Clinical Manifestations and Complications of Von Willebrand Disease

Journal of Rawalpindi Medical College (JRMC); 2012;16(1):19-21
Original Article
Clinical Manifestations and Complications of von

Willebrand Disease
Shahida Mohsin*, Maria Aslam*, Shabbir Hussain*, Shahla Suhail**
*Department of Pathology, University of Health Sciences, Lahore;
** Hemophilia Patients Welfare Society, Lahore.
Abstract
mennorhagia are common clinical features5,6. Bleeding

tendency is less severe in vWD so regular treatment is
not required. Replacement of deficient protein before
surgery, invasive procedure or at the time of bleeding
is required.. 7-11
Background: To describe the clinical presentation and

complications of von Willebrand disease(vWD).
Methods: In this descriptive study, out of 426
patients,visiting the hemophilia welfare society Lahore, 57

cases of vWD, diagnosed on the basis of clinical features,
prolonged bleeding time (BT), prolonged APTT and
decreased vWF antigen were enrolled.
Results: Most of the patients (49.1%) were diagnosed at
less than one year of age while 35% patients were
diagnosed between 1-5 years of age and 15.8% were
diagnosed at the age of more than 5 years. Family history
of bleeding disorder was found in 60%. Common clinical
presentation of disease was epistaxis (77.2%), easy
bruising (64.9%) and mennorhagia (21.1%). Disease
complications were seen in 35% patients. Hepatitis C was
the commonest complication (31.6%). Arthropathy was
seen in 22.8%. CNS complications and Hepatitis B were
seen in 1.8% each.
Conclusion: In inherited bleeding disorders patients ,
with soft tissue bleeds, vWD is the commonest
Key Words: von Willebrand disease; Bleeding time.
Patients and Methods

Patients reporting to Pakistan Hemophilia Welfare
Association Lahore were included in this study. Out of
426 patients, 57 patients were diagnosed as vWD.
Informed consent was taken from all patients.
Proforma included personal and family history,
clinical presentation of patients like epistaxis, easy
bruising, menorrhagia, and mucous membrane
bleeding during dental work. Family history of an
autosomal dominant or recessive inherited bleeding
disorder or easy bruising with indurations, which
could also indicate the presence of vWD. The history
of first bleed and bleeding episodes per month were
also recorded. Complications of disease like
arthropathy, joint deformities, CNS complications,
hepatitis B, C and HIV infection were also recorded.
Coagulation tests were performed on venous blood
samples collected in vaccutainers containing 3.2%
sodium citrate (BD). APTT, platelet count, and
bleeding time, vWF levels, factor VIII levels and VWD:
RCo assay were performed to establish the diagnosis.
Introduction
Von Willebrand disease (vWD) is the most common
inherited bleeding disorder,which occurs due to
quantitative or qualitative defects of von Willebrand
factor (vWF) 1,2. VWF is a large multimeric protein
which causes platelet adhesion to blood vessel. It also
acts as a carrier protein for clotting factor VIII. VWD is
classified into three major types. Type I occurs due to
partial deficiency of vWF. Type II includes functional
defects in vWF. Patients with type III have complete
deficiency of vWF and a secondary severe deficiency
of F VIII. Type II is further divided into four subtypes
2A, 2B, 2N and 2M. Type 2A and 2B occur due to
absence of largest vWF multimers. Type 2M is
associated with specific defects in platelet and type 2N
with F VIII binding domains3, 4. Patient usually
presents with mucosal bleeding. Epistaxis, gum
bleeding, bleeding after trauma or surgery and
Results
A total 57 patients of vWD were enrolled in this
study. Most of the patients 28 (49.1%) were diagnosed
at less than one year of age while 20 (35%) patients
were diagnosed between 1-5 years of age. Only 9
(15.8%) patients were diagnosed at more than 5 years
of age (Table-1). Majority(60%) patients had positive
family history of bleeding disorder. Out of these
positive family history patients , 28 patients had family
history of VWD, 5 had history of haemophilia A and
one had unknown bleeding disorder. Relation with
19

these patients is shown in Table 2. First cousin
marriages were seen in 39 (68.4%), while marriages
within family but not first cousins in 11(19.2%) and out
of family marriages in 7(12%) patients. (Table 1).
patient only.Hepatitis C was the most common

infection which was present in these patients 18(31.6%)
while hepatitis B was only seen in one.
Table 3: Bleeding History of Patients

Bleeding Episodes/Month
<1
Table 1:Demographic data of patients
1-3
17(29.8)
First Presentation of Disease
Age Profile
Age
Up to 1 year
1-5 years
5-23 years
Frequency
28 /57
20/57
9 /57
Consanguinity
39 /57
First Cousin
Family marriages
Out of family
marriages
11/57
7/57
Percentage (%)
49.1
35.1
15.8
Circumcision
Simple Injury
Easy Bruisibility
Others
Sister
Brother
Maternal
uncle
Maternal
cousin
Cousin,
nephew
Paternal
uncle
Aunt
Discussion
19.2
12
vWD is a hereditary bleeding disorder. It occurs

due to absence or reduction in the amount of vWF or
loss of its function. vWF is synthesized by
megakaryocytes and endothelial cells. It is a
glycoprotein that causes platelet adhesion to subendothelium and platelet aggregation at sites of
vascular injury to form platelet plug. It also acts as a
carrier of clotting factor VIII in the circulation thus
plays important role in primary haemostasis 12, 13.
Manifestations of disease are different ranging from
minor to severe life threatening bleeding.
Mucocutaneous
bleed
are
the
commonest
presentation, while in hemophilia joint bleed is the
commonest. A study conducted in India to see the
prevalence and spectrum of vWD showed comparable
results14. Shahbaz N et al reported in their study that
mucocutaneous bleeding is the primary presentation
of patients15. Another study in Eastern India showed
the most common presentation of vWD is mucocutaneous bleeding. 14-16
Important aspect of disease we have noted in this
study is consanguinity and family marriages among
parents. It was also reported by Shahbazi et al in Iran
that most of the patients were off springs of
consanguineous marriages 17. A study conducted in
Northern Pakistan showed consanguinity in 40.6% of
parents.15
Family history of bleeding is present in 60%
patients. Family history of bleeding reported in a
study by Metjian D.A et al was 58% 18. A study
conducted in Karachi reported frequency of vWD
among patients with positive family history of
bleeding as 21.3% 19. In western India positive family
history was noted in 15 families by Trasi S 14.
Disease complications were seen in 35% of patients.
Most common complication was hepatitis C infection
(31%). Arthopathy and joint deformity was present in
Male
Female
34 /57
59.6%
23 /57
40.3%
Relation with patient
11
32.3%
9
26.4%
6
17.6%
4
11.7%
5.8%
2.9%
1
21
13
25(43.9)
11(19.3)
11(19.3)
10(17.5)
68.4
Table 2:Family History of Bleeding Diathesis

Positive
Negative
Number(%)
38(66.7%)
2.9%
Sex of relative
61.8%
38.2%
In majority of the cases (66.7%) the frequency of

bleeding episodes was less than one per month. In 17
patients bleeding episodes were 1-3 per month and 2
patients presented with more than 3 episodes /
month. Most of the patients 25(43.9%) presented with
first bleed at circumcision and 11(19.3%) each with
simple injuries and easy bruisibility while 10(17.5%)
patients presented with others like menorrhagia, gum
bleed and epistaxis. (Table: 3).
Common clinical presentations seen during the
whole course of disease was epistaxis in 44(77.2%)
patients. Easy bruising was present in 37(65%) and
menorrhagia in 12(21.1%). Disease complications were
noted in 20 out of 57 patients. arthopathy in 15, joint
deformity in four and CNS complications in one
20

26% and 7% respectively. Manifestation of CNS
complication was 1.7%. Metjian D.A et al also reported
that joint bleed is present upto 45% and muscular
bleed upto 28% in vWD.18 The high degree of Hepatitis
C positivity shows that the screening profile of the
transfused plasma is not upto the quality control
standards which results into the transfer of hepatitis B
and C to the von Willebrand disease patients.
8.
Conclusion
12.
9.
10.
11.
1. Many cases of vWD remain undiagnosed due to

varied clinical presentations and confounding
impediments in lab diagnosis.
2.Comprehensive evaluation of patients, followed by
meticulous laboratory testing is necessary to diagnose
vWD.
13.
14.
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Journal of Rawalpindi Medical College (JRMC); 2012;16(1):19-21

Clinical Manifestations and Complications of von

mennorhagia are common clinical features5,6. Bleeding

Background: To describe the clinical presentation and

Methods: In this descriptive study, out of 426

patients,visiting the hemophilia welfare society Lahore, 57

Patients and Methods

Journal of Rawalpindi Medical College (JRMC); 2012;16(1):19-21

patient only.Hepatitis C was the most common

Table 3: Bleeding History of Patients

Table 1:Demographic data of patients

vWD is a hereditary bleeding disorder. It occurs

Table 2:Family History of Bleeding Diathesis

In majority of the cases (66.7%) the frequency of

Journal of Rawalpindi Medical College (JRMC); 2012;16(1):19-21

1. Many cases of vWD remain undiagnosed due to

Kujovich J L. von Willebrand disease and pregnancy. J

Budde U. Diagnosis of von Willebrand disease subtypes:

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