Characterization of platelet functionality in pediatric patients with
kaposiform hemangioendothelioma / Kasabach-Merritt phenomenon
Background. Kaposiform hemangioendothelioma (KHE) is a rare vascular
tumor of infancy commonly associated with Kasabach-Merritt phenomenon
(KMP) that includes thrombocytopenia and coagulation dysfunction.
Platelet receptor CLEC-2 -tumor cell podoplanin interaction is
considered the key mechanism of thrombocytopenia in KMP, however, the
effect of long-term exposure to podoplanin on platelet function is
Procedure. Here we examined blood samples from 7 patients
with KHE/KMP. Platelet calcium signaling and functional
responses to conventional activation and CLEC-2 stimulation were
analyzed by continuous and endpoint live cell flow cytometry. Platelet
aggregation in response to ADP or rhodocytin was analyzed by low-angle
light scattering approach (LaSca). Additionally, ex vivo thrombus
formation on collagen was observed in parallel-plate flow chambers.
Results. We demonstrate that in KHE/KMP platelet functional responses to
strong stimulation were on the lower boundary of age-matched normal
ranges, while calcium mobilization and fibrinogen binding upon
stimulation with ADP alone were significantly lower than control values.
Platelet di-aggregate formation in response to ADP was also diminished
in most of the patients. Formation of platelet aggregates in
collagen-coated parallel plate flow chambers was also noticeably lower
than in the age-matched control group. Calcium mobilization in response
to CLEC-2 stimulation was unaltered in the patients and could be blocked
by low-molecular-weight inhibitors, 2CP and HB125.
platelet responsiveness in KHE/KMP is moderately altered, platelet CLEC-2
receptors remain functional and respond to inhibition. Therefore, our
findings suggest that CLEC-2-targeting molecules are new potential
agents in therapeutic management of this life-threatening condition.