Drug-induced thrombocytopenia and thrombosis: Evidence from patients receiving an oral glycoprotein IIb/IIIa inhibitor in the Orbofiban in Patients with Unstable coronary Syndromes- (OPUS-TIMI 16) trial

Scirica, Benjamin M.; Cannon, Christopher P.; Cooper, Richard A.; Aster, Richard H.; Brassard, Jacqueline; McCabe, Carolyn H.; Charlesworth, Andrew; Skene, Allan M.; Braunwald, Eugene

doi:10.1007/s11239-006-8669-4

Cited by 14 publications

(19 citation statements)

References 30 publications

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“…The percentage of current smokers was lower in the TP group compared to ACS patients without acquired TP in 7 out of 8 studies. 8,9,11,20,23–25 Finally, patients with TP had a higher frequency of previous myocardial infarction (7 out of 8 studies 8,9,11,19,21–23 ), CABG surgery (6 out of 7 studies 9,11,19,21–23 ) and renal insufficiency (3 out of 3 studies 9,20,23 ) (Table 1). No significant differences were observed between groups with regard to treatment with unfractionated heparin, even though this ranged significantly between studies (39.9% to 100% in the TP group versus 40.3% to 100% in the no TP group).…”

Section: Resultsmentioning

confidence: 97%

“…8,9,11,19–25 Eligible studies were all retrospective analyses derived from ACS clinical trials, except for the study by Gore et al that was based on a global registry for acute coronary events. 22 A total of 134,028 patients without TP vs. 8,133 with TP were included and the overall risk of bias for the primary endpoint of all-cause mortality was found to be moderate in all studies.…”

Section: Resultsmentioning

confidence: 99%

“…Six studies examined patients with non-ST-segment elevation ACS (NSTE ACS), 8,9,11,19,21,23 2 studied patients with ST-segment elevation myocardial infarction (STEMI), 20,24 while the rest included patients with any type of ACS. 22,25 In one study TP was defined as a nadir platelet count <150 x 10 9 /L or a >50% drop from baseline 9 and in another the cut-off for TP was set at 80 x 10 9 /L. 25 However the rest of the studies met the goal cut-off of 100 x 10 9 PLT/L.…”

Section: Resultsmentioning

confidence: 99%

“…22,25 In one study TP was defined as a nadir platelet count <150 x 10 9 /L or a >50% drop from baseline 9 and in another the cut-off for TP was set at 80 x 10 9 /L. 25 However the rest of the studies met the goal cut-off of 100 x 10 9 PLT/L. The incidence of TP ranged from 0.68% to 16.4% (total pooled incidence was 5.72%).…”

Section: Resultsmentioning

confidence: 99%

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The effect of in-hospital acquired thrombocytopenia on the outcome of patients with acute coronary syndromes: A systematic review and meta-analysis

Oikonomou

Repanas²,

Papanastasiou

et al. 2016

Thrombosis Research

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Background In-hospital acquired thrombocytopenia (TP) is relatively common among patients hospitalized with acute coronary syndromes (ACS). However, its effect on short-term and long-term outcomes has yet to be reviewed systematically. Methods We conducted a systematic review and meta-analysis of clinical studies assessing the relationship between new-onset in-hospital TP and adverse outcomes among ACS patients. MEDLINE, Scopus and the Cochrane Library were searched for eligible studies published before March 20 2016. Results Ten studies reporting on a total of 142,161 ACS patients were identified. 8,133 patients showed evidence of new-onset TP during the course of their hospitalization. Compared with patients with normal platelet counts, patients with new-onset TP had a prolonged in-hospital stay, significantly higher risk of both short-term mortality (<30 days) (Odds ratio (OR) [95% confidence interval (CI)]: 5.58 [3.63–8.57]) and late death (6 months to 1 year) (OR [95%CI]: 3.45 [2.35–5.07]), as well as a significantly higher risk of major bleeding events in the first 30 days (OR [95%CI]: 6.93 [5.13–9.38]). In addition, risk for other secondary cardiovascular endpoints, including recurrent myocardial infarction, stroke, in-hospital heart failure, stent thrombosis and unplanned revascularization was also significantly higher in the TP versus the no TP group. Conclusions Development of TP during the in-hospital management of ACS patients is a significant predictor of both short- and long-term adverse events, including mortality. In the light of this evidence, clinicians should be cautious and closely monitor abnormal platelet counts that present early following an ACS.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

The effect of in-hospital acquired thrombocytopenia on the outcome of patients with acute coronary syndromes: A systematic review and meta-analysis

Oikonomou

Repanas²,

Papanastasiou

et al. 2016

Thrombosis Research

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“…Large clinical studies revealed that thrombocytopenia associated with antiplatelet treatment not only increased risk of bleeding, but also thrombotic events [8]. For the first time, we demonstrated directly relationship between thrombocytopenia and thrombosis (indicated by D-dimer level).…”

Section: Discussionmentioning

confidence: 54%

Severe Isolated Thrombocytopenia Associated with the Use of Clopidogrel

Zhang¹,

Zhou²,

Han³

2014

CRCM

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Clopidogrel is used as a frontline antiplatelet drug in patients with coronary artery disease, peripheral vascular disease and cerebrovascular disease. Though it is frequently reported that clopidogrel is associated with thrombotic thrombocytopenic purpura (TTP), severe isolated thrombocytopenia induced by this drug is rare. Here we report a case with isolated thrombocytopenia due to clopidogrel therapy. As this agent is widely used in clinical practice, the occurrence of this rare but dangerous adverse effect should be considered.

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Structure-based virtual screening of small-molecule antagonists of platelet integrin αIIbβ3 that do not prime the receptor to bind ligand

Negri

Naini

et al. 2012

J Comput Aided Mol Des

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Integrin αIIbβ3 has emerged as an important therapeutic target for thrombotic vascular diseases owing to its pivotal role in mediating platelet aggregation through interaction with adhesive ligands. In the search for effective anti-thrombotic agents that can be administered orally without inducing the high-affinity ligand binding state, we recently discovered via high-throughput screening of 33,264 compounds a novel, αIIbβ3-selective inhibitor (RUC-1) of adenosine-5′-diphosphate (ADP) -induced platelet aggregation that exhibits a different chemical scaffold and mode of binding with respect to classical Arg-Gly-Asp (RGD)-mimicking αIIbβ3 antagonists. Most importantly, RUC-1 and its higher-affinity derivative, RUC-2, do not induce major conformational changes in the protein β3 subunit or prime the receptor to bind ligand. To identify additional αIIbβ3-selective chemotypes that inhibit platelet aggregation through similar mechanisms, we screened in silico over 2.5 million commercially available, 'lead-like' small molecules based on complementarity to the predicted binding mode of RUC-2 into the RUC-1-αIIbβ3 crystal structure. This first reported structure-based virtual screening application to the αIIbβ3 integrin led to the identification of 2 αIIbβ3-selective antagonists out of 4 tested, which compares favorably with the 0.003 % "hit rate" of our previous high-throughput chemical screening study. The newly identified compounds, like RUC-1 and RUC-2, showed specificity for αIIbβ3 compared to αVβ3 and did not prime the receptor to bind ligand. They thus may hold promise as αIIbβ3 antagonist therapeutic scaffolds.

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Drug-induced thrombocytopenia and thrombosis: Evidence from patients receiving an oral glycoprotein IIb/IIIa inhibitor in the Orbofiban in Patients with Unstable coronary Syndromes- (OPUS-TIMI 16) trial

Abstract: Thrombocytopenia, though uncommon, was associated with orbofiban use and an increased risk of bleeding, but also death and MI. This study provides further evidence that drugs that lead to thrombocytopenia are, in a significant proportion of patients associated with thrombotic events.

Cited by 14 publications

References 30 publications

The effect of in-hospital acquired thrombocytopenia on the outcome of patients with acute coronary syndromes: A systematic review and meta-analysis

The effect of in-hospital acquired thrombocytopenia on the outcome of patients with acute coronary syndromes: A systematic review and meta-analysis

Severe Isolated Thrombocytopenia Associated with the Use of Clopidogrel

Structure-based virtual screening of small-molecule antagonists of platelet integrin αIIbβ3 that do not prime the receptor to bind ligand

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