Mr 2.24.14

SAMREEN RAZA, MDPGY-3

Immune thrombocytopenic purpura

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

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

Incidence

Incidence greater in children than adultsDanish study from 1973 to 1995 estimated annual incidence of ITP

among adults to be 22 per million per year, using a platelet count cut-off 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?

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

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

Other causes

Beverages and herbal remedies that can cause thrombocytopenia include:QuinineTonic water Sulfonamides including sulfamethoxazoleHeparin

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

Differential diagnosis

TTP/HUSDICGestational thrombocytopeniaDrugsInfectionHypersplenismMyelodysplasiaCongential thrombocytopenias

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

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

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

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