Changes in von Willebrand Factor Multimers, Concentration, and Function During Pediatric Extracorporeal Membrane Oxygenation
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Published on: August 14, 2017
Suelyn Van Den Helm1,2, Natasha Letunica1, Rebecca Barton1,2,3,4,5,6,7,8,9,10,11
1Haematology Research, Murdoch Children's Research Institute, Melbourne, VIC, Australia.
Insights
Pediatric extracorporeal membrane oxygenation (ECMO) alters von Willebrand factor (VWF) structure and function, but VWF monitoring is not useful for predicting bleeding. Further research into other hemostatic factors is needed.
Area of Science:
- Pediatric critical care medicine
- Hematology
- Cardiovascular surgery
Background:
- Extracorporporeal membrane oxygenation (ECMO) is a life-support measure for critically ill neonates and children.
- Bleeding complications are common in pediatric ECMO patients.
- Understanding hemostatic changes during ECMO is crucial for patient management.
Purpose of the Study:
- To investigate alterations in von Willebrand factor (VWF) concentration, function, and multimers in pediatric ECMO patients.
- To determine if routine VWF monitoring can predict bleeding events during ECMO.
Main Methods:
- Prospective observational study of 25 pediatric patients on venoarterial ECMO.
- Serial blood sampling pre-ECMO, during ECMO, and post-ECMO.
- Analysis of VWF:Ag, VWF:RCo, VWF:CB, and VWF multimers.
Main Results:
- Patients on ECMO showed a decrease in high molecular weight VWF multimers (HMWM) and increased intermediate molecular weight multimers.
- VWF antigen levels increased, while VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag ratios decreased compared to baseline and healthy controls.
- These VWF changes occurred irrespective of bleeding status.
Conclusions:
- Pediatric ECMO patients exhibit significant changes in VWF, including loss of HMWM and reduced VWF function.
- Routine VWF monitoring during ECMO is unlikely to be useful for predicting bleeding.
- Further investigation into other hemostatic factors is warranted to understand and manage bleeding in ECMO patients.
Objectives:
To investigate changes in von Willebrand factor (VWF) concentration, function, and multimers during pediatric extracorporeal membrane oxygenation (ECMO) and determine whether routine monitoring of VWF during ECMO would be useful in predicting bleeding.
Design:
Prospective observational study of pediatric ECMO patients from April 2017 to May 2019.
Setting:
The PICU in a large, tertiary referral pediatric ECMO center.
Patients:
Twenty-five neonates and children (< 18 yr) supported by venoarterial ECMO.
Interventions:
None.
Measurements And Main Results:
Arterial blood samples were collected within 24 hours pre-ECMO, daily for the first 5 days of ECMO, every second day until decannulation, and 24 hours post-ECMO. The STA R Max analyzer was used to measure VWF antigen (VWF:Ag) and ristocetin cofactor (VWF:RCo) activity. VWF collagen binding (VWF:CB) was measured using an enzyme-linked immunosorbent assay. VWF multimers were measured using the semi-automated Hydragel 11 VWF Multimer assay. Corresponding clinical data for each patient was also recorded. A total of 25 venoarterial ECMO patients were recruited (median age, 73 d; interquartile range [IQR], 3 d to 1 yr). The median ECMO duration was 4 days (IQR, 3-8 d) and 15 patients had at least one major bleed during ECMO. The percentage of high molecular weight multimers (HMWM) decreased and intermediate molecular weight multimers increased while patients were on ECMO, irrespective of a bleeding status. VWF:Ag increased and the VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag ratios decreased while patients were on ECMO compared with the baseline pre-ECMO samples and healthy children.
Conclusions:
Neonates and children on ECMO exhibited a loss of HMWM and lower VWF:CB/VWF:Ag and VWF:RCo/VWF:Ag ratios compared with healthy children, irrespective of major bleeding occurring. Therefore, monitoring VWF during ECMO would not be useful in predicting bleeding in these patients and changes to other hemostatic factors should be investigated to further understand bleeding during ECMO.
