Abstract 4684

Background:

Thrombocytopenia is a major medical problem associated with bleeding. Etiology of thrombocytopenia includes myelosuppression, splenic sequestration and increased peripheral consumption and/or destruction. Vascular Endothelial Growth Factor (VEGF) is produced in both endothelial cells and platelets and is stored in alpha granules in the platelets. It plays multiple roles in the regulation of vascular endothelial cell proliferation and vascular integrity.

Hypothesis:

VEGF release from the platelets in vivo due to platelet activation or destruction may result in changes in plasma and serum VEGF levels, and the level could be associated with various etiologies of thrombocytopenia.

Methods:

This was a prospective IRB approved on-going study. Eligibility includes platelet count less than 120,000/ul, no current diagnoses of solid tumor and thrombocytopenia is not due to chemotherapy. Blood was collected at the time of diagnosis, and VEGF was measured in serum and plasma specimens using a commercial ELISA kit from Ray Biotech (Norcross, GA). Plasma adjusted VEGF levels are defined as plasma VEGF value divided by the platelet count.

Results:

Forty seven patients were enrolled, the clinical diagnoses included AML or MDS (designated as A/M, n=6), hypersplenism (n=13), ITP (n=14), sepsis (n=11) and confirmed TTP (n=3). Blood was also collected from 4 healthy volunteers as controls. Plasma VEGF levels and plasma adjusted VEGF levels (defined as plasma VEGF value divided by the number of platelets) were selected as the main measurements of outcome as shown below

DiagnosisPlatelet count × 103/ml Mean ± SDPlasma VEGF level Pg/ml Mean ± SDPlasma adjusted VEGF level Pg/ml Mean ± SDPlasma adjusted VEGF level Pg/ml RangesSerum VEGF level Pg/ml Mean ± SD
AML/MDS 38.2±34 21.2±45.2 0.5±0.83 0–1.9 62.1±56.2 
Hypersplenism 56.3±31.3 31.8±66.5 0.7±1.75 0–6.4 311±396.3 
ITP 35 ±32.2 78.1±276.6 0.9±2.71 0–10 616±235.2 
Sepsis 48.5±26.4 159±304.9 3.7±6.71 0–19.2 814.2±495.9 
TTP 32±19 75±106 1.8±1.9 0–3.7 355.6±419 
Healthy control 253±70 14.3±29.2 0.08±0.17 0–0.34 468.6±406 
P value  Not significant Not significant   
DiagnosisPlatelet count × 103/ml Mean ± SDPlasma VEGF level Pg/ml Mean ± SDPlasma adjusted VEGF level Pg/ml Mean ± SDPlasma adjusted VEGF level Pg/ml RangesSerum VEGF level Pg/ml Mean ± SD
AML/MDS 38.2±34 21.2±45.2 0.5±0.83 0–1.9 62.1±56.2 
Hypersplenism 56.3±31.3 31.8±66.5 0.7±1.75 0–6.4 311±396.3 
ITP 35 ±32.2 78.1±276.6 0.9±2.71 0–10 616±235.2 
Sepsis 48.5±26.4 159±304.9 3.7±6.71 0–19.2 814.2±495.9 
TTP 32±19 75±106 1.8±1.9 0–3.7 355.6±419 
Healthy control 253±70 14.3±29.2 0.08±0.17 0–0.34 468.6±406 
P value  Not significant Not significant   
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Conclusion:

Plasma VEGF adjusted with platelet count should be the measurement for in vivo release of VEGF from endothelial or platelet sources. Plasma adjusted VEGF level has a wide range of variation in patients with thrombocytopenia, about 50% of our test subjects had undetectable VEGF plasma levels. Although not statistically significant, patients with thrombocytopenia due to AML or MDS had lowest plasma VEGF values and least variation, while patients with sepsis had highest plasma VEGF readings and variations, probably due to increased endothelial cell production. The study is ongoing in large scales, and we are also interested in following the trend of serial plasma adjusted VEGF levels along with platelet recovery.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
biological markers, plasma, thrombocytopenia, vascular endothelial growth factor a, granules, sepsis, hypersplenism, inosine triphosphate, purpura, thrombocytopenic, idiopathic, chemotherapy regimen

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2011 by The American Society of Hematology
2011
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