Addressing Platelet Refractoriness: Giving Hematology-Oncology Patients the Best Chance of Success

The activation of platelets is a well-documented phenomenon. It is now clear that many donated platelet transfusions contain activated platelets. This situation can lead to serious implications for the treatment of hematology-oncology patients who are dependent on platelet transfusion support during their treatment. This webinar will introduce activated platelets and their prevalence, discuss the impacts of activated platelet transfusions, and present a practical solution to this situation.

Platelet activation refers to the transition of resting, discoid platelets to dendritic spheres. This phenomenon occurs in response to a variety of stressors, is reversible to a certain extent, and does not necessarily culminate in clot formation¹. Evidence is accumulating that the primary source for activated platelets in a platelet transfusion is the donor. The donor’s immunological and inflammatory state at the time of donation appears to influence the activation status of their platelets². These donor factors are often asymptomatic and are not caught in donor screening resulting in a surprisingly high number of activated platelets being transfused. The rate of activated platelets ranges between 30% and 50% of the platelet inventory⁹. Activation rates falling in this range have been observed across North America and Europe.

Transfusions with activated platelets tend to result in lower count increments³. Hospitals that transfused exclusively non-activated platelets to their hematology-oncology patient populations have seen drastic reductions in the rate of patients requiring massive transfusion support, and the average number of transfusions per patient⁹. The above observations have been attributed to interactions between activated platelets and the recipient’s innate immune system. In particular, complement opsonization may be the cause of many otherwise unexplained occurrences of platelet refractoriness.

In addition to the implications of activated platelets on platelet refractoriness, a growing body of literature is suggesting activated platelets may interfere with certain immunotherapies. It was shown that activated platelets contain various upregulated factors, suggesting that platelets may be highly immunomodulatory. Specifically, TGFβ⁴, IL-6⁵, CD40L⁶ and complement⁷ are found in conjunction with activated platelets. This serves to add complexity to the treatment of already very complex patients.

To reduce the complexity and risk associated with activated platelet transfusions, it is recommended to transfuse hematology-oncology patients with exclusively non-activated platelets. This is most practically achieved through routine screening of platelet transfusions in the hospital blood bank. Selective allocation and transfusion of non-activated platelets to hematology-oncology patients promises to significantly improve patient care.

References
1. Room temperature activates human blood platelets. Lab Invest 2001; 81: 581-92.
2. Platelets are versatile cells: New discoveries in hemostasis, thrombosis, immune responses, tumor metastasis and beyond. Crit Rev Clin Lab Sci 2016; 53: 409-30.
3. Platelet quality measured with dynamic light scattering correlates with transfusion outcome in hematologic malignancies. Transfusion; 49(11):2276-84, 2009
4. Platelets Subvert T Cell Immunity Against Cancer via GARP-TGFβ Axis. Sci Immunol. 2(11):eaai7911, 2017.
5. Increased tumor necrosis factor alpha (TNF alpha), interleukin 1, and interleukin 6 (IL-6) levels in the plasma of stored platelet concentrates: 6. relationship between TNF alpha and IL-6 levels and febrile transfusion reactions. Transfusion 1993; 33: 195-9.
7. Platelet transfusion – the new immunology of an old therapy. Front Immunol 2015; 6: 28.
8. Complement activation on platelets: implications for vascular inflammation and thrombosis. Mol Immunol 2010; 47: 2170-5.
Portable dynamic light scattering instrument and method for the measurement of blood platelet suspensions. Physics in Medicine and Biology 2006; 51: 3747-58.
9. Unpublished data; publications in preparation.

Speaker

Dr. Elisabeth Maurer-Spurej, PhD, Founder, LightIntegra Technology

Dr. Maurer-Spurej has over twenty years of research experience devoting her career to understanding platelet function and the application of dynamic light scattering. She is the principal inventor of ThromboLUX® and the founder of LightIntegra Technology. She was a scientist with Canadian Blood Services and has also held the position of Adjunct Scientist with CBS since 2010. Elisabeth also holds a position as Clinical Associate Professor with the University of British Columbia and is an active member of a number of organizations with a focus on blood transfusion such as AABB, CSTM, ISTH, BEST and the UBC CBR. She received her Ph.D. in physical chemistry from the Karl-Franzens University in Graz, Austria.

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