Haematopathology: Anaemias and Leukemias Flashcards

Question

Describe the process of auto-immune haemolysis.

Answer 1

- Antibody produced directed against RBC membrane antigens - Spleen recognises Fc fragment of immunoglobulin - Loss of membrane and shortened RBC survival. As a result, cells turn into spheres, which then pop

Answer 2

- Basically, underproduction of blood. - Marrow turns empty and more fatty, resulting in decline of all cell productions (becomes 90% fat with little islands of marrow cells, when it should be 50:50) - It is a predictable dose related side effect of chemotherapy/radiation - Also an idiosyncratic side effect of chloramphenicol - Idiopathic, do not know why becomes aplastic

Answer 3

- Myeloma (cancer arising from plasma cells) - Leukaemia (cancer developing from leukocytes) - Lymphoma (cancers developing from lymphocytes) - Metastatic tumour (secondary malignancy) By occupying space in the marrow, thus crowding out red cell production (and possibly causing a fracture).

Answer 4

Lack of erythropoietin production leads to less drive for marrow to produce red cells.

Answer 5

Cytokine effect from infections or inflammatory disease (such as arthritis, inflammatory bowel disease), by dampening red cell production in marrow

Answer 6

-Symptoms of anaemia, large spleen (resulting in distended abdomens), bone pain, angina in older patients -Occurs in all age groups -Anaemia, high WBC and platelet count -Typically a chronic phase (4-5 years) and then accelerated and blast phase (very short survival). -95% of cases have an identical cytogenetic and molecular mutation -Reciprocal translocation between chromosome 9 and 22. Material of long arm of chromosome 9 is swapped for material on long arm of chromosome 22. End up with switch of material between two chromosomes leading to shorter chromosome 22 (and longer chromosome 9) + juxtaposition of BCR gene with ABL gene (BCR gene was already on chromosome 22 but ABL gene was originally on chromosome 9) on chromosome 22) -Translocated chromosome 22 = Philadelphia chromosome (with juxtaposition of BCR gene with ABL gene)

Answer 7

IMATINIB (=Gleevec) - (BCR-ABL?) code for tyrosine kinase enzyme which phosphorylates proteins to active them - In CML, massive activation through phosphorylation - If block kinase site competitively by Imatinib on bcr-abl tyrosine kinase enzyme, that stops substrate being phosphorylated and activated - Since pretty much everyone has same mutation, drug effective to most of the affected population - Treatment well tolerated (once a day oral medication) - Effect monitored (by measuring percentage of bcr-abl product in the cells) - Drug resistance unusual INTERFERON CHEMOTHERAPY

Answer 8

``` Imatinib = 90% Interferon = 60% Chemo = 45% ```

Answer 9

- More common with increasing age - Become ill within period of days-weeks - Presents with symptoms of marrow failure including anaemia, bleeding, infections (gross expansion of malignant WBCs means production of normal WBC affected, hence more vulnerable to infections) - Other symptoms include angina, shortness of breath - Histologically, increased presence of (large) B cells, and presence of Auer rods (clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of myeloid leukemic blasts) - Diverse cytogenetic changes so no single target for chemotherapy

Answer 10

CHEMOTHERAPY - To produce marrow aplasia - Rely on ability of marrow to regenerate from residual stem cells (rely on ability of residual stem cells to grow back better than remaining leukaemic cells) - Whole process take 4 to 5 weeks, beginning to end (the treatment or the illness ?)

Answer 11

Cytogenetic profile

Answer 12

- Infections (Not so much from other people. Instead, bugs in normal microbiota become more invasive as a result of chemo) - Bleeding (Due to underproduced platelets as a result of chemotherapy. E.g. distended retinal vessels and retinal haemorrhage) - Psychological (Due to staying in hospital) - Venous access (Relying on veins in hands and arms is a problem because need lots of blood samples, transfusions, antibiotics, chemotherapy. Hence, commonly use semi-permanent into jugular or subclavian vein)

Answer 13

Those with CML (for all age categories)

Answer 14

Because: a) Not so fit b) Poorer cytogenetic changes

Answer 15

Yes (but still lower survival rate than those treated with Imatinib for CML) The increase in survival rate is thanks to patient support, better chemo, better selection of patients (targeting certain patient groups with certain drugs according to particular disease categories)