MRCP revision battle 38.1: Von Willebrands Disease

We're about to enter a 2 day fest of haematology.  Try to get through the dull battles of B and T cell disorders as the topics on the other side of them are slightly more stimulating.  Good luck!


MRCP revision battle 38.1: Von Willebrands Disease
MRCP revision battle 38.2: B cell disorders
MRCP revision battle 38.3: T cell disorders
MRCP revision battle 38.4: Combined B and T cell disorders
MRCP revision battle 38.5: Thrombotic thrombocytopenic purpura
MRCP revision battle 38.6: Microangiopathic haemolytic anaemia
MRCP revision battle 38.7: Sideroblastic anaemia




MRCP revision battle 38.1: Von Willebrands Disease


Von Willebrand's disease is the commonest inherited coagulopathy in the UK.


Von Willebrand's factor is a substance made in epithelial cells which:

• helps platelets bind to the exposed subendothelium
• helps platelets bind to each other
• binds to factor VIII,  helping prevent its destruction in the circulation

There are many types of Von Willebrand's disease.  The commonest 3 are:

• Type 1: decrease in Von Willebrand's factor 
• accounts for 80% of Von Willebrand Disease
• autosomal dominant
• Type 2: abnormal form of Von Willebrand's factor
• autosomal dominant
• Type 3: total lack of Von Willebrand's factor
• autosomal recessive

Symptoms/signs of Von Willebrand's disease include bruising, menorrhagia, epistaxis and increased bleeding after tooth extraction (a favourite in MRCP exams)


Diagnosis is by:

• low levels factor VIII
• low levels VWF antigen
• deficient ristocetin-induced platelet aggregation

Treatment is:

• DDVAP (=desmopressin) in mild disease
• factor VIII concentrate/cryoprecipitate in severe disease
• avoid NSAIDs.

Next up.... B cell disorders

MRCP revision battle 38.2: B cell disorders

B cells are lymphocytes involved in humoral immunity.  Their functions are:

• production of antibodies (=plasma B cells)
• memory of antigen (=memory cells, live for a long time and able to respond rapidly if body encounters same antigen again)
• antigen presenting cells

B cell disorders result in a failure of antibody synthesis, resulting in either hypogammaglobulinaemia or agammaglobulinaemia.  This causes recurrent infections with pyogenic bacteria and fungi.


Examples of B cell disorders include:


1. Common variable immunodeficiency

• commonest cause of hypogammaglobulinaemia
• not familial
• bone marrow shows a normal number of B cells but they fail to mature

2. IgA deficiency

• commonest isolated Ig in UK
• increased risk of giardiasis

3. Bruton's agammaglobulinaemia

• x-linked recessive
• no circulating B cells
• usually presents between 3 months and 2 yrs of age

Now on to the T cell disorders......

MRCP revision battle 38.3: T cell disorders

T cells are lymphocytes involved in cell-mediated immunity.  T cells mature in the thymus.

T cell disorders result in increased susceptibility to virus', mycobacteria and fungi.


Examples of T cell disorders include:




1. DiGeorge

• defect in development of thymus and 3rd/4th branchial arches
• mnemonic CATCH-22:
• cardiac abnormalities (tetralogy of fallot)
• abnormal faies
• thymic aplasmia --> lack of T cells
• cleft palate
• hypocalcaemia (due to absent parathyroids)
• 22 - recessive inheritance on chromosome 22

2. Nezelof syndrome

• absent thymus
• often some B cell involvement

3. Purine nucleoside phosphorylase deficiency

• prevents development of T cells

Onto the final battle of this dull triad - combined B and T cell disorders

MRCP revision battle 38.4: Combined B and T cell disorders

So having skated through B cell disorders and T cell disorders its on to combined disorders, the main 3 of which may be recalled as SCID WAS ATAXIC.


1. Severe Combined Immundeficiency

• autosomal recessive
• sometimes due to lack of adenosine deaminase

2. Wiskott-Aldrich Syndrome

• x-linked recessive
• characterised by recurrent infections, eczema and thrombocytopenia
• associated with an increased risk of maligancy

3. Ataxic telangiectasia

• autosomal recessive
• cerebellar ataxia and telangiectasia
• increased risk of malignancy
• low IgE and IgA

Lets now move back a bit more mainstream with thrombotic thrombocytopenic purpura...

MRCP revision battle 38.5: Thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura is a condition in which large multimers of Von Willebrand's factor clump platelets together, activating the coagulation system, forming fibrin strands and causing microangiopathic haemolytic anaemia (MAHA).


The 5 key features are:

• Thrombocytopenia
• Fever
• Fluctating CNS signs (visual disturbance, fits, hemiparesis)
• MAHA
• Renal failure

Adult females are most commonly affected


The cause is often unknown.  Implicated factors include:

• drugs - clopidogrel, ciclosporin, COC
• pregnancy
• HIV
• SLE

 Treatment is:

• plasma exchange
• IV vincristine  (promotes premature release of platelets from marrow)
• steroids

Next up... more microangiopathic haemolytic anaemia...

MRCP revision battle 38.6: Microangiopathic haemolytic anaemia

Microangiopathic haemolytic anaemia (MAHA) is a nice condition to learn about as you can easily visualise it: it is mechanical disruption of red blood cells in the circulation, so in your mind's eye see the little RBC's being mangled by prosthetic heart valves or sliced by fibrin strands and then imagine them on the other side, reduced in number (anaemia), all with different amounts of haemoglobin in them after being sliced (polychromasia) and lots of partial fragments (schistocytes and helmet cells).


So to put that above paragraph into a nice list of haematological features of MAHA:

• anaemia
• polychromasia
• helmet cells
• schistocytes

Causes of MAHA include:

• DIC
• HUS
• TTP
• malignant hypertension
• severe pre-eclampsia
• prosthetic heart valves
• septocaemia

Now onwards to the last MRCP revision battle of the day, sideroblastic anaemia...

MRCP revision battle 38.7: Sideroblastic anaemia

Sideroblastic anaemia is a form of anaemia in which the body is not able to incorporate iron successfully in the haem molecule.


This results in:

• anaemia
• sideroblasts in bone marrow
• rarely haemosiderosis as the body keeps absorbing iron in its futile attempt to correct the anaemia (haemosiderosis may be revised in MRCP revision battle 28.1)

The image below from Wiki Commons shows ring sideroblasts:

Causes of sideroblastic anaemia include:

• congenital causes
• delta-aminolevulinate synthase deficiency
• x linked recessive, rare
• responds to pyridoxine
• acquired causes
• myelodysplasias
• alcohol
• lead
• chemotherapy
• anti-TB meds

Treatment is to treat the cause, supportive care and pyridoxine.