Selectins in the HIT syndrome: pathophysiologic role and therapeutic modulation.
The pathophysiology of heparin-induced thrombocytopenia (HIT) is now known to be a complex process which involves platelets, vascular endothelium, and leukocytes. The activation products from these sites also contribute to the activation of coagulation and to the fibrinolytic deficit. While many of the markers of hemostatic activation processes have been found to be at increased levels during acute phases of the HIT syndromes, the circulating levels of soluble P-, E-, and L- selectins have not been reported. Since the pathophysiology of HIT involves the activation of platelets, endothelium, and leukocytes, it is expected that activation products related to these hemostatic systems, including soluble selectins, will also be increased in circulating blood. These alterations may provide an index of the pathophysiologic process. With the availability of highly sensitive ELISAs for soluble P-, E-, and L-selectins, it is now possible to measure these adhesion molecules in biological fluids. This study reports on the circulating levels of P-, E-, and L-selectins in HIT patients and their modulation after therapeutic intervention. With the availability of recombinant hirudin, it is now possible to provide alternate anticoagulants to HIT patients. However, the immunoactivation of platelets and other cells may require additional adjunct therapeutic approaches.
Fareed
J
J
Department of Pathology, Cardiovascular Institute, Loyola University Chicago, Maywood, Illinois, USA.
Walenga
J M
JM
Hoppensteadt
D A
DA
Jeske
W P
WP
Lietz
H
H
Ahmad
S
S
Callas
D
D
Messmore
H L
HL
Haas
S
S
D000925:Anticoagulants / Q000009:adverse effects*; D000991:Antithrombins / Q000627:therapeutic use; D001120:Arginine / Q000031:analogs & derivatives; D006487:Hemostasis / Q000187:drug effects; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D008954:Models, Biological; D010875:Pipecolic Acids / Q000627:therapeutic use; D019087:Selectins / Q000097:blood / Q000187:drug effects / Q000502:physiology*; D013449:Sulfonamides; D013577:Syndrome; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*
D000925:Anticoagulants; D000991:Antithrombins; D010875:Pipecolic Acids; D019087:Selectins; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; C031942:argatroban