A 23-year-old man is evaluated for excessive bruising since childhood. He says some of his family members "bleed easily" and sometimes require blood transfusions. Temperature is 36.7 C (98.1 F). Physical examination is unremarkable. Complete blood cell count is unremarkable. Platelet aggregometry is abnormal. Genetic testing identifies a defect in a platelet surface glycoprotein receptor that normally binds fibrinogen to support platelet aggregation. The abnormal glycoprotein receptor found in this patient is most likely targeted by which of the following medications?

Question

A 23-year-old man is evaluated for excessive bruising since childhood.  He says some of his family members "bleed easily" and sometimes require blood transfusions.  Temperature is 36.7 C (98.1 F).  Physical examination is unremarkable.  Complete blood cell count is unremarkable.  Platelet aggregometry is abnormal.  Genetic testing identifies a defect in a platelet surface glycoprotein receptor that normally binds fibrinogen to support platelet aggregation.  The abnormal glycoprotein receptor found in this patient is most likely targeted by which of the following medications?

Quizplus · Accepted Answer

11ec160b_3be2_4a8c_9249_5b7fed01f6e0_MD0001_00 This patient likely has Glanzmann thrombasthenia, an autosomal recessive disorder that is caused by a deficient or defective glycoprotein (GP) IIb/IIIa on platelet surfaces and that typically presents in childhood with mucocutaneous bleeding. Peripheral smear shows no platelet clumping (an important clue for diagnosis). Platelets are responsible for formation of platelet plugs that stop bleeding from injured vessels (primary hemostasis). Vessel wall injury exposes the subendothelial collagen and matrix. Platelet attachment to exposed collagen is strengthened by GP Ib binding to von Willebrand factor on the vessel wall. The resulting platelet activation leads to the following: Abciximab, a GP IIb/IIIa receptor antagonist, inhibits binding of this receptor to fibrinogen. Abciximab and other GP IIb/IIIa inhibitors are useful for treatment of unstable angina and acute coronary syndrome, particularly in patients undergoing percutaneous coronary intervention. (Choices B, E, F, and G) Argatroban (used in heparin-induced thrombocytopenia) and dabigatran (used in atrial fibrillation or venous thromboembolism) are direct thrombin inhibitors. Heparin potentiates antithrombin III activity, leading to inactivation of thrombin and factor Xa; warfarin prevents K-mediated carboxylation of several coagulation factors. All these medications have anticoagulant effects. (Choices C and D) Aspirin, a cyclooxygenase (COX)-1 and 2 inhibitor, inhibits TXA2 (via platelet COX acetylation), thereby preventing platelet aggregation. Clopidogrel inhibits platelet aggregation by blocking P2Y12 on platelet ADP receptors. Educational objective: Abciximab is a blocker of glycoprotein (GP) IIb/IIIa receptor, which normally promotes platelet binding to fibrinogen. GP IIb/IIIa is either deficient or defective in patients with Glanzmann thrombasthenia.

A 23-Year-Old Man Is Evaluated for Excessive Bruising Since Childhood