ristocetin and Purpura--Thrombocytopenic--Idiopathic

The thrombopoietin receptor agonist romiplostim is used for the long-term treatment of chronic immune thrombocytopenia (ITP). ITP patients have an increased thrombotic risk, which could be exacerbated if romiplostim increased platelet hyperreactivity or caused spontaneous platelet aggregation. To investigate this possibility, this study examined platelet function in romiplostim-treated ITP patients and healthy subjects. Light transmission platelet aggregometry utilizing arachidonic acid, collagen, epinephrine, ristocetin, ADP, and saline (to assess spontaneous aggregation) was performed for each subject. In addition, the ADP AC

Topics: Adenosine Diphosphate; Adult; Aged; Arachidonic Acid; Blood Platelet Disorders; Collagen; Epinephrine; Female; Humans; Male; Middle Aged; Platelet Aggregation; Purpura, Thrombocytopenic, Idiopathic; Receptors, Fc; Receptors, Thrombopoietin; Recombinant Fusion Proteins; Ristocetin; Thrombophilia; Thrombopoietin; Young Adult

Bernard-Soulier syndrome (BSS) is an inherited bleeding disorder caused by a defect in the platelet glycoprotein (GP) Ib/IX complex. The GPIX W127X mutation is the most common genetic defect in Japanese patients with BSS, which is often misdiagnosed as immune thrombocytopenic purpura, presumably due to residual expression of GPIbα. Neither the mechanism by which this mutation leads to a mild bleeding diathesis, nor whether functional GPIbα is expressed on platelet surfaces is known. We investigated GPIbα expression and function in platelets with a GPIX W127X mutation (GPIXW127X). GPIbα complexed with GPIbβ by disulfide bonding was expressed on GPIXW127X platelets and stable CHO-K1 cells lacking GPIX but expressing GPIbα and GPIbβ. Expression of GPIbα/β on GPIXW127X platelets was sufficient to support adhesion to immobilized von Willebrand factor and type III collagen and ristocetin-induced platelet agglutination. A residual amount of functional GPIbα/β heteromer expressed on GPIXW127X platelets partially compensates for the absence of the GPIb/IX complex. This may account for the mild bleeding phenotype of the BSS variant characterized by a non-sense mutation in GPIX.

Topics: Adult; Animals; Antibodies, Monoclonal; Bernard-Soulier Syndrome; Blood Platelets; CHO Cells; Codon, Nonsense; Collagen Type III; Cricetinae; Cystine; Diagnostic Errors; Female; Humans; Membrane Glycoproteins; Phenotype; Platelet Adhesiveness; Platelet Glycoprotein GPIb-IX Complex; Point Mutation; Pregnancy; Pregnancy Complications, Hematologic; Purpura, Thrombocytopenic, Idiopathic; Recombinant Fusion Proteins; Ristocetin; Transfection; von Willebrand Factor