Mechanisms of hemolysis-associated platelet activation.
J Thromb Haemost
; 11(12): 2148-54, 2013 Dec.
Article
in En
| MEDLINE
| ID: mdl-24119131
ABSTRACT
BACKGROUND:
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 in vitro and in vivo, 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.OBJECTIVE:
To elucidate the mechanism of hemolysis-mediated platelet activation.METHODS:
We used flow cytometry to detect PAC-1 binding to activated platelets for in vitro experiments, and a Siemens' Advia 120 hematology system to assess platelet aggregation by using platelet counts from in vivo experiments in a rodent model.RESULTS:
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. In vivo infusions of ADP and purified (ADP-free) Hb, as well as hemolysate, resulted in platelet aggregation, as shown by decreased platelet counts.CONCLUSION:
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Platelet Activation
/
Hemolysis
Type of study:
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
J Thromb Haemost
Journal subject:
HEMATOLOGIA
Year:
2013
Document type:
Article
Affiliation country:
Estados Unidos