Thrombocytopenia

Dr Chamilka Jayasinghe
Introduction & definition
Haemopoeisis
Mechanism of platelet plug formation
Pathophysiology
Causes of thrombocytopenia
History & examination
Laboratory investigations
Immune thrombocytopenia



Introduction & definition
Thrombocytopenia is defined as a platelet
count less than 150,000/mm
3

Platelets circulate in vivo with a life span
of 10-14 days.
Thrombopoeitin is the major hormone that
controls its production.
Platelets are non nucleated cellular
fragments produced by megakaryocytes
within the bone marrow & other tissues.
The normal platelet count is
150-400 *10
9/L

Haemostasis
Occurs in 3 phases
1. Vascular spasm primary haemostasis
2. Platelet plug formation
3. Coagulation (2ry haemostasis)
MECHANISM OF PLATELET PLUG
FORMATION
OCCURS IN THREE PHASES
1. Platelet adhesion- The first phase begins when platelets
detect damage to a blood vessel and begin to adhere to
the exposed surfaces.

2. Platelet release reaction- once stuck to a site of damage
the platelets begin to change. Firstly they create
extensions so that they can contact each other & then
they release their contents. There are 2 types of
chemical packages(granules) held within the cytoplasm of
platelets; alpha granules that contain clotting factors,
growth factors & fibroblasts ; & dense granules that
contain ADP,ATP,Calcium ions & Serotonin.Other
components are also present within the platelet that aids
its function.Nearby platelets are stimulated into action
by the release of ADP and Thromboxane A2(A
prostoglandin found within platelets) Thromboxane and
Serotonin act to cause vasoconstriction.
3. Platelet aggregation:
The ADP acts to make the nearby platelets
sticky & adhere to the other recruited
platelets,& when the collection is large
enough it creates a platelet plug stopping
the loss of blood through holes in small
vessels.
Platelet defects lead to signs & symptoms
of primary haemostasis.
1ry haemostatic disorders are
characterized by prolonged bleeding time
And the characteristic physical
examination findings are petechiae &
purpura.
Causes of thrombocytopenia
1. Decreased production-
congenital/acquired
2. Sequestration of platelets within an
enlarged spleen or other organ
3. Increased destruction-
immune/nonimmune
4. Spurious
5. Dilutional

1. Immune thrombocytopenic purpura
2. Drug induced thrombocytopenia-immune
process/megakaryocyte injury
Na valproate,phenytoin,sulfonamides,cotrimoxazole
3.Non immune platelet destruction- DIC/HUS/TTP
Kassabach Merrit
4.Sequestration-massive splenomegaly
infections,Infiltrative,neoplastic,obstructive,haemolytic conditions
5.Congenital Thrombocytopenic syndrome
TAR
Wiskott Aldrich syndrome
6. Neonatal alloimmune thrombocytopenic purpura
7.Acquired disorders causing decreased production
Infiltrative disorders-Malignancies-ALL,Lymphomas
Aplastic processes acquired/constitutional
Platelet function disorders
Congenital-Von Willebrand disease,Bernard Soulier,Glanzman
Acquired liver ,renal disease ,eosinophilia
History & examination
Purpose is to differentiate between 1ry & 2ry haemostatic
disorders & whether an inherited or acquired disorder.
Epistaxis,bleeding gums,bleeding from tooth extractions
Haemoptysis,haematemesis,haematuria,haematochezia,mele
na rarely the initial symptoms
Menstrual history
Bleeding after childbirth
Details of previous surgery
Bleeding following circumcision
Delayed bleeding from umbilical stump/defective wound
healing
Drug history
Haemarthrosis *

Examination
Petechiae ,purpura,ecchymoses

Splenomegaly,hepatomegaly*
Lymphadenopathy*

Haemarthrosis,deep muscle haematomas*
Pallor*
Features of collagen vascular disorders-SLE*
Dysmorphism*

* atypical features

Laboratory investigations
FBC
Blood picture- platelet clumps,Giant platelets,
RBC fragmentation
Prolonged bleeding time
Platelet function tests
Bone marrow examination
Normal bone marrow -Megakaryocytes
Immune thrombocytopenic
purpura
One of the most common autoimmune disorders
It occurs in 2 distinct clinical types
1. An acute self limiting form observed almost exclusively in
children 5 per 100,000 persons
2. A chronic form observed mostly in adults 3-5 per
100,000 & rarely in children.
It is caused by autoantibodies to platelets.The antigenic
target appears to be the glycoprotein 11b/111a complex
The complex is trapped in the spleen and removed by splenic
macrophages.The mechanism of origin of Abs is not
known.
Occurs commonly in healthy individuals & is only rarely
the initial manifestation of lupus, HIV other auto immune
disorders
Clinical features-ACUTE ITP
Onset is usually acute
In>50% cases follows a viral
infection,1-4 weeks later
Cutaneous bleeding
Mucosal bleeding-palatal
petechiae,epistaxis,haematuria,G.I
bleeding,menorrhagia
Intracranial haemorrhage
No hepatosplenomegaly OR
lymphadenopathy
Natural history
In 70-80% of children with acute ITP
spontaneous resolution will occur within 6
months


10-20% of children will go on to develop
chronic ITP
Investigations

FBC
Blood picture
to exclude other causes of
thrombocytopenia
Indications for bone marrow aspiration
1. Presence of atypical features e.g
organomegaly,significant
lymphadenopathy,abnormal blood
counts,suspicious blood picture
2. Before starting steroid therapy
3. Not responding to IV Ig therapy
4. Persistent thrombocytopenia beyond 6
months
5.Thrombocytopenia that recurs after
initial response to treatment



If atypical presentation
ANA
Coombs
Ultrasound abdomen
HIV testing
Indications for hospitalization

1. Severe life threatening bleeding
(e.g ICH) regardless of platelet
count
2. Plt count <20,000 with evidence of
bleeding
3. Plt count <20,000 without bleeding
but inaccessible to health care
4. Parents request admission
*most childhood ITP remit
spontaneously
Indications for treatment
1. Life threatening bleeding episode
(e.g ICH) regardless of platelet
count
2. Plt count <20,000with mucosal
bleeding
3. Plt count <10,000 with any bleeding
Treatment modalities
1. Oral prednisolone 1-4 mg/kg for 2-3 wks or till plt
count>20,000/mm
3
then taper rapidly
2. IV methylprednisolone
3. IV Immunoglobulin 0.8-1g/kg/day *1-2 days
Gives a rapid rise in platelets in 95% of patients
4. IV Anti Rh(D) immunoglobulin in Rhesus positive patients
*all are effective in raising platelet count
IVIG is the quickest
No evidence that any of these treatments reduce complications or
mortality from ITP. No influence on progression to chronic ITP.

**platelet transfusions are CONTAINDICATED in acute ITP
unless in the management of ICH.
Intracranial Haemorrhage
The most feared complication of ITP with
a 50% mortality rate
Cumulative risk of ICH in newly diagnosed
ITP child within 1
st
year is <1%
Risk is highest with platelet count
<20,000,history of head trauma,aspirin use
&presence of cerebral AV malformation.
50% of all ICH occurs after 1 month of
presentation,30% after 6 months

Emergency treatment of
ITP with ICH
1. IVIG 1g/kg/day for 2 days
2. IV anti Rh(D) 50-75 micrograms/kg
3. High dose IV Methylprednisolone
30mg/kg/day for 3 days
4. Platelet transfusion
5. Neurosurgical intervention if
indicated
6. Splenectomy if other modalities fail
& craniotomy required
Chronic ITP
Persistent thrombocytopenia after 6
months of onset (20%)
Wide spectrum of manifestations
-mild symptomless low platelet count
-intermittent relapsing symptomatic
thrombocytopenia
Persistent symptomatic,haemorrhagic
disease
Management of chronic
ITP
Majority will remit with time
Exclude other causes of thrombocytopenia
(immunodeficiency,lymphoproliferative
disorders,collagen disorders &HIV infection)
Symptomless children can be left without
therapy and followed up in clinic
Symptomatic children may require short courses
of therapy for relapses
1. Intermittent pulses of IVIg
2. Intermittent anti-Rh(D) antibody treatment
3.Intermittent pulses of steroid
Indications for
splenectomy
1. Persistence of disease after 12
months with
2. Bleeding symptoms and
3. platelet count <10,000/mm
3

4. No response or only transient
success with intermittent IVIg and
Anti D or pulse steroids
5. No contraindications to surgery
* restriction of lifestyle
Over 70% remission following splenectomy

Pre-splenectomy immunization against
pneumococci,haemophilus influenzae type b and
menenigococci ,mandatory 2 weeks before surgery

Post splenectomy penicillin prophylaxis
Preferable to avoid till child is at least over 5
years of age.
Post splenectomy relapse
Causes unknown in most cases
- accessory spleen/s
Treatment options:
1. Danazol 6. Cyclosporine
2. Vincristine 7.Dapsone
3. Azathioprine
4. Cyclophosphamide
5. Alpha interferon



END