Platelet Transfusions, Mortality, and ABO Identicality in Premature Newborns

Bahr et al report a series of neonates who received very large numbers of platelet transfusions (>25), with dire outcomes, potentially in part related to the toxicity of repeated ABO mismatched platelet transfusions.[1] For many years platelets were thought of as purely hemostatic in function. However, approximately 20 to 25 years ago it became clear platelets were involved in host defense and contained large amounts of immunomodulatory mediators such as sCD40L, VEGF, IL-6, etc. Platelet transfusions have been shown to be proinflammatory and prothrombotic, both in vitro and in vivo in patients.[2] Recent randomized trials, including those in premature neonates, have demonstrated that aggressive platelet transfusions are associated with increased bleeding and mortality.[3] The patients reported by Bahr et al likely reflect, at least in part, the reality that ABO nonidentical platelet transfusions contribute to inflammation and bleeding and perhaps even mortality. One take home lesson is to transfuse fewer prophylactic platelet transfusions to newborns who are not bleeding, contrary to long-standing practice. There is little or no evidence of efficacy and accumulating evidence of harm.

There is an abiding dogma, unsupported by credible data, that ABO blood group does not matter for platelet transfusions. This dogma ignores substantial scientific and clinical evidence, as two randomized trials and one large observational study demonstrate increased platelet transfusion refractoriness following ABO nonidentical platelet transfusions.[4] [5] [6] When ABO identical and leukoreduction are combined, the refractoriness rate is close to zero, compared with 10 to 20% in the literature.[4] The mechanism of refractoriness, in patients such as those described, is the infusion of both ABO nonidentical antigen and antibody through repetitive transfusions that do not respect the patient's ABO blood group. The effect is cumulative and lasts days to weeks in our experience. Indeed, we have never seen a newborn who is platelet transfusion refractory.

Newborns are unlikely to mount de novo antibody responses of their own. However, transfusing ABO nonidentical antibody and antigen mimics the situation in older children and adults, in which use of nonleukoreduced, ABO nonidentical transfusions historically led to refractoriness in the range of 50% of repeatedly transfused patients (Personal observation). Refractoriness is associated with early mortality.[7] Additional observational and epidemiological studies provide evidence that ABO nonidentical transfusions are associated with increased bleeding, sepsis, lung injury, and mortality in a variety of clinical settings.[8] [9] [10] [11]

Neonatologists, intensivists, hematologists, anesthesiologists, etc., need to insist their transfusion services adopt universal leukoreduction (largely achieved outside the United States) and make greater efforts to avoid infusing ABO nonidentical antibody and cellular/soluble antigen. This can be achieved or fostered by employing some combination of ABO identical blood components, employing restrictive transfusion thresholds, and removing ABO nonidentical supernatant through washing or other means. Neonatologists also should consider adopting more conservative platelet transfusion practices (prophylaxis for counts of less than 10–20,000/µL), rather than higher platelet counts as at present. There is no evidence that higher thresholds provide clinical benefit.

Another potential approach to reducing platelet transfusion toxicity is to reduce the volume transfused from the typical 15 to 20 mL/kg to 3 to 5 mL/kg. The latter is the dose that has successfully reduced bleeding in adult randomized trials of prophylactic platelet transfusions.[12] Extraordinarily high infused volumes very likely increase toxicity with no clinical benefit and are not evidence based. Transfusion services should strive to avoid providing ABO nonidentical platelets unless ABO nonidentical cellular/soluble antigen and antibody have been substantially reduced/avoided.

Publication History

Received: 13 July 2023

Accepted: 19 October 2023

Accepted Manuscript online:
20 October 2023

Article published online:
08 November 2023

• References

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