title: Increased PAC-1 expression among patients with multiple myeloma on concurrent thalidomide and warfarin.
abstract: Treatment with thalidomide is associated with vascular thrombosis. The effect of thalidomide on platelet activation is unclear, although the use of aspirin is justified for thromboprophylaxis. A study on platelet activation markers was done among multiple myeloma patients receiving thalidomide therapy with warfarin as thromboprophylaxis. Strict criteria and procedure were set to avoid misinterpretation of platelet activation other than due to the thalidomide's effect. Blood specimen pre and post thalidomide therapy were used for flow cytometric analysis. Platelet surface P-selectin, CD62P expression and PAC-1 (antibody that recognizes conformational change of the GPIIb/IIIa complex) were examined by using three-colour flowcytometer. Increased expression marker for PAC-1 was observed after 4 weeks of thalidomide treatment (P < 0.05) indicating one aspect of platelet activation activity seen in these patients. The mechanism of thrombosis by thalidomide is probably multifactorial and one of them is likely through platelet activation. Further study on the affected pathway/s in the platelet activation process would confirm the exact mechanism of thalidomide-induced thrombosis and potential extended usage of this drug in future.
authors.affiliation: aDepartment of Haematology bDepartment of Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.
authors.forename: Wan Z
authors.initials: WZ
authors.lastname: Abdullah
authors.forename: Tariq M
authors.initials: TM
authors.lastname: Roshan
authors.forename: Azlan
authors.initials: A
authors.lastname: Hussin
authors.forename: Wan S W Md
authors.initials: WS
authors.lastname: Zain
authors.forename: Dzarr
authors.initials: D
authors.lastname: Abdullah
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism*; D000925:Anticoagulants / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D019007:P-Selectin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000276:immunology; D013792:Thalidomide / Q000009:adverse effects*; D013927:Thrombosis / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D007166:Immunosuppressive Agents; D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C546937:SELP protein, human; D013792:Thalidomide; D014859:Warfarin