A Step toward Combined Platelet and Erythrocyte Recovery

Cell salvage is one of the cornerstones of perioperative blood conservation.¹  Its use has been associated with a reduction in allogeneic erythrocyte transfusion in a number of clinical scenarios where excessive bleeding is experienced.^2,3  Autologous erythrocyte transfusions may reduce transfusion-associated adverse reactions due to their favorable immunologic profile (patient’s own blood) and possible immunological benefit of fresh blood (immune-suppressive effects of storage).⁴  Traditional centrifugation-based devices can only recover erythrocytes while platelets and other coagulation factors are lost in the process. Although there is now an increasing number of alternatives to replace fibrinogen (e.g., fibrinogen concentrate) or specific coagulation factors (e.g., 4-factor prothrombin complex concentrate) in the context of acquired coagulopathy, allogeneic platelet transfusion remains the only option to treat thrombocytopenia and potential platelet dysfunction. Because allogeneic platelets carry the highest risk of transfusion reactions,⁵  one could argue that the transfusion of autologous platelets could offer a comparable benefit.

In this issue of Anesthesiology, Mansour et al. report their evaluation of a novel autotransfusion device that was designed as a filtration-based autotransfusion tool capable of recovering both erythrocytes and platelets.⁶  Using a combination of washing and filtration of salvaged blood, the device allows for the concentration of erythrocytes, leukocytes, and platelets while removing heparin, free hemoglobin, coagulation factors, and inflammatory mediators. In the current ex vivo study, the authors evaluated their autotransfusion device using human whole blood with the goal of determining the performance of the technology in terms of platelets and erythrocyte recovery, both qualitatively and quantitatively. They measured the percentage of erythrocytes and platelets recovered, the degree of hemolysis, erythrocyte deformability, and performed flow-cytometric evaluation of platelet function and activation and flow-cytometric evaluation of leukocyte viability and activation. The authors found that the device achieved an erythrocyte recovery of approximately 85 to 90%, with product hematocrits of approximately 50%. Platelet recovery was approximately 35 to 40%, with platelet counts in the washed product of approximately 100 × 10⁹/l. Recovered leukocytes were not activated and the device prevented from reinfusion of heparin and plasma proteins. Both erythrocytes and platelets were found not to suffer from changes in cell integrity and function by the measures used.

Platelets are complex cells involved in hemostasis, inflammatory reaction, and wound healing. Some studies have suggested that the biologic changes occurring during storage and the lack of ABO compatibility often tolerated for platelet transfusions (among other causes) might explain the risk of platelet-associated transfusion reactions.⁵  Platelet recovery using autotransfusion devices has been previously studied, but the use of a centrifugation technique has been found challenging as both the speed and duration of the centrifugation influence the physical and functional properties of the salvaged platelets. In addition, the suction forces (–150 to –400 millibars) used during cell salvage are associated with a risk of physical alteration of both erythrocytes and platelets.⁷  Although the concept of autologous platelet transfusion described in the current study is attractive and might help decrease the need for allogeneic platelets and the risk associated with their transfusion, clinical studies are needed before determining the value of this approach for a few reasons.

Platelets are dynamic and highly responsive cells. Platelets undergo a series of activations dependent on the level of stimulation encountered, and how they react to a certain stimulus will determine what clinical outcome will occur. If the platelets underreact to a stimulation, the clinical phenotype will be bleeding, while platelet overactivation can lead to thrombotic complications. In addition, platelet hemostatic properties are highly influenced by blood flow and the degree of shear stress.⁸  Due to the very sensitive nature of those cells and the way they interact with their milieu, it is extremely challenging for platelets to maintain “physiologic” hemostatic properties when moved or removed from their biologic environment. In the study published by Mansour et al.,⁶  platelet surface receptor expression was not excessively increased and responded to one of the most powerful platelet agonists (thrombin receptor activating peptide); however, normal ranges of surface receptor responses to thrombin receptor–activating peptide or references to the clinical relevance of these parameters were not provided. Furthermore, clinically significant platelet dysfunction (such as that induced by extracorporeal circulation) is measured by adenosine diphosphate agonist testing, not thrombin receptor–activating peptide, and platelet aggregation was not assessed. Evidence of surface receptor activation in response to thrombin receptor–activating peptide does not, therefore, equate to evidence of adequate or normal function. While the value of the device in restoring platelet count and hemostasis in a bleeding situation will have to be studied, the risk of complications, including thrombotic events, after the transfusion of autologous platelets will have to be evaluated as well.

Allogeneic platelet units in the United States (predominantly single-donor apheresis units) must contain at least 300 × 10⁹ platelets per 250 to 300 ml (typically there are more than this minimum), in contrast with the product with the autotransfusion device, which will contain approximately 25 × 10⁹ in 200 ml. An allogeneic unit will increase the platelet count by 20 to 40 × 10⁹/l in a 70-kg adult, whereas over 2,000 ml of autotransfusion product would be required to provide the same number of platelets. This is unlikely to provide the same increment, as well over 2,000 ml of spilled blood would have to be processed to generate such a platelet dose. Administration of a concentrated product is far more successful at producing a higher incremental response, as is seen with clotting factor concentrates compared with plasma.⁹  As such, while initially attractive, further studies will be needed to assess the clinical impact on platelet transfusion requirements in patients experiencing different severities of blood loss. Because the hematocrit of the product is lower than that in many cell savers, a direct comparison of the authors’ autotransfusion device with other existing cell savers would be informative.

Finally, the authors also report a significant presence of leukocytes in the salvaged blood. Although leukocytes appear not be activated ex vivo, the clinical consequences of reinfusing leukocytes will have to be studied in vivo bearing in mind that the use of a leukocyte filter would retain the platelets.

In summary, the autotransfusion device here studied by Mansour et al. appears to be a promising tool for the recovery of erythrocytes and platelets in bleeding patients. The use of such a technology could be associated with a decreased need for both allogenic erythrocyte and platelet transfusions. However, further analyses of the effect of the device on the physical and functional properties of the salvaged platelets in vivo as well as the risk of adverse events after reinfusing them will be needed before such a device can be considered clinically.