Dilutional Coagulopathy in Patients Undergoing Elective Surgery
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Blood Coagulation Disorder |
Drug: Fibrinogen |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double-Blind Primary Purpose: Diagnostic |
- Dynamic whole blood clot formation.
- A) Single coagulation factor activities B) Platelet function C) Whole blood clot stability. D) Thrombin generation.
| Estimated Enrollment: | 20 |
| Study Start Date: | June 2007 |
| Study Completion Date: | April 2008 |
| Primary Completion Date: | April 2008 (Final data collection date for primary outcome measure) |
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| Denmark | |
| Aarhus University Hospital, Department of Anaesthesiology | |
| DK-8200 Aarhus N, Denmark | |
| Principal Investigator: | Else Tønnesen, MD, Prof | Aarhus University Hospital, Department of Anaesthesiology |
More Information
Publications:
| ClinicalTrials.gov Identifier: | NCT00493272 History of Changes |
| Other Study ID Numbers: | 20070037 |
| Study First Received: | June 27, 2007 |
| Last Updated: | May 5, 2008 |
| Health Authority: | Denmark: The Regional Committee on Biomedical Research Ethics Denmark: National Board of Health |
Keywords provided by University of Aarhus:
|
Blood coagulation disorder, acquired Hemodilution Fibrinogen Hemostasis HES |
Additional relevant MeSH terms:
|
Blood Coagulation Disorders Hemostatic Disorders Hematologic Diseases |
Vascular Diseases Cardiovascular Diseases Hemorrhagic Disorders |
ClinicalTrials.gov processed this record on May 23, 2013