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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.
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.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Platelet transfusion | Other | Transfusion of platelet concentrates according to routine practice. |
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Treatment of infection. | Use of antibiotics. | Prior to transfusion. |
| Signs of infection - fever. | Body temperature measurement. | Prior to transfusion. |
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Inclusion Criteria:
Exclusion Criteria:
- Participant requiring HLA-matched platelet transfusions.
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Participants with malignant hematologic disorders undergoing cancer treatment at the Hematology ward.
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| Name | Affiliation | Role |
|---|---|---|
| Sofia Ramström, Ass. Prof | Örebro University, Sweden | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Region Östergötland | Linköping | 58185 | Sweden | |||
| Örebro University |
Individual results from flow cytometry analysis of platelet concentrates that underlie results in a publication after deidentification (text, tables and figures).
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Starting 6 months after publication, ending 18 months following article publication.
Researchers who provide a sound methodological proposal in order to achieve aims in the approved proposal. Proposals should be adressed to the principal investigator.
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| ID | Term |
|---|---|
| D013921 | Thrombocytopenia |
| D019337 | Hematologic Neoplasms |
| ID | Term |
|---|---|
| D001791 | Blood Platelet Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D000095542 | Cytopenia |
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| ID | Term |
|---|---|
| D017713 | Platelet Transfusion |
| ID | Term |
|---|---|
| D016913 | Blood Component Transfusion |
| D001803 | Blood Transfusion |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
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Samples without DNA retained from the platelet concentrates used for 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. |
| Örebro |
| 70182 |
| Sweden |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |