title: Investigation of a potential protective mechanism against heparin-induced thrombocytopenia in patients on chronic intermittent hemodialysis.
abstract: BACKGROUND
  Heparin-induced thrombocytopenia (HIT) develops as a result of platelet (PLT) activation by anti-platelet factor 4 (PF4)/heparin complex antibodies. Despite repeated exposure to heparin, patients undergoing chronic intermittent hemodialysis (HD) rarely develop HIT. We investigated the possibility that HD decreases/removes PF4 from PLT surfaces and/or plasma, thereby disfavoring immune complex formation as a mechanism of protection against HIT.
  
  
  METHODS
  We enrolled 20 patients undergoing chronic HD at the Penn Presbyterian Medical Center. Blood samples were drawn before, during and after treatment in the presence and absence of heparin. PF4, anti-PF4/heparin antibody, heparin, and P-selectin levels were measured.
  
  
  RESULTS
  No patients demonstrated clinical symptoms of HIT. PLT surface PF4 levels decreased and plasma PF4 levels increased concurrently with the increase in plasma heparin concentration. In the absence of heparin, PLT surface and plasma PF4 levels were unchanged. Anti-PF4/heparin antibodies, which were non-functional by the serotonin release assay, were detectable in 8 patients. PLT surface P-selectin levels did not change during treatment.
  
  
  CONCLUSIONS
  Removal of PLT surface and/or plasma PF4 as a mechanism of protection against HIT in patients undergoing HD is not supported by the results of our study, although the transient decrease in PLT surface PF4 in the presence of large amounts of heparin remains a candidate mechanism. The small sample size, single type of dialyzer membrane, and early sampling time points may have led to the inability to detect changes in PF4 levels. Future studies should explore other potential protective mechanisms.
authors.affiliation: Department of Pathology and Cell Biology, Division of Transfusion Medicine, Columbia University, New York, NY, United States.
authors.forename: Yvette C
authors.initials: YC
authors.lastname: Tanhehco
authors.forename: Adam
authors.initials: A
authors.lastname: Cuker
authors.forename: Michael
authors.initials: M
authors.lastname: Rudnick
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Sachais
mesh_terms: D000368:Aged; D001792:Blood Platelets / Q000166:cytology; D005260:Female; D006493:Heparin / Q000009:adverse effects* / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000188:drug therapy; D008297:Male; D008567:Membranes, Artificial; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects; D010978:Platelet Factor 4 / Q000097:blood* / Q000276:immunology; D006435:Renal Dialysis / Q000009:adverse effects*; D012701:Serotonin / Q000378:metabolism; D013499:Surface Properties; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000517:prevention & control
chemical_list: D008567:Membranes, Artificial; D019007:P-Selectin; D012701:Serotonin; D010978:Platelet Factor 4; D006493:Heparin