Thrombocytopenia and Bleeding in Wiskott-Aldrich Syndrome (WAS) Patients

Effects Of Eltrombopag On Thrombocytopenia, Platelet Function and Bleeding In Patients With Wiskott-Aldrich Syndrome/X-Linked Thrombocytopenia.

The purpose of this project is to describe the pathophysiology of thrombocytopenia and bleeding in patients with Wiskott-Aldrich Syndrome (WAS) and determine the response to thrombopoietic agents in vitro and in vivo.

Wiskott Aldrich Syndrome is an X-linked disease characterized by immunodeficiency, eczema and thrombocytopenia; a milder form of the disease known as X-Linked thrombocytopenia also exists. The thrombocytopenia in both WAS and XLT is characterized by: severe thrombocytopenia with platelet counts frequently less than 10-30,000/ul; small platelets which may be dysfunctional; and, as a result, a high rate of serious bleeding including intracranial hemorrhage.

Because eltrombopag has been shown to be remarkably efficacious in substantially increasing platelet counts in a high percentage of ITP patients, this study seeks to effectively treat patients who exhibit similar pathologies, as well as evaluate the state of platelets in patients with WAS and relate it to clinical bleeding. It also aims to demonstrate whether eltrombopag administered daily will enhance stem cell function, increase platelet production and platelet count, and reduce bleeding in patients with WAS.

Inclusion Criteria:

In order to be eligible for study entry, subjects must comply with the following:

• Males from 3 months old to 80 years old
• Signed written informed consent obtained prior to study entry
• Clinical diagnosis of WAS or XLT
• Platelet levels less than 100 x 109/L
• Adequate renal and hepatic function (creatinine and bilirubin less than or equal to 1.5 x IULN, AST and ALT less than or equal to 2.5 x IULN)

Exclusion Criteria:

Any patient is ineligible for study entry if he/she:

• Over the age of 80
• Women (only males are eligible)
• fertile men who are not practicing or who are unwilling to practice birth control while enrolled in the study or until at least 6 months after treatment
• Aspirin, aspirin-containing compounds, salicylates, non-steroidal anti-inflammatory medications (NSAIDS), clopidogrel or ticlopidine, warfarin or other vitamin K antagonists, unfractionated or low molecular heparin within 7 days of first infusion
• Red blood cell transfusion in the past four weeks
• Elevated (> 1.5 x ULN) prothrombin time (PT) or partial thromboplastin time (PTT)
• New York Heart Classification III or IV heart disease. Other severe cardiovascular or cardiopulmonary disease, including COPD.
• Known HIV infection, hepatitis B or C infection
• Any infection requiring antibiotic treatment within 3 days
• Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.
• Prior malignancy with less than a 5-year disease-free interval, excluding nonmelanoma skin cancers and carcinoma in situ of the cervix