The impact of clot composition on its mechanical properties

Stroke is the second leading cause of death worldwide1. Recently, randomised
controlled trials aiming at revascularisation demonstrated the efficacy of
intra-arterial treatment to remove the occluding thrombus2. Unfortunately,
complete revascularisation is still achieved in less than half of cases and
20-30% of thrombi cannot be retrieved at all3. Moreover, the treatment carries
the risk of inducing thrombus fragmentation and distal embolization4. To
improve procedural success rates, we need to understand how thrombi fracture in
response to mechanical deformations during retrieval. It is extremely
challenging to determine this experimentally as both the time point and the
location at which soft matter fracture initiates are unpredictable. While a
handful of recent studies have conducted macroscopic fracture of simplified
fibrin gels5 and thrombus analogs with differing haematocrit6, the
micro-structure of the thrombus at the fracture point and how it changes during
fracture has yet to be studied. This is particularly pressing because thrombi
between patients are heterogeneous in structure, molecular and cellular
composition7. Thus, fracture occurs differently for different thrombi. The
central question we address here is how the micro-structure of different
thrombi affect the macroscopic fracture mechanics leading thrombus formation
and embolization. To investigate this is a systematic manner, we need to
generate clots made from fresh human blood.

Primary Objective: We want to develop a model that predicts the propensity of
thrombi to fracture depending on their composition, structure, and
heterogeneity. We will develop methods to create both homogeneous and
heterogeneous thrombus analogs to better mimic real thrombi, and evaluate their
mechanical properties using various platforms.

This is fundamental research, using blood from healthy volunteers. Blood from
healthy volunteers is regularly needed for the coming 4 years (approximately
once every two weeks). The blood will be used as a source for fibrinogen, red
blood cells, immune cells, platelets and plasma to optimize methods and to
investigate the effect of clot composition on the mechanical properties. For
example, the impact of platelet induced clot contraction on clot stiffness will
be measured using unconfined compression experiments. Furthermore, we aim to
quantify the effect of fibrinogen content on clot properties. Both will be
linked to pre-clinical imaging to translate these findings for treatment
optimization.

The procedure involves standard blood withdrawal, very much comparable to the
standard procedure when you would be a blood donor. The procedure will be
carried out by qualified personnel in a safe environment. There is no
additional risk associated with this study.