FBC cases (+answers) - Learninglearning.ufs.ac.za/INTERNAL_MEDICINE_ON/Resources/3. ACADEMIC... · Hypoproliferative Renal failure Aplastic Anemia MDS Bone Marrow infiltrate Bone

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


� F Pancytopenia

� G Polycythaemia




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


� F Pancytopenia

� G Polycythaemia




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.



� Aplastic Anemia

� MDS







failure





� Thalassaemia


A patient with chronic obstructive pulmonary disease.

� A Anaemia

� B Lymphocytosis

� C Lymphopenia

� D Neutropenia


� F Pancytopenia

� G Polycythaemia




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


� F Pancytopenia

� G Polycythaemia




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)


� Aplastic Anemia

� MDS







failure





� Thalassaemia


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.











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.











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.











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



� Aplastic Anemia

� MDS


� Bone Marrow suppression or




� Anemia of Chronic Disease � Bone Marrow suppression or failure

� Sepsis � Chemotherapy� Radiotherapy

� Blood transfusion !!



� Thalassaemia


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.









� I Myelofibrosis


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.









� I Myelofibrosis


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.









� I Myelofibrosis


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.









� I Myelofibrosis


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

Documents

FBC cases (+answers) - Learninglearning.ufs.ac.za/INTERNAL_MEDICINE_ON/Resources/3. ACADEMIC... · Hypoproliferative Renal failure Aplastic Anemia MDS Bone Marrow infiltrate Bone