynamic whole blood clot formation.60 minutes
Secondary Outcome Measures
NameTimeMethod
A) Single coagulation factor activities B) Platelet function C) Whole blood clot stability. D) Thrombin generation.60 minutes

Trial Locations

Locations (1)

Aarhus University Hospital, Department of Anaesthesiology

🇩🇰

DK-8200 Aarhus N, Denmark

© Copyright 2025. All Rights Reserved by MedPath