Comprehensive Analysis of Von Willebrand Disease: Types, Symptoms

This report provides a detailed overview of Von Willebrand Disease (VWD), a common inherited bleeding disorder caused by dysfunction in the von Willebrand factor gene. It discusses the various types of VWD, including types 1, 2 (2A, 2B, 2M, 2N), and 3, each characterized by different defects in the VWF. The report outlines the symptoms associated with VWD, such as easy bruising, prolonged bleeding, frequent nosebleeds, and heavy menstrual periods. It also explores the aetiology and pathogenesis of the disease, including genetic mutations and the role of VWF in platelet adhesion and blood clotting. The report further differentiates between inherited and acquired forms of VWD, highlighting the clinical signs and symptoms associated with each type, and touches on related conditions like iron deficiency anemia and leukemia. The document also mentions that the website Desklib provides past papers and solved assignments for students.

Von Willebrand Disease 1
VON WILLEBRAND DISEASE
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Von Willebrand Disease 2
Von Willebrand Disease
The Von Willebrand disease is a frequent disorder in bleeding, and it is an inheritable
disorder. Von will stamp the dysfunctions cause illness to the von Will brand factor gene. There
is mediation from the plasma protein and meshing of platelets at the injured site which stabilises
and binds blood clotting factor. Thus defects in von Willebrand factor result in bleeding due to
impairing platelets adhesion or because of reduced blooding clotting factor concentration
(Haberichter, 2015, 1755). Therefore there is a prolonged period for flowing to stop and blood to
clot. There various types of von will brand disease, and each depends on whether either one or
both parents passed dysfunctional genes on someone. However, the linkage is not identified
approximately in type 1 case. In von Willebrand type 1 disease, has a strong association and
therefore level of von Willebrand factor is lower. Von Willebrand factor is affected by known
and unidentified environmental and genetic factors in various standards such as age, thyroid
status, blood type, stress, inflammation and hormone stress( Peyvandi et al. 2009 p 351). The
mutation that affects the expression may cause von Willebrand type 1. The specific variation that
influences functional epitopes has been recognised to cause type 2 disease.
Meanwhile, most of these mutations are in the 134 amino acid segment encoded by exon
28. The mutation leading to type 3 von Willebrand diseases are usually little mutation due to
small deletions. The splice site mutations are caused by splice mutation. However, mutations
missense are not common.
Von Willebrand disease is a more frequent disorder patients suffer from. This disease
infects both the males and the females. Meanwhile, it is a less severe condition compared to
other bleeding complications(Dong, 2005, 1714). Many people having this condition might not
realise they have this disorder because their bleeding conditions are very mild. VWD cause little

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or no distraction in people's lives unless there is serious injury or in case there is a need for
surgery. There can be a bleeding problem in all forms of VWD( Ruggeri, 2001, 263)
VWD is associated with the various sign and symptoms. In case a person has this
condition they exhibit the following symptoms. In fact, there is injury, little or no injury the
person experiences bruising (Catasman & Fedric 2003, 101). This may often occur maybe one to
four times per month. The bruise is usually large or has a raised lump. There is also longer than
normal bleeding. This is after surgery procedures, injury, dental work, childbirth, and the
bleeding occur more than five minutes following a skin cut.
Meanwhile extended or heavy bleeding during or after surgery or surgical bleeding and
after dental work occurs. This may stop and eventually start again hours or days later. A person
may also experience spontaneously nosebleeds that are usually hard to stop (Catasman &
Goodeve, 2013, 669). This bleeding keeps on occurring frequently and often happens five times
or more in a year, or it might last longer than ten times a year. In women, a person suffering from
VWD, usually have heavy menstrual periods that last more than seven days( Sadler &
Bodde,2006, 2013). The symptoms of this condition include clots that are larger than a quarter.
Changing menstrual pad tampon more often or use of double sanitary protection to control the
menstrual flow. VWD might also result in the diagnosis of anemia whose symptoms includes
tiredness, fatigue, and breath shortage. During birth, a person may suffer from massive blood
loss.
In some instances, other bleeding events in people having von Willebrand disease might
include blood in the stool as a result of stomach or intestine bleeding. Also, the urine might
contain blood due to bleeding in the bladder or kidneys. Although it is rare, they might occur
bleeding into joints or internal organs.

Von Willebrand Disease 4
Von Willebrand disease is brought about a result of abnormality, which is von
Willebrand disease quantitative or qualitative factor. It is a huge multimeric glycoprotein
necessary for platelets meshing (Sadler 2009, 38). Also, it acts as the protein carrier for element
VIII. With this von Willebrand factor have the responsibility in both primary that involves the
platelets adhesion and platelets formation plug. Secondly, it consists FVIII that is usually
hemostasis. The von Willebrand disease factor primary hemostasis holds to the platelets using its
receptor to a glycoprotein of the platelets surface and functions as a link between the injury part
in the site of damage and then platelets. The secondary hemostasis, von Willebrand factor shields
FVIII against degradation as well as transport in the location of the damaged part. There von
Willebrand disease is divided into two categories inherited and the acquired. The inherited forms
consist of types 1, 2 and 3. Class 2 is further categorized into 2M, 2N, 2A, and 2B. These types
differ regarding intensity and type of defect in von Willebrand factor.
Aetiology of the disease
Iron deficiency anemia is a situation in which blood lacks adequate red blood cells. Iron
deficiency is caused by lack of enough iron. Leukemia is an example of iron deficiency disease.
Leukemia is also known to as a cancer of blood or bone marrow. It is a disease one of the major
cancers in childhood although it is occurring frequently in adults. Leukemia is caused when the
immature DNA blood cells usually white blood cells are damaged is a certain way. This makes
the blood cells to continuously divide as they grow hence they are multiple.
Leukemia is a genetic disease although in most cases are not seen as hereditary.
Meanwhile, a wide range of factors can likely make you more prone get the disease. It is
believed that various types of leukemia are due to DNA mutations in the blood cells. This
mutation in the genetics affects the reproduction of the blood cells in the bone marrow. Also,

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proper functioning of the blood cells can be modified. The modifications are genetics however
they are not hereditary. Thus leukemia is caused by the gene mutations. The abnormalities in
genetics often are not inherited from the family. They are therefore referred to as acquired gene
mutation. The causes of these mutations are not well known. In some instance, one can be
genetically predisposed to leukemia, but risk factors arise from their lifestyle such as smoking
cigarette can make you prone to developing leukemia.
The Clinical signs and symptoms of the disease
It is essential to state various forms of the inherited forms of von Willebrand disease.
VWF is altered genetically such as the low factor level. The intracellular transports of the
subunits of the glycoprotein have interfered with the mutation in type 1 dominant severe. This
represents for 70-80% of the incidents. It is associated with the slow quantitative reduction in
qualitative normal von Willebrand disease. Usually, a person suffering von Willebrand type 1
disease experiences severe to moderate of diagnosis symptoms. The von Willebrand factor has a
reduced plasma level. This type is passed as the autosomal dominant gene having incomplete
penetration. However in a single family may vary widely. The person suffers a spectrum of
mucocutaneous bleeding symptoms. This is mostly related to a deficiency in von Willebrand
factor (Redoghien & Castman 2007, 117). Other evidence associated argues that the cause of
mild von Willebrand reduction is considered to involve the contribution from other genes apart
from the ABO blood groups genes and von Willebrand factor (Albanez & Ogiwara, 2016, 957).

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Pathogenesis of the disease
The type 2 disease is accountable for 16-21% of the Willebrand disease incidences.
Usually is a wide variety of illness consisting the von Willebrand factor qualitative deficiency.
The type 2 von Willebrand disease is mostly the autosomal recessive and the autosomal
dominant. The type is subdivided further into four which is 2N, 2B, 2M, 2A. This is where the
plasma Von Willebrand factor although it appears normal it is structurally and functionally
defensive (Dimino & Canaro, 2013, 2015). The 2A von Willebrand disease acts as an inheritable
due to the dominant trait of the autosomal and is related to normal and reduced plasma level
factorVillic and von Willebrand factor. The analysis reveals that there is a relatively compressed
multimeter in the intermediate and multimeter complexes high molecular weight. The
multimetric disorders are affected by degradation to proteolytic of von Willebrand factor. The
anomalies experienced in the multimetric defects are similar to the ones found in the plasma.
Von Willebrand type 2B diseases are caused by the autosomal trait. This disease is linked
with the lowered quantity in the von Willebrand factor multimeters high molecular weight.
Increased fragments of low-molecular-weight characterize this. Individuals having type 2B, von
Willebrand disease suffer homeostatic defects brought by intermittent thrombocytopenia and the
qualitatively abnormal von Willebrand factor. This result to gaining of mutation activity in von
Willebrand factor that causes meshing at the platelets spontaneously with von Willebrand factor
multimeters and platelets rapid clearance of both high molecular weight (Hampshire, 2001, 476)
This unusual Willebrand factor experiences increased affinity platelets glycoprotein Ib. Platelets
may lower further at the pregnancy period in conjunction with operational processes, or
desmopressin acetate has been administered.

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Type 2M is very rare, and the results from the laboratory are same to those people having
von Willebrand disease type 2A disease. Type 2M of von Willebrand disease is related with
decreasing of platelets the in directed function which is never affected by a high molecular
weight multimeter decrease. The von Willebrand factor activity is lowered. However, analysis
of the von Willebrand factor FVIII, antigen, multimeters located around the range reference. This
is because of impairment occurring to the von Willebrand factor gene which causes absent or
decreased platelets glycoprotein ib bindings, and its inheritance is a form of autosomal
dominant(Castman & Lethagen 2008, 3533).
Type 2N von Willebrand disease is not universal. However, it is associated with the von
Willebrand factor decreasing significant affinity or FVIII because of the mutations of the genes
of the factor VIII meshing part of the Willebrand factor. Hence, because of this, FVIII levels are
usually lowered to around 5-25% of the range reference. The FVIII-binding defects in the
patients are inheritable in the manner of autosomal recessive manner. The type 2N male patient
is regularly confused about suffering mild hemophilia A. Due to this condition, the type 2N von
Willebrand disease is not supposed to be regarded to individual suffering bleeding disorder and
FVIII deficiency and is not transmitted directly as the X-linked disease (Castman & Federic,
2012, 635). Also, this applies to the patients who do not respond completely to hemophilia A
therapy.
The type 3 von Willebrand disease is rarest among all categories. It is also the mildest
type of the condition. It is autosomal inheritable recessive trait, and patients are combined
heterozygous or homozygous. The von Willebrand disease is linked with significant
abnormalities of von Willebrand factor and FVIII in the plasma, lack of von Willebrand factor in
endothelial cells with the platelets and the DDAVP lacks to respond (Dong 2005, 1714). The

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type 3 von Willebrand disease is associated to worse bleeding clinical symptoms. This
characteristic is found both in the mucous membrane and external bleeding and the muscle and
joint bleeds. These conditions are inheritable as the autosomal recessive trait. Kindreds are the
most current continuity with this variant.
Von Willebrand acquired disease occurs, because of von Willebrand factor clearance to
the plasma forming a complex with its antibody. They may be caused as a result of adhesion to
the tumor cells or generated due to the availability of von Willebrand factor that distracts the
multimer or even slowing the digestion of the protein and is also observed with patients suffering
the aortic stenosis (Albahez & Ogiwara, 2016, 958).
Epidemiological aspects of the disease
Von Willebrand disease prevalence is 0.6-1.3 %. The autosomal inheritance patterns
suggest an equal distribution of female’s patients and male’s patients. However, the disease is
diagnosed more in females due to female-homeostatic challenges. These data were collected
through laboratory criteria and conservative clinical. However, most people will have only minor
bleedings in their lifetime; most of them may likely never be referred to medical assistance. The
availability of those related cases to specialized centers for bleeding diagnosis is estimated to be
one example for 10000 people with a cumulative incidence of hemophilia B and A are similar
(Sadler, 2009, 39). The worse von Willebrand disease is very rare disorder and its occurrence
case is one for 1million people and this dependent on ethnic background.
The von Willebrand disease symptoms vary across patients, depending on the residual
level of von Willebrand factor functions. The postpartum disease bleeding secondary and
primary occurs frequently. Due to this von Willebrand factor physiologic levels rise throughout
the life. Those suffering the type 1 von Willebrand factor may have standards that are within the

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normal range when they become older. Still, it is not recognized whether the rise is because of
the reduced bleeding episodes (Topez & Franchini, 2009, 95). The most common von
Willebrand disease symptoms in children are epistaxis and bleeding. In adult menorrhagia,
hematomas, and bleeding from small injuries are the most common symptoms. Majority of
patients experiences bleeding after surgery or dental work. A possible life-threatening and severe
well known bleeding complication is the gastrointestinal bleeding from angiodysplasia. Type 2
and 3 von Willebrand disease is frequent in elderly patients. The intraarticular bleeding is the
frequent complication in patients with hemophilia.
Meanwhile, there has not been reporting as a severe problem to patients with von
Willebrand disease. These conditions might be associated symptoms to type 2N or type 3
infections. Joint bleeding is identified to appear in a wide range of severely affected patients and
has a potential of leading to arthropathy and reduced joint function. The level of the residual
factor VIII strongly determines the collective bleeding risk, as well as the worsening of the von
Willebrand disease (Manucci & Franchini, 2001, 205). Patients in type 3 with the greatest threat
are those with deficient factor VIII levels. Lowered health quality of the patient's life for the
people with von Willebrand disease. Most women in the von Willebrand disease suffer from
menorrhagia, which damages the life quality.
Diagnostic strategy
The von Willebrand disease diagnosis is determined by the personal bleeding history or
the family bleeding history, or both, together with the laboratory tests signifying abnormalities in
von Willebrand factor, factor VIII or both( Favaloro, 2011, 345 ). Assessment of the bleeding
phenotype starts with full history information of the bleeding symptoms of the family members
and the patients. The severity rating of the von Willebrand disease has received significant

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attention in recent years. Numerical scoring symptoms based on a structured questionnaire
usually referred to as bleeding assessment. They have developed and endorsed by the ISTH.
These tools have less diagnostic use because they depend firmly on the number of previous
hemostatic challenges and the age. The method of tools in diagnostic is challenging to use in
young children who have not undergone dental intervention or surgery yet. Another problem to
bleeding-assessment tools is the application of the cumulative scoring. This means that the
patient experienced severe episodes of bleeding earlier and the bleeding score will remain high
even though bleeding does not occur again.
The diagnostic approach begins with assessing the person clinically to an individual who
has symptoms of bleeding mucocutaneous bleeding. Evaluation initially takes into account
family and personal history manifestation of bleeding. These evaluations are aimed at identifying
the sign of bleeding such as severity, spontaneity, and localization. Various tools have been
invented to assist in the diagnosis of disorders in bleeding. These tools are general while others
are symptoms specific.
The von Willebrand factor antigen measurement forms a basis to the diagnosing von
Willebrand disease. Platelets adhesion is factor dependent by the level of von Willebrand factor.
When von Willebrand factor antigens are unable to detect the type 3 of von Willebrand disease is
diagnosed. Meanwhile, usage of a cutoff level of 5 IU shows that the patients with detection 5
strong but shallow, von Willebrand factor antigen levels are supposed to be classified as
possessing type 3 disease (Domino & Canaro, 2013, 1496). Measurement of von Willebrand
propeptide factor, that includes cleaning product formed during the synthesis by von Willebrand
factor. Usually, type 3 disease both propeptide and von Willebrand factor antigen are generally
absent or at deficient levels if present (Battle & Topez, 2009, 95). However, in the severe type 1

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disease, there is a shallow level of the antigen, but the level of the propeptide is normal or
reduced. In instances the von Willebrand factor antigen is measurable. This standard is regarded
in relation to the ristocetin von Willebrand factor with the cofactor activity essay.
The proportional reduction in the von Willebrand factor ristocetin cofactor activity and
von Willebrand factor antigen fits type 1 von Willebrand disease diagnosis. Disproportional
reduction in von Willebrand factor ristocetin cofactor are compared with von Willebrand factor
antigen, this indicates the presence of type 2 disease (Federici & Mannucci, 2005, 538).
Additional striping tests, such as essays of von Willebrand factor multimeters and ristocetin-
induced platelets aggression are supposed to determine the phenotypic characteristics that define
type 2M, 2B, and 2A von Willebrand disease. Factor VIII activity is also measured as the first-
line test6 because the level is reduced frequently in von Willebrand disease types. A reduction in
factor VIII is more significant than the decrease in the von Willebrand factor antigen. Bellow
than 0.2 % Willebrand factor antigen indicates that type 2N von Willebrand disease. This
situation is confirmed by measuring the meshing of factor VIII and von Willebrand factor of
ruling out milder hemophilia A.
Methods used to describe the nature of the disease fully
The Von Willebrand disease disorder is diverse and is categorized into 3 major
categories. Quantitative this includes Type 3 and 1 or qualitative which are type 2B, 2M, 2A,
2N, and the anormalities. Type 1 is differentiated simply from type 3 because of its severe
inadequacy that ranges from 21-40 % of the autosomal dominant in the inheritance transmission
and most of the mutation and mild bleeding manifestation bleeding (Castman & Lethagen, 2008,
3533). The level below 30% suggests the diagnostic of von Willebrand disease, while from 30-
50% are regarded as low von Willebrand factor with major risk of mild bleeding. The type is

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related with total lack in von Willebrand factor at platelets and plasma. Type 3 victims 80% of
them are null allege in the von Willebrand factor. The most people are compound heterozygous
or homozygous. The type 2 von Willebrand diseases are autosomal dominant disorders having
large intrusive and are as a result of missense mutations. Type 2N and 3 are the inheritable
manners in an autosomal recessive.
Von Willebrand is mostly milder in type 1 and severity increases in type 3 and 2. The
gravity of the likelihood in bleeding is equal to a deficiency at the primary level of the von
Willebrand factor and secondary lack of FVIII. Mucocutaneous bleeding is an eminent and
typical manifestation of disease and might influence the life quality. FVIII is mildly lowered and
there is the rare manifestation of severe coagulation except in type 3 von Willebrand diseases.
Bleeding after dental work is frequently found in bleeding postoperative manifestation. The
bleeding after surgical work may occur to patients who are affected severely by type 1 & 2
diseases. Post-delivery bleeding is rare to see in type 1 because FVIII/VWF levels try to adjust at
the last stage of pregnancy in the docile type 1 von Willebrand disease.
Disease progression and monitoring of progression
The type 1 von Willebrand disease is caused by an incomplete quantitative defect
generated advanced clearance of von Willebrand factor or reduced secretion. Type 3 is a rare von
Willebrand disease disorder with a complete absence of the von Willebrand factor. Type 2 von
Willebrand disease is caused by obstruction of von Willebrand factor functioning and it is
divided into various variants. Type 2A is due to lofty von Willebrand factor multimeters
molecular weight in the plasma and von Willebrand factor reduced meshing to complex
glycoprotein. Type 2B von Willebrand disease is indicated with an enhanced accord of von
Willebrand factor, though the multimeter plasma distribution is normal. Type 2N von Willebrand