fbc cases (+answers) - learninglearning.ufs.ac.za/internal_medicine_on/resources/3. academic... ·...
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FBC CASESVernon Louw
Clinical Haematology
2010
FOR EACH OF THE FOLLOWING
PATIENTS, SELECT THE MOST LIKELY
FINDING FROM THE ANALYSIS OF
THE PERIPHERAL BLOOD.
A patient with infectious mononucleosis.
� A Anaemia
� B Lymphocytosis
� C Lymphopenia
� D Neutropenia
� E Neutrophilia� E Neutrophilia
� F Pancytopenia
� G Polycythaemia
� H Reticulocytosis
� I Thrombocytopenia
� J Thrombocytosis
Answer
� B. Lymphocytosis. Many viral infections, including infectious mononucleosis, cause a lymphocytosis.
A patient who just started treatment with B12 and folate for megaloblastic anaemia.
� A Anaemia
� B Lymphocytosis
� C Lymphopenia
� D Neutropenia
� E Neutrophilia� E Neutrophilia
� F Pancytopenia
� G Polycythaemia
� H Reticulocytosis
� I Thrombocytopenia
� J Thrombocytosis
Answer
� H. Reticulocytosis. The administration of haematinics results in a brisk increase in erythropoiesis with a transient rise in the peripheral blood reticulocyte count.
Reticulocytes
� Juvenile RBCs
� Contain remnants of RNA and ribosomes
� # reticulocytes reflects erythropoietic activity
Pearl
A reticulocyte count is one of the most underused, yet one of the most underused, yet one of the most
valuable tests to decide on the cause of an anaemia!!
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
“Shift cells”
� Shift cells are bigger than RBCs
� May result in an elevated MCV
� Reported as polychromasia
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)
Reticulocyte index
3.5 1.0
Hct (%) Marrow retics (days) PB retics (days)
45
3.0
2.5
1.5
1.5
2.0
2.5
35
25
15
Reticulocyte Production Index
patient HCT
RPI = Reticulocyte count x normal HCT
NormalNormal ReticulocyteReticulocyte Production IndexProduction Index: 1: 1--3% 3%
RPI < 1% (Decreased RBC production)
� Hypoproliferative� Renal failure
� Aplastic Anemia
� MDS
� Bone Marrow infiltrate
Bone Marrow suppression or
� Maturation disorder� Iron Deficiency Anemia
� Vitamin B12 Deficiency
� Folate Deficiency
� Anemia of Chronic Disease � Bone Marrow suppression or
failure
� Sepsis � Chemotherapy or
radiotherapy � Blood transfusion !!
� Anemia of Chronic Disease
� Endocrine deficiencies
� Thalassaemia
� Sideroblastic Anemia
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 � 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
A patient with chronic renal failure.
� A Anaemia
� B Lymphocytosis
� C Lymphopenia
� D Neutropenia
� E Neutrophilia� E Neutrophilia
� F Pancytopenia
� G Polycythaemia
� H Reticulocytosis
� I Thrombocytopenia
� J Thrombocytosis
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, folateloss into the dialysate and shortened red cell survival.
RPI < 1% (Decreased RBC production)
� Hypoproliferative� Renal failure
� Aplastic Anemia
� MDS
� Bone Marrow infiltrate
Bone Marrow suppression or
� Maturation disorder� Iron Deficiency Anemia
� Vitamin B12 Deficiency
� Folate Deficiency
� Anemia of Chronic Disease � Bone Marrow suppression or
failure
� Sepsis � Chemotherapy or
radiotherapy � Blood transfusion !!
� Anemia of Chronic Disease
� Endocrine deficiencies
� Thalassaemia
� Sideroblastic Anemia
A patient with chronic obstructive pulmonary disease.
� A Anaemia
� B Lymphocytosis
� C Lymphopenia
� D Neutropenia
� E Neutrophilia� E Neutrophilia
� F Pancytopenia
� G Polycythaemia
� H Reticulocytosis
� I Thrombocytopenia
� J Thrombocytosis
Answer
� G. Polycythaemia. Chronic hypoxia stimulates the production of erythropoietin causing an increase in the red cell mass.
A patient with disseminated intravascular coagulation.
� A Anaemia
� B Lymphocytosis
� C Lymphopenia
� D Neutropenia
� E Neutrophilia� E Neutrophilia
� F Pancytopenia
� G Polycythaemia
� H Reticulocytosis
� I Thrombocytopenia
� J Thrombocytosis
Answer
� I. Thrombocytopenia. The intravascular coagulation depletes peripheral blood of platelets.
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 x10^9/L, platelets 20 x 10^9/L and the haemoglobin is 6 g/dl.
� A Aplastic anaemia
� B Folic acid deficiency
� C Iron deficiency
� D Multiple myelomatosis
� E Myelofibrosis� E Myelofibrosis
� F Peptic ulcer disease
� G Pernicious anaemia
� H Rheumatoic arthritis
� I Vitamin B12 deficiency
� J Vitamin C deficiency
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.
RI < 1% (Decreased RBC production)
� Hypoproliferative� Renal failure
� Aplastic Anemia
� MDS
� Bone Marrow infiltrate
Bone Marrow suppression or
� Maturation disorder� Iron Deficiency Anemia
� Vitamin B12 Deficiency
� Folate Deficiency
� Anemia of Chronic Disease � Bone Marrow suppression or
failure
� Sepsis � Chemotherapy or
radiotherapy � Blood transfusion !!
� Anemia of Chronic Disease
� Endocrine deficiencies
� Thalassaemia
� Sideroblastic Anemia
Aplastic anaemia
� Usually pancytopenia
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 Aplastic anaemia
� B Folic acid deficiency
� C Iron deficiency
� D Multiple myelomatosis
� E Myelofibrosis� E Myelofibrosis
� F Peptic ulcer disease
� G Pernicious anaemia
� H Rheumatoic arthritis
� I Vitamin B12 deficiency
� J Vitamin C deficiency
Answers
� C. Iron deficiency. This patient’s menorrhagiaresulted in excessive blood loss and iron deficiency anaemia. The low mean corpuscular volume and mean corpuscular haemoglobin concentration are in keeping with that diagnosis.
Laboratory findings
� ↓ MCV (microcytosis)
� ↓MCH (hypochromia)
� ↓ ferritin� ↓ ferritin
� ↓ BM iron stores
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 Aplastic anaemia
� B Folic acid deficiency
� C Iron deficiency
� D Multiple myelomatosis
� E Myelofibrosis� E Myelofibrosis
� F Peptic ulcer disease
� G Pernicious anaemia
� H Rheumatoic arthritis
� I Vitamin B12 deficiency
� J Vitamin C deficiency
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.
Plasma cells in Bone Marrow
Myeloma - diagnosis
� Monoclonal band serum and/or
� Monoclonal band urine (Bence-Jones proteinuria)
� BM plasmacytosis
� CRAB criteria (one of the following):� CRAB criteria (one of the following):
� C – Calcium increased (hypercalcaemia)
� R – Renal failure
� A – Anaemia
� B – Bone disease
Myeloma – vertebral fracture
Myeloma – osteolytic lesions
Myeloma - Investigations
� FBC + smear
� Normochromic normocytic anemia
� Pancytopenia
Rouleaux� Rouleaux
� ESR
� Raised ESR (often >100)
Myeloma - Investigations
� Serum protein electrophoresis
Myeloma – rouleaux on blood smear
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 anaemiawith a haemoglobin concentration of 7 g/dl.
� A Aplastic anaemia
� B Folic acid deficiency
� C Iron deficiency
� D Multiple myelomatosis
� E Myelofibrosis� E Myelofibrosis
� F Peptic ulcer disease
� G Pernicious anaemia
� H Rheumatoic arthritis
� I Vitamin B12 deficiency
� J Vitamin C deficiency
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 megaloblasticanaemia.
� Pernicious anaemia is the term applied to B12 deficiency specifically due to an autoimmune destruction of the intrinsic factor producing cells in the stomach.
Megaloblastic anaemias
� Most commonly due to:
� B12 or folate deficiency
Laboratory findings
� Macrocytic anaemia
� Oval macrocytes,hypersegmented neutrophilsand megaloblasts
� Often wbc and plts ↓� BM – erythroid hyperplasia
� Nuclear-cytoplasmicasynchrony
↓ B12 and/or folate
� Parietal cell and Intrinsic Factor antibodies
RPI < 1% (Decreased RBC production)
� Hypoproliferative� Renal failure
� Aplastic Anemia
� MDS
� Bone Marrow infiltrate
� Bone Marrow suppression or
� Maturation disorder� Iron Deficiency Anemia
� Vitamin B12 Deficiency
� Folate Deficiency
� Anemia of Chronic Disease � Bone Marrow suppression or failure
� Sepsis � Chemotherapy� Radiotherapy
� Blood transfusion !!
� Anemia of Chronic Disease
� Endocrine deficiencies
� Thalassaemia
� Sideroblastic Anemia
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 Acute lymphocytic leukaemia
� B Acute myeloblastic leukaemia
� C Chronic lymphocytic leukaemia
� D Chronic myeloid leukaemia
� E Essential thrombocythaemia� E Essential thrombocythaemia
� F Hodgkin’s lymphoma
� G Monoclonal gammopathy of uncertain significance
� H Multiple myeloma
� I Myelofibrosis
� J Non-Hodgkin’s lymphoma
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, fusiformcytoplasmic inclusions that stain red with Wright-Giemsa stain and are virtually pathognomonic of AML.
Leukemia
LeukemiaLeukemia LymphoidLymphoid MyeloidMyeloid
AcuteAcute ALLALL AMLAMLAcuteAcute ALLALL AMLAML
ChronicChronic CLLCLL CMLCML
Bone marrow blasts – myeloid or lymphoid?
Why is patient pancytopaenic?
Failure of cell maturationFailure of cell maturation
Proliferation of immature cellsProliferation of immature cells
Accumulation of useless cells in bone marrowAccumulation of useless cells in bone marrow
Why is patient pancytopaenic?
Abnormal cells take up more and more space in BMAbnormal cells take up more and more space in BM
Bone marrow failure Leukemic cells spillsover in blood
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 Acute lymphocytic leukaemia
� B Acute myeloblastic leukaemia
� C Chronic lymphocytic leukaemia
� D Chronic myeloid leukaemia
� E Essential thrombocythaemia� E Essential thrombocythaemia
� F Hodgkin’s lymphoma
� G Monoclonal gammopathy of uncertain significance
� H Multiple myeloma
� I Myelofibrosis
� J Non-Hodgkin’s lymphoma
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.
Molecular basis CML
Detail from Nowell and Hungerford's paper in 1960 identifying the Philadelphia chromosome
Ph+ chromosome is the hallmark of CML
• CML first cancer demonstrated to have underlying genetic abnormality1,2
� Associated with Ph chromosome
• Result of translocation between chromosomes 9 and 223
• Detected in ~95% of patients with CML4
1. Nowell PC. Science. 1960;132:1497. 2. Nowell PC et al. J Natl Cancer Inst. 1961;27:1013-1035. 3. Rowley JD. Nature. 1973;243:290-293. 4. Sawyers CL. N Engl J Med. 1999;340:1330-1340.
Normal Bcr-Abl Signaling
�The kinase domain activates a substrate protein, eg, PI3 kinase, by phosphorylation
�This activated substrate Bcr-Abl
Substrate
Effector
�This activated substrate initiates a signaling cascade culminating in cell proliferation and survival
PP P
ADP P
P
PP P
ATP
SIGNALINGADP = adenosine diphosphate; ATP = adenosine triphosphate; P = phosphate.
Savage and Antman. N Engl J Med. 2002;346:683Scheijen and Griffin. Oncogene. 2002;21:3314.
Imatinib Mesylate: Mechanism of Action
� Imatinib mesylate occupies the ATP binding pocket of the Abl kinase domain
� This prevents substrate
Bcr-Abl
� This prevents substrate phosphorylation and signaling
� A lack of signaling inhibits proliferation and survival
P
PP P
ATP
SIGNALING
Imatinibmesylate
Savage and Antman. N Engl J Med. 2002;346:683.
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 Acute lymphocytic leukaemia
� B Acute myeloblastic leukaemia
� C Chronic lymphocytic leukaemia
� D Chronic myeloid leukaemia
� E Essential thrombocythaemia� E Essential thrombocythaemia
� F Hodgkin’s lymphoma
� G Monoclonal gammopathy of uncertain significance
� H Multiple myeloma
� I Myelofibrosis
� J Non-Hodgkin’s lymphoma
Answers
� C. Chronic lymphocytic leukaemia. This patient has no symptoms but his peripheral blood count and bone marrow are characteristic of this disorder.
Morphology
Matutes, E et al; Rev Clin Exp Haem 4 (1), 22-47
A 25-yr-old man is seen in the clinic with a 2/12 history of painless lymphadenopathyin 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 Acute lymphocytic leukaemia
� B Acute myeloblastic leukaemia
� C Chronic lymphocytic leukaemia
� D Chronic myeloid leukaemia
� E Essential thrombocythaemia� E Essential thrombocythaemia
� F Hodgkin’s lymphoma
� G Monoclonal gammopathy of uncertain significance
� H Multiple myeloma
� I Myelofibrosis
� J Non-Hodgkin’s lymphoma
Answers
� F. Hodgkin’s lymphoma.
� Reed-Sternberg cells are characteristic of Hodgkin’s lymphoma.
Hodgkin’s disease
� Thomas Hodgkin
� Described disease in1832 at the age of 34
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 Acute lymphocytic leukaemia
� B Acute myeloblastic leukaemia
� C Chronic lymphocytic leukaemia
� D Chronic myeloid leukaemia
� E Essential thrombocythaemia� E Essential thrombocythaemia
� F Hodgkin’s lymphoma
� G Monoclonal gammopathy of uncertain significance
� H Multiple myeloma
� I Myelofibrosis
� J Non-Hodgkin’s lymphoma
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.concentration.
� The patient may progress to develop myeloma or may remain stable for many years.
MGUS
� Serum protein electrophoresis
MGUS
� No CRAB criteria
� BM plasmacytosis < 10%
� Only small peak on serum or urine electrophoresis