What does this research mean for the field?

Monoclonal antibodies targeting the platelet GPIIb/IIIa receptor can prevent in vivo vasoocclusive thrombus formation at doses lower than those required to abolish platelet aggregation, allowing for thrombosis prevention while maintaining a nearly normal bleeding time. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To investigate the effects of monoclonal antibodies targeting GPIIb/IIIa receptors on platelet thrombus formation and related parameters.

December 1, 1989Circulation

Abolition of in vivo platelet thrombus formation in primates with monoclonal antibodies to the platelet GPIIb/IIIa receptor. Correlation with bleeding time, platelet aggregation, and blockade of GPIIb/IIIa receptors.

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Why the study?

Do monoclonal antibodies to the platelet GPIIb/IIIa receptor prevent in vivo platelet thrombus formation in a primate model of arterial stenosis?

Population

Primate model with carotid artery stenosis, intimal damage, and infusion of subaggregating doses of…

Design

Preclinical

Authors

BCBarry S. CollerCross-Cutting Cardiology JFJohn D. FoltsGeneral / Preventive / Lipids SSSusan R. SmithUnited States Geological Survey

Discussion

Member takes

Implication

Supports GPIIb/IIIa antibody development for thrombosis; leaves open human translation and safety.

Key Points

To investigate the effects of monoclonal antibodies targeting GPIIb/IIIa receptors on platelet thrombus formation and related parameters.
Utilized a monkey model with carotid artery stenosis and provoked thrombus formation.
Administered F(ab')2 fragments of monoclonal antibodies 7E3 and 10E5 at varying doses to evaluate dose-response effects.
Measured outcomes including thrombus formation, platelet aggregation, and bleeding time post-treatment.
Both antibodies abolished thrombus formation at a mean dose of -0.2 mg/kg.
Bleeding times were moderately prolonged at effective doses (9.1 +/- 1.4 minutes), but significantly increased with higher doses (14.2 +/- 1.5 minutes).
A minority of functional GPIIb/IIIa receptors may suffice to maintain normal bleeding times despite the prevention of thrombus formation.

Structured PICO

Do monoclonal antibodies to the platelet GPIIb/IIIa receptor prevent in vivo platelet thrombus formation in a primate model of arterial stenosis?

Population

Primate (monkey) model with carotid artery stenosis, intimal damage, and infusion of subaggregating doses of epinephrine to provoke thrombus formation

Intervention

F(ab')2 fragments of murine monoclonal antibodies to the platelet GPIIb/IIIa receptor (7E3 and 10E5) at varying doses

Outcome

In vivo platelet thrombus formationsurrogate

Partial blockade of GPIIb/IIIa receptors is sufficient to prevent vasoocclusive thrombus formation while maintaining a nearly normal bleeding time in a primate model.

Cite This Study

Coller et al. (1989) studied this question.

synapsesocial.com/papers/6a1dd6aacd67cee37334eb91 https://doi.org/10.1161/01.cir.80.6.1766

Topics

Dual antiplatelet therapy

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Abolition of in vivo platelet thrombus formation in primates with monoclonal antibodies to the platelet GPIIb/IIIa receptor. Correlation with bleeding time, platelet aggregation, and blockade of GPIIb/IIIa receptors.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Abolition of in vivo platelet thrombus formation in primates with monoclonal antibodies to the platelet GPIIb/IIIa receptor. Correlation with bleeding time, platelet aggregation, and blockade of GPIIb/IIIa receptors.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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