34 Seiten als pdf - MedRSD - Heinrich-Heine-Universität Düsseldorf

Doktorandenkongress der Medical Research School Düsseldorf 2011
5.11 aIIbß3 dependent platelet adhesion with
mutated and wildtype von Willebrand factor
under fl ow conditions
Vivian Bleyer, Volker R. Stoldt, Rüdiger E. Scharf
Institut für Hämostaseologie und Transfusionsmedizin
Studies of our research group have documented
that a mutation in the integrin aIIbß3, a platelet
receptor for fi brinogen and von Willebrand factor
(vWF), causes an increasing platelet thrombogenicity
which is associated with premature manifestation
of myocardial infarction in patients with coronary
artery disease. More recently we have also shown that
a distinct mutation (F2561Y) of vWF can enhance
the prevalence of myocardial infarction in women.
The F2561Y mutation of vWF is in close proximity
to the binding domain of vWF to integrin aIIbß3.
The aim of this dissertation project was to explore
whether mutated vWF diff erently infl uences platelet
adhesion, as compared to wildtype vWF. Moreover,
the rate of platelet adhesion should be quantifi ed
under various shear rates simulating arterial or
venous fl ow conditions. In initial experiments, the
fl ow chamber was coated with wildtype or mutated
vWF (antigen 100%, activity 50%). Platelets were
fl uorescently stained with mepacrine in citrateanticoagulated
whole blood. Adherent platelets were
detected and quantifi ed by laser scanning microscopy
and digital imaging (Image J). Blockage of aIIbß3 with
abciximab abrogated platelet adhesion onto wildtype
vWF by more than 99%, whereas platelet adhesion
onto mutated vWF was reduced by only 60%. No
unspecifi c adhesion of platelets was observed on
BSA. aIIbß3-dependent stable platelet adhesion onto
vWF was sensitive upon exposure to arterial shear
rates (1000 sec-1). Thus, initially adherent platelets
detached again after 4 or 5 min of fl ow. On the
other side, intermediate and venous fl ow conditions
(shear rates of 500 sec-1 and 50 sec-1) revealed a
progressive increase and stable platelet adhesion onto
both wildtype and mutated vWF over the time. These
preliminary fi ndings suggest that fl ow conditions can
have a crucial impact on aIIbß3-mediated platelet
adhesion onto vWF. Therefore, the eff ect of diff erent
shear rates will be examined in future experiments. *
supported by SFB 612
24
5.12 Evaluation of prognostic factors
regarding fl ap failure
Stefan Burghardt (1), Günther Giers (2), Jörg
Handschel (1)
(1) Klinik für Kiefer- und Plastische Gesichtschirurgie, (2)
Institut für Hämostaseologie und Transfusionsmedizin
Background: Thromboembolic incidents and bleeding
events are typical complications following pedicled or
microsurgical fl ap in Oral and Maxillofacial Surgery.
Currently, diagnosis is unsatisfying, relying mainly
on clinical examination that is often only defi nite
once fl ap failure is already imminent. Our goal was to
fi nd out if analysis of select biochemical parameters
could indicate the above mentioned complications
earlier and more defi nite. Methods: Patients awaiting
pedicled or microsurgical fl ap surgery were included.
We drew venous blood samples 1 day before surgery
and 1,3,5,7 and 14 days afterwards. We analyzed
diff erent parameters biochemically that could hint
at one of the possible complications. Decision to
revise was based on routine clinical examination
and performed immediately if necessary. We
compared the parameters in the bleeding events
(„B“) and the thromboembolic complications („T“)
group and in the control group („C”). Results: The
majority of complications occurred on days 1 or 2
postoperatively, one on day 9 (B) and one on day 13
(T). Preoperatively, hemoglobin was signifi cantly
higher in the “B” group than in “C” (14.58 g/dl vs.
12.14 g/dl, p=0.01) as well as hematocrite (42.85%
vs. 36.58%, p=0.001). On day one postoperatively,
hemoglobin was lower in “T” than in “C” (9.07 g/dl
vs.10 g/dl; p=0.04). On days 3 and 5 postoperatively,
thrombocyte count was signifi cantly lower in “B” than
in “C” (119/104.5X1000/μl vs. 177.45/227,82X1000/
μl; p=0.021/0.008). In the last sample before
revision became necessary, thrombocyte count was
lower in “B” than in “T” (131.7582X1000/μl vs.
260.3382X1000/μl; p=0.01). Conclusion: In patients
undergoing pedicled or microsurgical fl ap surgery,
hemoglobin levels should not drop below 10 g/
dl to prevent thromboembolic complications. Low
thrombocyte count might hint at possible bleeding
complications.