ITP is immune mediated acquired hemorrhagic disorder of adults and children characterized by transient or persistent thrombocytopenia and depending upon severity of thrombocytopenia, increased risk of bleeding

1. Acute Immune
Thrombocytopenia
Dr. Liza Bulsara

2. Immune Thrombocytopenia(ITP)
• Also known as Werlhof Disease
• ITP is immune mediated acquired
hemorrhagic disorder of adults and children
characterized by transient or persistent
thrombocytopenia and depending upon severity of
thrombocytopenia, increased risk of bleeding
– Cut off platelet count < 100,000/mm3
– 3-8 children/million/year
Rodeghiero et al, BLOOD, 12 MARCH 2009 VOLUME 113, NUMBER 11

3. TYPES
PRIMARY
• An autoimmune disorder
characterized by isolated
thrombocytopenia
(peripheral blood platelet
count < 100,000/mm3) in
the absence of other causes
or disorders that may be
associated with
thrombocytopenia
• Diagnosis of exclusion
SECONDARY
• All forms of immune-
mediated
thrombocytopenia except
primary ITP
• Example
Secondary ITP (HIV Induced)
Secondary ITP (Drug Induced)
Secondary ITP (malignancy
Induced)
Rodeghiero et al, BLOOD, 12 MARCH 2009 VOLUME 113, NUMBER 11

4. Secondary ITP

5. Phases of disease
American Society of Hematology 2019 Guidelines
• Newly Diagnosed ITP: ITP duration of < 3 months.
• Persistent ITP: ITP duration of 3-12 months.
• Chronic ITP: ITP duration of >12 months.

6. Definitions of terms
• Corticosteroid-dependent: Ongoing need for continuous
prednisone >5 mg/d (or corticosteroid equivalent) or frequent
courses of corticosteroids to maintain a platelet count
≥30×109 /L and/or to avoid bleeding.
• Durable response: Platelet count ≥30×109 /L and at least
doubling of the baseline count at 6 months.
• Early response: Platelet count ≥30×109 /L and at least
doubling baseline at 1 week
• Initial response: Platelet count ≥30×109 /L and at least
doubling baseline at 1 month
• Remission: Platelet count >100×109 /L at 12 months.
American Society of Hematology 2019
Guidelines

7. Bleeding Definitions
• Major Bleeding :
1. WHO grade 3 - Epistaxis, Bleeding from mucous membranes,
vaginal bleeding, malena, hematemesis, hemoptysis,
hgematochezia,hematuria,bleeding from puncture sites.
2. WHO grade 4 - Retinal hemorrage with vision impairement, CNS
bleeding, hemorrahges in other organs with functional impairement
(liver, kidneys, lungs etc.)
3. Buchanan severe grade - Mucosal bleeding or suspected internal
hemorrhage (brain, lung,muscle, joint, etc) that requires immediate
medical attention or intervention.
4. Bolton-Maggs and Moon severe bleeding - Bleeding episodes
requiring hospitalisation and/ or transfusions, interfering with daily
living and QOL.
5. ITP Bleeding Scale (IBLS) grade 2 or higher.
6. Life-threatening or intracerebral hemorrhage bleeding.
American Society of Hematology 2019
Guidelines

8. ITP Bleeding Scale (IBLS)

9. • Minor Bleeding - Any bleeding not meeting
the criteria for “major bleeding”.
American Society of Hematology 2019
Guidelines

10. Pathogenesis
• Immune thrombocytopenia is caused by increased platelet destruction and
impaired platelet production
• involves alterations in cellular immunity and immune-mediated
megakaryocyte injury.
• antibodies directed against specific platelet glycoproteins (GPs), specifically
GPIIb/IIIa or GPIb/IX,
• rapid destruction in the RES, particularly the spleen.
• Peptides released from phagocytosed platelets processed and presented
to specific T cells, stimulate B cells produce additional platelet
autoantibodies. known as epitope spreading,
• platelet production does not compensate for increased platelet destruction
s/o BM megakaryocytes may also be impaired.
• Megakaryocytes also express GP receptors, which may render them targets
of ITP autoantibodies
• mechanisms invoked to explain the development of thrombocytopenia in
the face of platelet autoantibodies include opsonization and clearance,
direct activation of complement, or cellular destruction via apoptosis.

12. Clinical Features

13. Clinical features

14. Diagnosis
• History
• Clinical Examination- Signs of malignant disease or
congenital thrombocytopenia syndromes.
• CBC-Isolated Thrombocyopenia (<100×109 /L)
• Peripheral Smear - Large Platelets and to exclude
abnormal cells.
The American Society of Hematology 2011 evidence-based
practice guideline for immune thrombocytopenia

17. Bone Marrow Examination
NOT DIAGNOSTIC, it only:
– Supports the diagnosis
with findings of normal or
increased meagkaryocytes
– Excludes the aplasia,
infiltration, other causes
BMA should be done if
• Very young age(<2 years)
• Family history of
thrombocytopenia or bleeding
• Anemia disproportionate to
the degree of bleeding
• Abnormalities of WBC
count/Morphology
• Fever, bone or joint pains
• Non Petechial Rashes
• Systemically unwell child
• Significant lymphadenopathy,
hepato-splenomegaly
• Deranged clotting screen
The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia

18. Recommendations for investigations
• BMA is not necessary in children and adolescents with the typical features
of ITP
• BMA is not necessary in children who fail IVIg therapy
• BMA is also not necessary in similar patients prior to initiation of
treatment with corticosteroids or prior to splenectomy
• No indication of: Routine use of anti-platelet, antiphospholipid and anti-
nuclear antibodies, thrombopoietin levels,Ig levels,reticulate platelets or
platelet parameters obtained on automated analyzers
The American Society of Hematology 2019 evidence-based practice guideline for
immune thrombocytopenia

19. Management Recommendations
Outpatient vs inpatient management
• In children with newly diagnosed ITP who have no or mild
bleeding (skin manifestations) only, the ASH guideline panel
suggests against admission to the hospital rather than
outpatient treatment.
• Remark: For patients with uncertainty about the diagnosis,
those with social concerns, those who live far from the
hospital, and those for whom follow-up cannot be
guaranteed, admission to the hospital may be preferable.

20. Treatment vs observation
• In children with newly diagnosed ITP who
have no or minor bleeding, the ASH guideline
panel suggests observation rather than
corticosteroids, IVIG or anti-D immunoglobulin

21. First line therapy
• In children with newly diagnosed ITP who
have non–life threatening mucosal bleeding
and/or diminished HRQoL, the ASH guideline
panel suggests corticosteroids rather than
anti-D immunoglobulin or IVIG.
• If corticoseroids are not given then either anti-
D immunoglobulin or IVIG is recommended.

22. Corticosteroid duration and type
• In children with newly diagnosed ITP who have
non–life threatening bleeding and/or diminished
HRQoL, the ASH guideline panel recommends
courses of corticosteroids 7 days or shorter.
• Prednisone (2-4 mg/kg per day; maximum, 120 mg
daily, for 5-7 days) rather than dexamethasone (0.6
mg/kg per day; maximum, 40 mg/kg per day, for 4
days)

23. • Management of children with ITP who do not have
a response to first-line treatment
• In children with ITP who have non–life-threatening
mucosal bleeding and/or diminished HRQoL and do
not respond to first-line treatment, the ASH guideline
panel suggests the use of TPO-RAs (eltrombopag,
romiplostim) rather than rituximab or splenectomy
• If TPO-RA is not used, then the ASH guideline panel
suggests rituximab rather than splenectomy.

24. Intracranial Hemorrahge
• The most significant complication.
• Incidence in children: 0.1-0.5%
• Mortality: 25%
• Potential risk factors include
– Platelet counts below 10 to 20x109/L,
– Nonsteroidal anti-inflammatory drugs (NSAIDs)
– Head trauma
– Vasculitis associated with systemic lupus erythematosis
(SLE), Varicella infection
– Cerebral arteriovenous malformations (AVMs)
Psaila et al. Blood 2009

25. General Measures
• Educate parents about nature of disease & signs
/symptoms of bleeding
• Expected gain vs side effects of drugs
• Avoid drugs interfering with platelet function
• Avoid contact sports/IM Injections
• Routine activities, schooling, walking, jogging should be
encouraged
• 24 hrs hospital contact point
• Monitoring

26. Treatment of Newly Diagnosed ITP
Oral Corticosteroid
Dose: Prednisone (2-4 mg/kg per day; maximum, 120 mg daily, for 5-7
days)
Mech of action:
• Decreasing production of antiplatelet antibodies
• Decreasing binding of antibodies to the platelets
• Decreasing phagocytosis of opsonised platelets
Adverse effects:
• Mood Changes
• Gastritis
• Hypertension
• Immunosupression

27. IVIG
• Highly effective in increasing the platelet counts (PC)
– A single dose of IVIg (0.8-1 g/kg) to be given if corticoseroids
are not given.
– Can be used if a more rapid increase in the PC is desired
• Response rate : Up to 80% within 24 hrs lasting up to 1-2
weeks
• Mechanism of action:
– Blockade of receptors on RE cells, resulting in survival of opsonised
platelets
– Inhibition of binding of antibodies to platelet antigens
– Decreased antibody production by suppressing B cells

28. Disadvantages of IVIG
• Higher doses associated with side effects:
– Allergic reaction
– Fever, headache, nausea, vomiting
– Neutropenia and hemolytic anemia
– Acute kidney injury
– Aseptic meningitis
• Expensive
• Relapse in 1/3rd patients after 6 weeks
• Longer duration infusion
• Not easily available

29. Anti-D immunoglobulin
Role of anti-D:
• Anti-D Ig can be used intravenously to treat pt with acute and chronic
ITP who have not undergone splenectomy
Dose and response:
• The recommended infusion dose is 50-75 mcg/kg given as single dose
or two divided doses on separate days
• Significant response in 50-77% cases within 1 to 3 days, peaking at a
mean of eight days after infusion.
• The duration of response may last 3 weeks or longer.
Mechanism of action:
• Phagocytic cell blockade due to occupancy of the phagocytic cell Fc
receptors by the IgG-sensitized RBCs, which prevents the platelets from
binding to these receptors.

30. • Adverse effects:
– Fever, chills, nausea, vomiting, headache
– Hemolysis : Fall in Hb occurs within 1 week, recovers
by day 21. (more with higher dose)
– Intravascular hemolysis: causes anemia, renal failure,
DIC and death
• Advantages over IVIG:
– Less expensive
– Easily available
– I.v. infusion over 3-5min
– Headache, fever, chills less common

31. Emergency Treatment
• Increase the circulating platelet count rapidly
• Larger than usual (two to threefold) infusion of donor
platelets ranging from transfusions every 30 minutes to
8 hours
• IVIG infusion(1g/kg)
• IV administration of methylprednisolone (30 mg/kg,
maximum dose 1 g) over 20 to 30 minutes
• Efficacy of antifibrinolytic agents is unproven
• Consider recombinant factor VIIa
• Consider emergency splenectomy in truly life-
threatening bleeding

32. THANK YOU!