Low-density lipoprotein apheresis reduces platelet factor 4 on the surface of platelets: a possible protective mechanism against heparin-induced thrombocytopenia and thrombosis.
BACKGROUND
Heparin-induced thrombocytopenia and thrombosis (HITT) is characterized by thrombocytopenia due to the formation of antibodies against heparin : platelet factor 4 (PF4) complexes. Despite the exposure to heparin during treatment and predisposition of patients with atherosclerosis to HITT, HITT in patients undergoing low-density lipoprotein (LDL) apheresis is rare. We investigated the possibility that LDL apheresis decreases PF4 on platelet (PLT) surfaces and/or plasma HITT antibody levels, either of which would disfavor HITT.


METHODS
We enrolled 25 patients undergoing LDL apheresis at the Hospital of the University of Pennsylvania. Blood samples were drawn before and after treatment. Plasma samples were drawn proximal and distal to the LA-15 treatment column. PF4, HITT antibodies, heparin levels, and P-selectin were measured.


RESULTS
No patient had clinical symptoms of HITT. The LA-15 column was found to efficiently remove PF4. PF4 levels in peripheral blood plasma did not change significantly after LDL apheresis. However, PLT surface PF4 significantly decreased after treatment. HITT antibodies were found in only two patients and were nonfunctional. PLT surface P-selectin did not change during treatment.


CONCLUSIONS
We have demonstrated that LDL apheresis via dextran sulfate absorption removes plasma PF4 and reduces the amount of PF4 on the surface of circulating PLTs. Reduced surface PF4 may decrease antibody formation and/or recognition by HITT antibodies. These data provide a potential explanation for the near lack of HITT in hypercholesterolemic patients undergoing LDL apheresis. They also suggest the possibility that LDL apheresis using dextran sulfate adsorption may have therapeutic value in the treatment of HITT.
Tanhehco
Yvette C
YC
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Rux
Ann H
AH
Sachais
Bruce S
BS
D000925:Anticoagulants / Q000009:adverse effects; D001781:Blood Component Removal / Q000379:methods*; D001792:Blood Platelets / Q000378:metabolism; D005260:Female; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000628:therapy; D008077:Lipoproteins, LDL / Q000097:blood*; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000628:therapy; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism; D010978:Platelet Factor 4 / Q000378:metabolism*; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control
D000925:Anticoagulants; D008077:Lipoproteins, LDL; D019007:P-Selectin; D010978:Platelet Factor 4; D006493:Heparin