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Effect of blood flow on platelets, leukocytes, and extracellular vesicles in thrombosis of simulated neonatal extracorporeal circulation.

Abstract

BACKGROUND

Extracorporeal membrane oxygenation (ECMO) has frequent and sometimes lethal thrombotic complications. The role that activated platelets, leukocytes, and small (0.3-micron to 1-micron) extracellular vesicles (EVs) play in ECMO thrombosis is not well understood.

OBJECTIVES

To test the effect of blood flow rate on the generation of activated platelets, leukocytes, and EVs in a simulated neonatal ECMO circuit using heparinized human whole blood.

METHODS

Simulated neonatal roller pump circuits circulated whole blood at low, nominal, and high flow rates (0.3, 0.5, and 0.7 L/min) for 6 h. Coagulopathy was defined by thromboelastography (TEG), STA® -procoagulant phospholipid clot time (STA®- Procoag-PPL), and calibrated automated thrombogram. High-resolution flow cytometry measured the cellular expression of prothrombotic phospholipids and proteins on platelets, leukocytes, and EV.

RESULTS

Despite heparinization, occlusive thrombosis halted flow in two of five circuits at 0.3 L/min and three of five circuits at 0.7 L/min. None of the five circuits at 0.5 L/min exhibited occlusive thrombosis. Phosphatidylserine (PS)-positive platelets and EVs increased at all flow rates more than blood under static conditions (P < .0002). Tissue factor (TF)-positive leukocytes and EVs increased only in low-flow and high-flow circuits (P < .0001). Tissue factor pathway inhibitor (TFPI), at 50 times more than the concentration in healthy adults, failed to suppress thrombin initiation in low-flow and high-flow circuits.

CONCLUSIONS

This in vitro study informs ECMO specialists to avoid low and high blood flow that increases TF expression on leukocytes and EVs, which likely initiate clot formation. Interventions to decrease TF generated by ECMO may be an effective approach to decrease thrombosis.

Authors+Show Affiliations

Division of Pediatric Critical Care, Department of Pediatrics, University of Texas Health, San Antonio, Texas. Coagulation and Blood Research, U.S. Army Institute of Surgical Research (USAISR), Ft. Sam Houston, Texas.Division of Pediatric Critical Care, Department of Pediatrics, University of Texas Health, San Antonio, Texas.Coagulation and Blood Research, U.S. Army Institute of Surgical Research (USAISR), Ft. Sam Houston, Texas.Coagulation and Blood Research, U.S. Army Institute of Surgical Research (USAISR), Ft. Sam Houston, Texas.Extracorporeal Life Support, U.S. Army Institute of Surgical Research (USAISR), Ft. Sam Houston, Texas.Thrombosis and Hemostasis Program, Division of Hematology and Oncology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina.Coagulation and Blood Research, U.S. Army Institute of Surgical Research (USAISR), Ft. Sam Houston, Texas.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31628728

Citation

Meyer, Andrew D., et al. "Effect of Blood Flow On Platelets, Leukocytes, and Extracellular Vesicles in Thrombosis of Simulated Neonatal Extracorporeal Circulation." Journal of Thrombosis and Haemostasis : JTH, 2019.
Meyer AD, Rishmawi AR, Kamucheka R, et al. Effect of blood flow on platelets, leukocytes, and extracellular vesicles in thrombosis of simulated neonatal extracorporeal circulation. J Thromb Haemost. 2019.
Meyer, A. D., Rishmawi, A. R., Kamucheka, R., Lafleur, C., Batchinsky, A. I., Mackman, N., & Cap, A. P. (2019). Effect of blood flow on platelets, leukocytes, and extracellular vesicles in thrombosis of simulated neonatal extracorporeal circulation. Journal of Thrombosis and Haemostasis : JTH, doi:10.1111/jth.14661.
Meyer AD, et al. Effect of Blood Flow On Platelets, Leukocytes, and Extracellular Vesicles in Thrombosis of Simulated Neonatal Extracorporeal Circulation. J Thromb Haemost. 2019 Oct 19; PubMed PMID: 31628728.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of blood flow on platelets, leukocytes, and extracellular vesicles in thrombosis of simulated neonatal extracorporeal circulation. AU - Meyer,Andrew D, AU - Rishmawi,Anjana R, AU - Kamucheka,Robin, AU - Lafleur,Crystal, AU - Batchinsky,Andriy I, AU - Mackman,Nigel, AU - Cap,Andrew P, Y1 - 2019/10/19/ PY - 2019/05/30/received PY - 2019/10/10/accepted PY - 2019/10/20/pubmed PY - 2019/10/20/medline PY - 2019/10/20/entrez KW - blood cells KW - extracellular vesicles KW - extracorporeal membrane oxygenation KW - thrombosis KW - tissue factor JF - Journal of thrombosis and haemostasis : JTH JO - J. Thromb. Haemost. N2 - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has frequent and sometimes lethal thrombotic complications. The role that activated platelets, leukocytes, and small (0.3-micron to 1-micron) extracellular vesicles (EVs) play in ECMO thrombosis is not well understood. OBJECTIVES: To test the effect of blood flow rate on the generation of activated platelets, leukocytes, and EVs in a simulated neonatal ECMO circuit using heparinized human whole blood. METHODS: Simulated neonatal roller pump circuits circulated whole blood at low, nominal, and high flow rates (0.3, 0.5, and 0.7 L/min) for 6 h. Coagulopathy was defined by thromboelastography (TEG), STA® -procoagulant phospholipid clot time (STA®- Procoag-PPL), and calibrated automated thrombogram. High-resolution flow cytometry measured the cellular expression of prothrombotic phospholipids and proteins on platelets, leukocytes, and EV. RESULTS: Despite heparinization, occlusive thrombosis halted flow in two of five circuits at 0.3 L/min and three of five circuits at 0.7 L/min. None of the five circuits at 0.5 L/min exhibited occlusive thrombosis. Phosphatidylserine (PS)-positive platelets and EVs increased at all flow rates more than blood under static conditions (P < .0002). Tissue factor (TF)-positive leukocytes and EVs increased only in low-flow and high-flow circuits (P < .0001). Tissue factor pathway inhibitor (TFPI), at 50 times more than the concentration in healthy adults, failed to suppress thrombin initiation in low-flow and high-flow circuits. CONCLUSIONS: This in vitro study informs ECMO specialists to avoid low and high blood flow that increases TF expression on leukocytes and EVs, which likely initiate clot formation. Interventions to decrease TF generated by ECMO may be an effective approach to decrease thrombosis. SN - 1538-7836 UR - https://www.unboundmedicine.com/medline/citation/31628728/Effect_of_Blood_Flow_on_Platelets,_Leukocytes,_and_Extracellular_Vesicles_in_Thrombosis_of_Simulated_Neonatal_Extracorporeal_Circulation L2 - https://doi.org/10.1111/jth.14661 DB - PRIME DP - Unbound Medicine ER -