Von Willebrand Factor-GP1bα Interactions in Venoarterial Extracorporeal Membrane Oxygenation Patients

Mazzeffi, Michael; Hasan, Shaheer; Abuelkasem, Ezeldeen; Meyer, Michael J.; Deatrick, Kristopher B.; Taylor, Bradley S.; Kon, Zachary N.; Herr, Daniel; Tanaka, Kenichi A.

doi:10.1053/j.jvca.2018.11.031

Cited by 27 publications

(23 citation statements)

References 25 publications

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“…Adhesion and aggregation improved but did not normalize with in vitro addition of VWF concentrate. The circulating glycocalicin level was found to be elevated, consistent with an increased GPIb proteolysis [11].…”

Section: Platelet Activation Aggregation and Ecmomentioning

confidence: 80%

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

Mansour

Roussel

Gaussem

et al. 2020

JCM

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Extracorporeal membrane oxygenation (ECMO) is an extracorporeal circulation used to manage patients with severe circulatory or respiratory failure. It is associated with both high bleeding and thrombosis risks, mainly as a result of biomaterial/blood interface phenomena, high shear stress, and complex inflammatory response involving the activation of coagulation and complement systems, endothelial cells, leukocytes, and platelets. Besides their critical role in hemostasis, platelets are important players in inflammatory reactions, especially due to their ability to bind and activate leukocytes. Hence, we reviewed studies on platelet function of ECMO patients. Moreover, we addressed the issue of platelet–leukocyte aggregates (PLAs), which is a key step in both platelet and leukocyte activation, and deserves to be investigated in these patients. A reduced expression of GPIb and GPVI was found under ECMO therapy, due to the shedding processes. However, defective platelet aggregation is inconsistently reported and is still not clearly defined. Due to the high susceptibility of PLAs to pre-analytical conditions, defining and strictly adhering to a rigorous laboratory methodology is essential for reliable and reproducible results, especially in the setting of complex inflammatory situations like ECMO. We provide results on sample preparation and flow cytometric whole blood evaluation of circulating PLAs.

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Section: Platelet Activation Aggregation and Ecmomentioning

confidence: 80%

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

Mansour

Roussel

Gaussem

et al. 2020

JCM

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“…Patients on ECMO may develop acquired coagulopathies from exposure of blood to artificial surfaces and high shear stresses [ 72 , 73 ]. This was prevalent in our patient population.…”

Section: Resultsmentioning

confidence: 99%

A Dedicated Veno-Venous Extracorporeal Membrane Oxygenation Unit during a Respiratory Pandemic: Lessons Learned from COVID-19 Part II: Clinical Management

et al. 2021

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(1) Background: COVID-19 acute respiratory distress syndrome (CARDS) has several distinctions from traditional acute respiratory distress syndrome (ARDS); however, patients with refractory respiratory failure may still benefit from veno-venous extracorporeal membrane oxygenation (VV-ECMO) support. We report our challenges caring for CARDS patients on VV-ECMO and alterations to traditional management strategies. (2) Methods: We conducted a retrospective review of our institutional strategies for managing patients with COVID-19 who required VV-ECMO in a dedicated airlock biocontainment unit (BCU), from March to June 2020. The data collected included the time course of admission, VV-ECMO run, ventilator length, hospital length of stay, and major events related to bleeding, such as pneumothorax and tracheostomy. The dispensation of sedation agents and trial therapies were obtained from institutional pharmacy tracking. A descriptive statistical analysis was performed. (3) Results: Forty COVID-19 patients on VV-ECMO were managed in the BCU during this period, from which 21 survived to discharge and 19 died. The criteria for ECMO initiation was altered for age, body mass index, and neurologic status/cardiac arrest. All cannulations were performed with a bedside ultrasound-guided percutaneous technique. Ventilator and ECMO management were routed in an ultra-lung protective approach, though varied based on clinical setting and provider experience. There was a high incidence of pneumothorax (n = 19). Thirty patients had bedside percutaneous tracheostomy, with more procedural-related bleeding complications than expected. A higher use of sedation was noted. The timing of decannulation was also altered, given the system constraints. A variety of trial therapies were utilized, and their effectiveness is yet to be determined. (4) Conclusions: Even in a high-volume ECMO center, there are challenges in caring for an expanded capacity of patients during a viral respiratory pandemic. Though institutional resources and expertise may vary, it is paramount to proceed with insightful planning, the recognition of challenges, and the dynamic application of lessons learned when facing a surge of critically ill patients.

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“…The presence of these MPs has already been established in a paediatric ECMO model [ 24 ]. They could be generated following the shear-induced platelet activation mediated by the glycoprotein (GP) Ib α-Von Willebrand factor (VWF) interaction [ 25 , 26 ] or by a direct traumatic effect of high shear stress under VA-ECMO [ 27 , 28 ]. Although the association between platelet count—which was actually found to modulate the anti-FXa/aPTT interaction in our multivariate model—and the effect of MPs is difficult to establish, some data support this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

“…Although the association between platelet count—which was actually found to modulate the anti-FXa/aPTT interaction in our multivariate model—and the effect of MPs is difficult to establish, some data support this hypothesis. The thrombocytopenia observed under ECMO is in part the result of apoptosis induced by high shear stress, yet this same trigger is at the origin of platelet MPs generation [ 25 , 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…This high shear stress leads to conformational changes in the VWF, allowing its proteolytic cleavage by the metalloprotease ADAMTS-13 into smaller but less efficient fragments, and promote GPIb α-mediated interaction between this protein and platelets. High shear stress has also been shown to cause loss of platelet surface receptors, particularly GPIb α and GPIV shedding and can trigger platelets apoptosis through GPIb α-VWF interaction [ 25 , 26 , 27 , 28 , 29 , 30 ]. The resulting platelet functional changes along with the platelets count loss are critical in haemostatic complications observed during VA-ECMO.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of Anti-Activated Factor X Activity and Activated Partial Thromboplastin Time Relations and Their Association with Bleeding and Thrombosis during Veno-Arterial ECMO Support: A Retrospective Study

Moussa

Soquet

Lamer

et al. 2021

JCM

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Background: We aimed to investigate the relationship between anti-activated Factor X (anti-FXa) and activated Partial Thromboplastin Time (aPTT), and its modulation by other haemostasis co-variables during veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. We further investigated their association with serious bleeding and thrombotic complications. Methods: This retrospective single-center study included 265 adults supported by VA-ECMO for refractory cardiogenic shock from January 2015 to June 2019. The concordance of anti-FXa and aPTT and their correlations were assessed in 1699 paired samples. Their independent associations with serious bleeding or thrombotic complications were also analysed in multivariate analysis. Results: The concordance rate of aPTT with anti-FXa values was 50.7%, with 39.3% subtherapeutic aPTT values. However, anti-FXa and aPTT remained associated (β = 0.43 (95% CI 0.4–0.45) 10−2 IU/mL, p < 0.001), with a significant modulation by several biological co-variables. There was no association between anti-FXa nor aPTT values with serious bleeding or with thrombotic complications. Conclusion: During VA-ECMO, although anti-FXa and aPTT were significantly associated, their values were highly discordant with marked sub-therapeutic aPTT values. These results should favour the use of anti-FXa. The effect of biological co-variables and the failure of anti-FXa and aPTT to predict bleeding and thrombotic complications underline the complexity of VA-ECMO-related coagulopathy.

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Von Willebrand Factor-GP1bα Interactions in Venoarterial Extracorporeal Membrane Oxygenation Patients

Cited by 27 publications

References 25 publications

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

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

A Dedicated Veno-Venous Extracorporeal Membrane Oxygenation Unit during a Respiratory Pandemic: Lessons Learned from COVID-19 Part II: Clinical Management

Evaluation of Anti-Activated Factor X Activity and Activated Partial Thromboplastin Time Relations and Their Association with Bleeding and Thrombosis during Veno-Arterial ECMO Support: A Retrospective Study

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