We study the journal that talks about the epidemiology and clinical manifestations of immune thrombocytopenia, which published on Hämostaseologie in Feb.2019. This article not only focuses on the age distribution of ITP but also on the symptoms of ITP. It also points out the difference between children and adult IPT patients. Hopefully, our note can help you to know about ITP deeply.

1. 指導老師：王建德 主任
報告者：PGY 蕭淨真‧ R1曾子政‧ R1陳其延

3. Introduction
• Immune thrombocytopenia (ITP)
 Characterization: isolated thrombocytopenia, affecting individuals of all
ages, races and either sex
 Cause:
Autoimmune destruction of platelets
→ Antibodies against platelet glycoproteins
→ Opsonization and destruction of platelets, inhibition of platelet
production
 Anti-platelet antibodies are detected in approximately 60% of patients
‒ Mostly against glycoprotein IIb/ IIIa

4. Introduction

5. Introduction
• Immune thrombocytopenia (ITP)
 Primary or secondary associated with an underlying infectious,
autoimmune or neoplastic condition
 Bleeding symptoms are the predominant clinical manifestation
 In children, particularly in the first decade of life
‒ Less likely to present with significant bleeding or to be associated
with an underlying disorder
‒ More likely to remit spontaneously

7. Epidemiology of Acute and Chronic ITP
• We searched the MEDLINE database from 1970 to 2018 using MeSH
terms describing ITP along with MeSH subheadings and keywords for
study design
• Only publications in English were included

8. Incidence of Acute ITP
• Incidence rates: ranging from 1.1 to 5.8 per 100,000 person years among
children

9. Incidence of Acute ITP
• Incidence rates: ranging from 1.6 to 3.9 per 100,000 person years among
adult

10. Incidence of Acute ITP
• Heterogeneous in their design, inclusion criteria and outcomes
→ Precluded the generation of pooled analyses and may also account for
the wide variation in estimates
• Schoonen and colleagues:
 General Practice Research Database covering over 3.4 million
persons in the United Kingdom
 Overall ITP incidence rate of 3.9 over 100,000 patient-years
 Higher rate in women(4.4) than men(3.4)
 Bimodal distribution among males: <18 years of age and 75-85 years
old

11. Incidence of Acute ITP
• Another analysis of incidence of ITP:
 <18 years: 4.2 per 100,000 person years
 2-5 years: boys(9.7) > girls (4.7)
 13-17 years: lower (2.4), similar rates in boys and girls

12. Incidence of Acute ITP
• Moulis et al:
 Insurance database covering the entire population of France
 Overall incidence rate of 2.9 per 100,000 patientyears
 Peaks in childhood (age 1–5 years) and the elderly (>60 years)
 Overall rates were higher in women but peaks of incidence were noted
for younger boys (0–5 years) and older men (>75 years)
 Seasonal variation with a peak in January and a nadir in summer in
almost all age groups (except infants that demonstrated a peak in
spring)
− Viral infections, supported by a history of a flu-like illness preceding
ITP diagnosis in up to two-thirds of children

13. Prevalence of Chronic ITP in Adults and Children
• Chronic ITP:
 Definition: thrombocytopenia that persists for more than 12 months
from initial presentation
• International Working Group:
 Persistent ITP, ITP lasting between 3 to 12 months given the
significant chance of spontaneous remission during this period

14. Prevalence of Chronic ITP in Adults and Children
• The point prevalence of chronic ITP in the United States was estimated as
9.5 to 11.2 per 100,000 persons
 Based on analysis of insurance claims data from individual states
• Prevalence was higher in adults(12.1) than children(8.1)

15. Prevalence of Chronic ITP in Adults and Children
• Bennett et al:
 18-year period prevalence of chronic ITP in the United Kingdom was
50.29 per 100,000 adults
 Prevalence increasing with age
 Childhood ITP:
‒ The majority remits spontaneously, often within 6 months
‒ 20 to 30% of children go onto develop chronic ITP
‒ Risk factors for developing chronic ITP:
1. Older age
2. Less severe thrombocytopenia at the initial diagnosis
3. Insidious onset of symptoms
4. Lack of platelet count recovery at 4 weeks
5. Lack of preceding infection or vaccination as a trigger

16. Prevalence of Chronic ITP in Adults and Children
• TIKI trial:
 Randomized children with acute ITP to observation or immunoglobulin
therapy
 No statistically significant reduction in progression to chronic ITP
among children who received immunoglobulin
• Spontaneous remission is relatively uncommon in adults with ITP
• The majority (66.7%) of adults with acute ITP develop chronic ITP
• Disease control at 6 months:
Rituximab or Eltrombopag + high-dose Dexamethasone > Corticosteroids
alone

17.  20% of ITP cases
 Associated with an underlying disorder
 SLE, HIV infection, HCV, Helicobacter pylori, malignancies, primary
immunodeficiency
 Increases with age
Group % of secondary ITP Most common underlying cause
children 2.4% primary immunodeficiency, SLE
adults 18% malignant lymphoid disorders
Secondary ITP

18.  Pathologic mechanisms
 Antibodies cross react with platelets
 Viral illness, vaccination, H.pylori, HIV, HCV
 Hypersplensism
 HCV
 Suppression of megakaryopoiesis
 HCV
 Direct megakaryocyte toxicity
 HIV, cytomegalovirus
 Autoantibody production
 SLE
Secondary ITP

20.  Thrombocytopenia and bleeding symptoms
 Diagnosis of ITP: platelet count <100,000/uL
 Concern for bleeding is greatest: platelet <20k ~ 30k/uL
 2/3 had manifestations
 Typical: petechiae, bruising, epistaxis, gum bleeding, hemorrhagic
blisters
 Uncommon: ICH, GI bleeding, GU bleeding, menstrual bleeding
Clinical Manifestations

21.  Predictors of severe bleeding
 Platelet count < 10k/uL ~ 20k/uL
 Not universally reliable
 Advanced age
 Previous minor bleeding
 Acute ITP > chronic ITP
*Age group Odds ratio of risk of major bleeding
> 60 years 28.9
40~60 years 2.8
< 40 years 1
*Cortelazzo et al
$diagnosis time Bleeding rates (PPY)
Newly 2.67
Chronic 0.73
$Altomare et al
Clinical Manifestations

22. Clinical Manifestations

23.  Early study: platelet count of 7,000 to 8,000/μL is required to maintain
vascular haemostasis.
 Several studies have identified extremely low platelet counts
(<10,000/μL or <20,000/μL) as predictors of severe bleeding.
Association between Platelet Counts and Bleeding

24.  In a large follow-up study of ITP patients treated with romiplostim, 61%
of severe bleeding events occurred at a platelet count <20,000/μL
 Page et al noted that while platelet count correlates with bleeding,
overall, this relationship disappeared at platelet counts <30,000/μL.
 In the ICIS registry, a platelet count <20,000/μL had a sensitivity of 88%
but a specificity of only 21% in predicting severe bleeding.
Association between Platelet Counts and Bleeding

25. Middelburg RA, Hematology 2016
Panzer S, Eur J Clin Invest 2007
 Increased platelet activation, measured as increased expression of
platelet P-selectin, is associated with lower bleeding risk in ITP.
Tantawy AA, Pediatr Hematol Oncol 2010
 Elevated levels of microparticles (a by-product of platelet activation) are
associated with less bleeding in ITP.
Association between Platelet Counts and Bleeding

26.  The cause of fatigue in ITP is unclear, but has been attributed to the
pro-inflammatory effects of immune dysregulation in ITP.
 Health related quality of life (HRQOL) is impaired in chronic ITP.
 An early study using the short form-36 in 73 adults with ITP found that
HRQOL was significantly worse than the general population.
Fatigue and Quality of Life

27.  Impairments in HRQOL have also been demonstrated in children with
ITP using the Kids’ ITP Tool (KIT).
 In adults with ITP, treatment with splenectomy or rituximab improved
HRQOL scores.
 In randomized, placebo-controlled trials, romiplostim therapy
significantly improved HRQOL in both adults and children.
 Fatigue and poor HRQOL are not yet generally accepted indications for
treatment in ITP.
Fatigue and Quality of Life

29.  Chronic ITP is associated with a modestly increased risk of
thromboembolism.
 Venous thromboembolism among patients with ITP of 0.40 to 0.53
per 100 patient years,
 Incidence rate of arterial thromboembolism in ITP ranged from 1.0 to
2.8 per 100 patient-years
 Splenectomy further increases the risk of venous thromboembolism.
Thromboembolic Risk

30.  In a Danish population-based cohort, mortality rates at 5, 10 and 20
years were 22, 34 and 49%.
 Causes of death including cardiovascular causes, infection, bleeding
and haematological cancer.
 The risk of infections may be associated with splenectomy or
immunosuppressive medications.
Mortality

31.  Common acquired bleeding disorder with peaks of incidence in
childhood and in the elderly (>60 years).
 Many patients are asymptomatic.
 Bleeding is the most common presenting feature and can occur as
minor bleeding or more severe bleeding.
Conclusion

32.  Lower platelet counts, advanced age and prior hemorrhage are
associated with increased risk of severe bleeding.
 ITP is also associated with a slightly increased risk of venous and
arterial thrombosis.
 Recent studies have identified fatigue and reduced quality of life
associated with ITP.
 ITP is also associated with a higher mortality rate than the general
population
Conclusion