Heparin-induced thrombocytopenia: mechanism of interaction of the heparin-dependent antibody with platelets.
The interaction of the heparin-dependent antibody with heparin and platelets has been studied using the sera and purified IgG of four patients with heparin-induced thrombocytopenia. Both normal platelets and Bernard-Soulier syndrome (BSS) platelets which lack glycoprotein (GP) Ib. GPV and GPIX, aggregated in response to patient serum or IgG, but only in the presence of heparin. A monoclonal antibody (Mab) against platelet Fc II receptor (IV.3) strongly inhibited the heparin-dependent aggregation of both normal and BSS platelets induced by patient sera/IgG. Inhibition by the anti-GPIb Mab (AK2) was variable and occurred only with normal platelets. Anti-GPIX Mab (FMC 25) was not inhibitory with either normal or BSS platelets. Similar results were obtained using 14C-serotonin release instead of platelet aggregation as a measure of platelet activation. These findings suggest that (1) the reaction of the heparin-dependent antibody with platelets and heparin is mediated by a Fc-dependent mechanism, (2) GPIb, GPV and GPIX are not involved in this reaction, and (3) the inhibitory effect of anti-GPIb Mab on normal platelets is due to steric interference consistent with the platelet Fc receptor being in close proximity to GPIb.
Chong
B H
BH
Department of Haematology, St George Hospital, Kogarah, NSW, Australia.
Fawaz
I
I
Chesterman
C N
CN
Berndt
M C
MC
D000911:Antibodies, Monoclonal; D001323:Autoantibodies / Q000502:physiology*; D001606:Bernard-Soulier Syndrome / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism*; D006023:Glycoproteins / Q000276:immunology; D006493:Heparin / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects; D011961:Receptors, Fc / Q000276:immunology; D013921:Thrombocytopenia / Q000139:chemically induced*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D006023:Glycoproteins; D011961:Receptors, Fc; D006493:Heparin