Immune Thrombocytopenia

Resident: Adam J. Bottrill
Date: 02MAR11
Region: Providence
Article title: Immune Thrombocytopenia
Author(s): Cuker, Adam et al.
Journal: Hematology
Page #s: 377-384
Vol:No Date: 2010
Major topic: Immune Thrombocytopenia
Minor topic(s): None
Type of Article: Topic Summary and Discussion

Main Purpose: Provide a comprehensive review of immune thrombocytopenia

Key points in the article discussion:

I. General

A. Immune Thrombocytopenia (ITP) is an autoimmune syndrome inolving AB and cell mediated destruction of platelets and suppression of platelet production that may predispose a pt to bleeding. This review focuses on PRIMARY ITP in ADULTS.
B. No current studies on observed untreated ITP because most patients present with bleeding problems that require treatment.

II. Demographics:

A. Incidence: 1.6-3.9 per 100,000 persons per year.
B. Prevalence: 9.5-23.6 per 100,000 persons per year (UK). US stats are lower.
C. Due to vagaries in Dx codes, these numbers may be low.
D. Younger adults: Females>Males, Older Adults: Females=Males.

III. Etiology:

A. Underlying defects are unknown.
B. Heritability is uncommon.
C. "Molecular mimicry" seems to play a role in formation of anti-platelet antibodies after certain vaccinations or viral infections (HIV, Hep C).

IV. Pathogenesis:

A. Platelet life-span is reduced as a consequence of AB-mediated clearance by tissue macrophages.
B. Possible involvement of other mechanisms: AB-mediated apoptosis, antigen shedding and T-cell mediated platelet destruction or marrow suppression.

V. Dx:

A. Primary ITP is Dx of exclusion from both NON-autoimmune causes and secondary causes.
B. Can be quite difficult without historic platelet count.
C. 20% of ITP in USA is secondary.
D. Often, Pt's assumed to have primary ITP are found later to have secondary.
E. Uncommon for pt's presenting with ACTUAL primary ITP to develop another clinically overt autoimmune disease.
F. 150 x 10^9 / L ... needed level of platelets for the Dx currently.
G. In general, the incidence of remission lessens as the duration of the disease increases.
1. This has led to the SUB-Dx of: Newly Dx (<3mo),>12mo)

VI: Management:

A. Principles: Goal of Tx is to provide a protracted platelet count of >30x10^9/L while minimizing toxicity.
B. Platelet count: (evidence suggests it is predictive of serious bleeding in ITP)
1. Other LIFE factors that effect platelet level and bleeding risk must be considered when treating patients with ITP (age, activity level, medications etc...)
C. Remission: Early intervention CRICIAL as more chronic ITP patients can develop stronger, mor specific auto-antibodies.
D. Quality of Life: Patients with ITP tend to experience fatique, apprehension of bleeding, withdrawl from normal daily activities.
E. Who to Treat: Typically don't treat when platelet count greater than 30x10^9/L. However may consider treating surgical patients due to increased risk of bleeding.

VII. 1st-line therapy for Newly Dx:

A. Corticosteroids with supplemental immunoglobulin or anti-RhD as needed to stop bleeding and increase platelet count.
B. Studies being performed with Dexamethasone and anti-CD20 AB.

VIII. Hospitalization and Emergency Therapy:

A. ITP patients should be hospitalized if: Internal bleeding, platelets under 10 and Hx of sig bleeding or non-compliance, platelets of 10-20 for pt's who have not been effectively treated yet. Otherwise, outpatient setting is appropriate.
B. Platelet transfusion appropriate in case of life-threatening emergency, organ-threatening emergency or head trauma.

IX. 2nd-line Therapy:

A. Should be used in the absence of robust response by one of the 1st-line therapies.
B. Fewer steroid dosages, or lower level of steroid-sparing agents.
C. Splenectomy: 2/3 of pt's obtain long term remission.
1. Complications and risks extensive... HOWEVER it is low cost and highly effective.
D. Anti-CD20: Single course induces complete remission in approximately 40% of Pt's.
1. Clinical trials in process for a number of CD-20 drugs.
E. TRA's (thrombopoeitin receptor agonist): Two types currently approved by FDA for primary ITP treatment.
1. Possible side-effects include rebound thrombocytopenia with lower counts than before therapy. Careful administration of these drugs in NECESSARY.

X. 3rd-line Therapy:

A. Multiple immunosuppresive agents have been tested but are only used as "last resort" due to their quesitonable "safety profile".

XI. Summary:

A. ITP is a syndrome of various disorders that have in common immune-mediated thrombocytopenia,
B. As understanding of ITP grows, the Dx of PRIMARY ITP will apply to a smaller and smaller group of individuals.
C. The cause of impaired platelet poiesis remains uncertain.
D. TRA's APPEAR capable of overriding AB-mediated platelet clearance in most patients.
E. Platelet count is the current diagnostic tool of choice but hopefully will be replaced someday by biomarkers of pathogenesis or response.
F. There is still a school of thought that spontaneous remission may likely occur, but this is being challenged by a high response rate in EARLY, AGGRESSIVE intervention.
G. Long term, prospective studies still needed for MANY of the new therapies.
H. Currently, the most reliable and cost-effective solution for second-line therapy is corticosteroids followed by splenectomy... keeping in mind long term side-effects of splenectomy and steroid use.
I. Currently, TRA's pose the most exciting front line of treatment options.

Assessment of Article: Clinically, this article doesn't have much practical application. However, it does educate us on the path, Dx, and Tx of the disease. The take-away from the article is to have more of an awaremess of how ITP (primary AND secondary) may effect our pt's bleeding tendancy. Also, given a platelet count and ITP Dx, we should know when a hospital referal is indicated. Good, THOROUGH article.