The effect of chemotherapy on procoagulant microparticles in patients with cancer

Chemotherapy is one of the most important factors adding to the risk of
thrombosis in cancer patients. The risk of thrombosis varies among different
chemotherapeutic regimes. The pathogenesis of chemotherapy-associated
hypercoagulability is not completely understood, but may include cytotoxicity
on both malignant and non-malignant cells leading to increased apoptosis,
interactions with blood cells and vascular toxicity.
Microparticles are thought to contribute to the procoagulant state in cancer
patients. Microparticles are small, membrane-bound vesicles that are released
from various types of cells. Also cancer cells can release these 200-1500 nm
sized membrane fragments. These vesicles bear at least some characteristics of
the parent cell and are therefore considered as being active players in
processes such as cellular communication, angiogenesis, coagulation and
invasiveness. High levels of microparticles have been described in patients
with different types of cancer. Significantly higher levels of microparticles
have been found in cancer patients with venous thrombosis compared with cancer
patients without thrombosis.
Reports on the influence of chemotherapy on microparticle levels are scarce.
Microparticles are not only procoagulant in cancer, but also play an important
role in tumour progression. Reports on the rol of microparticle release in
resistance of the tumor to chemotherapy are scarce but interesting. Two
research groups reported the existence of tumour cell derived microparticles
containing chemotherapeutic, which suggests that the shedding of
microparticles, plays a role in the resistance of cancer cells to chemotherapy.
However, no in vivo careful monitoring of microparticle levels in respons to
chemotherapy has been done. Therefore, the aim of the present study is to
evaluate the effect of chemotherapy on microparticle levels and activity in
patients with cancer and observe changes in microparticle levels and activity
after a gift of chemotherapeutic.

A second question which will be addressed by this study is whether
microparticle levels measured after blood withdrawal via vein puncture are
significantly different from microparticle levels measured after blood
withdrawal via a peripheral venous catheter. Blood withdrawal via a venous
catheter, which is already present because chemotherapy will be administered
via this catheter, is more convenient for patients compared to an additional
vein puncture. Therefore, when we find in this study that both methods are
equal to each other in measured microparticle levels, this would prevent
unnecessary blood withdrawals for patients in future studies.

Primary objective: To monitor levels of microparticles in response to a gift of
chemotherapy on short term and in response to multiple gifts of chemotherapy.
Secondary objective 1: To compare microparticle levels measured in blood
acquired via a vein puncture with microparticles levels in blood acquired via a
peripheral venous catheter.
Secondary objective 2: To determine the correlation between levels of
microparticles and markers of coagulation activation.

We will collect blood samples from patients with different types of cancer,
treated with specific chemotherapy regimes. Participation consists of donations
of serial blood samples. Each donation 5 tubes containing 2,5 ml of citrated
blood will be withdrawn. Patients will not be asked to attend the hospital for
research purposes only.
Microparticles will be measured via flow cytometry, Xa Clotting Test and the
Fibrin Generation Test. Also, markers of blood coagulation will be determined.

No benefits can be expected for individual patients who participate in this
study. However, more information on this subject can help in the identification
of patients with cancer receiving chemotherapy with the highest risk of venous
thrombosis. Extra knowledge on the effects and side-effects of chemotherapy
might in the future lead to a greater understanding of chemo-resistance and
factors who determine whether or not patients will respond to chemotherapy. If
knowledge on this subject becomes incorporated into patient care, it will be in
the same group of patients who participate in the present study.