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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 4, July/August 2016
AFRICA
225
in 20 (33.3%). Of the 20 patients, 11 had aortic stenosis (six
had mild stenosis, three had moderate stenosis and two had
severe stenosis), and nine had pulmonary stenosis (one mild, six
moderate and two severe).
PFA-100 collagen epinephrine closure time was prolonged in
34 (56.6%) patients. Of these, 19 had aortic stenosis (12 mild,
four moderate, three severe) and 15 had pulmonary stenosis (one
mild, 12 moderate, two severe). A total of 16 of 60 patients who
underwent PFA-100 ADP collagen closure time and PFA-100
collagen epinephrine closure time evaluation had a positive
bleeding story (26.6%) (Tables 9, 10).
Discussion
VWD is classified into three main types. Type 1 VWD is the
most common form of disorder and is characterised by a mild-
to-moderate decrease in the plasma levels of VWF. Plasma VWF
from these individuals has a normal structure. Plasma levels of
ristocetin co-factor and factor VIII tend to be proportionately
decreased.
Type 2A VWD is associated with the absence of large high-
molecular-weight (HMW) multimers from the plasma and
platelets, which results in impaired ability to mediate platelet
adhesion to the endothelium. This type is common in patients
with cardiac stenotic diseases, especially in aortic stenosis,
because of mechanical destruction of the HMW multimers of
VWF under high shear stress.
Type 2B VWD is a rare form of VWD characterised
by partial loss of plasma HMW multimers and increased
responsiveness when exposed
ex vivo
to the antibiotic ristocetin.
In Type 3 VWD, plasma levels of factor VIII and VWF are
virtually undetectable.
12
Studies to investigate the prevalence of VWD in patients with
heart disease are mainly carried out in adults. Although there are
few reports in children, the relationship between congenital heart
defects and VWD has been elucidated. In a study by Arslan
et
al.
, the prevalence of VWD was reported as 12.2% in 49 children
with congenital heart disease.
13
We found a similar ratio in our
study (11.6%).
In a study by Gill
et al
.,
14
abnormal von Willebrand factor
multimers was detected in all patients with congenital heart
disease, but only six of them had low VWF:Ag levels. In this
study, multimer analysis was repeated on five patients after
surgical correction, and four patients had a normal multimeric
Table 7.The comparison of haematological parameters of patients with
pulmonary stenosis according to degree of stenosis
Mild pulmonary
stenosis (
n
=
3)
(mean
±
SD)
Moderate pulmo-
nary stenosis
(
n
=
25)
(mean
±
SD)
Severe pulmonary
stenosis (
n
=
4)
(mean
±
SD)
p-
value
Platelet
(cells/mm³)
308.330
±
52.596
d
345.800
±
97.395 459.000
±
123.018
0.01
PT (s)
13.667
±
0.152 13.204
±
0.649
e
14.000
±
0.812 0.05
aPTT (s)
36.267
±
7.691
f
29.920
±
2.186 29.775
±
3.313 0.007
Factor VIII (%) 93.33
±
21.07 116.80
±
44.65 149.50
±
73.07 0.28
VWF:Ag (%)
91.67
±
28.00 95.88
±
28.72 119.50
±
48.37 0.35
VWF:RCo (%) 115.00
±
22.71 93.88
±
33.86 105.25
±
46.21 0.54
PFA-100
CADP (s)
163.00
±
98.73 110.72
±
39.85 124.50
±
29.49 0.18
PFA-100
CEPI (s)
157.00
±
37.16 169.64
±
54.78 167.75
±
81.80 0.93
VWF:RCo/
VWF:Ag
1.33
±
0.57
0.99
±
0.33
0.87
±
0.14
0.20
PT: prothrombin time; aPTT: activated partial thromboplastin time; PFA-100
CADP: platelet-function analyser-100 adenosine diphosphate collagen closure
time; PFA-100 CEPI: platelet-function analyser-100 collagen epinephrine closure
time; VWFAg: von Willebrand factor antigen; VWF:RCo: ristocetin co-factor.
d
p
=
0.04, severe versus mild pulmonary stenosis.
e
p
=
0.003, severe versus moderate pulmonary stenosis.
f
p
=
0.002, mild versus moderate pulmonary stenosis,
p
=
0.009, mild versus
severe pulmonary stenosis.
Table 10. Relationship between VWF components and
PFA-100 CEPI and CADP
PFA-100 CADP
p-
value
PFA-100 CEPI
p-
value
Normal
(
n
=
40)
Prolonged
(
n
=
20)
Normal
(
n
=
26)
Prolonged
(
n
=
34)
Low VWF:Ag
1
2
0.20
–
3
0.12
Low VWF:RCo 1
3
0.06
–
4
0.07
Positive bleed-
ing history
3
5
0.06
2
6
0.26
VWF:Ag: von Willebrand factor antigen; VWF:RCo: ristocetin co-factor;
PFA-100 CADP: platelet-function analyser-100 adenosine diphosphate collagen
closure time; PFA-100 CEPI: platelet-function analyser-100 collagen epineph-
rine closure time.
Table 9. Abnormal haematological parameters between the study groups
Aortic stenosis
(
n
=
28)
Pulmonary stenosis
(
n
=
32)
p-
value
Low VWF:Ag,
n
(%)
0
3 (100)
0.08
Low VWF:RCo,
n
(%)
3 (75)
1 (25)
0.16
Prolonged PFA-100 CADP,
n
(%)
11 (55)
9 (45)
0.36
Prolonged PFA-100 CEPI,
n
(%)
19 (56)
15 (44)
0.10
Low VWF:RCo/VWF:Ag,
n
(%)
1 (50)
1 (50)
0.66
VWF:Ag: von Willebrand factor antigen; VWF:RCo: ristocetin co-factor;
PFA-100 CADP: platelet-function analyser-100 adenosine diphosphate collagen
closure time; PFA-100 CEPI: platelet-function analyser-100 collagen epinephrine
closure time.
Table 8.The clinical and laboratory features of patients with abnormal platelet aggregation tests and low VWF:RCo/VWF:Ag
Age
Diagnosis
Gender
Symptoms Blood group
VWF:
Ag (%)
VWF:
Rco (%)
PFA-100
CADP
PFA-100
CEPI
VWF:RCo/
VWF:Ag
PPG
(mmHg)
MPG
(mmHg)
18
PS
F
No
B RH+ 55 (
↓
)
99 (N)
100 (N)
179 (
↑
)
1.8 (N)
49
25
3
PS
M No
AB RH+ 52 (
↓
)
46 (
↓
)
135 (
↑
)
263 (
↑
)
0.88 (N)
42
20
7
PS
F
No
AB RH+ 64 (
↓
)
131 (N)
277 (
↑
)
196 (
↑
)
2 (N)
30
12
5
AS
M Yes
O RH+ 56 (N)
49 (
↓
)
115 (N)
212 (
↑
)
0.87 (N)
36
18
10
AS
F
No
A RH+ 62 (N)
49 (
↓
)
210 (
↑
)
182 (
↑
)
0.79 (N)
40
21
6
AS
M No
O RH+ 58 (N)
46 (
↓
)
155 (
↑
)
185 (
↑
)
0.79 (N)
56
25
8*
AS
F
Yes
O RH+ 75 (N)
53 (N)
137 (
↑
)
217 (
↑
)
0.7 (N)
34
18
AS: aortic stenosis; F: female; M: male; MPG: mean pressure gradient; N: normal; PS: pulmonary stenosis; PFA-100 CADP: platelet-function analyser-100 adenos-
ine diphosphate collagen closure time; PFA-100 CEPI: platelet-function analyser-100 collagen epinephrine closure time; VWF:Ag: von Willebrand factor antigen;
VWF:RCo: ristocetin co-factor; PPG: peak pressure gradient.
*This patient’s platelet aggregation curve induced by ristocetin was horizontal.