Bleeding Disorders:

Immune Thrombocytopenia
Suraj Jayveenth Babu
Melvin Nicholas
Haspreet Gill
Learning Outcomes
At the end of this session, the students would be able to:

• Define and classify types of immune thrombocytopenia in neonates

and older children.
• Discuss the pathophysiology, epidemiology, the clinical presentations
and complications.
• Establish a differential diagnosis based on history and physical
examination.
• Develop the plans for investigations and management.
• Discuss the prognosis.
NEONATAL ALLOIMMUNE
THROMBOCYTOPENIA
(NAIT)
SURAJ JAYVEENTH BABU
• Results from transplacental passage of maternal antibodies, which
adhere to foetal platelets expressing paternal antigens that the
mother lacks.
• Occurs at an estimated incidence of 1/1000 to 2000 live births.
Pathogenesis
 Fetomaternal
fetal platelets are
incompatibility of g Production of a Maternal IgG Fetal and neonatal
cleared in the
certain human maternal IgG crosses the thrombocytopenia
reticuloendothelial
platelet antigens alloantibody placenta
system
(HPAs)
Clinical features
• In an otherwise healthy neonate, born after an uneventful pregnancy
and delivery, exhibiting petechiae or widespread purpura within 24 to
48 hours of birth associated with severe thrombocytopenia.
• Intracranial hemorrhage (ICH), porencephaly, or ventriculomegaly is
discovered during fetal life.
Investigation
• Platelet antigen incompatibility is demonstrated by genotyping (PCR
techniques).
• Phenotyping (flow cytometry, various immunoassay methods).
• maternal alloantibody directed against the identified alloantigen
(ELISA).
• Neuroimaging (CT and MRI)
Treatment
• Platelet transfusion.
• IVIG.
Immune Thrombocytopenia(ITP)
Melvin Nicholas
Haspreet Gill
Introduction
• Autoimmune disorder: Antibody-mediated destruction of platelets
• Characterized by isolated thrombocytopenia
• Self-limiting
Classifications

Newly diagnosed
ITP

Primary Persistent ITP

Immune
Thrombocytopenia
(ITP)
Secondary Chronic ITP
Epidemiology
• The most common cause of
thrombocytopenia in
childhood.
• 1 and 6.4 cases per 100,000
children, per year.
• Peak in incidence between
two and five years
• A recent history of viral
illness is described in 50-65%
of cases of childhood ITP.
Aetiology
• Autoantibody stimulation
• Autoantibody specificity
• Role of spleen
• Platelet destruction
• Viral infection
Pathophysiology
Clinical Features
• Petechial rash
• Purpura
• Bruising
• Epistaxis
• Blood-filled bullae
Bleeding Symptoms
Grade Bleeding Severity Clinical Symptoms
Grade I Minor/minimal Few petechiae (≤100 total) and/or ≤5 small bruises (≤3 cm in diameter)
Grade II Mild Many petechiae (>100 total) and/or >5 large bruises (>3 cm in diameter)
Grade III Moderate Mucosal bleeding ("wet purpura") that does not require immediate medical
attention or supervision, such as brief epistaxis, intermittent gum bleeding,
menorrhagia, and/or a lifestyle that increases bleeding risks
Grade IV Severe Mucosal bleeding or suspected internal haemorrhage that requires immediate
medical attention (i.e., severe GI bleeding, severe prolonged epistaxis,
pulmonary haemorrhage, muscle or joint haemorrhage)
Life-threatening Documented intracranial haemorrhage or life-threatening or fatal
haemorrhage in any site
Mucocutaneous Bleeding

• Petechiae • Epistaxis
• Purpura • Buccal mucosa
• Ecchymoses bleeding
• Gingival mucosa
bleeding
‘Dry’ ‘Wet’
Purpura Purpura
Serious Haemorrhage
Factors associated with increased risk of serious bleeding include:
• Severe thrombocytopenia
• Previous wet bleeding
• Trauma
• Exposure to antiplatelet medications
Differential Diagnosis
• Leukaemia • Thrombotic Thrombocytopenic
• Active infection Purpura (TTP)
• Autoimmune haemolytic anaemia • Disseminated Intravascular
Coagulation (DIC)
• Systemic autoimmune disease
• Inherited disorders causing
• Immunodeficiency syndromes thrombocytopenia
• Drug exposure
• Bone marrow failure syndromes
• Haemolytic uremic syndrome
 INVESTIGATION &
MANAGEMENT OF
IMMUNE
THROMBOCYTOPAENIA
PURPURA
haspreet gill
 Diagnosis of ITP:
1.Based in history taking ,physical examination ( absent of hepatoslenomegaly or
lymphadenopathy).

2. Blood count - reduced platelet count < 100 , 000 /L

- isolated thromboctyopenia , normal Hb & Wbc

3. Peripheral blood smear-

-decreased number of platelets,
- The morphology of red blood cells (RBCs) and leukocytes is normal
-The morphology of platelets is typically normal, with varying numbers of large platelets
-If most of the platelets are large, approximating the diameter of red blood cells, or if they lack
granules or have an abnormal color, consider an inherited platelet disorder
- increased number of normal or atypical lymphocytes on the peripheral smear, reflecting a
recent viral illness.-
- ** absence of immature leukocytes (as in leukemia) and fragmented erythrocytes (a
in thrombotic thrombocytopenic purpura) and no clumps of platelets (as in
pseudothrombocytopenia).
3. Bone marrow aspiration indicated:
- before starting steroid therapy
( to avoid partially undiagnosed acute leukemia)
-failure responding to immunoglobulin theraphy
-presents of thrombocytopenia > 6 months
-thrombocytopenia recurrs after initial response to treatment.

4. other test:
-Negative antinuclear antibody (ANA) - for chronic & persistent ITP
-positive direct antiglobulin coomb's test-can also diagnoses evan'
syndrome
-cmv serology for < 1yrs old
-coagulation profile for suspect non-accidental ingury, inherited blood
disorder
- HIV testing
-Immunoglobulin level for those with recurrent infection
 Management :
Only require hospitalisation if :
1.life- threatening bleeding (ICH) with evidence of bleeding
2. platelet count< 20 ×10 9 /L without evidence of bleeding
3. plt count < 20×10 9 /L with bleeding
4. parents request due to lack of confidence in monitoring child
** 70 % child achieve > 50×10 9 /L by end of 3rd week.

- precautions with physical activity , avoidance of contact sports

- observation & monitoring of platelet count > 20×10 9 /L without
bleeding or > 30×10 9 /L

-repeat blood count in 7-10 days to ensure no evedence of serious

evolving marrow condition.
Treatment:

- individualised ( treat the child clinical status not the

platelet count)
-choice is oral prednisolone 2mg/kg/day for 14 dyas
then taper off
or 4mg/kg/day for 4 days,
- iv immunoglobulin (IVIG) 0.8 g/kg/dose for single
dose
( side effect: 15-70% fever, flushing, headache, nausea,
aseptic meningitis, transmission of hep c .)
For those with Persistent bleeding, Second line therapies includes:
-Pulses of steroids: (acute) High dose IV Methylprednisolone 30 mg/kg/day for 3 days
(chronic) oral Dexamethasone 1 mg/kg given on 4 consecutive days every 4 weeks for 4
months.
-Intermittent anti-Rh(D) Immunoglobulin treatment for those who are Rhesus D positive: 45
- 50 ug/kg. May cause drop in Hb levels.

Second line therapy should only be started after discussion with a Paediatric
haematologist.
- Care must be taken with any pulse steroid strategy to avoid treatment related steroid
side effects.
-Family and patient must be aware of immunosuppressive complications e.g. risk of severe
varicella.

**Other useful agents are Rituximab and Cyclosporine.

 Emergency treatment:
-life threatening (ICH) can occur in .0.1-0.5 % and increase risk in
platelet count < 20 ×10 9 L
- severe epistaxis or GIT bleed and Hb reduced

treated with:
1.High dose methylprednisolone 30 mh/kg/day
2. IVIG 0.8 g/kg/day as a single dose
3. platelet transfussion in life threatening haemorrhage 8-12 units/m2
body surface area ( 2-3 folds larger tha usual unit )
4. emergency splenectomy
5. neurosurgical interevention for ICH.
 Indication of splenectomy:
-up to 15 years from diagnosis. The risk of dying from ITP is very low - 0.002% whilst the
mortality-
associated with post-splenectomy sepsis is higher at 1.4 - 2.7 %.
- Justified when there is Life-threatening bleeding event, Severe life-style restriction
with no or transient success with intermittent IVIG, pulsed steroids or anti-D
immunoglobulin.

Pre-splenectomy preparation of the child with immunization against

-pneumococcus, haemophilus and meningocccus must be done
- postsplenectomy
-life-long penicillin prophylaxis must be ensured.
-Pneumococcal booster should be given every 5 years.
**Up to 70% of patients achieve complete remission post-splenectomy.
 complication of ITP:
• easily bleed and bruised
• patients with immune thrombocytopenic purpura
(ITP) who have undergone splenectomy that their
natural defense against acute bacterial infection is
decreased.
• Intracranial haemorrhage can lead to seizure or
even paralysis.

prognosis:
-More than 80% of children with untreated immune
thrombocytopenic purpura (ITP) have a spontaneous
recovery with completely normal platelet counts in 2-
8 weeks. Fatal bleeding occurs in 0.9% upon initial
presentation.
References
Bussel, J. B., Armsby, C., & Mahoney Jr., D. H. (2018). Immune thrombocytopenia (ITP) in children:
Clinical features and diagnosis. Norwegian Health Library.

Haji Muhammad Ismail, H., Ng, H., & Thomas, T. (2012). Paediatric Protocols For Malaysian Hospitals
(3rd Edition). Kuala Lumpur: Kementerian Kesihatan Malaysia.

Kessler, C. M., Talavera, F., Sacher, R. A., Nagalla, S., Bhanji, R., & Sandler, S. G. (2018, April 23).
Immune Thrombocytopenic Purpura (ITP). Retrieved from Medscape:
https://emedicine.medscape.com/article/202158-overview

Lakshmanaswamy, A. (2010). Clinical Paediatrics: History Taking and Case Discussion (3rd Edition).
Gurgaon: Wolters Kluwer Health (India).

Lim, Y., & Mohamed, M. (2014, June 20). Immune Thrombocytopenia Purpura (ITP). Retrieved from
MyHEALTH Kementerian Kesihatan Malaysia: http://www.myhealth.gov.my/en/immune-
thrombocytopenia-purpura-itp/

Lissauer, T., & Clayden, G. (2012). Illustrated Textbook of Paediatrics (4th Edition). London: Mosby
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Lakshmanaswamy, A. (2010). Clinical Paediatrics: History Taking and Case Discussion (3rd Edition).
Gurgaon: Wolters Kluwer Health (India).

References
Lim, Y., & Mohamed, M. (2014, June 20). Immune Thrombocytopenia Purpura (ITP). Retrieved from
MyHEALTH Kementerian Kesihatan Malaysia: http://www.myhealth.gov.my/en/immune-
thrombocytopenia-purpura-itp/

Lissauer, T., & Clayden, G. (2012). Illustrated Textbook of Paediatrics (4th Edition). London: Mosby
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Neunert, C., Noroozi, G., Buchanan, G., Goy, J., Nazi, I., Kelton, J., & Arnold, D. (2015). Severe
bleeding events in adults and children with primary immune thrombocytopenia: a
systematic review. J Thromb Haemost, 457.

Provan, D., Stasi, R., Newland, A., Blanchette, V., Bolton-Maggs, P., Bussel, J., . . . Kuter, D. (2010).
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