Mechanisms of hemolysis‐associated platelet activation. (December 2013)

• Record Type: Journal Article
• Authors: Helms, C. C.; Marvel, M.; Zhao, W.; Stahle, M.; Vest, R.; Kato, G. J.; Lee, J. S.; Christ, G.; Gladwin, M. T.; Hantgan, R. R.; Kim‐Shapiro, D. B.
• Is Part Of: Journal of thrombosis and haemostasis. Volume 11:Number 12(2013:Dec.)
• Page Start: 2148
• Page End: 2154
• Publication Date: 2013-12
• Subjects: Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.12422
• Languages: English
• ISSNs: 1538-7933

Abstract

<abstract abstract-type="main" id="jth12422-abs-0001"> <title>Summary</title> <sec id="jth12422-sec-0001" sec-type="section"> <title>Background</title> <p>Intravascular hemolysis occurs after blood transfusion, in hemolytic anemias, and in other conditions, and is associated with hypercoagulable states. Hemolysis has been shown to potently activate platelets <italic>in vitro</italic> and <italic>in vivo</italic>, and several mechanisms have been suggested to account for this, including: (i) direct activation by hemoglobin (Hb); (ii) increase in reactive oxygen species (ROS); (iii) scavenging of nitric oxide (NO) by released Hb; and (iv) release of intraerythrocytic ADP.</p> </sec> <sec id="jth12422-sec-0002" sec-type="section"> <title>Objective</title> <p>To elucidate the mechanism of hemolysis‐mediated platelet activation.</p> </sec> <sec id="jth12422-sec-0003" sec-type="section"> <title>Methods</title> <p>We used flow cytometry to detect PAC‐1 binding to activated platelets for <italic>in vitro</italic> experiments, and a Siemens' Advia 120 hematology system to assess platelet aggregation by using platelet counts from <italic>in vivo</italic> experiments in a rodent model.</p> </sec> <sec id="jth12422-sec-0004" sec-type="section"> <title>Results</title> <p>We found that Hb did not directly activate platelets. However, ADP bound to Hb could cause platelet activation. Furthermore, platelet activation caused by shearing of red blood cells (RBCs) was reduced in the presence of apyrase, which metabolizes ADP to AMP. The use of ROS scavengers did not affect platelet activation. We also found that cell‐free Hb enhanced platelet activation by abrogating the inhibitory effect of NO on platelet activation. <italic>In vivo</italic> infusions of ADP and purified (ADP‐free) Hb, as well as hemolysate, resulted in platelet aggregation, as shown by decreased platelet counts.</p> </sec> <sec id="jth12422-sec-0005" sec-type="section"> <title>Conclusion</title> <p>Two primary mechanisms account for RBC hemolysis‐associated platelet activation: ADP release, which activates platelets; and cell‐free Hb release, which enhances platelet activation by lowering NO bioavailability.</p> </sec> </abstract>