Haematology Flashcards
Define Leukemia.
Malignant neoplastic monoclonal proliferation of haematopoietic (stem) blood cells. When abnormal blood cells/precusors accumulate in the bone marrow.
State the 4 types of Leukemia.
Acute lymphoid leukemia. Acute myeloid leukemia. Chronic lymphoid leukemia. Chronic myeloid leukemia.
Give 2 examples of neoplastic infiltration.
Bone marrow (bone pain). Thymus (palpable mass, airway compensation). Liver and spleen (hepatosplenomegaly). Lymph nodes (lymphadenopathy). Meningeal infiltration (headaches, vomiting, nerve palsies, nuchal rigidity).
State what a hematopoietic stem cell differentiates into.
Myeloblasts. Lymphoblasts.
State what a myeloblast differentiates into.
Erythrocyte. Thrombocyte. Monocyte. Granulocyte.
State what a lymphoblast differentiates into.
Pre-B Cell - B lymphocyte. Pre-T Cell - T lymphocyte.
State what a granulocyte differentiates into.
Neutrophil. Basophil. Eosinophil.
State what a lymphoblast differentiates into.
B lymphocyte. NK cell. T lymphocyte.
State what acute lymphoblastic leukemia (ALL).
Malignancy of lymphoid cells affecting B or T lymphocyte cell lineages in bone marrow. Prevents maturation and promotes uncontrolled proliferation of immature blast cells.
State the 2 types of ALL.
B cell acute lymphoblastic leukemia. T cell acute lymphoblastic leukemia.
State a cause of B cell acute lymphoblastic leukemia.
Translocations - t(12,21); t(9,22)
State what a T cell acute lymphoblastic leukemia.
Pre-T cells in the thymus. Associated with NOTCH1 mutation.
State a risk factor for Acute Lymphoblastic Leukemia.
Common with Young Children. Ionizing radiation - during pregnancy. Down syndrome (after age of 5)
State a sign of acute lymphoblastic leukemia (ALL).
1) Abrupt onset.
2) Loss of normal marrow function (anaemia - fatigue, shortness of breath, pallor/thrombocytopenia - bruising, petechiae (round spots on the skin), neutropenia - bacterial infections (fever, pneumonia, sepsis).
3) Infiltration of organs - hepatomegaly/splenomegaly, lymphadenopathy/mediastinal mass (growth in area of chest that separates lungs)
4) CNS manifestations - headaches, nausea, nerve palsy
State how acute lymphoblastic leukemia (ALL) is diagnosed.
1) Blood count (increased lymphocytes, increased white blood cells)
2) Bone marrow smear - lymphoblasts (small cells) - glycogen granules
3) Immunophenotyping:
B cells - express tumour markers (CD10, CD19, CD20)
T cells - express tumour markers (CD1, CD2, CD5, CD7, CDH)
4) Karotyping
5) Chest X ray/CT scan - mediastinal and abdominal lymphadenopathy
6) Lumbar puncture - look for CNS involvement
State a treatment for acute lymphoblastic leukemia (ALL).
1) Support - blood transfusion, IV fluids, allipurinol (prevent tumour lysis syndrome).
2) Chemotherapy - anthracycline, vincristine, dexamethasone, asparaginase, methotrexate, cyclophosphamide, cytarabine.
3) Allogeneic haemopoietic stem cell transplant
State a side effect of chemotherapy.
Tumour lysis syndrome.
Define a tumour lysis syndrome.
Rapid release of cellular components into circulation as a result of massive destruction of rapidly proliferating malignant cells.
State some risk factors for tumour lysis syndrome.
Pre-existing renal failure. Drugs that increase urate levels. High tumour proliferation rate.
Define a treatment for a tumour lysis syndrome.
Hydration. Allopurinol. Monitoring with blood tests. Treat hyperkalaemia. May need dialysis.
Define an Acute Myeloid Leukaemia (AML).
Neoplastic proliferation of myelogenous stem cells (myeloblasts) in bone marrow.
State a type of Acute Myeloid Leukaemia (AML).
Acute promyelocytic leukemia (associated with a translocation t(15, 17) - disruption of retinoic acid receptor. Acute monocytic leukemia. Acute megakaryocytic leukemia.
Define hyperviscosity.
If white cell count > 100x10^9/L, white blood cell thrombi may form in the brain, lung and heart (leukostasis).
State a problem associated with hyperviscosity
Cerebral problem - headache, blurred vision, claudication. Cardiovascular problems - heart failure. Bleeding - skin, retina, post injury. Pulmonary congestion - shortness of breath. Do not transfuse red cells (increase viscosity).
State the different types of Acute Myeloid Leukaemia (AML).
Acute promyelocytic leukemia (granulocytes). Acute myelomonocytic leukemia. Acute monocytic leukemia (monocytes). Acute erythroid leukemia (red blood cells). Acute megakaryoblastic leukemia (platelets).
State a risk factor for Acute Myeloid Leukaemia (AML).
Adults. Associated with myelodysplastic syndrome (immature blood cells in the bone marrow do not mature - therefore do not become healthy blood cells). Chemotherapy. Down’s syndrome.
As disease progresses, are there more or less myeloblasts?
Myeloblasts <20% initially, then >20% as disease progresses.
State a symptom of Acute Myeloid Leukaemia (AML).
Anaemia, infection and bleeding. Swelling of gums - monocytic infiltration. DIC - acute promyelotcytic leukemia (release of thromboplastin). Infiltration - hepatomegaly, splenomegaly).
State of symptom of both AML and ALL.
Fatigue. Easier bleeding. Abdominal fullness. Increased infections. Pain in the lymph nodes. Pain and tenderness in the bones. Swelling of the gums. Mass or growth in the mediastinum.
State how Acute Myeloid Leukaemia (AML) is diagnosed.
Blood count (WCC increased). Blood smear. Bone marrow smear. Immunophenotyping.
How are myeloblasts differentiated from lymphoblasts on the blood smear?
Myeloblasts have Auer Rods. Lymphoblasts have glycogen granules.
What should you expect when immunophenotyping ALL?
DNA polymerase only in lymphoblasts (TdT).
State a treatment of immunophenotyping.
Chemotherapy - daunorubicin, cytarabine. Bone marrow transplant - pluripotent haematopoietic stem cells collected from bone marrow (ciclosporin +/- methotrexate used to reduce effect of new bone marrow rejection).
Define chronic lymphocytic leukemia.
Sustained proliferation of mature B lymphocytes in bone marrow, blood, lymph nodes.
What is the most commonest leukemia?
Chronic lymphocytic leukemia.
What is the difference between acute and chronic leukemia?
Acute - cells don’t mature. Chronic - cells mature partially (therefore don’t work effectively, divide too quickly, don’t die as they should).
State a cause of chronic leukemia.
Chromosomal abnormalities - deletion, trisomy, translocation. Mutations can result in abnormal proteins affecting tyrosine kinase pathway (e.g. Bruton’s tyrosine kinase) - prevents lymphocyte maturation and cell death.
State a risk factor for Chronic Lymphocytic Leukemia (CLL).
Affects older people (> 50). Men > women (2:1).
State a symptom of Chronic Lymphocytic Leukemia.
Anaemia (fatigue, shortness of breath, pallor). Thrombocytopenia - bruising, petechiae (spots on skin)
Neutropenia - bacterial infections (fever, pneumonia, sepsis)
Liver and spleen - hepatosplenomegaly
Lymphadenopathy - lymph nodes swell up
Meningeal infiltration - headaches, vomiting, nerve palsies, nuchal rigidity (inability to flex neck)
State a complication of Chronic Lymphocytic Leukemia (CLL).
Infection - due to hypogammaglobulinemia (reduced antibodies - to fight infection). Autoimmune hemolytic anemia and thrombocytopenia.
State how a Chronic Lymphocytic Leukemia (CLL) is diagnosed.
Blood count, blood smear (lymphocytosis), smudge cells (disruption of fragile cell membranes of abnormal lymphocytes). Immunophenotyping (CD5, CD20, CD23). Surgery (lymph node biopsy - increasing small round lymphocytes infiltration).
State a treatment of Chronic Lymphocytic Leukemia (CLL).
Chemotherapy drug e.g. fludarabine, rituximab, cyclophosphamide. Ibrutinib, chlorambucil, bendamustine, ofatumumab. Steroids (helps with autoimmune haemolysis). Radiotherapy (helps lymphadenopathy and splenomegaly). Stem cell transplantation.
Define Chronic Myeloid Leukemia (CML).
Monoclonal proliferation of mature granulocytes/precursors. They accumulate in bone marrow to prevent maturation. Occur between 40-60 years. Male dominance.
State a cause of Chronic Myeloid Leukemia (CLL).
Associated with Philadelphia chromosome (no. 22) - translocation from 9 to 22. Results in a BCR-ABL fusion, increasing tyrosine kinase activity and cell division.
State a sign of Chronic Myeloid Leukemia (CLL).
Fatigue/weight loss/loss of energy/fever. Bleeding (platelet dysfunction). Abdominal enlargement (splenic enlargement). Anaemia and bruising.
State a diagnosis of Chronic Myeloid Leukemia (CLL).
Blood count, blood sugar (increased granulocytes - basophils, eosinophils, neutrophils). Bone marrow biopsy (hypercellularity - cells of myeloid cell line/precursors) - fluorescent in situ hybridization (FISH)/PCR.
State a treatment of Chronic Myeloid Leukemia (CLL).
Tyrosine kinase inhibitor (imatinib, more potent 2nd generation - dasatinib, nilotinib, bosutinib). Chemotherapy drug - hydroxycarbamide. Stem cell transplantation.
Define Disseminated Intravascular Coagulation.
Myeloblasts activate the clotting cascade
State a feature of the tumour in Hodgkin’s Lymphoma.
Tumour contains large mononuclear cells (Hodgkin cells). Red-Stenberg cels (two cells fused).
State a feature of the tumour in Hodgkin’s Lymphoma .
Tumour contains large mononuclear cells (Hodgkin cells). Red-Stenberg cels (two cells fused).
Define the 2 types of Hodgkin’s Lymphoma.
Classical Hodgkin’s Lymphoma (CHL). Nodular Lymphocyte Predominant Hodgkin’s Lymphoma.
Define Hodgkin’s Lymphoma.
Malignant proliferations of lymphocytes. Spread to nearby lymph nodes. Are B cell tumours.
State a feature of the tumour in Hodgkin’s Lymphoma .
Tumour contains large mononuclear cells (Hodgkin cells). Red-Stenberg cels (two cells fused).
Define the 2 types of Hodgkin’s Lymphoma.
Classical Hodgkin’s Lymphoma (CHL). Nodular Lymphocyte Predominant Hodgkin’s Lymphoma.
What are Reed-Sternberg cells?
Multi-nucleated cells.
State the 4 sub-types of Classical Hodgkin’s Lymphoma (CHL).
Nodular sclerosis Hodgkin’s Lymphoma (70%). Mixed cellularity (20-25%). Lymphocyte-rich (5%). Lymphocyte depleted (<1%).
Define the Nodular Sclerosis Hodgkin’s Lymphoma (70%).
Consist of lacunar cells (Reed-Sternberg cells with shrunken cytoplasm). Neoplastic cells surrounded by collagen from fibroblasts and inflammatory cells.
What are Hodgkin cells?
Large, mononuclear cells.
Define a Mixed Cellularity (20-25%) lymphoma.
Prevalent HIV positive individuals.
Define a Lymphocyte-rich (5%) lymphoma.
Reed-Sternberg cells surrounded by lymphocytes.
Define a Lymphocyte depleted (<1%) lymphoma.
Worst prognosis.
Define a Nodular Lymphocyte Predominant Hodgkin’s Lymphoma.
Abnormal B cells (express CD20/CD25). Lymphocyte-predominant cells (No Reed-Sternberg cells), large groups of lymphocytes form NODULES around Popcorn cells.
Define the Ann Arbor system.
Staging system for both Hodgkin’s and Non-Hodgkin’s Lymphoma.
Define the staging of Ann Arbor system.
Stage 1 - limited to one lymph node group/region
Stage 2 - involvement of 2/more nodal areas on same side of the diaphragm
Stage 3 - involvement of nodes on both sides of the diaphragm
Stage 4 - spread beyond lymph nodes e.g. liver/bone marrow
State a symptom of Hodgkin Lymphoma.
Painless, enlarged, non-tender, rubbery lymph nodes (lymphadenopathy). Mediastinal mass (emergency with bronchial/superior vena cava obstruction). Alcohol-induced lymph node pain. Cytokine release (fever, weight loss, drenching night sweats). Hepatosplenomegaly.
State a way to diagnose Hodgkin Lymphoma.
Lymph node biopsy (Reed-Sternberg cells). Imaging (splenomegaly). Bloods (FBC).
State a treatment of Hodgkin Lymphoma.
Stage I - short courses of chemotherapy and radiotherapy
Stage 2 - long courses of chemotherapy and radiotherapy. ABVD (Adriamycin/Bleomycin/Vinblastine/Dacarbazine). Monoclonal antibody binds to CD20 (apoptosis) e.g. Rituximab
Define Non-Hodgkin Lymphomas.
Include all lymphomas (B+T cells), but NO Reed-Sternberg cells. Have extranodal sites (e.g. skin, GI tract, brain).
State the subtypes of B cell lymphoma.
Follicular lymphoma (slow growing indolent). Chromosomal translocation (chromosome 14 to 18) - inhibits apoptosis so cell proliferation (BCL gene over-expression).
Diffuse large B cell lymphoma (most common).
Burkitt Lymphoma
Mantle Cell Lymphoma
Marginal Zone Lymphoma
Lymphoplasmacytic Lymphoma
State the subtypes of B cell lymphoma.
Follicular lymphoma (slow growing indolent). Chromosomal translocation (chromosome 14 to 18) - inhibits apoptosis so cell proliferation (BCL gene over-expression). Diffuse large B cell lymphoma
Define a follicular lymphoma.
Slow growing (indolent). Chromosomal translocation (chromosome 14 to 18) - inhibits apoptosis therefore cell proliferation (BCL2 gene over-expression).
Define diffuse large B cell lymphoma.
Aggressive. More common.
Define Burkitt Lymphoma.
Starry sky appearance (starry - tingible bodies (macrophages that phagocytose dead neoplastic cells; sky - dark neoplastic lymphocytes). Chromosomal translocations (8 and 14) - MyC gene moved to IgH promoter sequence.
What should you expect from Burkitt Lymphoma in Africa?
Extranodal movement of jaw and EBV link.
What should you expect from Burkitt Lymphoma in Non-Africa?
Extranodal abdominal movement and less EBV association.
Define a Mantle Cell lymphoma.
Aggressive. Chromosomal translocation t(11,14) - BCL1 gene moved to Ig promoter (upregulation of BCL1 gene - cell growth).
Define Marginal Zone Lymphoma.
Associated with Mucosa-associated lymphoid tissue (MALT).
Define Waldenstrom Macroglobulinemia.
Type of cancer affecting two types of B cells: lymphoplasmacytoid cells and plasma cells.
Define adult T cell lymphoma.
When there are abnormal leukocytes in the bloodstream - can cause human T-lymphotropic virus (HTLV)
State the 2 types of T cell lymphoma.
Adult T cell lymphoma. Mycosis fungoides.
Define mycosis fungoides.
T cell lymphoma of skin resembles fungal infection. Neoplastic cells (CD4 and helper T cells circulate in the blood) - Sezary syndrome (erythroderma).
State a sign of T cell lymphoma.
Painless lymphadenopathy. Fever. Drenching night sweats. Weight loss.
Define extranodal involvement.
GI tract - bowel obstruction. Bone marrow - fatigue, easy bruising, recurrent infections, anaemia. Spinal cord - loss of sensation (legs).
Define the diagnosis of a T cell lymphoma.
Low grade lymphomas (low proliferation fraction). High grade lymphoma (high proliferation fraction).
Give an example of a low grade lymphoma.
Follicular lymphoma. Marginal zone lymphoma/MALT. Lymphocytic lymphoma. Lymphoplasmacytoid lymphoma.
Give an example of a high grade lymphoma.
Burkitt lymphoma. Lymphoblastic lymphomas. Diffuse large B-cell lymphoma.
State a treatment of T cell lymphoma.
Stage I/II disease - 3 cycles of R-CHOP and radiotherapy.
Stage IB, II, III, IV - 6 cycles of R-CHPO
Define R-CHOP regimen.
Rituximab Cyclophosphamide Hydroxydaunorubicin Onconin (vincristine) Prednisolone
State the difference between Hodgkin’s Lymphoma and Non-Hodgkin’s Lymphoma.
Hodgkin’s lymphoma - spread contiguosly, rarely extranodal, Reed-Sternberg cells.
Non-hodgkin’s lymphoma - spreads contiguously, extranodal sites (skin, GI tract, brain), no Reed-Sternberg cells.
State a cause of myeloproliferative disorders.
Caused by clonal proliferation of haematopoietic myeloid stem cells in bone marrow (cells retain ability to differentiate into RBCs, WBCs or platelets).
State the proliferating cell type referring to red blood cells.
Polycythaemia vera (PRV).
State the proliferating cell type referring to white blood cells.
Chronic myeloid leukaemia (CML).
State the proliferating cell type referring to platelets.
Essential thrombocythaemia.
State the proliferating cell type referring to fibroblasts.
Myelofibrosis.
Define polycythaemia vera (PRV).
Malignant proliferation of haematopoietic stem cells (red blood cells).
State a cause of polycythaemia vera (PRV).
Mutation of Janus Kinase 2 (JAK2) gene - cells divide in the absence of erythropoietin.
Define polycythemia.
Increased blood viscosity and increased total blood volume - abnormal blood flow and blood clots.
State a symptom of polycythemia vera.
Fatigue. Dizziness. Increased sweating. Redness in face. Blurred vision. Itchiness especially after a hot shower (increased basophils, mast cells - release histamine). Splenomegaly - spleen enlargement (helps with removing excess cells). Gout and kidney stones - build up of uric acid.
State the diagnosis of polycythemia vera.
Routine blood test - increase Hb, hematocrit (ratio of volume of RBC: total volume of blood), increased white blood cell, increased platelet count.
Decreased erythropoietin
Bone marrow tissue examination - look for fibrosis signs
Genetic testing - JAK2 mutation
State a treatment of polycythemia vera.
Hydroxyurea (reduce RBC production).
Ruxolitinib - JAK2 inhibitor to reduce RBC production
Interferon-alpha - increase RBC production
Aspirin - reduce risk of thrombosis
Phlebotomy - blood drawn through vein every few months
Define Essential Thrombocythaemia.
Clonal proliferation of megakaryocytes (haematopoietic stem cells) leads to increased platelets.
State a symptom of Essential Thrombocythaemia.
Fatigue. Dizziness. Headache. Nausea. Numbness in hands and feet.
State a complication of Essential Thrombocythaemia.
Bleeding. Microvascular occlusion - headache, chest pain, light-headedness.
State a treatment of Essential Thrombocythaemia.
Aspirin - reduced blood clots. Hydroxycarbamide - lower platelet count.
Define Myelofibrosis.
Hyperplasia and proliferation of megakaryocytes which produce platelet-growth factor - leads to marrow fibrosis and haematopoiesis in spleen and liver (hepatosplenomegaly).
State a symptom of Myelofibrosis.
Fever. Weight loss. Night sweats. Abdominal discomfort.
Define pancytopenia.
Deficiency of red blood cells, white blood cells, platelets.
State what would be found on a blood smear for myelofibrosis.
Tear-drop shaped red blood cells. Immature nucleated red blood cells. Immature white blood cells. Immature platelet.
State a treatment of myelofibrosis.
Stem cell transplantation.
Define myeloma.
A chief plasma cell dyscrasia (PCD) - clonal accumulation of plasma cells in bone marrow (increases secretion of antibodies, causing dysfunction of many organs e.g. kidneys).
State a risk factor for myeloma.
Age normally over 70. Background - Afro Carribean. Males > Females. IgG > IgA > IgD > IgM.
State a symptom of a myeloma.
1) Osteolytic bone lesion - back pain, collapse.
2) Anaemia, neutropenia, thrombocytopenia - anaemia, infection, bleeding.
3) Hypercalcaemia - increased osteoclast activation (large multinucleated bone cell which absorbs tissue during growth and healing).
4) Recurrent bacterial infections - due to neutropenia
5) Renal impairment - antibody deposition cause kidney damage, also due to amyloid light chain (AL) amyloidosis
State the test/diagnosis of myeloma.
Blood test - increased monoclonal antibodies in serum. Increased plasma cells in marrow kidney. Evidence of end-organ damage - hypercalcaemia, renal insufficiency, anaemia.
Bone lesions - X-ray, MRI, low-dose CT scan.
State a complication of myeloma.
Hypercalcaemia - due to osteoblast activation (treated IV biphosphonates).
Spinal cord compression - treated with dexamethasone/radiotherapy (limb weakness, walking difficulty, sphincter disturbance)
Hyperviscosity - causes reduced cognition, disturbed vision, bleeding, heart failure
Acute kidney injury - treated with rehydration
State a treatment for myeloma.
Bone pain - analgesia.
Bone protection - biphosphonates e.g. clodronate, zolendronate, pamidronate.
Anaemia - transfusion, erythropoeitin
Renal failure - rehydrate, reduce fluid intake
Infections - treat with broad spectrum antibiotics
Radiotherapy - for pain/palliation
