Infusible Platelet Membrane may be Effective and Safe: A Mini Review

Editorial

Thromb Haemost Res. 2019; 3(1): 1021.

Infusible Platelet Membrane may be Effective and Safe: A Mini Review

Nasiri S*

Department of Biotechnology, Higher Institute for Research and Education in Transfusion Medicine, Iran

*Corresponding author: Nasiri S, Department of Biotechnology, Blood Transfusion Research Centre, Higher Institute for Research and Education in Transfusion Medicine, Hemmat Ave, Next to the Milad Tower, Tehran, Iran

Received: January 21, 2019; Accepted: March 21, 2019; Published: March 28, 2019

Editorial

Platelets are small, disc shaped cells that have a critical role in helping our blood clot and stop bleeding. Platelet concentrates are usually stored in blood transfusion centers for 3 to 5 days, then they are discarded; therefore, blood transfusion centers are under considerable pressure to produce platelet concentrates for transfusion. Many approaches have been investigated experimentally to produce novel hemostatically active platelet products that are capable of longterm storage [1].

Infusible Platelet Membrane (IPM) as a platelet substitute may be the most feasible approach to reach the target market [2]. Previous in vitro experiments have confirmed that lysed platelets shorten prolonged coagulation times [3,4]. Preliminary studies in animals showed that disintegrated platelets are toxic and may not be effective [5,6]. When large amounts of these platelets were given intravenously over a short period of time, severe circulatory and respiratory effects were regularly observed in irradiated thrombocytopenic dogs and this also had a marked effect on prothrombin consumption. It was interpreted that these side effects are caused mainly by serotonin when they were markedly reduced when dogs were given a serotonin analogue for 4 days before transfusions [7,8]. Due to side effects problems, this sort of investigations was abandoned for nearly three decades because these materials produced considerable distress in experimental animals [7], until experiments in thrombocytopenic rabbits with infusible platelet membrane indicated preclinical evidence of their hemostatic efficacy without significant morbidity [9]. On the other hand, some clinical observations in thrombocytopenic patients showed that platelets may have hemostatic effect, even if they are not intact and improve hemostasis with no evidence of serious toxicity or thrombosis [6,10].

One company, Cypress Bioscience Incorporated (San Diego, CA, USA) has manufactured a microparticulate, known as IPM Cyplex™ from fresh or outdated blood bank human platelets by lysis and differential centrifugation and treatment to inactivate blood-borne viruses [11]. IPM has been successfully administrated in normal human volunteers and thrombocytopenic patients in phase I and II clinical trials and have provided some indication of improvement (cessation of bleeding) in some patients with a single dose of IPM (ranging from 2 to 6 mg/kg) [12-14]. Results of phase III clinical trials were not reported. This might be due to the difficulties in demonstrating IPM efficacy.

The results of perfusion studies have shown that platelet fragments or nonviable platelets (IPM) [15,16] and synthetic phospholipids [17] promote a procoagulant activity that can be demonstrated on the surface of damaged cells.

Our recent experiences have shown that major platelet adhesion (CD41b) and aggregation (CD41/CD61) receptors presence on the membrane with platelet factor 3 activity in lyophilized IPM preparation [18]. As well, our newer animal studies of IPM have demonstrated its efficacy with dose-dependent property [19,20], without any pyrogenic side effect [21] or toxicity [22]. Nasiri et al results in rabbits showed that the maximum hemostatic effectiveness was at 2 hours after IPM administration, while Chao et al had been reported 4 hours [11]. Also, the major aggregation receptor of platelets CD41/CD61 was present on our IPM, but was absent in Chao experiment may be due to our modified IPM processing with lower detrimental effects on platelet membrane receptors. These findings confirms more improving of its hemostatic effectiveness.

In brief, although platelet concentrate transfusions are highly effective in many clinical conditions but the rate of transfusion reactions is rather high. In addition to febrile non-hemolytic transfusion reactions, transfusion-associated graft-versus-host disease, allergic and anaphylactic reactions, rare but dangerous transfusion reactions related to platelet concentrates such as transfusion-related acute lung injury, septic complications induced by bacterially contaminated products, and hemolytic transfusion reaction may be observed [23]. On the opposite side, previous and recent studies have shown that IPM may promote lower side effects with acceptable tolerability, without any adverse effects on biochemical or coagulation indices, no evidence of thrombogenicity, immunogenicity or toxicity, by removal of extracellular and intracellular immune and non-immune proinflamatory mediators. Thus, IPM may be safer than conventional platelet concentrates, but its effectiveness, as a platelet substitute needs to be more confirmed. It seems that further human clinical studies are required in the all aspects to more fully define the exact role of platelet membranes as a drug in the management of patients with thrombocytopenia.

References

  1. Blajchman MA. Substitutes and alternatives to platelet transfusions in thrombocytopenic patients. J Thromb Haemost. 2003; 1:1637-1641.
  2. Nasiri S. Infusible platelet membrane as a platelet substitute for transfusion: an overview. Blood Transfus 2013; 11: 337-342.
  3. Bode AP, Eick L. Lysed platelets shorten the Activated Coagulation Time (ACT) of heparinized blood. Am J Pathol. 1989; 91: 430-434.
  4. Bode AP, Castellani WJ, Hodges EA, Yelberton S. The effects of lysed platelets on neutralization of heparin in vitro with protamine as measured by the Activated Coagulation Time (ACT). Theromb Hemost. 1991; 66: 213-217.
  5. Fliender TM, Sorensen DK, Bond VP, Cronkite EP, Jackson DP, Adamik E. Comparative effectiveness of fresh and lyophilized platelets in controlling irradiation hemorrhage in the rat. Proc Soc Exp Biol Med. 1958; 99: 731-733.
  6. Klein E, Toch R, Farber S, Freeman G, Fiorentino R. Hemostasis in thrombocytopenic bleeding following infusion of stored, frozen platelets. Blood. 1956; 11: 693-699.
  7. Hjort PF, Perman V, Cronkite EP. Fresh, disintegrated platelets in radiation thrombocytopenia: Correction of prothrombin consumption without correction of bleeding. Proceedings of the Society of Experimental Biology and Medicine. 1959; 102: 31-35.
  8. Wooley DW, Edelman PM. Displacement of serotonin from tissues by a specific antimetabolite. Science. 1958; 127: 281-282.
  9. McGill M, Fugman DA, Vittorio N, Darrow C. Platelet membrane vesicles reduced microvascular bleeding times in thrombocytopenic rabbits. Journal of Laboratory and Clinical Medicine. 1987; 109: 127-133.
  10. Klein E, Farber S, Djerassi I, Toch R, Freeman G, Arnold P. The preparation and clinical administration of lyophilized platelet material to children with acute leukemia and aplastic anemia. The Journal of Pediatrics. 1956; 49: 517-522.
  11. Chao FC, Kim BK, Houranieh AM, Liang FH, Konrad MW, Swisher SN, et al. Infusible platelet membrane microvesicles: a potential transfusion substitute for platelets. Transfusion. 1996; 36: 536-542.
  12. Goodnough, LT, Kolodziej M, Ehlenbeck C. A phase I study of safety and efficacy for infusible platelet membrane in patients. Blood. 1995; 86: 610a.
  13. Scigliano E, Enright H, Telen M, et al. Infusible platelet membrane (IPM) for control of bleeding in thrombocytopenic patients. Blood. 1997: 90: 267a.
  14. Alving BM, Reid TJ, Fratantoni JC, Finlayson JS. Frozen platelets and platelet substitutes in transfusion medicine. Transfusion. 1997; 37: 866-876.
  15. Galan AM, Bozzo J, Hernández MR, Pino M, Reverter JC, Mazzara R, et al. Infusible platelet membranes improve hemostasis in thrombocytopenic blood: experimental studies under flow conditions. Transfusion. 2000; 40: 1074-1080.
  16. Alemany M, Hernandez MR, Bozzo J, Galan AM, Reverter JC, Mazzara R, et al. In vitro evaluation of the hemostatic effectiveness of non viable platelet preparations: Studies with frozen-thawed, sonicated or lyophilized platelets. Vox Sang. 1997; 73: 36-42.
  17. Galan AM, Hernandez MR, Bozzo J, Reverter JC, Estelrich J, Roy T, et al. Preparations of synthetic phospholipids promote procoagulant activity on damaged vessels: studies under flow conditions. Transfusion. 1998; 38: 1004-1010.
  18. Nasiri S, Teke K, Mousavi Hosseini K. Flow cytometric measurement of CD41/CD61, CD42b platelet receptors and platelet factor 3 activity in lyophilized infusible platelet membrane preparation. Iranian Journal of Blood & Cancer. 2018; 10: 39-42.
  19. Nasiri S, Heidari M and Rivandi S. Evaluation of hemostatic effectiveness of infusible platelet membrane in rabbits as a potential substitute for platelet transfusion. Journal of Drug Delivery & Therapeutics. 2012; 2: 1-3.
  20. Nasiri S, Heidari M and Rivandi S. Infusible platelet membranes improve hemostasis in thrombocytopenic rabbits: studies with two different injection doses. Intennational Journal of Pharmaceutical Sciences and Research. 2012; 3: 4895-4898.
  21. Gholizadeh S, Nasiri S, Noorbakhsh SA, Mirabzadeh Ardakani E, Rivandi S. Rabbit pyrogen test study of infusible platelet membrane as a platelet substitute for blood transfusion. Journal of Drug Delivery and Therapeutics. 2014; 4: 53-57.
  22. Gholizadeh S, Nasiri S, Mirabzadeh Ardakani E, Seyfkordit A. Evaluation of toxicity test on infusible platelet membrane in mice. Journal of Rafsanjan University of Medical Sciences. 2015; 13: 1091-1096.
  23. Nasiri S, Mousavi Hosseini K. Infusible platelet membrane versus conventional platelet concentrate: benefits and disadvantages. Iranian Journal of Blood & Cancer. 2014; 2: 87-93.

Download PDF

Citation: Nasiri S. Infusible Platelet Membrane may be Effective and Safe: A Mini Review. Thromb Haemost Res. 2019; 3(1): 1021.

Home
Journal Scope
Online First
Current Issue
Editorial Board
Instruction for Authors
Submit Your Article
Contact Us