- Disorder of cation transport system in RBC membrane with dehydrated RBC (high MCHC)- autosomal dominant mode of transmission
Familial Hemolytic Uremic Syndrome (HUS)
- Microangiopathic hemolytic anemia with fragmented erythrocytes in the peripheral blood smear, thrombocytopenia (usually mild), and acute renal failure.
- Mutations in any one of several genes encoding complement regulatory proteins: complement factor H (CFH), CD46 or membrane cofactor protein (MCP), complement factor I (CFI), complement component C3, complement factor B (CFB), and thrombomodulin.
- Treatment-anti-CD52 monoclonal antibody Campath - especially effective in younger MDS patients (younger) ,who bear the histocompatability antigen HLA-DR15.
- Th commonest type with more blasts-Refractory anemia with excess blasts, type 2 (RAEB-2) - (blast 5-19%)
- The commonest type of MDS is Refractory anemia with excess blasts, type 1 (RAEB-1)
WHO Classification of Chronic Myeloproliferative Disorders
- Chronic myelogenous leukemia, bcr-abl–positive
- Chronic neutrophilic leukemia
- Chronic eosinophilic leukemia, not otherwise specified
- Polycythemia vera
- Primary myelofibrosis
- Essential thrombocytosis
- Myeloproliferative neoplasms, unclassifiable
Renal Disease- with POLYCYTHEMIA
- Renal artery stenosis
- Focal sclerosing or membranous glomerulonephritis
- Postrenal transplantation
- Renal cysts
- Bartter's syndrome
- Erythropoietin receptor mutation
- VHL mutations- (Chuvash polycythemia)
- Erythropoietin may worsen splenomegaly
- for unexplained reasons, splenectomy increases the risk of blastic transformation
- Allogeneic bone marrow transplantation is the only curative treatment
- JAK2 inhibitors -phase III clinical trials.(18th)
New drug for CML
Bosutinib - Src and Abl TK inhibitor.
MANTLE CELL LYMPHOMA
Overexpression of the ALK protein is an important prognostic factor, with patients over expressing this protein having a superior treatment outcome.
The ALK inhibitor crizotinib appears highly active.
Splenic Marginal Zone Lymphoma
- Mainly small lymphocytes.
- Splenic hilar nodes, bone marrow, and peripheral blood may be involved. The circulating tumor cells have short surface villi and are calledvillous lymphocytes.
- Express surface immunoglobulin and CD20, but are negative for CD5, CD10, and CD103.
- Mid-fifties and men and women are equally represented.
- Autoimmune anemia or thrombocytopenia may be present.
- About 40% of patients have either deletions or translocations involving 7q21, the site of the CDK6 gene. The genetic lesions typically found in extranodal marginal zone lymphomas [e.g. trisomy 3 and t(11;18)] are uncommon in SMZL.
- The clinical course of disease is generally indolent. -undergo histologic progression to diffuse large B cell lymphoma.