The primary objective of this study is to investigate the additive value of new diagnostic tests to categorize patients with currently unexplained bleeding in order to refine therapeutic interventions.
ID
Source
Brief title
Condition
- Coagulopathies and bleeding diatheses (excl thrombocytopenic)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine the association between the bleeding phenotype (based on medical
history and / or bleeding score), new diagnostic tests and bleeding
complications during a one year follow-up period.
Secondary outcome
The (number of) abnormalities identified or localised (platelet related,
primary or secondary hemostasis, fibrinolysis) in the individual patients
coagulation potential based on new diagnostic tools. These abnormalities can
be:
o Abnormalities in ROTEM® pattern
o Abnormalities in thrombin generation pattern
o Abnormalities in clot lysis pattern
o Combined abnormalities in global hemostatic assays
o Abnormalities in platelet proteomics
o Abnormalities on electron microscopy
o Abnormalities on flowcytometry
o Abnormalities in megakaryocyte development
o Novel DNA mutations
o Secondary abnormalities in patients with low VWF-levels
o Secondary abnormalities in patients with heterozygous factor deficiencies
o Abnormalities in fibrinolytic activators or inhibitors
Evaluation of treatment advice during two years follow-up, by means of:
o Type of bleeding symptoms
o Frequency of bleeding symptoms
o Treatment advice given in patients with unexplained bleeding
o Treatment advice followed during (dental) surgical procedures or after trauma
o Management of bleeding: Local treatment, Antifibrinolytic agents or DDAVP,
Transfusion of red blood cells (RBC), platelets, plasma, PCC or other factor
concentrates, Surgical, endoscopic or radiologic interventions to control
bleeding
o Thromboemolic complications within 30 days after treatment of bleeding
Most optimal timing of diagnostic evaluation in premenopausal women with
unexplained bleeding based on the cyclic variation of hemostatic variables.
Background summary
Each year approximately 150 patients, both adults and children, are referred to
the Erasmus University Medical Center and the Erasmus MC * Sophia Children*s
Hospital due to an experienced subjective or objective bleeding tendency.
Retrospective data analysis (unpublished) shows that, despite extensive history
taking combined with routine laboratory tests, in approximately 60% of these
patients a bleeding disorder cannot be confirmed. Of this group 25% is younger
than 12 years of age. This is unfortunate as a diagnosis is of great
significance with regard to preferred treatment in case of trauma, (dental)
surgery or other situations requiring medical intervention. Currently, if a
bleeding tendency is regarded significant and no bleeding disorder is
diagnosed, general treatment guidelines are followed.
In this study, we intend to evaluate the role of novel diagnostic tools and
tests in all patients with a currently unexplained bleeding tendency and the
effect of hormonal influences in women with bleeding symptoms. Novel diagnostic
tools will include a validated and a novel international (pediatric) bleeding
assessment tool. Novel diagnostic tests will include tests that assess the
global hemostatic potential e.g. Thromboelastometry (ROTEM®) and Thrombin
Generation Assay (TGA) as well as test that aims to quantify the fibrinolytic
potential of the individual e.g. plasma clot lysis assay (CLA). In addition a
third category of tests will be performed that aims to quantify and study the
proteomic constellation of the platelet in order to identify potential platelet
disorders. As hemostatic testing is currently a developing field, informed
consent will be obtained for blood sample storage in order to perform novel
techniques in the near future currently under development (e.g. whole exome
sequencing, other platelet specific techniques).
Study objective
The primary objective of this study is to investigate the additive value of new
diagnostic tests to categorize patients with currently unexplained bleeding in
order to refine therapeutic interventions.
Study design
Prospective case-control study
Study burden and risks
Burden: After obtaining informed consent by the patient when aged >12 years of
age and also by his parents when the or caregivers when the patient is <18
years of age, bleeding symptoms will be quantified by both a validated adult
and pediatric bleeding assessment tool (BAT). Blood samples will obtained in
combination with routine laboratory tests. A maximum of eight (eleven for
evaluating the cyclic variation of hemostatic variables) (see appendix 5 *
Blood sampling CRESCENDO study) extra tubes will be taken.
Risks: The risks associated with study participation are considered negligible
and the extra burden is minimal. Patients participating in the study will
receive the same routine diagnostic tests and treatment advice as patients not
included in the study, according to current clinical practice guidelines. In
the patients participating in the study, additional diagnostic tests will be
performed in a small amount of extra blood extracted from the patient during
blood sampling moments required for the standard diagnostic work up.
Benefits: In current practice, patients (and parents) experience a burden of
uncertainty when a bleeding tendency cannot be specified and only general
treatment can be recommended. We aim to increase knowledge with regard to the
aetiology of the bleeding tendency in patients with currently unexplained
bleeding by systematic documentation of the bleeding symptoms by bleeding
assessment tools and by performance of novel tests that investigate the global
hemostatic potential or focus on a defect in part of the coagulation cascade
which is not tested in routine laboratory testing. In the future this might
allow for targeted therapy of bleeding complications and prevent patients from
getting unnecessary treatment, avoidable medical intervention or (prolonged)
hospitalization.
Wytemaweg 80
Rotterdam 3015 CN
NL
Wytemaweg 80
Rotterdam 3015 CN
NL
Listed location countries
Age
Inclusion criteria
Patients of all ages;
Patients with a significant history of bleeding tendency according to physician opinion or abnormal bleeding score based on a BAT
o with no defined diagnosis after routine testing (see appendix 4 of the research protocol),
o with a heterozygous factor deficiency or low Von Willebrand Factor levels that do not
correspond with the experienced bleeding tendency,
o with aberrant laboratory results not fitting a diagnosis;
Informed consent should be provided prior to any study specific procedure.
Exclusion criteria
Patients with a defined bleeding disorder after routine testing (see appendix 4 of the research protocol, except when they serve as controls for the trombocytopathy arm);
Patients under therapy with anticoagulants and / or antiplatelet and / or anti-inflammatory agents whom cannot stop their medication during the diagnostic work-up;
Patients with thrombocytopenia < 80 x 109/L (with exception to the patients with suspected or volunteers in the control group with a proven platelet disorder);
Patients with a bleeding tendency due to an acquired platelet function disorder (e.g. idiopathic thrombocytopenic purpura * ITP);
Patients with impaired liver function, eg a documented liver cirrhosis or signs of acute liver failure;
Women that are pregnant or up to three months postpartum;
Patients who are inable to give informed consent.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL55101.078.16 |
| OMON | NL-OMON23281 |