2. Immune thrombocytopenic
purpura
SAMREEN RAZA, MD
PGY-3

3. Immune thrombocytopenic purpura
 There are only two criteria required in order to make this diagnosis:
 1. Isolated thrombocytopenia is present – rest of blood count is
normal including peripheral smear
 2. Clinically apparent associated conditions absent (eg, systemic lupus
erythematosus, antiphospholipid syndrome, chronic lymphocytic
leukemia)
 Patients with these associated conditions are described as having
"secondary immune thrombocytopenia
 Herbal supplements and drugs not considered part of etiology

4. Pathogenesis
 Related to a combination of increased platelet destruction along with
inhibition of megakaryocyte platelet production via the production of specific
IgG autoantibodies by the patient's B cells, most often directed against
platelet membrane glycoproteins such as GPIIb/IIIa
 Inciting events - etiology of ITP is unclear, but is thought to include genetic as
well as acquired factors
 Some cases of ITP are associated with a preceding viral infection:
 Resulting anti-viral antibodies cross-react with platelet glycoproteins
 Infection with HIV, HCV, CMV and VZV may be associated with such antibodies
therefore cause secondary ITP.
 Alterations in the immune response might induce loss of peripheral tolerance
and promote the development of self-reactive antibodies
 Abnormalities in the immune system may predispose to the development of
ITP

5. Incidence
 Incidence greater in children than adults
 Danish study from 1973 to 1995 estimated annual incidence of ITP
among adults to be 22 per million per year, using a platelet count cutoff of 50,000/microL
 Incidence rose during the study period due to increased recognition of
asymptomatic patients
 Among adults with ITP, approx 70% are women and 72% of these
women are less than 40 years of age
 The Denmark survey reported a sex difference in the incidence of ITP
only for those <60 years of age
 Generalizability?

6. Physical examination features
 Mucocutaneous features related to thrombocytopenia and bleeding
 Not visceral hematomas which are characteristic of coagulation disorders
eg hemophilia
 Petechiae, purpura, ecchymoses
 Epistaxis, gingival bleeding, menorrhagia
 Overt gastrointestinal bleeding and gross hematuria are rare
 Intracranial hemorrhage – very rare
 The clinical manifestations of thrombocytopenia vary with age
 Patients may have more severe bleeding manifestations including GI
bleeding or ICH due to comorbidities such as hypertension

10. Diagnostic testing
 Peripheral smear — Examination of the blood smear may provide evidence for other
causes of thrombocytopenia eg presence of schistocytes
 Examination of the peripheral blood smear is essential to exclude
pseudothrombocytopenia due to the artifact of platelet agglutination induced by the
standard blood count anticoagulant, EDTA
 EDTA-dependent agglutinins are present in approximately 0.1% people in the general
population

naturally occuring platelet antibody against normally concealed epitope on GpIIb/IIIa which
becomes exposed by EDTA-induced dissociation of GpIIb/IIIa
 You can make a presumptive diagnosis based on history, physical examination, CBC
and examination of peripheral blood smear with isolated thrombocytopenia
 H pylori infection – generally do not screen for this in patients with mild or moderate
thrombocytopenia
 Can do breath test or fecal antigen testing only in patients if ITP is chronic or
refractory or if positive test would change management

11. Other causes
Beverages and herbal remedies that can cause
thrombocytopenia include:
 Quinine
 Tonic water
 Sulfonamides including sulfamethoxazole
 Heparin

12. Antiplatelet antibodies
The American Society of Hematology ITP Practice
Guidelines do not recommend antiplatelet antibody
studies in patients thought to have ITP
No evidence that antiplatelet antibody studies are
important for diagnosis of ITP

13. Differential diagnosis
TTP/HUS
DIC
Gestational thrombocytopenia
Drugs
Infection
Hypersplenism
Myelodysplasia
Congential thrombocytopenias

14. Inherited platelet disorders
 von Willebrand disease type 2B: with greater than expected bleeding for the degree of
thrombocytopenia
 Wiskott-Aldrich syndrome and its variant, X-linked thrombocytopenia, with small platelets and
recurrent infections
 Alport syndrome (hereditary nephritis) variants, with giant platelets, renal failure, and hearing loss
 May-Hegglin anomaly, with giant platelets and Döhle bodies in granulocytes, and other manifestations
of MYH9 gene mutations (the gene encoding the nonmuscle myosin heavy chain IIA)
 Fanconi syndrome, with short stature, anemia, and neutropenia
 Bernard-Soulier syndrome, with giant platelets and greater than expected bleeding for the degree of
thrombocytopenia
 Thrombocytopenia with absent radius (TAR) syndrome, with skeletal abnormalities
 Gray platelet syndrome, with giant platelets lacking alpha granules and predisposition to myelofibrosis

15. Treatment
 Major bleeding is rare in patients with ITP - platelet count <10,000
 Goal for treatment is to provide a safe platelet count to prevent major
bleeding rather than returning the platelet count to normal
 Adults with severe thrombocytopenia (< 30,000) at the time of diagnosis are
almost always treated even if they are asymptomatic or have only minor
bleeding symptoms, course of the disease and future risk is unknown
 Pts with severe chronic thrombocytopenia who have only partial response to
treatment is uncertain – individual management decisions

16. Treatment
 Glucocorticoids
 The goal of initial glucocorticoid treatment is not to "cure" the ITP, but to
support the platelet count in a safe range with minimal and tolerable side
effects until a spontaneous remission occurs or until more definitive therapy
established
 Prednisone – standard practice – oral 1mg/kg single daily dose, most respond
within 2 weeks, can taper once responds
 High-dose dexamethasone – role of this is being actively investigated
 Dosing of 40mg per day with PO or IV for 4-8 days
 Follow response to treatment
 IVIG: temporarily supports platelet count
 Dose: 1g/kg/day for 1 or 2 days
 Can use for life-threatening bleeding

17. References
Immune thrombocytopenic purpura. NEJM
2002;346(13):995
Idiopathic thrombocytopenic purpura: a practice
guideline developed by explicit methods for the
American Society of Hematology. Blood 1996; 88:3
UTDOL