Thrombocytopenia associated with the use of GPIIb/IIIa inhibitors: position paper of the ISTH working group on thrombocytopenia and GPIIb/IIIa inhibitors

Drug-induced thrombocytopenia: MIBS trumps LIBS

“…3 As a result, myeloablative allo-SCT was abandoned and the procedure is not recommended as part of frontline therapy in patients with symptomatic de novo MM. 4 Although the introduction of RIC regimens has resulted in a decrease in the high incidence of TRM associated with myeloablative conditioning, an intense debate is currently ongoing regarding the question of whether patients should be subjected to the substantial morbidity, especially graft-versushost disease (GVHD), and the risk of mortality associated with RIC allo-SCT as part of first-line therapy compared with the relatively safe procedure of auto-SCT. [5][6][7][8][9][10][11] Lokhorst et al performed a donor versus no-donor analysis of patients included in the phase 3 HOVON-50 MM trial.…”

“…Serious bleeding including fatal cerebral hemorrhage has been reported. 4 Although the thrombocytopenia usually resolved within a week or 2 after drug withdrawal, at present there is no drug to rapidly increase patient platelet count or to stop serious bleeding if it occurs during the thrombocytopenic phase.…”

“…The antibody is known to recognize and bind in a drug-dependent manner to the platelet integrin, ␣ IIb ␤ 3 , but the precise antibody binding site remains unclear. [3][4][5] It is also known that binding of fibrinogen, RGD peptides, or RGD mimetic drugs to the RGD recognition site of ␣ IIb ␤ 3 induces conformational changes and emergence of cryptic epitopes previously "unseen" by the immune system. 3 These epitopes are popularly termed LIBS (ligand-induced binding sites) and are recognized by several well-characterized murine monoclonal antibodies such as PMI-1, AP5, and D3.…”

“…1 Their findings suggest that it might not be safe to administer tirofiban to a patient with eptifibatide-induced thrombocytopenia and vice versa. One approach is to assess antibody cross-reactivity before administration of an alternative RGD mimetic as some clinical laboratories may be able to detect eptifibatide-and tirofibandependent antibodies 4 and assess antibody cross-reactivity using flow cytometry. However, the clinical usefulness of such laboratory investigations will have to await confirmation by future studies.…”

Dissolution of arterial platelet thrombi in vivo with a bifunctional platelet GPIIIa49-66 ligand which specifically targets the platelet thrombus

“…A further advantage is that it does not present foreign Ag to the human host with a potential for immunologic hypersensitivity. 22 One reason A11 produces little thrombocytopenia is the lack of an Fc domain. We have previously shown that injection of HIV-1-ITP patient's anti-GPIIIa49-66 IgG into C57BL/6 mice induces a 80% drop in platelet count, versus only a 25% drop when anti-GPIIIa49-66 F(abЈ) 2 is injected.…”