Function of Platelets Used for Transfusions

Flödescytometrisk utvärdering av Den Blodstillande förmågan Hos Trombocyter Avsedda för Transfusion

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Thrombocytopenia; Hematologic Malignancy
• Intervention / Treatment: Other: Platelet transfusion

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.

• Study Type: Observational
• Enrollment (Estimated): 240

Contacts and Locations

Study Locations

• Sweden
  • Linköping, Sweden, 58185
    • Region Östergötland
  • Örebro, Sweden, 70182
    • Örebro University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Participants with malignant hematologic disorders undergoing cancer treatment at the Hematology ward.

Description

Inclusion Criteria:

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

Exclusion Criteria:

- Participant requiring HLA-matched platelet transfusions.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Corrected count increment (CCI)	CCI relates the increase in platelet concentration in participants after transfusion to the number of platelets transfused and the participants blood volume.	1- and 24 hours after transfusion.
Spontaneous and agonist induced expression of platelet activation markers on platelets in platelet concentrates.	Percentage of platelets expressing P-selectin, LAMP-1, phosphatidylserine and the active conformation of fibrinogen receptor.	Measured on the day of transfusion prior to transfusion.
Spontaneous and agonist induced formation of platelet subpopulations in platelet concentrates.	Percentage of normal sized platelets, small platelets and platelet fragments (microparticles).	Measured on the day of transfusion prior to transfusion.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment of infection.	Use of antibiotics.	Prior to transfusion.
Signs of infection - fever.	Body temperature measurement.	Prior to transfusion.
Bleeding.	Signs of bleeding according to WHO-scale (0-4, where 4 is the worst outcome).	Prior to platelet transfusion and 24-hours after the transfusion.
Number of platelet transfusions	Total number of platelet transfusions a participant recieved before being incuded in the study (i.e before being transfused with the study specific platelet concentrate) in the treatment cycle.	From beginning of the cytotoxic treatment cycle to inclusion in the study, i.e receiving a study concentrate.
Days to next platelet transfusion.	The number of days until the next platelet transfusion occured after being transfused with the study specific platelet concentrate.	After the study platelet concentrate was transfused, followed for up to two weeks after transfusion.

Collaborators and Investigators

• Sponsor: Sofia Ramström
• Investigators: Principal Investigator: Sofia Ramström, Ass. Prof, Örebro University, Sweden

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2018
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: August 24, 2021
• First Submitted That Met QC Criteria: September 2, 2021
• First Posted (Actual): September 9, 2021

Study Record Updates

• Last Update Posted (Actual): July 13, 2023
• Last Update Submitted That Met QC Criteria: July 12, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Hematologic Diseases; Blood Platelet Disorders; Hematologic Neoplasms; Thrombocytopenia
• Other Study ID Numbers: 2020-05968

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual results from flow cytometry analysis of platelet concentrates that underlie results in a publication after deidentification (text, tables and figures).
• IPD Sharing Time Frame: Starting 6 months after publication, ending 18 months following article publication.
• IPD Sharing Access Criteria: Researchers who provide a sound methodological proposal in order to achieve aims in the approved proposal. Proposals should be adressed to the principal investigator.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No