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

Abstract

Clot formation within membrane oxygenators (MOs) remains a critical problem during extracorporeal membrane oxygenation (ECMO). The composition of the clots—in particular, the presence of von Willebrand factor (vWF)—may be an indicator for prevalent nonphysiological flow conditions, foreign body reactions, or coagulation abnormalities in critically ill patients. Mats of interwoven gas exchange fibers from randomly collected MOs (PLS, Maquet, Rastatt, Germany) of 21 patients were stained with antibodies (anti‐vWF and anti‐P‐selectin) and counterstained with 4′,6‐diamidino‐2‐phenylindole. The extent of vWF‐loading was correlated with patient and technical data. While 12 MOs showed low vWF‐loadings, 9 MOs showed high vWF‐loading with highest accumulations close to crossing points of adjacent gas fibers. The presence and the extent of vWF‐fibers/“cobwebs,” leukocytes, platelet–leukocyte aggregates (PLAs), and P‐selectin‐positive platelet aggregates were independent of the extent of vWF‐loading. However, the highly loaded MOs were obtained from patients with a significantly elevated SOFA score, severe thrombocytopenia, and persistent liver dysfunction. The coagulation abnormalities of these critically ill patients may cause an accumulation of the highly thrombogenic and elongated high‐molecular‐weight vWF multimers in the plasma which will be trapped in the MOs during the ECMO therapy.

Expert consensus on the diagnosis and treatment of thrombocytopenia in adult critical care patients in China

“…VA-ECMO is more likely than VV-ECMO to cause thrombocytopenia. This is related to platelet consumption due to athrombus caused by membrane oxygenator-induced vWF aggregation [203]. The duration of ECMO is largely unrelated to thrombocytopenia [204].…”

Adsorption of Blood Components to Extracorporeal Membrane Oxygenation (ECMO) Surfaces in Humans: A Systematic Review

“…Identified plasma proteins included fibrin [ 11 , 12 ], von Willebrand factor (vWF) [ 13 , 14 , 15 ] and other plasma proteins [ 13 , 16 ] as well as blood cells, which included erythrocytes [ 11 , 12 ], leukocytes [ 14 , 15 , 17 ], platelets [ 11 , 12 , 15 ] and progenitor cells [ 17 ]. Five of the seven studies utilized immunofluorescent techniques (e.g., flow cytometry, fluorescence microscopy, western blotting) to label specific blood components that adhered to the circuit [ 11 , 13 , 14 , 15 , 17 ]. One study used two-dimensional (2-D) electrophoresis as a method for the identification of specific blood components [ 16 ] whilst two studies implemented scanning electron microscopy (SEM) to visualize biomass accumulations.…”

“…However, in three of the seven studies, the identification of the blood components bound to the ECMO circuit were not the main aim of the studies. Wilm et al [ 14 ] and Steiger et al [ 15 ] observed ECMO oxygenator accumulations as potential predictors for coagulation abnormalities whilst Lehle et al [ 11 ] identified surface deposits as indicators for increased blood flow resistance in ECMO circuits. These articles were therefore limited in terms of the detail that was specified in relation to the ECMO circuit adsorption.…”

“…Three of the seven studies identified the accumulation of vWF in the ECMO oxygenators collected from adult patients following the termination of the ECMO support or replacement of the membrane oxygenator [ 13 , 14 , 15 ]. Targeted immunofluorescence was performed using monoclonal antibodies to identify vWF deposits on the gas exchange fibers of the membrane oxygenators.…”

Chinese expert consensus on diagnosis and treatment of coagulation dysfunction in COVID-19

“…Choi et al [61] reported that the rate of thrombocytopenia in patients receiving ECMO is as high as 83%. VA-ECMO is more likely than VV-ECMO to cause thrombocytopenia, because of platelet consumption caused by membrane oxygenator induced vWF aggregation [62]. The incidence of HIT can reach 20% during ECMO.…”