FBC CASES Vernon Louw Clinical Haematology 2010
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1 FBC CASES Vernon Louw Clinical Haematology 2010
2 FOR EACH OF THE FOLLOWING PATIENTS, SELECT THE MOST LIKELY FINDING FROM THE ANALYSIS OF THE PERIPHERAL BLOOD.
3 A patient with infectious mononucleosis. A B C D E F G H I J Anaemia Lymphocytosis Lymphopenia Neutropenia Neutrophilia Pancytopenia Polycythaemia Reticulocytosis Thrombocytopenia Thrombocytosis
4 Answer B. Lymphocytosis. Many viral infections, including infectious mononucleosis, cause a lymphocytosis.
5 A patient who just started treatment with B12 and folate for megaloblastic anaemia. A B C D E F G H I J Anaemia Lymphocytosis Lymphopenia Neutropenia Neutrophilia Pancytopenia Polycythaemia Reticulocytosis Thrombocytopenia Thrombocytosis
6 Answer H. Reticulocytosis. The administration of haematinics results in a brisk increase in erythropoiesis with a transient rise in the peripheral blood reticulocyte count.
7 Reticulocytes Juvenile RBCs Contain remnants of RNA and ribosomes # reticulocytes reflects erythropoietic activity
8 Pearl A reticulocyte count is one of the most underused, yet one of the most valuable tests to decide on the cause of an anaemia!!
9 The shift phenomenon Young, very large reticulocytes, that usually remains in the BM 2 or 3 days before release, are shifted out into the PB under the stimulus of high levels of erythropoietin Shift cells are common when anemia is severe and develops rapidly
10 Shift cells Shift cells are bigger than RBCs May result in an elevated MCV Reported as polychromasia
11 Reticulocyte Production Index Reticulocyte count is used to assess the appropriateness of the BM response to anemia. It must be corrected for the anemia to give a value known as the reticulocyte production index (RPI)
12 Reticulocyte index Hct (%) Marrow retics (days) PB retics (days)
13 Reticulocyte Production Index patient HCT RPI = Reticulocyte count x normal HCT Normal Reticulocyte Production Index: 1-3%
14 RPI < 1% (Decreased RBC production) Hypoproliferative Renal failure Aplastic Anemia MDS Bone Marrow infiltrate Bone Marrow suppression or failure Sepsis Chemotherapy or radiotherapy Blood transfusion!! Maturation disorder Iron Deficiency Anemia Vitamin B12 Deficiency Folate Deficiency Anemia of Chronic Disease Endocrine deficiencies Thalassaemia Sideroblastic Anemia
15 RPI > 3% (Increased RBC production) 1. Acute blood loss 2. Acute hemolytic anemia E.g. Autoimmune hemolytic anemia Usually ARC > 100 x10^6/l and Retic Count >2% 3. Post-Anemia Treatment Folate Supplementation Iron Supplementation Vitamin B12 Supplementation 4. Post-Splenectomy 5. Hemoglobinopathy Sickle Cell Anemia Thalassemia major 6. Discontinuation of marrow suppression e.g. withdrawal of alcohol
16 A patient with chronic renal failure. A B C D E F G H I J Anaemia Lymphocytosis Lymphopenia Neutropenia Neutrophilia Pancytopenia Polycythaemia Reticulocytosis Thrombocytopenia Thrombocytosis
17 Answer A. Anaemia. There are several mechanisms that may result in anaemia in patients with chronic renal failure, the most important being a reduced production of erythropoietin. Other mechanisms include iron deficiency due to blood loss from the gastrointestinal or genitourinary tracts, folate loss into the dialysate and shortened red cell survival.
18
19 RPI < 1% (Decreased RBC production) Hypoproliferative Renal failure Aplastic Anemia MDS Bone Marrow infiltrate Bone Marrow suppression or failure Sepsis Chemotherapy or radiotherapy Blood transfusion!! Maturation disorder Iron Deficiency Anemia Vitamin B12 Deficiency Folate Deficiency Anemia of Chronic Disease Endocrine deficiencies Thalassaemia Sideroblastic Anemia
20 A patient with chronic obstructive pulmonary disease. A B C D E F G H I J Anaemia Lymphocytosis Lymphopenia Neutropenia Neutrophilia Pancytopenia Polycythaemia Reticulocytosis Thrombocytopenia Thrombocytosis
21 Answer G. Polycythaemia. Chronic hypoxia stimulates the production of erythropoietin causing an increase in the red cell mass.
22 A patient with disseminated intravascular coagulation. A B C D E F G H I J Anaemia Lymphocytosis Lymphopenia Neutropenia Neutrophilia Pancytopenia Polycythaemia Reticulocytosis Thrombocytopenia Thrombocytosis
23 Answer I. Thrombocytopenia. The intravascular coagulation depletes peripheral blood of platelets.
24 A 60 year-old woman with a history of thyrotoxicosis complains of easy bruising and recurrent blood blisters in her mouth. Her white cell count is 1 x 10^9/L, platelets 20 x 10^9/L and the haemoglobin is 6 g/dl. A B C D E F G H I J Aplastic anaemia Folic acid deficiency Iron deficiency Multiple myelomatosis Myelofibrosis Peptic ulcer disease Pernicious anaemia Rheumatoic arthritis Vitamin B12 deficiency Vitamin C deficiency
25 Answers A. Aplastic anaemia. This patient s pancytopenia suggess marrow failure (aplastic anaemia). A bleeding tendency is the most common presentation of this disorder. In about half the cases, there is a history of exposure to an incriminating drug. The history of thyrotoxicosis was relevant in that this woman was taking carbimazole.
26 RI < 1% (Decreased RBC production) Hypoproliferative Renal failure Aplastic Anemia MDS Bone Marrow infiltrate Bone Marrow suppression or failure Sepsis Chemotherapy or radiotherapy Blood transfusion!! Maturation disorder Iron Deficiency Anemia Vitamin B12 Deficiency Folate Deficiency Anemia of Chronic Disease Endocrine deficiencies Thalassaemia Sideroblastic Anemia
27 Aplastic anaemia Usually pancytopenia
28 A 35 year-old woman with irregular periods complains of fatigue. She has a Hb of 8 g/dl with a low MCV and a low MCHC. Gastroscopy is normal. A B C D E F G H I J Aplastic anaemia Folic acid deficiency Iron deficiency Multiple myelomatosis Myelofibrosis Peptic ulcer disease Pernicious anaemia Rheumatoic arthritis Vitamin B12 deficiency Vitamin C deficiency
29 Answers C. Iron deficiency. This patient s menorrhagia resulted in excessive blood loss and iron deficiency anaemia. The low mean corpuscular volume and mean corpuscular haemoglobin concentration are in keeping with that diagnosis.
30 Laboratory findings MCV (microcytosis) MCH (hypochromia) ferritin BM iron stores
31 A 65-year-old man complains of low back pain and fatigue. He has a haemoglobin of 9 g/dl with a normal mean corpuscular volume and mean corpuscular haemoglobin concentration. His ESR is 120 mm/h. A B C D E F G H I J Aplastic anaemia Folic acid deficiency Iron deficiency Multiple myelomatosis Myelofibrosis Peptic ulcer disease Pernicious anaemia Rheumatoic arthritis Vitamin B12 deficiency Vitamin C deficiency
32 Answers C. Multiple myeloma. The low back pain is a key symptom and the high ESR a key sign suggestive of meylomatosis in this patient. The former is caused by vertebral fracture resulting from bone destruction due to the lytic myeloma lesions. The anaemia is usually normocytic and normochromic.
33 Plasma cells in Bone Marrow
34 Myeloma - diagnosis Monoclonal band serum and/or Monoclonal band urine (Bence-Jones proteinuria) BM plasmacytosis CRAB criteria (one of the following): C Calcium increased (hypercalcaemia) R Renal failure A Anaemia B Bone disease
35 Myeloma vertebral fracture
36 Myeloma osteolytic lesions
37 Myeloma - Investigations FBC + smear Normochromic normocytic anemia Pancytopenia Rouleaux ESR Raised ESR (often >100)
38 Myeloma - Investigations Serum protein electrophoresis
39 Myeloma rouleaux on blood smear
40 A 38-year-old woman who had a resection of her terminal ileum for Crohn s disease 6 years ago presents with breathlessness and fatigue. She has a megaloblastic anaemia with a haemoglobin concentration of 7 g/dl. A B C D E F G H I J Aplastic anaemia Folic acid deficiency Iron deficiency Multiple myelomatosis Myelofibrosis Peptic ulcer disease Pernicious anaemia Rheumatoic arthritis Vitamin B12 deficiency Vitamin C deficiency
41 Answers I. Vitamin B12 deficiency. B12 is absorbed in the terminal ileum. Resection of terminal ileum 6 years before has caused vitamin B12 deficiency leading to megaloblastic anaemia. Pernicious anaemia is the term applied to B12 deficiency specifically due to an autoimmune destruction of the intrinsic factor producing cells in the stomach.
42 Megaloblastic anaemias Most commonly due to: B12 or folate deficiency
43 Laboratory findings Macrocytic anaemia Oval macrocytes, hypersegmented neutrophils and megaloblasts Often wbc and plts BM erythroid hyperplasia Nuclear-cytoplasmic asynchrony B12 and/or folate Parietal cell and Intrinsic Factor antibodies
44 RPI < 1% (Decreased RBC production) Hypoproliferative Renal failure Aplastic Anemia MDS Bone Marrow infiltrate Bone Marrow suppression or failure Sepsis Chemotherapy Radiotherapy Blood transfusion!! Maturation disorder Iron Deficiency Anemia Vitamin B12 Deficiency Folate Deficiency Anemia of Chronic Disease Endocrine deficiencies Thalassaemia Sideroblastic Anemia
45 A 30-yr-old man presents with a 1 month h/o lethargy, malaise and shortness of breath. On exam, he is pale and has bruising on his skin. His Hb is 8,0 g/dl, WBC 89 x 109/l, platelets 40 x 109/l. A BM biopsy shows >30% blast cells with Auer rods in the cytoplasm. A B C D E F G H I J Acute lymphocytic leukaemia Acute myeloblastic leukaemia Chronic lymphocytic leukaemia Chronic myeloid leukaemia Essential thrombocythaemia Hodgkin s lymphoma Monoclonal gammopathy of uncertain significance Multiple myeloma Myelofibrosis Non-Hodgkin s lymphoma
46 Answers B. Acute myeloblastic leukaemia (AML). The patient is relatively young with quite a short history, making an acute leukaemia more likely than a chronic disease. The marrow shows large numbers of blast cells and the presence of Auer rods. The latter are slender, fusiform cytoplasmic inclusions that stain red with Wright- Giemsa stain and are virtually pathognomonic of AML.
47 Leukemia Leukemia Acute Lymphoid ALL Myeloid AML Chronic CLL CML
48 Bone marrow blasts myeloid or lymphoid?
49
50 Why is patient pancytopaenic? Failure of cell maturation Proliferation of immature cells Accumulation of useless cells in bone marrow
51 Why is patient pancytopaenic? Abnormal cells take up more and more space in BM Bone marrow failure Leukemic cells spills over in blood
52 A 58-yr-old woman presents with a 6-month h/o tiredness, weight loss and abdominal pain. On exam, she is pale, has skin bruising and splenomegaly. Her Hb is 10,5 g/dl, WBC 118 x 109/l with immature circulating cells (5% myeloblasts). Polymerase chain reaction (PCR) analysis of a BM shows the presence of chimeric Abelson-BCR gene. A B C D E F G H I J Acute lymphocytic leukaemia Acute myeloblastic leukaemia Chronic lymphocytic leukaemia Chronic myeloid leukaemia Essential thrombocythaemia Hodgkin s lymphoma Monoclonal gammopathy of uncertain significance Multiple myeloma Myelofibrosis Non-Hodgkin s lymphoma
53 Answers D. Chronic myeloid leukaemia. The splenomegaly associated with this blood picture is highly suggestive of chronic myeloid leukaemia. The BCR-ABL gene is the molecular equivalent of the Philadelphia chromosome (chromosome 22/9 translocation). This molecular rearrangement is seen in > 90% of patients with chronic myeloid leukaemia.
54 Molecular basis CML Detail from Nowell and Hungerford's paper in 1960 identifying the Philadelphia chromosome
55 Ph+ chromosome is the hallmark of CML CML first cancer demonstrated to have underlying genetic abnormality 1,2 Associated with Ph chromosome Result of translocation between chromosomes 9 and 22 3 Detected in ~95% of patients with CML 4 1. Nowell PC. Science. 1960;132: Nowell PC et al. J Natl Cancer Inst. 1961;27: Rowley JD. Nature. 1973;243: Sawyers CL. N Engl J Med. 1999;340:
56 Normal Bcr-Abl Signaling The kinase domain activates a substrate protein, eg, PI3 kinase, by phosphorylation This activated substrate initiates a signaling cascade culminating in cell proliferation and survival Bcr-Abl ADP P P P P ATP Substrate Effector P P P ADP = adenosine diphosphate; ATP = adenosine triphosphate; P = phosphate. Savage and Antman. N Engl J Med. 2002;346:683 Scheijen and Griffin. Oncogene. 2002;21:3314. SIGNALING
57 Imatinib Mesylate: Mechanism of Action Imatinib mesylate occupies the ATP binding pocket of the Abl kinase domain Bcr-Abl This prevents substrate phosphorylation and signaling A lack of signaling inhibits proliferation and survival Imatinib mesylate P ATP P P SIGNALING P Savage and Antman. N Engl J Med. 2002;346:683.
58 A 69-yr-old man seen at routine surgery clinic prior to hernia repair. His Hb is 9,8 g/dl, WBC 30 x 10^9/l, platelets 300 x 10^9/l. Review of his old medical notes reveals that 5 years ago his Hb was 10,3 g/dl, WBC 19 x 109/l and platelets 350 x 109/l. Bone marrow aspirate shows an increased number of B cells. A B C D E F G H I J Acute lymphocytic leukaemia Acute myeloblastic leukaemia Chronic lymphocytic leukaemia Chronic myeloid leukaemia Essential thrombocythaemia Hodgkin s lymphoma Monoclonal gammopathy of uncertain significance Multiple myeloma Myelofibrosis Non-Hodgkin s lymphoma
59 Answers C. Chronic lymphocytic leukaemia. This patient has no symptoms but his peripheral blood count and bone marrow are characteristic of this disorder.
60 Morphology Matutes, E et al; Rev Clin Exp Haem 4 (1), 22-47
61 A 25-yr-old man is seen in the clinic with a 2/12 history of painless lymphadenopathy in his neck. His FBC is normal but his ESR is 80 mm/h. A biopsy is reported as showing Reed-Sternberg cells in the lymph node. A B C D E F G H I J Acute lymphocytic leukaemia Acute myeloblastic leukaemia Chronic lymphocytic leukaemia Chronic myeloid leukaemia Essential thrombocythaemia Hodgkin s lymphoma Monoclonal gammopathy of uncertain significance Multiple myeloma Myelofibrosis Non-Hodgkin s lymphoma
62 Answers F. Hodgkin s lymphoma. Reed-Sternberg cells are characteristic of Hodgkin s lymphoma.
63
64 Hodgkin s disease Thomas Hodgkin Described disease in1832 at the age of 34
65 An 80-yr-old man is admitted to hospital after a stroke. His FBC, urea and electrolytes are normal. He has a marginally raised serum protein and electrophoresis shows a monoclonal band. Bone marrow aspirate shows 5% plasma cells. A B C D E F G H I J Acute lymphocytic leukaemia Acute myeloblastic leukaemia Chronic lymphocytic leukaemia Chronic myeloid leukaemia Essential thrombocythaemia Hodgkin s lymphoma Monoclonal gammopathy of uncertain significance Multiple myeloma Myelofibrosis Non-Hodgkin s lymphoma
66 Answers G. Monoclonal gammopathy of uncertain significance. There are relatively small numbers of plasma cells in the marrow and the monoclonal band is at low concentration. The patient may progress to develop myeloma or may remain stable for many years.
67 MGUS Serum protein electrophoresis
68 MGUS No CRAB criteria BM plasmacytosis < 10% Only small peak on serum or urine electrophoresis
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