Platelet analysis in patients with haematological diseases with increased risk of thrombosis and bleeding

Background:
Patients with hematological diseases and treatment thereof are at increased
risk for thrombosis or bleeding. Why this is, is not fully knwon.

With regards to thrombosis, patients with essential thrombocytosis and
polycytemia vera are at in increased risk for venous thrombosis. How this works
is currently not fully understood, with a possible role for platelet
activation, neutrophils and JAK2 mutation status.
Patients with chronic myeloid leukemia that are being treated with tyrosine
kinase inhibitors nilotinib and ponatinib are at increased risk for both
arterial and venous thrombosis. Also hereof pathophysiology is largely unkown,
with a possible role for increased endothelial cell activation, Von Willebrand
Factor expression and platelet adhesion.

On the contrary, patients treated with ibrutinib (eg. patients with chronic
lymfatic leukemia (CLL), mantle cell lymphoma and Morbus Waldenstrom (MW)) have
an increased bleeding risk. As ibrutinib is an important new treatment strategy
but requires life long treatment, management of bleeding complications is
crucial.

This study will increase pathofysiological knowledge on platelet function in
these patients and study which platelet function test are most altered in
patients experiencing thrombosis or bleeding.

To better treat and understand bleeding and thrombotic complications of these
diseases and treatments, more insight is needed into the pathophysiology. WIth
the findings of the current study we would like to increase knowledge on how
platelets (and thrombus formation) function in these patients.
More importantly, we will try to assess which platelet function tests are most
altered in patients with a bleeding or thrombosis event.

Cases and controls will be included.
Cases: patients are included if they have a hematological condition or
treatment and a thrombosis or bleeding event. Specifically this includes
patiens with polycytemia vera, essential trombocytosis and CML patients with
tyrosine kinase inhibitors and patients using ibrutinib e.g. CLL, mantle cell
lymphoma en morbus waldenstrom patients. Controls will be similar patients
(matched by disease characteristics, age, gender, etnicity) but without a
thrombosis or bleeding event.

Of these patients, clinical data will be stored regarding disease
characteristics, treatment and thrombosis and bleeding events at baseline and
after 1 year. There will be one blood draw (4 tubes, 24ml) for assessment of
thrombus formation and platelet function. This will happen by assesing
thrombusformation under flow (in the Maastricht flow chamber, a validated
instrument ), platelet stimulation and cytosolic calcium assessment and
measurement of platelet-leukocyte complex formation. Also, platelets will be
isolated and protein expression will be quantified. This will give direct
insight into which pathways and proteins are active in platelets of patients,
and this is correlated to thrombusformation under flow.

We will then assess whihch platelet function test are (most) altered in
patients with bleeding or thrombosis.

Little burden for patient as only a single blood draw