Glucosamine sulfate does not crossreact with the antibodies of patients with heparin-induced thrombocytopenia.
OBJECTIVE
To assess the crossreactivity of glucosamine sulfate, used for treatment of degenerative joint disease with antibodies induced in heparin-induced thrombocytopenia (HIT).


BACKGROUND
HIT is a severe adverse effect of heparin therapy induced by an immunological mechanism. The antibodies in HIT are induced by a complex of heparin and, in most cases, platelet factor 4. Hereby generation of the antigen is not strictly dependent on heparin. Heparin can be substituted by a variety of polysulfated carbohydrates. In vitro and in vivo crossreactivity of HIT antibodies has been demonstrated for a chemically polysulfated chondroitin-like substance (Arteparon, Luitpoldwerke, Munich, Germany), formerly used for chondroprotection. Another drug widely used in the treatment of degenerative joint disease is glucosamine sulfate. Glucosamine is a building block of glycosaminoglycans, of which heparin is the clinically most important. Many patients with degenerative joint disease use glucosamine sulfate. This group is also at the highest risk to develop HIT following joint replacement surgery.


METHODS
We examined the interactions of glucosamine sulfate (DONA 200-S, Opfermann, Wiehl, Germany) with platelets and antibodies of patients with HIT in and without the presence of heparin. Sera of 5 HIT patients and platelets of 4 healthy donors were used. The binding of HIT antibodies to PF4/glucosamine sulfate complexes was assessed by an ELISA.


RESULTS
HIT antibodies did not activate platelets in the presence of glucosamine sulfate in a serotonin-release assay. Preincubation with glucosamine sulfate did not inhibit platelet activation by HIT antibodies in the presence of heparin (0.2 IU/ml). Antibodies bonded to PF4/heparin but not to PF4/glucosamine sulfate complexes.


CONCLUSIONS
In contrast to sulfated glycosaminoglycans, there is no evidence for an immunological crossreactivity of HIT antibodies between heparin and glucosamine sulfate.
Weimann
G
G
Institut für Immunologie und Transfusionsmedizin, Ernst-Moritz-Arndt-University Greifswald, Sauerbruchstr/Diagnostikzentrum, 17487 Greifswald, Germany.
Lubenow
N
N
Selleng
K
K
Eichler
P
P
Albrecht
D
D
Greinacher
A
A
D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000276:immunology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D005944:Glucosamine / Q000276:immunology*; D006025:Glycosaminoglycans / Q000737:chemistry / Q000276:immunology; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D010003:Osteoarthritis / Q000188:drug therapy; D015539:Platelet Activation / Q000187:drug effects; D010978:Platelet Factor 4 / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000276:immunology
D001323:Autoantibodies; D006025:Glycosaminoglycans; D012701:Serotonin; D010978:Platelet Factor 4; D006493:Heparin; D005944:Glucosamine