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Methods of preventing platelet alloimmunization and alloimmune platelet refractoriness and induction of tolerance in transfused recipients

a technology of alloimmune platelet and transfusion recipient, which is applied in the direction of disinfection, other blood circulation devices, medical devices, etc., can solve the problems of complicated and difficult matching process, platelet refractoriness, and complications of blood product transfusion, so as to prevent alloimmunization, prevent alloimmunization, and prevent alloimmunization

Inactive Publication Date: 2020-05-07
BLOODWORKS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes a method to reduce the risk of a person receiving transfused platelets becoming ill with a disease caused by the platelets. This is done by filtering whole blood from a donor through a special filter and then treating it with a photosensitizer and light to remove any harmful microorganisms. The treated blood is then transfused into the person. This method also prevents the person from becoming sick from the donor's platelets. The treatment also results in a more tolerable platelet composition for the person, which can delay the development of immunization to the platelets.

Problems solved by technology

Transfusions of blood products is associated with complications, including immunologic transfusion reactions.
Alloimmunization can result in the rejection of transfused or transplanted tissues, such as platelets, which leads to platelet refractoriness.
This process of matching can be a complicated and difficult procedure due to the complexity of the marker system that determines compatibility.
Thus, the problem of alloimmunization of recipients against donor blood products is a major problem in transfusion medicine.

Method used

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  • Methods of preventing platelet alloimmunization and alloimmune platelet refractoriness and induction of tolerance in transfused recipients
  • Methods of preventing platelet alloimmunization and alloimmune platelet refractoriness and induction of tolerance in transfused recipients
  • Methods of preventing platelet alloimmunization and alloimmune platelet refractoriness and induction of tolerance in transfused recipients

Examples

Experimental program
Comparison scheme
Effect test

example 1

tal Design and Methods

[0076]The following experimental methods are used in the Examples that follow.

Experimental Design of the Dog Platelet Transfusion Studies

[0077]1) Perform baseline autologous radiolabeled platelet recovery and survival measurements in recipient dogs to ensure that their data is normal.

[0078]2) Select DLA, DRB mismatched and crossmatch negative random donor / recipient pairs.

[0079]3) Prepare platelets weekly from a single random donor.

[0080]4) Donor dog's platelets are unmodified (standard), filter-leukoreduced, γ-irradiated, UV-irradiated plus riboflavin (Mirasol pathogen reduction technology), or treatments are combined.

[0081]5) Donor dog's platelets, after modification, are radiochromium labeled prior to recipient transfusion.

[0082]6) Serial blood samples are drawn from the recipient to determine recovery and survival of the donor dog's radiolabeled platelets.

[0083]7) Recipient receives up to 8 weekly transfusions from their donor or until they become platelet r...

example 2

ness of Different Leukoreduction Methods

[0091]This example provides methods of modifying a donor dog's platelets prior to transfusion in a dog platelet transfusion model that would prevent alloimmune platelet refractoriness. In some aspects, methods of preventing platelet alloimmunization in a dog model could be successfully transferred to patients. Specifically, in some aspects, UV-B irradiation that was 45% successful in preventing alloimmunization in the dog was 81% successful in patients in the largest prevention of platelet alloimmunization trial ever conducted in patients (TRAP Trial). (See Slichter S J, Deeg H J, Kennedy M S. Prevention of platelet alloimmunization in dogs with systemic cyclosporine and by UV-irradiation or cyclosporine-loading of donor platelets. Blood 1987; 69(2):414-418; The Trial To Reduce Alloimmunization To Platelets Study Group. Leukocyte reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet tra...

example 3

ification

[0098]This Example describes experiments designed to characterize the WBCs that are removed and those that remain after F-LR and combined F-LR / C-LR procedures using monoclonal antibodies specific for canine WBCs.

[0099]The WBC identification method using FACS as described in Example 1 was employed for these studies.

[0100]As expected, the PRP was enriched for lymphocytes for example, B cells (CD21+), T cells (CD3+) and DLA Class II positive (CII+) cells (FIG. 3A). As canine granulocytes, monocytes and T cells express CD4; in the subject analysis CD4 positive cells are a mixture of all these cell types. Both Fenwal PLS-5A and Pall PL-1B filters removed most of the lymphocytes with the percentage of CD8+T cells and B cells in the leukocyte gate below 1% of the total CD45+ cells (FIG. 3A). The analysis of the number of events showed that most of the cells remaining were granulocytes (DM5+ cells) and CII+ cells (FIG. 3B). The percentage of cells and number of events in the low fo...

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Abstract

Methods and compositions for the prevention or reduction of platelet transfusion associated complications are provided. The subject methods include modifying donor whole blood or platelets prior to transfusion to prevent or reduce alloimmune platelet refractoriness.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. patent application Ser. No. 15 / 167,923 filed May 27, 2016, which is a continuation-in-part of U.S. patent application Ser. No. 14 / 886,815 filed Oct. 19, 2015, and U.S. Patent Application No. 62 / 342,831 filed May 27, 2016, both of which are hereby incorporated by reference in their entirety.STATEMENT OF GOVERNMENT SUPPORT[0002]This invention was made with United States Government support under U.S. Army Medical Research and Materiel Command Grant No. 07328001, W81XWH-07-1-0578 and Department of Defense, and in part, by a grant provided by Terumo BCT, Lakewood, Colo. The United States Government has certain rights in this invention.FIELD[0003]This invention is directed to methods of preventing transfusion related complications in recipients of donor blood or components thereof.INTRODUCTION[0004]Blood transfusion is the process of receiving blood products into one's circulation intravenously. Trans...

Claims

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Application Information

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IPC IPC(8): A61K41/17A01N1/02A61K35/14A61M1/02A61M1/36A61L2/00
CPCA61K41/17A01N1/0294A61K35/14A61L2/0076A61M1/0281A01N1/0215A61M2202/0427A61M1/3683A61L2202/11A61L2202/22A61L2/0047A61K35/19A61K41/10
Inventor SLICHTER, SHERRILL J.
Owner BLOODWORKS
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