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June 11, 2012HaematologicaOpen Access

Constitutively released adenosine diphosphate regulates proplatelet formation by human megakaryocytes

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Key result

Constitutively released adenosine diphosphate regulates proplatelet formation by human megakaryocytes via the P2Y13 receptor, and its specific inhibition reduces proplatelet formation by approximately 50%.

Population

Human megakaryocytes in culture, a patient with severe congenital P2Y12 deficiency, and a retrospective…

Comparison

In vitro administration of ADP scavengers and… vs Untreated control megakaryocytes, healthy…

Design

Preclinical

Authors

ABAlessandra BalduiniTufts UniversityCBChristian A. Di BuduoUniversity of PaviaAMAlessandro MalaraUniversity of Pavia

Discussion

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Implication

P2Y13 inhibition may impair platelet production in vitro; leaves open any therapeutic role in human thrombopoiesis.

Structured PICO

P
Population
In vitro experiments on human megakaryocytes combined with a retrospective analysis of 761 patients with platelet function disorders to assess the role of ADP in platelet formation.
I
Intervention
In vitro administration of ADP scavengers (apyrase, CP/CPK) and P2Y receptor inhibitors (cangrelor, 2-MeSAMP, MRS 2179, MRS 2211, clopidogrel-AM, prasugrel-AM).
C
Comparator
Untreated control megakaryocytes, healthy subjects, and patients with other platelet function disorders.
O
Outcome
Proplatelet formation by human megakaryocytes in culture.surrogate

Main Result

p-value: p=<0.05

This study provides the first evidence that constitutively released ADP regulates proplatelet formation in human megakaryocytes through the P2Y13 receptor, offering novel insights into thrombopoiesis.

Limitations

  • Retrospective nature of the clinical data analysis
  • Clinical relevance of the physiological role of ADP and P2Y13 requires further in vivo exploration

Cite This Study

Balduini et al. (2012) studied Delta-storage pool deficiency and platelet function disorders (n=761). P2Y13 receptor inhibition (MRS 2211) vs. Vehicle/Control was evaluated on Proplatelet formation by human megakaryocytes (p=<0.05). Constitutively released adenosine diphosphate regulates proplatelet formation by human megakaryocytes via the P2Y13 receptor, and its specific inhibition reduces proplatelet formation by approximately 50%.

synapsesocial.com/papers/6a9bf183182ce59ecd17943chttps://doi.org/10.3324/haematol.2011.059212
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Adenosine Derived From ADP Can Contribute to Inhibition of Platelet Aggregation in the Presence of a P2Y 12 Antagonist2010 · 35 citations
  2. 2Role of ADP Receptor P2Y12in Platelet Adhesion and Thrombus Formation in Flowing Blood2002 · 125 citations
  3. 3The platelet P2Y12 receptor for adenosine diphosphate: congenital and drug-induced defects2010 · 192 citations
  4. 4The role of ADP receptors in platelet function2006 · 197 citations
  5. 5Role of P2Y1 purinoceptor in ADP‐induced platelet activation1998 · 198 citations