Leukocyte Adhesion as an Indicator of Oxygenator Thrombosis During Extracorporeal Membrane Oxygenation Therapy?

Abstract

Thrombosis is the most common technical complication with extracorporeal membrane oxygenation (ECMO). Accumulations of leukocytes on the gas exchange membranes within a membrane oxygenator (MO) may initiate thrombosis and influence outcome. MOs (n = 41) were removed routinely from adult patients on ECMO, preserved, and analyzed for their cellular deposits using nuclear (4',6-diamidino-2-phenylindole) and cell type-specific markers (CD45; von Willebrand factor, vWF). The extent of cellular colonization was correlated with patient data. Blood contact caused adhesion of leukocytes and accumulation of vWF. Six MOs contained "pseudomembranes" (PM). MOs with PM were from younger patients (median [interquartile range {IQR}]; age, 36 [30-47] vs. 61 [51-71] years; p = 0.040) and the leukocyte count before ECMO was on average higher (21 [16-24] vs. 15 [8-18] ×10 per L; p = 0.051) compared with PM-free MOs. The development of PMs did not influence pressure drop across the MO. Data indicating coagulation disorder within the MOs (d-dimers, fibrinogen, and platelets) were not significantly different between the groups. There was only one acute MO thrombosis in a PM-free MO. The support time of the analyzed MOs with PM tended to be longer when compared with PM-free MOs (11 [6-19] vs. 8 [5-11] days). Nevertheless, all patients with MOs with PMs were successfully weaned (6/6 vs. 17/35) and discharged from hospital (6/6 vs. 17/35; p = 0.027) compared with patients with PM-free MOs. In conclusion, elderly people on ECMO showed reduced PM formation that may reduce the risk of MO thrombosis. Younger patients had no negative effect.

Accumulations of von Willebrand factor within ECMO oxygenators: Potential indicator of coagulation abnormalities in critically ill patients?

“…Additionally, the detected small granular structures in the vicinity of nucleated cells represent either endothelial cells that stored vWF within the Weibel–Palade bodies, or PLAs. However, in vivo endothelialization of PMP‐gas exchange fibers during the ECMO therapy was excluded . Therefore, these structures represent PLAs consisting of platelets either cell membrane bound on or phagocytosed by leukocytes.…”

“…Since we expected that high accumulations of vWF and leukocytes increase the diffusion path of the gas exchange fibers and worsen the performance of the MOs, we focused on the comparison of high versus low vWF‐loaded MOs. However, high vWF‐loading did not aggravate O 2 and CO 2 transfer capacities of the MOs, nor resulted in an increase of dpMO or alteration of coagulation and inflammatory factors .…”

“…When the deposition on the surface of the gas exchange fibers starts to grow into the blood ducting area, the flow velocity and shear stress will decrease due to the increasing resistance around this particular gas exchange fiber. This gives already captured and only reversibly bound platelets the time to bind irreversibly to vWF and form a stable clot …”

“…The analysis of thrombus specimens provides useful information regarding the pathophysiological process leading to thrombosis . The clots in membrane oxygenators (MOs) were comprised of fibrin strands, platelet‐rich aggregates, and trapped red blood cells as well as leukocytes and von Willebrand factor (vWF) accumulations . The crucial role of vWF in hemostasis and thrombosis during ECMO is of particular interest .…”

“…5 The clots in membrane oxygenators (MOs) were comprised of fibrin strands, platelet-rich aggregates, and trapped red blood cells 6,7 as well as leukocytes and von Willebrand factor (vWF) accumulations. 8,9 The crucial role of vWF in hemostasis and thrombosis during ECMO is of particular interest. [10][11][12] However, the significance of this protein during the ECMO therapy is controversial.…”