WERLHOF'S DISEASE, VON

WILLEBRAND DISEASE
Beulah Nwokotubo, Group 28
WERLHOF'S DISEASE
OVERVIEW
Werlhof's disease, also known as Immune Thrombocytopenia (ITP), is a
syndrome in which platelets become coated with autoantibodies to platelet
membrane antigens, resulting in splenic sequestration and phagocytosis by
mononuclear macrophages. The resulting shortened life span of platelets in
the circulation, together with incomplete compensation by increased platelet
production by bone marrow megakaryocytes, results in a decreased number
of circulating platelets.

This disease may be acute or chronic.

ACUTE vs CHRONIC ITP
Acute ITP: Chronic ITP:

● Often affects children following ● More often occurs in females

a viral infection
● Resolves spontaneously in 2
months
of reproductive age
● Duration of disease is more
than 6 months
● May be primary (with no
underlying trigger), or
secondary (following hepatitis
C, HIV infections or SLE)
CLINICAL MANIFESTATIONS
● Purpura (red/purple spots), ecchymoses, petechiae on the skin (which
could be induced by a suction-type ECG)
● Mucosal bleeding in severe cases - especially epistaxis but menorrhagia
can occur as well
● Less commonly - hematuria, retinal hemorrhage, joint bleeding
● The platelet count in acute ITP often ranges from 10,000-20,000/µL
● The platelet count in the chronic form is usually higher than in the acute.
The changes to skin and/or mucous membranes are minor or absent
● However, if the platelet count reduces below 10,000/µL, intracranial
hemorrhage is likely to occur

Findings suggestive of intracranial hemorrhage include:

● Headache, blurred vision, somnolence, or loss of consciousness

● Hypertension and bradycardia, indicative of ↑ICP
DIAGNOSIS
● CBC: ↓thrombocytes (10,000-20,000/µL in acute ITP; 30,000-75,000/µL in
chronic ITP), Hemoglobin, ESR, RBCs are usually normal
● PT, aPTT are normal
● Children or adults with post-viral appearance of the disease may have
lymphocytosis
MANAGEMENT
Corticosteroids are the drug of choice for acute ITP
Oral prednisolone, IV methylprednisolone, or pulse therapy with dexamethasone
● The second choice has been IV immunoglobulins
● For rhesus-negative patients with intact spleens, IV Rho immunoglobulin has
proven to be efficate but should not be used in concentrations less than 8 g/dL
because it can induce hemolysis
● Rituximab is the third drug of choice
● If therapy for 6 months does not bring platelets to a safe range, splenectomy
should be considered
● Thrombopoietin receptor agonists (eltrombopag, romiplostim) can help to
maintain safe platelet levels in patients with chronic ITP
VON WILLEBRAND DISEASE
OVERVIEW
● Von Willebrand Disease is a bleeding disorder caused by a deficiency in a
quantity or the quality of Von Willebrand Factor, a plasma glycoprotein
that plays a key role in forming blood clots needed to stop bleeding
● The disease was named after Erik Adolf Von Willebrand, a Finnish
physician who first described it in 1924
● Von Willebrand factor is synthesised and stirred in the endothelial cells
and megakaryocytes. It’s synthesis is regulated by a gene located on the
short arm of chromosome 12.
PHYSIOLOGY
● When there’s hemorrhage from a blood vessel, histamine and thrombin
stimulate local endothelial cells and megakaryocytes to release the VOn
Willebrand factor into the bloodstream.
● After its release, it attaches to the exposed collagen fibres in the wall of the
injured vessel where it serves as a glue-like substance sticking to platelet
receptors, known as GP 1b.
● As more of the factor is released, a mass is formed, over which fibrin fibres
deposit, forming what we know as a platelet plug in order to arrest bleeding.
● In addition, Von Willebrand factor also binds and carries Factor VIII which needs
to be bound to the factor to be protected from early degradation by Proteins C
and S.
PATHOPHYSIOLOGY AND CLASSIFICATION
In Von Willebrand disease, There is not enough of the factor to help form the
platelet plugs and to bind and carry factor VIII, of which the end result is
coagulopathy.
This disease is more often inherited - there’s a mutation in the Von Willebrand
gene
The inherited type is classified as:
● Type I: most common, autosomal dominant, mutation in one allele result
in insufficient or defective production (quantity affected).
CLASSIFICATION
● Type II: the quality of the factor is affected. 4 subtypes are distinguished:
In Type II A and M, it is unable to bind the platelet together to form the blug
In Type II B: binds normal platelets in the bloodstream, with no injury, forming
platelet plugs in the bloodstream which are taken out by the spleen and liver. This
eventually leads to thrombocytopenia and consequentially, a risk of bleeding.
In Type II N: poorly binds to factor VIII, causing a risk for bleeding
● Type III: rare, but severe. Autosomal recessive. People have no Von Willebrand
factor in the bloodstream.
CLASSIFICATION
Acquired forms of Von Willebrand disease may occur due to Some
autoimmune disorders like SLE (Antibodies against self-antigens, including
Von Willebrand factor).

In addition, drugs such as ciprofloxacin and valproic acid can interfere with
synthesis of the factor.
CLINICAL PRESENTATION
Symptoms depend on the form of the disease.
Those with Type I, IIA, IIB, IIM are often asymptomatic or present with mild forms of
hemorrhagic syndrome such as easy bruising, gum and nose bleeds, heavy
menstruation.
However, the situation can be severe in those taking anticoagulants, antiaggregants
and NSAIDs.
Severe cases of bleeding occur in those with type IIN or type III with joint and muscle
bleeding, as well as GI bleeding (rare).
Those with the acquired forms present with sudden bleeding on the background of
some autoimmune disorders, or antoicoagulants intake.
DIAGNOSIS
● CBC: Platelet count is usually normal except in type IIB
● Prothrombin time (PT): normal
● Activated partial thromboplastin time (aPTT): prolonged if factor VIII is
very low
● Von Willebrand factor antigen measurement
● Ristocetin cofactor assay: measures activity of VWF in blood. Will show no
coagulation
MANAGEMENT
● Desmopressin analogues - DDAVP for Type I & II to stimulate endothelial
cells and megakaryocytes to release VWF
● For Type II - IV VWF concentrate
● Antifibrinolytics - Tranexamic acid when bleeding is difficult to control