Platelet Function During Extracorporeal Membrane Oxygenation in Adult Patients

Abstract

Objective: Hemorrhagic and thromboembolic complications are common during support with extracorporeal membrane oxygenation (ECMO). As platelets play a pivotal role in hemostasis, we aimed to clarify how ECMO support affects platelet function. Methods: We included 33 adult patients undergoing ECMO support at a tertiary ECMO referral center at Aarhus University Hospital, Denmark. Blood samples were collected on the first morning following ECMO initiation, and subsequently every morning until the 7th (±1) day. Platelet aggregation was evaluated by whole blood impedance aggregometry (Multiplate ® Analyzer) using adenosine diphosphate (ADPtest), arachidonic acid (ASPItest), and thrombin-receptor-agonist-peptide-6 (TRAPtest) as agonists. A new model was applied, taking platelet count into consideration in interpretation of impedance aggregometry analyses. On the 1st and 3rd day, platelet activation was assessed by flow cytometry (Navios) using collagen-related peptide, ADP, TRAP, and arachidonic acid as agonists. Results: Blood samples from all 33 patients were analyzed on day 1 of ECMO support; 24 patients were still receiving ECMO and analyzed on day 3; 12 patients were analyzed on day 7 (±1). After ECMO initiation, platelet counts decreased significantly ( p < 0.002) and remained low during ECMO support. ECMO patients demonstrated significantly reduced platelet aggregation on day 1 compared with healthy controls (all p < 0.001). However, when taking platelet count into consideration, platelet aggregation relative to platelet count did not differ from healthy controls. Flow cytometry analyses demonstrated impaired platelet activation in ECMO patients on day 1 compared with healthy controls (all p < 0.03). No substantial difference was found in platelet activation from day 1 to day 3 on ECMO support. Conclusions: Employing impedance aggregometry and flow cytometry, we found both impaired platelet aggregation and decreased platelet activation on day 1 of ECMO support compared with healthy controls. However, platelet aggregation was not impaired, when interpreted relative to the low platelet counts. Furthermore, levels of bound fibrinogen, on the surface of activated platelets in ECMO patients, were higher than in healthy controls. Together, these findings suggestively oppose that platelets are universally impaired during ECMO support. No marked difference in activation from day 1 to day 3 was seen during ECMO support.

Platelet Functions During Extracorporeal Membrane Oxygenation. Platelet–Leukocyte Aggregates Analyzed by Flow Cytometry as a Promising Tool to Monitor Platelet Activation

“…With this method less dependent on platelet count, they found that platelets demonstrated a reduced ability to become activated. The authors suggested that this could actually be consecutive to the vast activation of platelets in the ECMO circuit, related to the high shear stress, consistent with the increased surface expression of the activated fibrinogen receptor at rest, and a decreased expression of P-selectin, probably due to its shedding [15]. This was in agreement with previous data from our group in the setting of cardiopulmonary bypass in children [16].…”

“…Samples were then diluted in phosphate buffer saline (final blood dilution 1:44) and analyzed, the events being acquired on Navios (Beckman Coulter) or Lyric (Becton Dickinson) ( Figure 2). We evaluated (i) the type of anticoagulant solution, (ii) the delay between sampling and immunolabeling (15,60, and 150 min), (iii) the sample stability after immunolabeling (0 and 90 min), and (iv) the effect of strong vortex agitation (10 s at 3200 rpm), prior to immunolabeling. Figure 2.…”

Clinical and pathophysiologic aspects of ECMO-associated hemorrhagic complications

“…Platelet counts were significantly lower in our study when bleeding had occurred despite our efforts to achieve target platelet levels above 80 thousand per μl. Platelet function as well as absolute counts play a considerable role in hemostasis [30]. Thrombocytopathy can also be an immediate cause of or contribute to ECMO-related hemorrhage [28].…”

Changes in Red Blood Cell Properties and Platelet Function during Extracorporeal Membrane Oxygenation

“…This effect was also seen in a study in twenty patients on VV ECMO where platelet function was impaired prior to the ECMO initiation; ECMO led to a further impairment but after two days the values recovered to baseline [15]. In a study with both VV and VA ECMO patients it was shown that the platelet aggregation was not impaired when the results were interpreted considering the low platelet counts [16].…”