Haematology

1. By
Ahmed Riyadh Abdul Rahman
Al-Noor University College
Disorders of haemostasis I:
platelets

2. Excessive bleeding caused by thrombocytopenia or
disordered platelet function is mucosal (e.g. epistaxis,
gastrointestinal bleeding or menorrhagia) or affects the
skin (purpura, petechiae and ecchymoses; Figs. 1).

3. Symptoms usually occur when the platelet count is <10 × 109/L,
but this may be higher when there is impaired platelet function.
Thrombocytopenia (platelets <140 × 109/L) may be congenital or
acquired (Box1).

4. Congenital forms are rare; causes include
1. congenital aplastic anaemia,
2. thrombocytopenia with absent radii syndrome
3. Wiskott–Aldrich syndrome (thrombocytopenia with
eczema and hypogammaglobulinaemia).
4. Congenital infection (e.g. rubella, cytomegalovirus)
frequently leads to thrombocytopenia.
Acquired causes include deficient platelet production or
accelerated platelet destruction.

5. Autoimmune thrombocytopenia
Mechanism of platelets destruction: The platelets are
coated with autoantibody (immunoglobulin) and are
prematurely destroyed by the macrophages of the
reticuloendothelial system.
Clinical findings: The acute form usually presents in
childhood (2–7 years) and often follows a viral
infection. Purpuric rash or epistaxis is frequent. It
typically resolves spontaneously.
Up to 20% develop chronic immune thrombocytopenia.
Immune thrombocytopenia in adults is less likely to
resolve without therapy and is usually chronic. It is
more common in females (male:female ratio is 1: 4)

6. Laboratory tests show normal haemoglobin and white
cell count; low platelets (often <20×109/L), normal
bone marrow and normal coagulation.
Immune thrombocytopenia also occurs in association
with some malignancies (e.g. chronic lymphocytic
leukaemia, nonHodgkin lymphoma), infections (e.g.
Epstein–Barr virus, HIV, malaria) and con nective tissue
disease (e.g. systemic lupus erythematosus).

7. Alloimmune thrombocytopenia
• Transplacental passage of antibody from a
mother with immune thrombocytopenia can lead to
neonatal thrombocytopenia, which typically resolves
spontaneously over a few weeks. Mothers who have
been sensitized (e.g. by blood transfusion or previous
pregnancy) to platelet antigens may develop antibodies
which cross the placenta and coat fetal and neonatal
platelets, which are then removed in the
reticuloendothelial system.
• Individuals with such platelet alloantibodies can
also become thrombocytopenic after blood transfusion
(post transfusion purpura). The antibody is then
directed against the HPA1a antigen on platelets.

8. Other causes of thrombocytopenia
Drugs cause thrombocytopenia by inhibiting marrow
production or by an immune mechanism.
Disseminated intravascular coagulation
Release of procoagulant material into the circulation or
endothelial cell damage causes generalized activation of
the coagulation and fibrinolytic pathways leading to
widespread fibrin deposition in the circulation.
The most frequent causes are infections, malignancy and
obstetric complications.

9. Thrombotic thrombocytopenic purpura (TTP) and
haemolytic uraemic syndrome (HUS)
TTP and HUS are characterized by thrombosis in small
vessels, red cell fragmentation, haemolytic anaemia
and thrombocytopenia. Fever, neurological changes
and liver dysfunction occur in TTP and renal failure
often occurs in HUS.
Serum lactate dehydroge nase (LDH) is raised. The
prothrombin time (PT) and activated partial
thromboplastin time (APTT) are normal.

10. Thrombotic thrombocytopenic purpura (TTP) and
haemolytic uraemic syndrome (HUS)
It is caused by an acquired deficiency due to an
autoantibody to a plasma protease ADAMTS13 which
normally cleaves von Willebrand factor (vWF).
Abnormally high molecular weight vWF complexes are
present in plasma.
Congenital TTP is due to lack of ADAMTS13 synthesis.
HUS occurs in childhood and follows infection with
verotoxin producing strains of Escherichia coli; or less
frequently is associated with Shigella, Salmonella and
streptococcal infection, pregnancy, autoimmune
diseases and drugs (e.g. ciclosporin). The ADAMTS13
levels are normal.

11. Disorders of platelet function (Box 2)
These are characterized by a normal platelet count,
abnormal PFA100 test and disordered platelet
aggregation.
Inherited disorders are rare and present with
bruising/excessive bleeding after surgery or injury in
childhood.
The most common acquired cause is aspirin or other
non steroidal anti inflammatory drugs.

13. Thanks