Clinical trial NCT05038722: Function of Platelets Used for Transfusions
Official title: Flödescytometrisk utvärdering av Den Blodstillande förmågan Hos Trombocyter Avsedda för Transfusion
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Thrombocytopenia
Hematologic Malignancy
Lead sponsor: Örebro University, Sweden
Sponsor class: OTHER
First posted: 2021-09-09
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Participants with malignant hematologic disorders undergoing cancer treatment at the Hematology ward.

Brief summary: Cytotoxic treatment for malignant hematologic disorders often casue thrombocytopenia that can result in life threatening bleedings. This is prevented by platelet transfusions but these can cause serious transfusion reactions and thus the number of transused platelet concentrates should be limited. It is therefore important that the platelet concentrates contain functional platelets with long circulation time in the bloodstream.

We have developed a method with flow cytometry to measure platelet function markers. It allows us to determine which pathways that are initiated upon activation.

The aim of this project is to assess to what degree spontaneous activation of platelets as well as their activation capacity affects the transfusion response (i.e. uptake in the circulation and circulation time) in the recipient.

The hypothesis is that transfusion of platelets with low spontaneous activation and high activation capacity will lead to a higher transfusion response in the recipient.

Detailed description: Cytotoxic treatment for malignant hematologic disorders often casue thrombocytopenia that can result in life threatening bleedings. This is prevented by platelet transfusions but these can cause serious transfusion reactions and thus the number of transused platelet concentrates should be limited. It is therefore important that the platelet concentrates contain functional platelets with long circulation time in the bloodstream.

The role of platelets in hemostasis is complex. Upon vascular injury, platelets adhere at the injured site where they become activated, release their granule content and aggregate. Activation include changes in receptors, expression of activation markers and become procaoagulant. We have developed a method with flow cytometry to measures these platelet function markers. It allows us to determine which pathways that are initiated upon activation.

Platelets can be stored a maximum of 5-7 days before transfusion. However, the preparation process and subsequent storage can result in platelet lesions, affecting their ability to promote hemostasis and circulate after transfusion.

The aim of this project is to assess to what degree spontaneous activation of platelets as well as their activation capacity affects the transfusion response (i.e. uptake in the circulation and circulation time) in the recipient.

The hypothesis is that transfusion of platelets with low spontaneous activation and high activation capacity will lead to a higher transfusion response in the recipient.

We will be able to examine how this relates to platelet processing methods and storage duration.

Platelets will be transfused on normal indications to participants at the hematology ward. The platelet concentrates choosen to be transfused will be done according to regular routines at the blood center. We will thus not control what concentrates are transfused (i.e. preparation method and storage time) and hence included in the study.

A small sample will be taken from the platelet concentrate shortly before transfusion and platelet function analysed with the flow cytometry method. Transfusion response will be assessed in the participant by calculation of corrected count increment (CCI) which relates the increase in platelet concentration after transfusion to the number of platelets transfused and the blood volume. CCI is calculated at 1 and 24-hours after transfusion. Clincial variables that might affect the transfusion response such as infection and fever will be registered as well as bleeding. The number of days to next platelet transfusion will be followed up.

Eligibility criteria: Inclusion Criteria:

* Participant undergoing treatment for malignant hematologic disorders
* Thrombocytopenia
* Require platelet transfusion

Exclusion Criteria:

- Participant requiring HLA-matched platelet transfusions.

Primary outcomes:
measure: Corrected count increment (CCI)
timeFrame: 1- and 24 hours after transfusion.
measure: Spontaneous and agonist induced expression of platelet activation markers on platelets in platelet concentrates.
timeFrame: Measured on the day of transfusion prior to transfusion.
measure: Spontaneous and agonist induced formation of platelet subpopulations in platelet concentrates.
timeFrame: Measured on the day of transfusion prior to transfusion.
Secondary outcomes:
measure: Treatment of infection.
timeFrame: Prior to transfusion.
measure: Signs of infection - fever.
timeFrame: Prior to transfusion.
measure: Bleeding.
timeFrame: Prior to platelet transfusion and 24-hours after the transfusion.
measure: Number of platelet transfusions
timeFrame: From beginning of the cytotoxic treatment cycle to inclusion in the study, i.e receiving a study concentrate.
measure: Days to next platelet transfusion.
timeFrame: After the study platelet concentrate was transfused, followed for up to two weeks after transfusion.
Other outcomes:
Locations:
city: Linköping
country: Sweden
facility: Region Östergötland
city: Örebro
country: Sweden
facility: Örebro University
Study officials:
affiliation: Örebro University, Sweden
name: Sofia Ramström, Ass. Prof
role: PRINCIPAL_INVESTIGATOR
References: