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Haematology Flashcards

1
Q

Define Leukemia.

A

Malignant neoplastic monoclonal proliferation of haematopoietic (stem) blood cells. When abnormal blood cells/precusors accumulate in the bone marrow.

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2
Q

State the 4 types of Leukemia.

A

Acute lymphoid leukemia. Acute myeloid leukemia. Chronic lymphoid leukemia. Chronic myeloid leukemia.

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3
Q

Give 2 examples of neoplastic infiltration.

A

Bone marrow (bone pain). Thymus (palpable mass, airway compensation). Liver and spleen (hepatosplenomegaly). Lymph nodes (lymphadenopathy). Meningeal infiltration (headaches, vomiting, nerve palsies, nuchal rigidity).

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4
Q

State what a hematopoietic stem cell differentiates into.

A

Myeloblasts. Lymphoblasts.

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5
Q

State what a myeloblast differentiates into.

A

Erythrocyte. Thrombocyte. Monocyte. Granulocyte.

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6
Q

State what a lymphoblast differentiates into.

A

Pre-B Cell - B lymphocyte. Pre-T Cell - T lymphocyte.

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7
Q

State what a granulocyte differentiates into.

A

Neutrophil. Basophil. Eosinophil.

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8
Q

State what a lymphoblast differentiates into.

A

B lymphocyte. NK cell. T lymphocyte.

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9
Q

State what acute lymphoblastic leukemia (ALL).

A

Malignancy of lymphoid cells affecting B or T lymphocyte cell lineages in bone marrow. Prevents maturation and promotes uncontrolled proliferation of immature blast cells.

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10
Q

State the 2 types of ALL.

A

B cell acute lymphoblastic leukemia. T cell acute lymphoblastic leukemia.

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11
Q

State a cause of B cell acute lymphoblastic leukemia.

A

Translocations - t(12,21); t(9,22)

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12
Q

State what a T cell acute lymphoblastic leukemia.

A

Pre-T cells in the thymus. Associated with NOTCH1 mutation.

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13
Q

State a risk factor for Acute Lymphoblastic Leukemia.

A

Common with Young Children. Ionizing radiation - during pregnancy. Down syndrome (after age of 5)

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14
Q

State a sign of acute lymphoblastic leukemia (ALL).

A

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

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15
Q

State how acute lymphoblastic leukemia (ALL) is diagnosed.

A

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

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16
Q

State a treatment for acute lymphoblastic leukemia (ALL).

A

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

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17
Q

State a side effect of chemotherapy.

A

Tumour lysis syndrome.

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18
Q

Define a tumour lysis syndrome.

A

Rapid release of cellular components into circulation as a result of massive destruction of rapidly proliferating malignant cells.

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19
Q

State some risk factors for tumour lysis syndrome.

A

Pre-existing renal failure. Drugs that increase urate levels. High tumour proliferation rate.

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20
Q

Define a treatment for a tumour lysis syndrome.

A

Hydration. Allopurinol. Monitoring with blood tests. Treat hyperkalaemia. May need dialysis.

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21
Q

Define an Acute Myeloid Leukaemia (AML).

A

Neoplastic proliferation of myelogenous stem cells (myeloblasts) in bone marrow.

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22
Q

State a type of Acute Myeloid Leukaemia (AML).

A

Acute promyelocytic leukemia (associated with a translocation t(15, 17) - disruption of retinoic acid receptor. Acute monocytic leukemia. Acute megakaryocytic leukemia.

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23
Q

Define hyperviscosity.

A

If white cell count > 100x10^9/L, white blood cell thrombi may form in the brain, lung and heart (leukostasis).

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24
Q

State a problem associated with hyperviscosity

A

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).

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25
Q

State the different types of Acute Myeloid Leukaemia (AML).

A

Acute promyelocytic leukemia (granulocytes). Acute myelomonocytic leukemia. Acute monocytic leukemia (monocytes). Acute erythroid leukemia (red blood cells). Acute megakaryoblastic leukemia (platelets).

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26
Q

State a risk factor for Acute Myeloid Leukaemia (AML).

A

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.

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27
Q

As disease progresses, are there more or less myeloblasts?

A

Myeloblasts <20% initially, then >20% as disease progresses.

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28
Q

State a symptom of Acute Myeloid Leukaemia (AML).

A

Anaemia, infection and bleeding. Swelling of gums - monocytic infiltration. DIC - acute promyelotcytic leukemia (release of thromboplastin). Infiltration - hepatomegaly, splenomegaly).

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29
Q

State of symptom of both AML and ALL.

A

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.

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30
Q

State how Acute Myeloid Leukaemia (AML) is diagnosed.

A

Blood count (WCC increased). Blood smear. Bone marrow smear. Immunophenotyping.

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31
Q

How are myeloblasts differentiated from lymphoblasts on the blood smear?

A

Myeloblasts have Auer Rods. Lymphoblasts have glycogen granules.

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32
Q

What should you expect when immunophenotyping ALL?

A

DNA polymerase only in lymphoblasts (TdT).

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33
Q

State a treatment of immunophenotyping.

A

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).

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34
Q

Define chronic lymphocytic leukemia.

A

Sustained proliferation of mature B lymphocytes in bone marrow, blood, lymph nodes.

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35
Q

What is the most commonest leukemia?

A

Chronic lymphocytic leukemia.

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36
Q

What is the difference between acute and chronic leukemia?

A

Acute - cells don’t mature. Chronic - cells mature partially (therefore don’t work effectively, divide too quickly, don’t die as they should).

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37
Q

State a cause of chronic leukemia.

A

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.

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38
Q

State a risk factor for Chronic Lymphocytic Leukemia (CLL).

A

Affects older people (> 50). Men > women (2:1).

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39
Q

State a symptom of Chronic Lymphocytic Leukemia.

A

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)

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40
Q

State a complication of Chronic Lymphocytic Leukemia (CLL).

A

Infection - due to hypogammaglobulinemia (reduced antibodies - to fight infection). Autoimmune hemolytic anemia and thrombocytopenia.

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41
Q

State how a Chronic Lymphocytic Leukemia (CLL) is diagnosed.

A

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).

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42
Q

State a treatment of Chronic Lymphocytic Leukemia (CLL).

A

Chemotherapy drug e.g. fludarabine, rituximab, cyclophosphamide. Ibrutinib, chlorambucil, bendamustine, ofatumumab. Steroids (helps with autoimmune haemolysis). Radiotherapy (helps lymphadenopathy and splenomegaly). Stem cell transplantation.

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43
Q

Define Chronic Myeloid Leukemia (CML).

A

Monoclonal proliferation of mature granulocytes/precursors. They accumulate in bone marrow to prevent maturation. Occur between 40-60 years. Male dominance.

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44
Q

State a cause of Chronic Myeloid Leukemia (CLL).

A

Associated with Philadelphia chromosome (no. 22) - translocation from 9 to 22. Results in a BCR-ABL fusion, increasing tyrosine kinase activity and cell division.

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45
Q

State a sign of Chronic Myeloid Leukemia (CLL).

A

Fatigue/weight loss/loss of energy/fever. Bleeding (platelet dysfunction). Abdominal enlargement (splenic enlargement). Anaemia and bruising.

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46
Q

State a diagnosis of Chronic Myeloid Leukemia (CLL).

A

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.

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47
Q

State a treatment of Chronic Myeloid Leukemia (CLL).

A

Tyrosine kinase inhibitor (imatinib, more potent 2nd generation - dasatinib, nilotinib, bosutinib). Chemotherapy drug - hydroxycarbamide. Stem cell transplantation.

48
Q

Define Disseminated Intravascular Coagulation.

A

Myeloblasts activate the clotting cascade

49
Q

State a feature of the tumour in Hodgkin’s Lymphoma.

A

Tumour contains large mononuclear cells (Hodgkin cells). Red-Stenberg cels (two cells fused).

50
Q

State a feature of the tumour in Hodgkin’s Lymphoma .

A

Tumour contains large mononuclear cells (Hodgkin cells). Red-Stenberg cels (two cells fused).

51
Q

Define the 2 types of Hodgkin’s Lymphoma.

A

Classical Hodgkin’s Lymphoma (CHL). Nodular Lymphocyte Predominant Hodgkin’s Lymphoma.

52
Q

Define Hodgkin’s Lymphoma.

A

Malignant proliferations of lymphocytes. Spread to nearby lymph nodes. Are B cell tumours.

53
Q

State a feature of the tumour in Hodgkin’s Lymphoma .

A

Tumour contains large mononuclear cells (Hodgkin cells). Red-Stenberg cels (two cells fused).

54
Q

Define the 2 types of Hodgkin’s Lymphoma.

A

Classical Hodgkin’s Lymphoma (CHL). Nodular Lymphocyte Predominant Hodgkin’s Lymphoma.

55
Q

What are Reed-Sternberg cells?

A

Multi-nucleated cells.

56
Q

State the 4 sub-types of Classical Hodgkin’s Lymphoma (CHL).

A

Nodular sclerosis Hodgkin’s Lymphoma (70%). Mixed cellularity (20-25%). Lymphocyte-rich (5%). Lymphocyte depleted (<1%).

57
Q

Define the Nodular Sclerosis Hodgkin’s Lymphoma (70%).

A

Consist of lacunar cells (Reed-Sternberg cells with shrunken cytoplasm). Neoplastic cells surrounded by collagen from fibroblasts and inflammatory cells.

58
Q

What are Hodgkin cells?

A

Large, mononuclear cells.

59
Q

Define a Mixed Cellularity (20-25%) lymphoma.

A

Prevalent HIV positive individuals.

60
Q

Define a Lymphocyte-rich (5%) lymphoma.

A

Reed-Sternberg cells surrounded by lymphocytes.

61
Q

Define a Lymphocyte depleted (<1%) lymphoma.

A

Worst prognosis.

62
Q

Define a Nodular Lymphocyte Predominant Hodgkin’s Lymphoma.

A

Abnormal B cells (express CD20/CD25). Lymphocyte-predominant cells (No Reed-Sternberg cells), large groups of lymphocytes form NODULES around Popcorn cells.

63
Q

Define the Ann Arbor system.

A

Staging system for both Hodgkin’s and Non-Hodgkin’s Lymphoma.

64
Q

Define the staging of Ann Arbor system.

A

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

65
Q

State a symptom of Hodgkin Lymphoma.

A

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.

66
Q

State a way to diagnose Hodgkin Lymphoma.

A

Lymph node biopsy (Reed-Sternberg cells). Imaging (splenomegaly). Bloods (FBC).

67
Q

State a treatment of Hodgkin Lymphoma.

A

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

68
Q

Define Non-Hodgkin Lymphomas.

A

Include all lymphomas (B+T cells), but NO Reed-Sternberg cells. Have extranodal sites (e.g. skin, GI tract, brain).

69
Q

State the subtypes of B cell lymphoma.

A

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

70
Q

State the subtypes of B cell lymphoma.

A 
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
71
Q

Define a follicular lymphoma.

A

Slow growing (indolent). Chromosomal translocation (chromosome 14 to 18) - inhibits apoptosis therefore cell proliferation (BCL2 gene over-expression).

72
Q

Define diffuse large B cell lymphoma.

A

Aggressive. More common.

73
Q

Define Burkitt Lymphoma.

A

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.

74
Q

What should you expect from Burkitt Lymphoma in Africa?

A

Extranodal movement of jaw and EBV link.

75
Q

What should you expect from Burkitt Lymphoma in Non-Africa?

A

Extranodal abdominal movement and less EBV association.

76
Q

Define a Mantle Cell lymphoma.

A

Aggressive. Chromosomal translocation t(11,14) - BCL1 gene moved to Ig promoter (upregulation of BCL1 gene - cell growth).

77
Q

Define Marginal Zone Lymphoma.

A

Associated with Mucosa-associated lymphoid tissue (MALT).

78
Q

Define Waldenstrom Macroglobulinemia.

A

Type of cancer affecting two types of B cells: lymphoplasmacytoid cells and plasma cells.

79
Q

Define adult T cell lymphoma.

A

When there are abnormal leukocytes in the bloodstream - can cause human T-lymphotropic virus (HTLV)

80
Q

State the 2 types of T cell lymphoma.

A

Adult T cell lymphoma. Mycosis fungoides.

81
Q

Define mycosis fungoides.

A

T cell lymphoma of skin resembles fungal infection. Neoplastic cells (CD4 and helper T cells circulate in the blood) - Sezary syndrome (erythroderma).

82
Q

State a sign of T cell lymphoma.

A

Painless lymphadenopathy. Fever. Drenching night sweats. Weight loss.

83
Q

Define extranodal involvement.

A

GI tract - bowel obstruction. Bone marrow - fatigue, easy bruising, recurrent infections, anaemia. Spinal cord - loss of sensation (legs).

84
Q

Define the diagnosis of a T cell lymphoma.

A

Low grade lymphomas (low proliferation fraction). High grade lymphoma (high proliferation fraction).

85
Q

Give an example of a low grade lymphoma.

A

Follicular lymphoma. Marginal zone lymphoma/MALT. Lymphocytic lymphoma. Lymphoplasmacytoid lymphoma.

86
Q

Give an example of a high grade lymphoma.

A

Burkitt lymphoma. Lymphoblastic lymphomas. Diffuse large B-cell lymphoma.

87
Q

State a treatment of T cell lymphoma.

A

Stage I/II disease - 3 cycles of R-CHOP and radiotherapy.

Stage IB, II, III, IV - 6 cycles of R-CHPO

88
Q

Define R-CHOP regimen.

A 
Rituximab
Cyclophosphamide
Hydroxydaunorubicin
Onconin (vincristine)
Prednisolone
89
Q

State the difference between Hodgkin’s Lymphoma and Non-Hodgkin’s Lymphoma.

A

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.

90
Q

State a cause of myeloproliferative disorders.

A

Caused by clonal proliferation of haematopoietic myeloid stem cells in bone marrow (cells retain ability to differentiate into RBCs, WBCs or platelets).

91
Q

State the proliferating cell type referring to red blood cells.

A

Polycythaemia vera (PRV).

92
Q

State the proliferating cell type referring to white blood cells.

A

Chronic myeloid leukaemia (CML).

93
Q

State the proliferating cell type referring to platelets.

A

Essential thrombocythaemia.

94
Q

State the proliferating cell type referring to fibroblasts.

A

Myelofibrosis.

95
Q

Define polycythaemia vera (PRV).

A

Malignant proliferation of haematopoietic stem cells (red blood cells).

96
Q

State a cause of polycythaemia vera (PRV).

A

Mutation of Janus Kinase 2 (JAK2) gene - cells divide in the absence of erythropoietin.

97
Q

Define polycythemia.

A

Increased blood viscosity and increased total blood volume - abnormal blood flow and blood clots.

98
Q

State a symptom of polycythemia vera.

A

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.

99
Q

State the diagnosis of polycythemia vera.

A

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

100
Q

State a treatment of polycythemia vera.

A

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

101
Q

Define Essential Thrombocythaemia.

A

Clonal proliferation of megakaryocytes (haematopoietic stem cells) leads to increased platelets.

102
Q

State a symptom of Essential Thrombocythaemia.

A

Fatigue. Dizziness. Headache. Nausea. Numbness in hands and feet.

103
Q

State a complication of Essential Thrombocythaemia.

A

Bleeding. Microvascular occlusion - headache, chest pain, light-headedness.

104
Q

State a treatment of Essential Thrombocythaemia.

A

Aspirin - reduced blood clots. Hydroxycarbamide - lower platelet count.

105
Q

Define Myelofibrosis.

A

Hyperplasia and proliferation of megakaryocytes which produce platelet-growth factor - leads to marrow fibrosis and haematopoiesis in spleen and liver (hepatosplenomegaly).

106
Q

State a symptom of Myelofibrosis.

A

Fever. Weight loss. Night sweats. Abdominal discomfort.

107
Q

Define pancytopenia.

A

Deficiency of red blood cells, white blood cells, platelets.

108
Q

State what would be found on a blood smear for myelofibrosis.

A

Tear-drop shaped red blood cells. Immature nucleated red blood cells. Immature white blood cells. Immature platelet.

109
Q

State a treatment of myelofibrosis.

A

Stem cell transplantation.

110
Q

Define myeloma.

A

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).

111
Q

State a risk factor for myeloma.

A

Age normally over 70. Background - Afro Carribean. Males > Females. IgG > IgA > IgD > IgM.

112
Q

State a symptom of a myeloma.

A

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

113
Q

State the test/diagnosis of myeloma.

A

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.

114
Q

State a complication of myeloma.

A

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

115
Q

State a treatment for myeloma.

A

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

Cancer (21 decks)

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