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Platelet transfusion refractoriness
Platelet reduction following transfusion

Platelet transfusion refractoriness is the repeated failure to achieve the desired level of blood platelets in a patient following a platelet transfusion. The cause of refractoriness may be either immune or non-immune. Among immune-related refractoriness, antibodies against HLA antigens are the primary cause. Non-immune causes include splenomegaly (enlargement of the spleen), fever, and sepsis.

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Cause

Platelet refractoriness can be due to immune causes or non-immune causes.3 Non-immune causes account for over 80% of cases of platelet refractoriness, and sepsis is one of the most common non-immune causes.4567 HLA alloimmunization is the commonest immune cause of platelet refractoriness.891011

Non-immune causes

Patient-related

Platelet component-related

  • Age of platelet component1213
  • ABO mismatch between platelet component and recipient1415
  • Number of platelets within the component if platelet increment (PI) is used to calculate platelet refractoriness16
  • Pathogen-reduced platelet component17

Immune causes

Diagnosis

Platelet transfusion refractoriness can be defined in several different ways. All measures of platelet refractoriness are defined by the timing of the post-transfusion platelet count, usually 1 hour post transfusion or 24 hours post transfusion or both.1819

Platelet increment (PI)

This is the simplest method, and only requires data on the platelet count before and after the transfusion.20 The platelet increment is also known as the absolute count increment and count increment.2122

PI = post-transfusion platelet count - pre-transfusion platelet count

However, it is affected by the number of platelets given in the transfusion (platelet dose) and the patient's blood volume. Larger patients and smaller platelet doses decrease the platelet increment.2324 These factors are adjusted for in the other methods of defining platelet refractoriness.252627

A 1-hour post-transfusion PI of less than 5 to 10 x 109/l is considered evidence of platelet refractoriness.2829 Due to lack of data on platelet dose this is often the only measure of platelet refractoriness that can be performed in routine clinical practice.30

Percentage platelet recovery (PPR)

Requires data on the platelet increment (PI), the patient's total blood volume (TBV) - estimated using the patient's weight multiplied by 0.075, and the number of platelets transfused (platelet dose)3132

PPR = ((PI x TBV)/PD) x 100

At 1 hour post-transfusion, a PPR < 20% is considered evidence of platelet refractoriness.3334 At 16 hours post-transfusion a PPR < 10% is considered evidence of platelet refractoriness.35

Percentage platelet increment (PPI)

PPI is very similar to the percentage platelet recovery (PPR) but there has been an additional adjustment for splenic pooling of platelets (PPR multiplied by 2/3)3637

PPI = PPR/0.67 = ((PI / 0.67) x TBV)/PD x 100

Corrected count increment (CCI)

This requires data on the platelet increment (PI, in platelets/μL), the patient's Body surface area (BSA, in m2), and the number of platelets transfused (PD, in 1011).383940

C C I = P I ∗ B S A P D {\displaystyle {CCI}=PI*{\frac {BSA}{PD}}}

For example, a PI of 25,000 platelets/μL, a BSA of 1.8m2 and a PD of 4x1011 gives a CCI of 11,250 platelets*m2/1011μL

At 1 hour post-transfusion a CCI greater than 7500 indicates a sufficient post-transfusion increment, whereas a CCI less than 7500 is considered diagnostic of platelet refractoriness.41 At 24 hours post transfusion a CCI less than 5000 suggests platelet refractoriness.42

Platelet dose

Some blood banks maintain records of the estimated number of platelets in each unit.43 Current requirements in the US stipulate that a unit of apheresis platelets must contain at least 3.0 x1011 platelets.44 In England only 1% of adult platelet components are tested to check the number of platelets meet the minimum required standard of 2.4 x 1011 platelets.4546 Only components that contain fewer than 1.6 x 1011 platelets are discarded.4748 This means that there can be a lot of variability in the number of platelets contained within each transfusion.49

Treatment

Treatment depends on the underlying cause.50

Non-immune causes are usually treated by treating the underlying cause e.g. sepsis.5152

If there is no obvious non-immune cause, a first step can be to use platelet components that are likely to produce the greatest platelet increment (less than 3 days old and ABO-matched), while further investigations are performed (testing for HLA antibodies).5354

If an immune cause is suspected and HLA antibodies are detected, then HLA-selected platelet components can be used.5556 Although HLA-selected platelets lead to improved platelet increments at 1 hour post-transfusion,57 there is currently insufficient evidence to demonstrate their clinical effectiveness at preventing bleeding.58

If HLA antibodies are not detected, and HPA antibodies are detected, then HPA-selected or crossmatched platelet components can be used.596061

HLA and HPA-selected components should not be used if no HLA or HPA antibodies are detected.62

Other strategies for managing patients with platelet refractoriness who require procedures include thrombopoietin receptor agonists,63 complement inhibitors such as eculizumab,64 and slow infusion.65

References

  1. Colman, Robert W.; Marder, Victor J.; Clowes, Alexander W.; George, James N.; Goldhaber, Samuel Z. (2005), Hemostasis and Thrombosis: Basic Principles and Clinical Practice (5th ed.), Lippincott Williams & Wilkins, p. 1195, ISBN 978-0-7817-4996-1 978-0-7817-4996-1

  2. Stanworth, Simon J.; Navarrete, Cristina; Estcourt, Lise; Marsh, Judith (2015). "Platelet refractoriness – practical approaches and ongoing dilemmas in patient management". British Journal of Haematology. 171 (3): 297–305. doi:10.1111/bjh.13597. ISSN 1365-2141. PMID 26194869. S2CID 9379017. https://doi.org/10.1111%2Fbjh.13597

  3. "Guidelines for the management of platelet transfusion refractoriness" (PDF). hospital.blood.co.uk. Archived from the original (PDF) on 2018-12-20. Retrieved 2018-12-28. https://web.archive.org/web/20181220230802/http://hospital.blood.co.uk/media/2130/d5795605-7d36-40ce-8fb9-8c77254e24c6.pdf

  4. Stanworth, Simon J.; Navarrete, Cristina; Estcourt, Lise; Marsh, Judith (2015). "Platelet refractoriness – practical approaches and ongoing dilemmas in patient management". British Journal of Haematology. 171 (3): 297–305. doi:10.1111/bjh.13597. ISSN 1365-2141. PMID 26194869. S2CID 9379017. https://doi.org/10.1111%2Fbjh.13597

  5. "Guidelines for the management of platelet transfusion refractoriness" (PDF). hospital.blood.co.uk. Archived from the original (PDF) on 2018-12-20. Retrieved 2018-12-28. https://web.archive.org/web/20181220230802/http://hospital.blood.co.uk/media/2130/d5795605-7d36-40ce-8fb9-8c77254e24c6.pdf

  6. "transfusion.com.au". transfusion.com.au. Retrieved 2018-12-28. https://transfusion.com.au/transfusion_practice/platelet_refractoriness

  7. Hod, Eldad; Schwartz, Joseph (2008). "Platelet transfusion refractoriness". British Journal of Haematology. 142 (3): 348–360. doi:10.1111/j.1365-2141.2008.07189.x. ISSN 1365-2141. PMID 18510692. S2CID 42013955. /wiki/Doi_(identifier)

  8. Stanworth, Simon J.; Navarrete, Cristina; Estcourt, Lise; Marsh, Judith (2015). "Platelet refractoriness – practical approaches and ongoing dilemmas in patient management". British Journal of Haematology. 171 (3): 297–305. doi:10.1111/bjh.13597. ISSN 1365-2141. PMID 26194869. S2CID 9379017. https://doi.org/10.1111%2Fbjh.13597

  9. "Guidelines for the management of platelet transfusion refractoriness" (PDF). hospital.blood.co.uk. Archived from the original (PDF) on 2018-12-20. Retrieved 2018-12-28. https://web.archive.org/web/20181220230802/http://hospital.blood.co.uk/media/2130/d5795605-7d36-40ce-8fb9-8c77254e24c6.pdf

  10. "transfusion.com.au". transfusion.com.au. Retrieved 2018-12-28. https://transfusion.com.au/transfusion_practice/platelet_refractoriness

  11. Hod, Eldad; Schwartz, Joseph (2008). "Platelet transfusion refractoriness". British Journal of Haematology. 142 (3): 348–360. doi:10.1111/j.1365-2141.2008.07189.x. ISSN 1365-2141. PMID 18510692. S2CID 42013955. /wiki/Doi_(identifier)

  12. Slichter, Sherrill J.; Granger, Suzanne; Kaufman, Richard M.; Hess, John R.; Ness, P. M.; Strauss, Ronald G.; Assmann, Susan F.; Triulzi, Darrell J. (2012-06-07). "The impact of platelet transfusion characteristics on posttransfusion platelet increments and clinical bleeding in patients with hypoproliferative thrombocytopenia". Blood. 119 (23): 5553–5562. doi:10.1182/blood-2011-11-393165. ISSN 1528-0020. PMC 3369689. PMID 22496156. /wiki/Susan_Assmann

  13. Petraszko, Tanya; Zeller, Michelle (2018). Chapter 18: Platelet Transfusion, Alloimmunization and Management of Platelet Refractoriness. Canadian Blood Services. https://professionaleducation.blood.ca/en/transfusion/guide-clinique/platelet-transfusion-alloimmunization-and-management-platelet

  14. Slichter, Sherrill J.; Granger, Suzanne; Kaufman, Richard M.; Hess, John R.; Ness, P. M.; Strauss, Ronald G.; Assmann, Susan F.; Triulzi, Darrell J. (2012-06-07). "The impact of platelet transfusion characteristics on posttransfusion platelet increments and clinical bleeding in patients with hypoproliferative thrombocytopenia". Blood. 119 (23): 5553–5562. doi:10.1182/blood-2011-11-393165. ISSN 1528-0020. PMC 3369689. PMID 22496156. /wiki/Susan_Assmann

  15. Petraszko, Tanya; Zeller, Michelle (2018). Chapter 18: Platelet Transfusion, Alloimmunization and Management of Platelet Refractoriness. Canadian Blood Services. https://professionaleducation.blood.ca/en/transfusion/guide-clinique/platelet-transfusion-alloimmunization-and-management-platelet

  16. Slichter, Sherrill J.; Granger, Suzanne; Kaufman, Richard M.; Hess, John R.; Ness, P. M.; Strauss, Ronald G.; Assmann, Susan F.; Triulzi, Darrell J. (2012-06-07). "The impact of platelet transfusion characteristics on posttransfusion platelet increments and clinical bleeding in patients with hypoproliferative thrombocytopenia". Blood. 119 (23): 5553–5562. doi:10.1182/blood-2011-11-393165. ISSN 1528-0020. PMC 3369689. PMID 22496156. /wiki/Susan_Assmann

  17. Estcourt, Lise J; Malouf, Reem; Hopewell, Sally; Trivella, Marialena; Doree, Carolyn; Stanworth, Simon J; Murphy, Michael F (2017-07-30). "Pathogen-reduced platelets for the prevention of bleeding". Cochrane Database of Systematic Reviews. 7 (9): CD009072. doi:10.1002/14651858.cd009072.pub3. ISSN 1465-1858. PMC 5558872. PMID 28756627. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5558872

  18. Stanworth, Simon J.; Navarrete, Cristina; Estcourt, Lise; Marsh, Judith (2015). "Platelet refractoriness – practical approaches and ongoing dilemmas in patient management". British Journal of Haematology. 171 (3): 297–305. doi:10.1111/bjh.13597. ISSN 1365-2141. PMID 26194869. S2CID 9379017. https://doi.org/10.1111%2Fbjh.13597

  19. Rebulla, Paolo (2005). "A mini-review on platelet refractoriness". Haematologica. 90 (2): 247–253. ISSN 1592-8721. PMID 15710579. /wiki/ISSN_(identifier)

  20. Rebulla, Paolo (2005). "A mini-review on platelet refractoriness". Haematologica. 90 (2): 247–253. ISSN 1592-8721. PMID 15710579. /wiki/ISSN_(identifier)

  21. Hod, Eldad; Schwartz, Joseph (2008). "Platelet transfusion refractoriness". British Journal of Haematology. 142 (3): 348–360. doi:10.1111/j.1365-2141.2008.07189.x. ISSN 1365-2141. PMID 18510692. S2CID 42013955. /wiki/Doi_(identifier)

  22. Pavenski, Katerina; Freedman, John; Semple, J. W. (2012). "HLA alloimmunization against platelet transfusions: pathophysiology, significance, prevention and management". Tissue Antigens. 79 (4): 237–245. doi:10.1111/j.1399-0039.2012.01852.x. ISSN 1399-0039. PMID 22385314. /wiki/Doi_(identifier)

  23. Stanworth, Simon J.; Navarrete, Cristina; Estcourt, Lise; Marsh, Judith (2015). "Platelet refractoriness – practical approaches and ongoing dilemmas in patient management". British Journal of Haematology. 171 (3): 297–305. doi:10.1111/bjh.13597. ISSN 1365-2141. PMID 26194869. S2CID 9379017. https://doi.org/10.1111%2Fbjh.13597

  24. Rebulla, Paolo (2005). "A mini-review on platelet refractoriness". Haematologica. 90 (2): 247–253. ISSN 1592-8721. PMID 15710579. /wiki/ISSN_(identifier)

  25. Stanworth, Simon J.; Navarrete, Cristina; Estcourt, Lise; Marsh, Judith (2015). "Platelet refractoriness – practical approaches and ongoing dilemmas in patient management". British Journal of Haematology. 171 (3): 297–305. doi:10.1111/bjh.13597. ISSN 1365-2141. PMID 26194869. S2CID 9379017. https://doi.org/10.1111%2Fbjh.13597

  26. "Guidelines for the management of platelet transfusion refractoriness" (PDF). hospital.blood.co.uk. Archived from the original (PDF) on 2018-12-20. Retrieved 2018-12-28. https://web.archive.org/web/20181220230802/http://hospital.blood.co.uk/media/2130/d5795605-7d36-40ce-8fb9-8c77254e24c6.pdf

  27. Rebulla, Paolo (2005). "A mini-review on platelet refractoriness". Haematologica. 90 (2): 247–253. ISSN 1592-8721. PMID 15710579. /wiki/ISSN_(identifier)

  28. Hod, Eldad; Schwartz, Joseph (2008). "Platelet transfusion refractoriness". British Journal of Haematology. 142 (3): 348–360. doi:10.1111/j.1365-2141.2008.07189.x. ISSN 1365-2141. PMID 18510692. S2CID 42013955. /wiki/Doi_(identifier)

  29. Pavenski, Katerina; Freedman, John; Semple, J. W. (2012). "HLA alloimmunization against platelet transfusions: pathophysiology, significance, prevention and management". Tissue Antigens. 79 (4): 237–245. doi:10.1111/j.1399-0039.2012.01852.x. ISSN 1399-0039. PMID 22385314. /wiki/Doi_(identifier)

  30. Hod, Eldad; Schwartz, Joseph (2008). "Platelet transfusion refractoriness". British Journal of Haematology. 142 (3): 348–360. doi:10.1111/j.1365-2141.2008.07189.x. ISSN 1365-2141. PMID 18510692. S2CID 42013955. /wiki/Doi_(identifier)

  31. Pavenski, Katerina; Freedman, John; Semple, J. W. (2012). "HLA alloimmunization against platelet transfusions: pathophysiology, significance, prevention and management". Tissue Antigens. 79 (4): 237–245. doi:10.1111/j.1399-0039.2012.01852.x. ISSN 1399-0039. PMID 22385314. /wiki/Doi_(identifier)

  32. Rebulla, P. (1993). "Formulae for the definition of refractoriness to platelet transfusion". Transfusion Medicine. 3 (1): 91–92. doi:10.1111/j.1365-3148.1993.tb00108.x. ISSN 1365-3148. PMID 8038900. S2CID 555511. /wiki/Doi_(identifier)

  33. Hod, Eldad; Schwartz, Joseph (2008). "Platelet transfusion refractoriness". British Journal of Haematology. 142 (3): 348–360. doi:10.1111/j.1365-2141.2008.07189.x. ISSN 1365-2141. PMID 18510692. S2CID 42013955. /wiki/Doi_(identifier)

  34. Pavenski, Katerina; Freedman, John; Semple, J. W. (2012). "HLA alloimmunization against platelet transfusions: pathophysiology, significance, prevention and management". Tissue Antigens. 79 (4): 237–245. doi:10.1111/j.1399-0039.2012.01852.x. ISSN 1399-0039. PMID 22385314. /wiki/Doi_(identifier)

  35. Pavenski, Katerina; Freedman, John; Semple, J. W. (2012). "HLA alloimmunization against platelet transfusions: pathophysiology, significance, prevention and management". Tissue Antigens. 79 (4): 237–245. doi:10.1111/j.1399-0039.2012.01852.x. ISSN 1399-0039. PMID 22385314. /wiki/Doi_(identifier)

  36. Hod, Eldad; Schwartz, Joseph (2008). "Platelet transfusion refractoriness". British Journal of Haematology. 142 (3): 348–360. doi:10.1111/j.1365-2141.2008.07189.x. ISSN 1365-2141. PMID 18510692. S2CID 42013955. /wiki/Doi_(identifier)

  37. Rebulla, P. (1993). "Formulae for the definition of refractoriness to platelet transfusion". Transfusion Medicine. 3 (1): 91–92. doi:10.1111/j.1365-3148.1993.tb00108.x. ISSN 1365-3148. PMID 8038900. S2CID 555511. /wiki/Doi_(identifier)

  38. Hod, Eldad; Schwartz, Joseph (2008). "Platelet transfusion refractoriness". British Journal of Haematology. 142 (3): 348–360. doi:10.1111/j.1365-2141.2008.07189.x. ISSN 1365-2141. PMID 18510692. S2CID 42013955. /wiki/Doi_(identifier)

  39. Pavenski, Katerina; Freedman, John; Semple, J. W. (2012). "HLA alloimmunization against platelet transfusions: pathophysiology, significance, prevention and management". Tissue Antigens. 79 (4): 237–245. doi:10.1111/j.1399-0039.2012.01852.x. ISSN 1399-0039. PMID 22385314. /wiki/Doi_(identifier)

  40. Rebulla, P. (1993). "Formulae for the definition of refractoriness to platelet transfusion". Transfusion Medicine. 3 (1): 91–92. doi:10.1111/j.1365-3148.1993.tb00108.x. ISSN 1365-3148. PMID 8038900. S2CID 555511. /wiki/Doi_(identifier)

  41. Pavenski, Katerina; Freedman, John; Semple, J. W. (2012). "HLA alloimmunization against platelet transfusions: pathophysiology, significance, prevention and management". Tissue Antigens. 79 (4): 237–245. doi:10.1111/j.1399-0039.2012.01852.x. ISSN 1399-0039. PMID 22385314. /wiki/Doi_(identifier)

  42. Pavenski, Katerina; Freedman, John; Semple, J. W. (2012). "HLA alloimmunization against platelet transfusions: pathophysiology, significance, prevention and management". Tissue Antigens. 79 (4): 237–245. doi:10.1111/j.1399-0039.2012.01852.x. ISSN 1399-0039. PMID 22385314. /wiki/Doi_(identifier)

  43. Hod, Eldad; Schwartz, Joseph (2008). "Platelet transfusion refractoriness". British Journal of Haematology. 142 (3): 348–360. doi:10.1111/j.1365-2141.2008.07189.x. ISSN 1365-2141. PMID 18510692. S2CID 42013955. /wiki/Doi_(identifier)

  44. AABB (2014). Standards for Blood Banks and Transfusion Services. AABB. ISBN 9781563958878. 9781563958878

  45. "Platelets, Apheresis, Leucocyte Depleted". www.transfusionguidelines.org. Retrieved 2018-12-29. https://www.transfusionguidelines.org/red-book/chapter-7-specifications-for-blood-components/7-10-platelets-apheresis-leucocyte-depleted

  46. "Platelets, Pooled, Buffy Coat Derived, in Additive Solution and Plasma, Leucocyte Depleted". www.transfusionguidelines.org. Retrieved 2018-12-29. https://www.transfusionguidelines.org/red-book/chapter-7-specifications-for-blood-components/7-11-platelets-in-additive-solution-and-plasma-leucocyte-depleted

  47. "Platelets, Apheresis, Leucocyte Depleted". www.transfusionguidelines.org. Retrieved 2018-12-29. https://www.transfusionguidelines.org/red-book/chapter-7-specifications-for-blood-components/7-10-platelets-apheresis-leucocyte-depleted

  48. "Platelets, Pooled, Buffy Coat Derived, in Additive Solution and Plasma, Leucocyte Depleted". www.transfusionguidelines.org. Retrieved 2018-12-29. https://www.transfusionguidelines.org/red-book/chapter-7-specifications-for-blood-components/7-11-platelets-in-additive-solution-and-plasma-leucocyte-depleted

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  50. Cohn CS (December 2020). "Platelet transfusion refractoriness: how do I diagnose and manage?". Hematology Am Soc Hematol Educ Program. 2020 (1): 527–532. doi:10.1182/hematology.2020000137. PMC 7727584. PMID 33275694. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727584

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  52. Nahirniak, Susan; Slichter, Sherrill J.; Tanael, Susano; Rebulla, Paolo; Pavenski, Katerina; Vassallo, Ralph; Fung, Mark; Duquesnoy, Rene; Saw, Chee-Loong (2015). "Guidance on platelet transfusion for patients with hypoproliferative thrombocytopenia". Transfusion Medicine Reviews. 29 (1): 3–13. doi:10.1016/j.tmrv.2014.11.004. ISSN 1532-9496. PMID 25537844. /wiki/Doi_(identifier)

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