The objective of this study is to investigate if the Thrombin Generation Curve has an additional, possible more accurate, value besides the conventional tests such as PT, APTT, INR, AT and the mearument of coagulationfactors for determining…
ID
Source
Brief title
Condition
- Coagulopathies and bleeding diatheses (excl thrombocytopenic)
- Hepatic and hepatobiliary disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Thrombin Generation Curve in PPP (platelet poor plasma) and PRP (platelet rich
plasma) using CAT
Thrombocyte function test using the Multiplate (aggregometer)
Measurement of the fibronolysis pathway by use of the Fibrinolysis ROTEM
Measurement of microparticles with influence on the haemostasis.
Secondary outcome
Coagulatie parameters
o Factor II
o Factor VIII
o Antitrombin
Background summary
In the Netherlands the prevalence of liver disease is just below 1%. When
reaching the terminal stage, liver diseases can cause severe complications and
life-threatening symptoms, such as ascites, variceal bleeding, icterus and
encefalopathy. Severe disfunctions in brain function, general circulation,
kidney function and coagulation can occur. Prognosis of patients with liver
cirrhosis and symptomatic complications as described above is poor: 50% of
patients die within a year.
During the progress of liver disease the production of coagulation factors
decreases in relation with the decrease in functional liver tissue, this
concerns both pro-coagulants as anti-coagulants. This decreased production
involves alterations in coagulation and fibrinolysis activity leading to severe
bleeding- or trombotic tendency. At the moment it is not fully clear what
influence the alternations in coagulationfactors have on patients with
cirrhosis and their bleedingrisk, because no suitable tests are available which
reflect the balance between pro-coagulant and anti-coagulant factors in vivo.
Conventional coagulation tests (PT, APPT, AT) do not entirely make activation
of all the factors in the coagulation cascade clear. In practice this leads to
an incomplete and unreliable evaluation of bleeding- or trombotic tendency.
Conventional coagulation tests are used in classifications such as the
Child-Pugh classification and the MELD-score, leading to a incomplete and
unrealistic reproduction of the reality. Using the Thrombin Generation Curve
(TGC) seems to be a reliable evaluation of the possible bleeding- or trombotic
risk. This because the endproduct from the (pro and anti-)coagulation cascade,
thrombin, is measured in stead of distinct factors in the (pro-)coagulation
cascade.
Study objective
The objective of this study is to investigate if the Thrombin Generation Curve
has an additional, possible more accurate, value besides the conventional tests
such as PT, APTT, INR, AT and the mearument of coagulationfactors for
determining coagulationfactordefects or disorders in patients with chronic
liver diseases.
Second objective of this study is to investigate, with the help of the Thrombin
Generation Curve, the possible changes in a patient with an acute decompensated
liver cirrhosis, according to the coagulationfactors and their metabolism,
alterations in the bleeding- versus trombotic risks will be explicitly
investigated.
Third objective is to follow the course of possible changes in
coagulationfactors and coagulation metabolism in patients with chronic liver
disease, using the Thrombin Generation Curve, alterations in the bleeding-
versus trombotic risks will be explicitly investigated.
Study design
This concerns a hypothesis generating study. The first part of the study will
be a cross-sectional observative comparative study.
A healty population A will be compared to population B, patients with chronic
liver diseases. The severity of the liver disease will be determined according
to the Child-Pugh score, during a regular check-up appointment at the
Gastro-enterology clinic (MUMC). Calculating the Child-Pugh score is also done
during regular check-up's to investigate severity of the disease.
Both populations will fill out a questionnaire (questions about comorbidity,
medication, lifestyle).
Every participant will donate 50 ml of blood (venapuncture), this blood will
be used to perform following tests: Thrombin Generation Curve, thrombocyte
aggregation (Multiplate), measuring coagulation factors.
Outcomes of both populations will be compared.
The second part of the study concerns a longitudinal follow up of only
population B (6, 12, 18 months) to investigate if, when the severity of the
liver disease increases, the Thrombin Generation Curve and the conventional
coagulation tests will yield different results.
Population B will also be asked (on forehand at the inclusion) to donate blood
for coagulation-testing during the follow up, when there is a clinical
admission because of a liver-related event (e.g. varicael bleeding).
Study burden and risks
For both populations the risk of the study are equal to the risk of regular
venapuncture.
Postbus 5800
6202 AZ Maastricht
NL
Postbus 5800
6202 AZ Maastricht
NL
Listed location countries
Age
Inclusion criteria
Healthy controls (population A):
- minimum age of 18-years old
- decision making capacity;Patients (group B) (minimum of 18 years old) with cirrhosis, as diagnosed by a GE-specialist, due to one of the following chronic liver diseases: Primary Biliairy Sclerosis (PBS), Primary Sclerosis Cholangitis (PSC), Hepatitis B, Hepatitis C, Non-Alcoholic Fatty Liver Disease (NAFLD), Alcoholic Liverdisease, Non-Alcoholic Steatosis Hepatitis (NASH), Haemochromatosis, Cryptogenic levercirrhosis.
Exclusion criteria
For both healthy controls (population A) as patients (population B):
- proven congenital diseases concerning primary hemostasis (e.g. M. von Willebrand), defects in fibrinolysis, coagulation factor deficiencies (e.g. hemophilia A and B), vasculair defects which leed to higher bleeding risk (e.g. M. Rendu-Osler-Weber).
Patients using medication interfering with primary hemostasis or coagulation. Coagulation factor deficiencies due to malignancies, sepsis or trauma.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL30724.068.09 |