الفهرس 
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Abstract
The AML is a hematopoietic stem cell disorder
characterized by a block in differentiation of
hematopoiesis, resulting in growth of a clonal population
of neoplastic cells or blasts. Bleeding complications in AML
patients is a common serious complication. It manifests in
40-70% of AML patients at presentation. Factors associated
with bleeding include thrombocytopenia, endothelial
injury, excessive fibrinolysis, acquired hemophilia and
adverse effect of drugs commonly used in the treatment.
The vWF is a multimeric glycoprotein essential for
normal hemostasis. It is synthesized in vascular endothelial
cells, where it is stored in the Weibel-Palade bodies and
BM megakaryocytes, and is also present in platelets. It
carries and protects coagulation factor VIII in the
circulation, cross-links platelets with exposed collagen at a
site of vessel damage, and together with fibrinogen, it
cross-links platelets during subsequent platelet
aggregation. The efficacy of vWF in primary hemostasis
depends on its level and function.
In this study, vWF-RCo activity (functional vWF: a
functional assay of plasma vWF based upon the degree of
platelet agglutination induced after the addition of
ristocetin) was assessed in newly-diagnosed (de novo) AML
patients and after two weeks post-chemotherapy, and this
activity was correlated with haemostatic complication,
known prognostic factors and outcome in AML patients. The study was carried out during 2013-2014. It was a
cross-sectional case control study carried on 30 AML
patients and 10 age- and sex-matched healthy subjects (as
a control group). The AML patients were subjected to full
history taking laying stress on bleeding manifestations,
clinical examination and laboratory investigations [such as
CBC, PT, APTT, FDPs, cytochemical staining, and
immunophenotyping (Lichtman and Liesveld, 2010a). The
vWF-RCO activity was measured, in both groups, using
platelet agglutination method (Siemens Health care
Diagnostics Products, Marburg/ Germany).
All data were collected, tabulated and statistically
analyzed. Results showed that the vWF-RCO activity
among AML patients ranged from 52.8 to 100.6%, with a
mean value of 80.5 ±12.6. Meanwhile, the range in the
control group was from 90.8 to 126.4% with a mean value
of 99.5 ±10.5%. A statistically highly significantly (p<0.001)
lower mean vWF-RCO activity was documented among the
patients’ group when compared to the controls, and a
statistically significantly increased activity that almost
returned to normal after two weeks of treatment.
Moreover, a statistically significantly reduced vWF-RCO
activity was found in AML patients with bleeding
symptoms versus non-bleeders. Also, there was a
statistically significantly reduced vWF-RCO activity in AML
patients with bad outcome.
On the other side, there was no statistically
significant association between vWF-RCO activity and
gender or organomegaly or laboratory parameters with prognostic significance, including white blood cell count,
hemoglobin, platelets, BM blasts %, PT & APTT or
cytogenetic findings among the AML patients. However,
there was border-line significant association between the
activity and different FAB subtypes, as lower activity was
associated with M2 and M3.
Roc curve analysis was performed to evaluate the
vWF-RCO activity in AML patients, and a cut- off point of
<= 90.2% provided a sensitivity of 80% and specificity of
100% discriminating AML patients from normal controls.
Meanwhile, a cut-off point of <= 85.2% provided a
sensitivity of 94.1% and a specificity of 69.2% for
predicting of AML patients who are prone to bleeding
manifestations, and a cut-off point of <= 82.6% provided a
sensitivity of 77.3% and specificity of 87.5% for predicting
bad outcome in AML patients.
Finally, the present study documented a significantly
reduced vWF-RCO activity in AML patients at diagnosis,
which significantly increased after two weeks posttreatment.
The vWF-RCO activity, at diagnosis, represented
a valuable prognostic marker for predicting bleeding
complications and bad outcome [relapse or death].
The study propose measuring the vWF-RCO activity,
using platelet agglutination method with the cut-offs ”<=
85.2%” for predicting the AML patients prone to bleeding
manifestations and ”<= 82.6%” for the prediction of bad
outcome in AML patients. The provided cut-offs for vWFRCO
activity in AML patients represent first steps for its
use as a prognostic marker for prediction of AML patients prone to bleeding manifestations and bad outcome,
although future studies with larger series of patients and
longer duration may be needed before its routine use.
Moreover, the present study indicated that the
prognostic impact of vWF-RCO activity is independent
from other established prognostic markers. A borderline
significant association was found between vWF-RCO
activity and different FAB subtypes, as lower activity was
associated with M2 and M3. The study recommends
adding measurement of vWF-RCO activity in all AML
patients at presentation and after two weeks of
chemotherapy, to the routine laboratory screening for the
evaluation of the associated hemostatic abnormalities.