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Published on: September 5, 2016
Microparticles from stored red blood cells promote a hypercoagulable state in a murine model of transfusion
Young Kim1, Brent T Xia1, Andrew D Jung1
1Department of Surgery, University of Cincinnati, Cincinnati, OH.
Background:
Red blood cell-derived microparticles are biologically active, submicron vesicles shed by erythrocytes during storage. Recent clinical studies have linked the duration of red blood cell storage with thromboembolic events in critically ill transfusion recipients. In the present study, we hypothesized that microparticles from aged packed red blood cell units promote a hypercoagulable state in a murine model of transfusion.
Methods:
Microparticles were isolated from aged, murine packed red blood cell units via serial centrifugation. Healthy male C57BL/6 mice were transfused with microparticles or an equivalent volume of vehicle, and whole blood was harvested for analysis via rotational thromboelastometry. Serum was harvested from a separate set of mice after microparticles or saline injection, and analyzed for fibrinogen levels. Red blood cell-derived microparticles were analyzed for their ability to convert prothrombin to thrombin. Finally, mice were transfused with either red blood cell microparticles or saline vehicle, and a tail bleeding time assay was performed after an equilibration period of 2, 6, 12, or 24 hours.
Results:
Mice injected with red blood cell-derived microparticles demonstrated an accelerated clot formation time (109.3 ± 26.9 vs 141.6 ± 28.2 sec) and increased α angle (68.8 ± 5.0 degrees vs 62.8 ± 4.7 degrees) compared with control (each P < .05). Clotting time and maximum clot firmness were not significantly different between the 2 groups. Red blood cell-derived microparticles exhibited a hundredfold greater conversion of prothrombin substrate to its active thrombin form (66.60 ± 0.03 vs 0.70 ± 0.01 peak OD; P<.0001). Additionally, serum fibrinogen levels were lower in microparticles-injected mice compared with saline vehicle, suggesting thrombin-mediated conversion to insoluble fibrin (14.0 vs 16.5 µg/mL, P<.05). In the tail bleeding time model, there was a more rapid cessation of bleeding at 2 hours posttransfusion (90.6 vs 123.7 sec) and 6 hours posttransfusion (87.1 vs 141.4 sec) in microparticles-injected mice as compared with saline vehicle (each P<.05). There was no difference in tail bleeding time at 12 or 24 hours.
Conclusion:
Red blood cell-derived microparticles induce a transient hypercoagulable state through accelerated activation of clotting factors.
Insights
Microparticles from aged red blood cells promote a temporary hypercoagulable state by accelerating clotting factor activation. This finding is crucial for understanding transfusion risks in critically ill patients.
Area of Science:
- Hematology
- Transfusion Medicine
- Biochemistry
Background:
- Red blood cell-derived microparticles (RMPs) are vesicles shed by erythrocytes during storage.
- Clinical studies link red blood cell storage duration to thromboembolic events in transfusion recipients.
- This study investigates the procoagulant potential of aged RMPs.
Purpose of the Study:
- To determine if microparticles from aged packed red blood cells induce a hypercoagulable state.
- To investigate the mechanism by which RMPs affect coagulation.
- To assess the impact of RMPs on bleeding times.
Main Methods:
- Isolation of microparticles from aged murine packed red blood cells.
- Transfusion of microparticles into healthy mice.
- Analysis of whole blood via rotational thromboelastometry.
- Measurement of serum fibrinogen levels.
- Assessment of prothrombin conversion by RMPs.
- Tail bleeding time assay.
Main Results:
- RMP injection accelerated clot formation and increased the α angle in thromboelastometry.
- RMPs significantly enhanced prothrombin to thrombin conversion.
- Serum fibrinogen levels decreased post-RMP injection, indicating thrombin-mediated fibrin formation.
- RMP-injected mice showed reduced bleeding times at 2 and 6 hours post-transfusion.
Conclusions:
- Red blood cell-derived microparticles induce a transient hypercoagulable state.
- Accelerated activation of clotting factors by RMPs is the underlying mechanism.
- These findings highlight a potential risk associated with stored red blood cell transfusions.
