Platelet function is the key cellular mechanism of primary hemostasis. Bleeding diatheses occur as a result of quantitative or qualitative disorders of platelets, which may be due to congenital or acquired causes. Acquired platelet dysfunction can be chronic, such as in leukemia, lymphoma, or bone marrow failure, or acute, such as in trauma, disseminated intravascular coagulation (DIC), or uremia. Maintaining platelet function and correcting defects in hemostasis in bleeding critically ill patients sometimes requires platelet transfusion from normal donors. At the blood donation center platelet units are provided in two forms: pooled multiple-donor whole-blood-derived or single-donor concentrates. The latter are collected via an apheresis instrument from a single donor, tested for bacterial contamination, and then stored at room temperature on a shaker until transfusion, which should occur within five days of collection. Whole blood (sometimes called random donor) platelet units, on the other hand, are collected via a separation technique from single whole blood units and stored on a shaker at room temperature until released within five days of collection. At that time, three to six random units are pooled in a single bag (one dose), tested for bacterial contamination, and then released for transfusion.
Transfusion of ABO-mismatched red blood cells (RBCs) can cause significant immune-mediated hemolytic transfusion reactions. As a result, critical complications including renal failure, DIC, end organ damage, and even death may occur. Therefore, only identical ABO RBCs are transfused, except in emergencies, when group O RBCs are transfused, despite containing anti-A and anti-B antibodies. In practice, this rule has been overlooked in fresh frozen plasma (FFP) and platelet transfusions in most centers despite reports of hemolytic reactions (acute or delayed) and some unexplained complications, such as multi-organ failure syndromes, transfusion-related lung injury (TRALI), and poor control of bleeding.1,2
Platelet transfusion is a critical component of tertiary medical care, with over nine million platelet concentrate equivalent units (about two million doses) transfused per year in the US.3
The frequency of complications is estimated to be approximately one in 1,000 platelet doses. Recent findings demonstrate that transfusion of ABO-non-identical platelets is associated with increased bleeding in surgical patients.4,5
Blunt trauma patients who received at least one ABO-non-identical blood product transfusion demonstrated significantly higher RBC usage.6
The pathogenesis of these complications remains controversial, but some evidence indicates that they may be caused by the effects of ABO incompatibility. Furthermore, in clinical practice specific ABO type platelets are required occasionally, and are considered a first-line therapy in the management of certain patients, such as those with leukemia, lymphoma, or poor responsiveness to platelet transfusion (platelet refractoriness).7,8
Considering these findings, along with our clinical observations in a blood bank/transfusion medicine practice, we formulated the following hypothesis. Since platelets possess A and B antigen on their surfaces (similar to RBCs but with lesser density),9,10
mismatched transfused or recipient platelets could become activated and/or hypofunctional by exposure to anti-A and anti-B antibodies found in the transfused or recipient plasma. Once activated, platelets undergo a shape change from the typical discoid shape to a globular form with pseudopodia. This change allows platelets to release a number of different coagulation factors, inflammatory mediators, and platelet-activating factors from their granules. This activation process mediates the transport of negatively charged phospholipids to the platelet surface, which provides a catalytic surface for clot formation.11,12
Therefore, an ABO-non-identical transfusion will cause platelet activation (either the patient’s platelets or the transfused platelets) by the anti-A and anti-B antibodies found in either the patient’s plasma or the transfused product. As a result, bleeding will be exaggerated in trauma patients, leading to more transfusion, whereas in some clinical settings excessive clot formation may occur in transfusion-dependent patients. Thus, to further characterize our preliminary clinical observations, we decided to investigate a model system to determine whether anti-A and anti-B antibodies found in plasma can mediate platelet or other hemostatic dysfunction.