Safety and Efficacy of 14-Day Cold Stored Platelets in Reversing Effects of Aspirin

Background: Aspirin is an antiplatelet therapy used to reduce the risk of vascular occlusive events. However, this therapy is associated with an increased risk of bleeding for which there is no antidote currently. Transfusion of 5-day room stored platelets (RSP) at 22°C can reverse the effect of aspirin but surprisingly, the recent randomized PATCH trial showed increased morbidity and mortality for patients who received RSP transfusion for intracranial hemorrhage while on aspirin. Prior studies have shown that cold stored platelets (CSP) at 4°C are mildly activated and may participate in clot formation immediately, thus may have the potential to reduce blood loss more rapidly than RSP in acutely bleeding patients. CSP also have the added advantages of decreased risk of bacterial contamination and longer shelf-life up to 14 days per current FDA variance. However, the function of 14-day CSP in plasma after transfusion is unclear and lacks high quality data. We aimed to evaluate the post-transfusion safety and efficacy of 14-day CSP in reversing the effects of aspirin therapy compared to that of 7-day RSP. Methods: Seven healthy human subjects were included in the analysis of this randomized, controlled, crossover study comparing transfusion of autologous 14-day CSP to 7-day RSP. Each subject participated in two study periods, which crossed over from one storage product to the other (CSP vs. RSP) according to randomization. For each study period, subjects underwent an apheresis platelet collection for autologous transfusion. Platelets were stored for either 14 days for CSP or 7 days for RSP. Subjects received a loading dose of aspirin 24 hours prior to transfusion. Blood was drawn at baseline, immediately pre-transfusion, at 1-hr, 4-hr, and 24-hr post-transfusion for an array of platelet function testing. After a washout period of 10-28 days, second study period commenced with similar sequence of events as the first study period using the other platelet storage product. The primary endpoint is the VerifyNOW Aspirin Reaction Units (ARU) at 1-hr after autologous transfusion. Secondary endpoints include ARU at 4-hr and 24-hr post transfusion, light transmission aggregometry in response to arachidonic acid and collagen, and the corrected count increment. Paired t-tests were used for statistical analysis between the two groups and, where appropriate, the change from pre-transfusion values were analyzed. Results: Transfusion of 14-day CSP and 7-day RSP units were well-tolerated by all subjects. Storage of platelets in the cold led to a non-significant trend for decreased platelet count, and the total platelet yield at the end of storage was significantly less in 14-day CSP compared to 7-day RSP (p=0.02). However, the corrected count increment did not differ significantly at 1-hr after transfusion. Platelet aggregation using the agonists, arachidonic acid 0.5mM and collagen 2.5ug/mL, did not reveal any significant difference between the two groups at any time points. The primary endpoint, platelet function testing by VerifyNOW, showed a larger change in platelet responsiveness at 1-hr post-transfusion in RSP than in CSP (p=0.03). Surprisingly, only RSP transfusion resulted in a significant change from the pre-transfusion VerifyNow measurements. Later time points showed a slight trend for improved platelet function as measured by VerifyNow with transfusion of both platelet products, but none were statistically significant. Conclusion: We report the first safety and efficacy data for 14-day cold stored platelets in in healthy humans. While prior in-vitro studies have demonstrated possible hemostatic superiority of cold stored over room temperature stored platelets, we observed inferior reversal of aspirin at early time points with CSP. This was in contrast to the results from our previous study, where 5 day-stored CSP were equivalent to RSP at early post transfusion time points. Further studies are needed to evaluate the maximal storage that provides functional equivalency between CSP and RSP. In addition, studies in actively bleeding patients are needed. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

How I treat anemia in the perisurgical setting

Anemia is a common finding in the perioperative setting with significant untoward consequences including worsening of outcomes and diminished quality of life as well as increased risk of allogeneic blood transfusions. Here, we present 3 cases that illustrate how anemia can be perioperatively managed in patients undergoing cardiac, orthopedic, and oncology surgeries. Timely detection of anemia prior to high-blood loss surgeries can allow clinicians to manage it and optimize hemoglobin level, making patients better prepared for the surgery. Treatment of anemia should be guided by the etiology and may include erythropoietic agents, folic acid, B12, and iron preparations. Other blood management strategies geared toward reducing surgical blood loss such as autologous transfusion techniques and agents to optimize hemostasis are used during surgery and in the immediate postoperative period. Patients should be closely monitored following surgery for signs of ongoing bleeding in need of control. Finally, screening for and management of anemia should continue in the postoperative and postdischarge period, as persistence and recurrence of anemia can further undermine patient’s outcomes.

Selling the role of salvage: Cell salvage past and present

The use of transfused blood, be it from an allogenic (donor) or autologous (same patient) source, is not a new treatment and in fact has been experimented with since the mid 1800s. The role of cell salvage and re-infusion of a patient’s own blood, however, has only begun to gain real popularity in the last 20 years, after the undertaking of several large scale meta-analyses which have shown that not only is autologous transfusion no less efficacious when compared to allogenic transfusion, but also potentially safer for a number of reasons. Autologous transfusion is also more cost effective overall and potentially quicker to initiate in an emergency situation. Despite the body of evidence to support the use of salvaged blood for transfusion, hesitation around its use still persists, with staff apprehension around set up of cell salvage equipment and general underestimation of intraoperative blood loss being key factors in its underuse.

A prospective study to evaluate the effects of acute normovolemic hemodilution on perioperative homologous transfusion requirements in patients undergoing major surgery

Background: Acute Normovolemic Hemodilution (ANH) and autologous transfusion can mitigate the harmful effects of banked blood intraoperatively. This study was planned to evaluate its effects on perioperative transfusion requirement, hemodynamic stability and safety profile.Methods: Hundred patients were randomized to Group 1, where assigned patients received ANH and autologous transfusion after hemostasis; and Group II where assigned patients received homologous transfusion. In group I, 350 to 700 ml of patient's blood was collected before induction of anaesthesia and was kept in the operation theatre at room temperature. This was followed by rapid infusion of calculated Hetastarch. Intraoperative blood loss, amount of transfused blood, serial haemoglobin (Hb) assessment, and change in hemodynamics were carefully monitored. The blood was reinfused once hemostasis was secured at the end of surgery.Results: It was observed that hemodynamic stability was maintained in both the groups during and after haemodilution. There was no significant change in bleeding and clotting time due to haemodilution. The mean intra-operative blood loss in both groups was comparable. 350 mL and 700 mL blood withdrawn in 27 and 23 patients and 500mL and 1000 mL HES infused respectively. There was an average fall in the mean Hb level by 1.74 gm % and in the mean haematocrit (Hct) level by 6.4 % after haemodilution. The mean 12th and 24th hour Hb and Hct levels were comparable. The requirement of homologous blood transfusion in group I was significantly low (p<0.0001). Need for homologous transfusion was 0.72 per patient treated in the Group I.Conclusions: Acute normovolemic hemodilution is a simple, safe and effective modality to reduce perioperative transfusion of banked blood and should be considered in patients undergoing surgical procedures where major blood loss is expected.