-
Harrison's Daily Dose - Haematology
Published on March 22, 2016, 3:55 p.m.

xerocytosis

  • 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.

Myelodysplasia

  • 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
  • Mastocytosis
  • 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)

TREATMENT-Primary myelofibrosis

  • Erythropoietin may worsen splenomegaly
  • for unexplained reasons, splenectomy increases the risk of blastic transformation
  • IFN-Alfa
  • Glucocorticoids
  • Thalidomide
  • 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.