Idiopathic (Autoimmune)

Thrombocytopenia
Seminar 9-Group D
Naveenah, Tan, Ng
Platelet Count
• Normal Platelet count= 150000-400000 per microliter
• <150000/μL: Thrombocytopenia
• 20000-50000/μL: Clinically significant bleeding is seen
• <20000/μL: Spontaneous bleeding becomes evident
Idiopathic Thrombocytopenia (ITP)

• In ITP, thrombocytopenia results from antibody-mediated destruction

of platelets in the spleen and liver.
• Classification:
 Acute -----a self-limited form seen mostly in children after viral infections.
 Initial platelet count= <20000/μL
 Commonly have antecedent infections(1-3weeks)
 Spontaneous remission ~90% of cases
 Chronic ---a relatively common disorder that tends to affect women between
20 and 40 years
 Initial platelet count= 30000-80000/μL
 Course of disease fluatuates
Pathogenesis

• The exact antigenic target for most such antibodies in most cases of
childhood acute ITP remains undetermined, although in chronic ITP many
patients demonstrate antibodies against αIIb-β 3 and GPIb.
• After binding of the antibody to the platelet surface, circulating antibody-
coated platelets are recognized by the Fc receptor on splenic macrophages,
ingested, and destroyed.
• Most common viruses have been described in association with ITP,
including Epstein-Barr virus and HIV.
• EBV-related ITP is usually of short duration and follows the course of
infectious mononucleosis. HIV-associated ITP is usually chronic. In some
patients, ITP appears to arise in children infected with Helicobacter
pylori or rarely following vaccines.
The following contribute to ITP

1.T-cell-mediated platelet destruction

2.Autoantibody-mediated platelet destruction
3.Suboptimal bone marrow platelet production
4.Autoantibody-mediated megakaryocyte damage
Epidemiology
• presents more frequently in the elderly~1 in 30,000 adults and 1 in 12,000
children are diagnosed with ITP each year
• A recent history of viral illness is described in 50–65% of children with ITP.
• More than 20% of patients with ITP have other immune disorders or
chronic infections
• The peak age is 1-4 yr, although the age ranges from early in infancy to
elderly.
• M:F=1:1
• ITP seems to occur more often in late winter and spring after the peak
season of viral respiratory illness.
Clinical Manifestations

• The classic presentation of ITP is a previously healthy 1-4 yr old child

who has sudden onset of generalized petechiae and purpura.
1. No symptoms
2. Mild symptoms: bruising and petechiae, occasional minor epistaxis,
very little interference with daily living
3. Moderate symptoms: more severe skin and mucosal lesions, more
troublesome epistaxis and menorrhagia
4. Severe symptoms: bleeding episodes—menorrhagia, epistaxis,
melena—requiring transfusion or hospitalization, symptoms interfering
seriously with the quality of life
Examples of visible ITP symptoms

1.Petechiae
2.Purpura and haematoma
3.Conjunctival haemorrhage
3 4.Submucosal bleeding

2 4
Purpura and haematomas and conjunctival haemorrhage images courtesy of Douglas Cines and James Bussel. Mucosal bleeding and petechiae images
courtesy of Drew Provan.
Outcome

• Severe bleeding is rare (<3% of cases in 1 large international study). In

70–80% of children who present with acute ITP, spontaneous
resolution occurs within 6 months.
• Fewer than 1% of patients develop an intracranial hemorrhage (ICH).
• Approximately 20% of children who present with acute ITP go on to
have chronic ITP.
• The outcome/prognosis may be related more to age; ITP in younger
children is more likely to resolve, whereas development of chronic ITP
in adolescents approaches 50%.
Differential diagnosis for Immune
thrombocytic purpura
Causes and pathophysiology
Myelodysplastic Syndrome
Definition
● Heterogenous group related clonal hematopoietic disorders.
● Bone marrow usually hypercellular or rarely hypocellular, which
display abberant morphology and maturation( dysmyelopoiesis)
resulting in inffective blood cell production.
Causes and pathogenesis
•
Symptoms
● Symptom of pancytopenia
● a) anemia ( fatigue, tired, SOB )
● b) leucopenia ( easy infection )
● c) Thrombocytopenia ( Bleeding manifestation, skin rashes, easy
bruises, nose bleed, melena)
Disseminated Intravascular coagulation
Definition
● Overactive clotting disorder due to serious complication of body such
as sepsis, surgery or trauma, cancer, pregnancy or child birth.
Pathophysiology
● Tissue factor – mediator of thrombin
● Dysfunctional anticoagulant mechanism
● Impaired fibrin removal lead to plasminogen activator
● Inflammatory activation
Sign and symptoms
● Coagulation: Thrombosis which lead to gangrene, infarction and
necrosis.
● Fibrinolysis: Easy hemorrhage ( hematuria, melena, prolong bleeding,
easy bruise like purpura, ecchymoses)
● Anemia
● Shock
Investigations
• Complete blood count: will distinguish between pancytopenia and isolated
thrombocytopenia. An increase in mean platelet volume (MPV, normal 5–9
fL) will suggest increased turnover (e.g., in ITP where in the bone marrow
attempts to replace peripherally destroyed platelets by younger larger
platelets quickly) or hereditary giant platelet syndromes while small
platelets (low MPV) suggest decreased platelet production and the Wiskott
Aldrich syndrome
• Serology test(EBV, HIV, Hep B)
• Helicobacter pylori test and peripheral blood smear
• Bone marrow aspirate and biopsy is essential to differentiate ITP from
leukemia and other infiltrative disorders when doubts arise clinically.
Normal or increased megakaryocytes seen in the marrow in ITP will help
resolve the issue.