Platelet transfusion refractoriness

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.<ref>

</ref><ref name=":0">Stanworth, Simon J.,

 Platelet refractoriness – practical approaches and ongoing dilemmas in patient management, 
 British Journal of Haematology, 
 
 Vol. 171(Issue: 3),
 pp. 297–305,
 DOI: 10.1111/bjh.13597,
 PMID: 26194869,</ref>

Cause

Platelet refractoriness can be due to immune causes or non-immune causes.<ref name=":1">

Guidelines for the management of platelet transfusion refractoriness(link). hospital.blood.co.uk.

Accessed 2018-12-28.

</ref> Non-immune causes account for over 80% of cases of platelet refractoriness, and sepsis is one of the most common non-immune causes.<ref name=":0" /><ref name=":1" /><ref name=":2">

transfusion.com.au(link). transfusion.com.au.

Accessed 2018-12-28.

</ref><ref name=":3">Hod, Eldad,

 Platelet transfusion refractoriness, 
 British Journal of Haematology, 
 
 Vol. 142(Issue: 3),
 pp. 348–360,
 DOI: 10.1111/j.1365-2141.2008.07189.x,
 PMID: 18510692,</ref> HLA alloimmunization is the commonest immune cause of platelet refractoriness.<ref name=":0" /><ref name=":1" /><ref name=":2" /><ref name=":3" />

Non-immune causes

Patient-related

• Sepsis

• Fever

• Disseminated intravascular coagulation

• Splenomegaly

• Treatment of infection, antibiotics (vancomycin), antifungals (amphotericin B)

• Graft-versus-host disease

• Hepatic veno-occlusive disease

• Bleeding

Platelet component-related

• Age of platelet component<ref name=":9">Slichter, Sherrill J.,

 The impact of platelet transfusion characteristics on posttransfusion platelet increments and clinical bleeding in patients with hypoproliferative thrombocytopenia, 
 Blood, 
 
 Vol. 119(Issue: 23),
 pp. 5553–5562,
 DOI: 10.1182/blood-2011-11-393165,
 PMID: 22496156,
 PMC: 3369689,</ref><ref name=":10">Tanya, 
  
 Chapter 18: Platelet Transfusion, Alloimmunization and Management of Platelet Refractoriness. online version, 
  
 Canadian Blood Services, 
 2018,</ref>

• ABO mismatch between platelet component and recipient<ref name=":9" /><ref name=":10" />
• Number of platelets within the component if platelet increment (PI) is used to calculate platelet refractoriness<ref name=":9" />
• Pathogen-reduced platelet component<ref>Estcourt, Lise J,

 Pathogen-reduced platelets for the prevention of bleeding, 
 Cochrane Database of Systematic Reviews, 
 
 Vol. 7,
 pp. CD009072,
 DOI: 10.1002/14651858.cd009072.pub3,
 PMID: 28756627,
 PMC: 5558872,</ref>

Immune causes

• Alloantibodies to platelet antigens
  • Human leucocyte antigen (HLA) antibodies
  • Human platelet antigen (HPA) antibodies

• Immune complexes

• Other antibodies
  • Drug-related antibodies

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.<ref name=":0" /><ref name=":4">Rebulla, Paolo,

 A mini-review on platelet refractoriness, 
 Haematologica, 
 
 Vol. 90(Issue: 2),
 pp. 247–253,
 
 PMID: 15710579,</ref>

Platelet increment (PI)

This is the simplest method, and only requires data on the platelet count before and after the transfusion.<ref name=":4" /> The platelet increment is also known as the absolute count increment and count increment.<ref name=":6" /><ref name=":3" />

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.<ref name=":0" /><ref name=":4" /> These factors are adjusted for in the other methods of defining platelet refractoriness.<ref name=":0" /><ref name=":1" /><ref name=":4" />

A 1 hour post-transfusion PI of less than 5 to 10 x 10⁹/l is considered evidence of platelet refractoriness.<ref name=":3" /><ref name=":6" /> 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.<ref name=":3" />

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)<ref name=":5">Rebulla, P.,

 Formulae for the definition of refractoriness to platelet transfusion, 
 Transfusion Medicine, 
 
 Vol. 3(Issue: 1),
 pp. 91–92,
 DOI: 10.1111/j.1365-3148.1993.tb00108.x,</ref><ref name=":6">Pavenski, Katerina, 
 HLA alloimmunization against platelet transfusions: pathophysiology, significance, prevention and management, 
 Tissue Antigens, 
 
 Vol. 79(Issue: 4),
 pp. 237–245,
 DOI: 10.1111/j.1399-0039.2012.01852.x,
 PMID: 22385314,</ref>

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

At 1 hour post-transfusion, a PPR < 20% is considered evidence of platelet refractoriness.<ref name=":3" /><ref name=":6" /> At 16 hours post-transfusion a PPR < 10% is considered evidence of platelet refractoriness.<ref name=":6" />

Percentage platelet increment (PPI)

PPI is very similar to the percentage platelet recovery (PPR) but the patient’s total blood volume is estimated using the patient’s weight multiplied by 0.07, and there has been an additional adjustment for splenic pooling of platelets (multiplied by 2/3)<ref name=":5" /><ref name=":3" />

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

Corrected count increment (CCI)

This requires data on the platelet increment (PI), the patient’s Body surface area (BSA), and the number of platelets transfused (PD).<ref name=":5" /><ref name=":3" /><ref name=":6" />

CCI = ((PI x BSA)/PD

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.<ref name=":6" /> At 24 hours post transfusion a CCI less than 5000 suggests platelet refractoriness.<ref name=":6" />

Platelet dose

Some blood banks maintain records of the estimated number of platelets in each unit.<ref name=":3" /> Current requirements in the US stipulate that a unit of apheresis platelets must contain at least 3.0 x10¹¹ platelets.<ref>,

 Standards for Blood Banks and Transfusion Services, 
  
 AABB, 
  
  
  
 ISBN 9781563958878,</ref> 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. <ref name=":7">

Platelets, Apheresis, Leucocyte Depleted(link). www.transfusionguidelines.org.

Accessed 2018-12-29.

</ref><ref name=":8">

Platelets, Pooled, Buffy Coat Derived, in Additive Solution and Plasma, Leucocyte Depleted(link). www.transfusionguidelines.org.

Accessed 2018-12-29.

</ref> Only components that contain fewer than 1.6 x 10¹¹ platelets are discarded.<ref name=":7" /><ref name=":8" /> This means that there can be a lot of variability in the number of platelets contained within each transfusion.<ref name=":3" />

Treatment

This depends on the underlying cause.

Non-immune causes are usually treated by treating the underlying cause e.g. sepsis.<ref name=":1" /><ref name=":11">Nahirniak, Susan,

 Guidance on platelet transfusion for patients with hypoproliferative thrombocytopenia, 
 Transfusion Medicine Reviews, 
 
 Vol. 29(Issue: 1),
 pp. 3–13,
 DOI: 10.1016/j.tmrv.2014.11.004,
 PMID: 25537844,</ref> 

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).<ref name=":1" /><ref name=":2" />

If an immune cause is suspected and HLA antibodies are detected, then HLA-selected platelet components can be used.<ref name=":1" /><ref name=":2" /> Although HLA-selected platelets lead to improved platelet increments at 1 hour post-transfusion,<ref name=":12">Pavenski, Katerina,

 Efficacy of HLA-matched platelet transfusions for patients with hypoproliferative thrombocytopenia: a systematic review, 
 Transfusion, 
 
 Vol. 53(Issue: 10),
 pp. 2230–2242,
 DOI: 10.1111/trf.12175,
 PMID: 23550773,</ref> there is currently insufficient evidence to demonstrate their clinical effectiveness at preventing bleeding.<ref name=":12" /> 

If HLA antibodies are not detected, and HPA antibodies are detected, then HPA-selected or crossmatched platelet components can be used.<ref name=":1" /><ref name=":10" /><ref name=":11" />

HLA and HPA-selected components should not be used if no HLA or HPA antibodies are detected.<ref name=":11" />

References

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