CLINICAL NEWS
small, CD61-positive thrombotic vessels)
• 47 had medium expression (defined as multiple
positive thrombotic vessels)
• 33 had high expression (defined as very large and/
or plenty of CD61-positive thrombotic vessels)
During a two-year follow-up period, 29 patients
(13.6%) developed VTE (including 15 deep vein
thromboses [DVTs] of the lower extremity, 13
pulmonary embolisms, and one DVT of the upper
extremity); 113 patients (53.1%) died.
Podoplanin expression was positively correlated
to grade of intravascular platelet aggregates in tu-
mor specimens, decreased blood platelet counts, and
increased plasma levels of D-dimer, suggesting “a
functional role of podoplanin-induced platelet activa-
tion in hypercoagulability in brain tumor patients,” the
authors reported.
In the entire population, the 6-, 12-, and 24-month
risks of VTE were 10.1 percent, 13.3 percent, and 14.8
percent, respectively, whereas the probabilities of sur-
vival were 84.3 percent, 65.1 percent, and 40.6 percent.
Both the risks of VTE and mortality were signifi-
cantly higher for patients with podoplanin-expressing
tumors compared with patients with podoplanin-
negative tumors, and both increased as expression
levels increased. The hazard ratios (HR) for VTE were
2.44 (95% CI 0.73-8.17; p=0.148) for low expression
levels and 5.71 (95% CI 1.52-21.36; p=0.068) for high
expression; the HRs for mortality were 2.14 (95% CI
1.18-3.89; p=0.012) for low expression levels and 2.58
(95% CI 1.29-5.15; p=0.007) for high
expression.
Patients with high podoplanin
expression also experienced the low-
est probability of survival at 6, 12, and
24 months:
• 98.4%, 88.2%, and 68% for
podoplanin-negative tumors
• 81.5%, 61.4%, and 39% for low
podoplanin expression
• 78%, 50.8%, and 12.2% for moder-
ate podoplanin expression
• 72.2%, 49.3%, and 21.9% for high
podoplanin expression
“Identifying patients at risk of VTE is
a challenge, because the risk factors
in this patient population are not
well understood,” co-author Cihan
Ay, MD, told ASH Clinical News. “As
podoplanin expression correlated
with intravascular platelet aggregates
in brain tumor specimens and low
platelet count in the circulation (as a
result of its ability to induce platelet
aggregation via the platelet receptor
CLEC-2) our study supports the hy-
pothesis that podoplanin might play
an important role in the pathogenesis
of VTE.”
Although the results “support the
concept that podoplanin expression
represents the missing pathobiologic
link between cancer and thrombotic
risk in patients with primary brain
tumors,” the study was not able to
provide “experimental in vivo evidence
for a mechanistic relationship between
podoplanin expression and develop-
ment of VTE,” which the authors noted
as a limitation of the study.
Future in vivo studies using animal
models of glioblastoma and thrombo-
sis are needed to confirm the current
study’s findings, and other research
should evaluate “the efficacy and
safety of primary thromboprophylaxis
in brain tumor patients with high risk
of VTE, based on podoplanin expres-
sion levels in tumor tissue.”
REFERENCE
Riedl J, Preusser M, Nazari PMS, et al. Podoplanin expression in
primary brain tumors induces platelet aggregation and increases
risk of venous thromboembolism. Blood. 2017 January 10. [Epub
ahead of print]
ASH Clinical News
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