22 Bone marrow aspiration BMA (16/3/2553) The specimen shows hypercellular marrow with mild erythroid and myeloid hyperplasia and normal maturation. Megakaryocytes were increased. Mildly increased mature histiocytes were observed. Conclusions : Increase peripheral destruction of platelet and erythroid series.
29 Diagnosis Infection Pneumonia √ Candidiasis √ CMV infection ? Septicemia x HIV infection x Bone marrow disease x Congenital bone marrow failure Infiltrative disease Anemia with thrombocytopenia due to peripheral destruction
64 Wiskott-Aldrich syndrome 1 st described by Wiskott in 1937 and was further characterized by Aldrich in 1954. 1 in 250,000 live male births X-linked recessive immunodeficiency disorder characterized by the triad of recurrent bacterial sinopulmonary infections eczema (atopic like dermatitis) bleeding diathesis caused by thrombocytopenia and platelet dysfunction. Pediatr. Dec 1994;125(6 Pt 1):876-85
65 Wiskott-Aldrich syndrome only 30% of patients with the syndrome have the classic triad 90% of patients have manifestations of thrombocytopenia at presentation 20% have only hematologic abnormalities 5% have only infectious manifestations, Mol There. May 2008;16(5):836-44.
66 Wiskott-Aldrich syndrome Wiskott-Aldrich syndrome gene localized to Xp11.22-23 consists of 12 exons encode a 502 amino acid (53 kD) protein Wiskott– Aldrich syndrome protein (WASP) WASP signal transduction and regulates actin filament assembly explains the abnormalities in platelet and lymphocyte cytoskeleton and signaling. J Leukoc Biol. Jun 2005;77(6):993-8.
67 Clinical manifestations The first clinical signs are petechiae and ecchymosis of the skin and oral mucosa and bloody diarrhea. One series of 154 patients found petechiae or purpura in 78% serious GI bleeding (hematemesis or melena) in 28% epistaxis in 16% intracranial bleeding in 2% of patients. J Pediatr. Dec 1994;125(6 Pt 1):876-85.
68 Hematologic Findings in WAS Thrombocytopenia (platelet count 10,000– 100,000/mm3); Microthrombocytes; low mean platelet volume (MPV).(This is not obvious in the newborn and the MPV is unreliable when the platelet count is low.) Platelets have abnormal aggregation in response to agonists such as ADP, epinephrine and collagen. Platelets have reduced platelet survival to half normal. Ineffective megakaryocytopoiesis reflected by a platelet turnover 25% that of normal megakaryocyte mass.
69 Hematologic Findings in WAS Anemia (due to blood loss). Leukocytosis (due to infection). Normal or increased megakaryocytes.
71 Other Manifestations Autoimmune manifestations Hemolytic anemia Vasculitis Inflammatory bowel disease Glomerulonephritis Arthritis Malignancies: adolescents, young adults The most common malignancy is non- Hodgkin lymphoma.
72 Diagnostic tests; immunologic Decrease CD3, CD4, CD8 T-cell Normal B-cell and NK cell Markedly decreased/ Absent isohemagglutinins (PHA) Decreased IgM Normal/ slightly low IgG Normal/ Elevated IgA, IgE Defective production of pneumococcal Ab Depressed lymphocyte response to mitogens
73 Treatment Allogeneic SCT is treatment of choice when matched donor available. If no matched donor is available the patient should be managed as follows: Aggressive treatment of infections Platelet transfusions for hemorrhagic episodes Steroid cream for eczema Splenectomy, reserved only for severe case with usual pre- and post-splenectomy precautions pertain Thrombopoietic agents are being explored.