Haematological changes in systemic disease

Question 1

What can be the first presentation of cancer?

Answer 1

Anaemia

Question 2

What are the 4 main types of anemia associated with cancer/systemic disease?

Answer 2

• Iron deficiency anemia - Anaemia of chronic disease - Leucoerythroblastic anaemia - Haemolytic anaemias

Question 3

What two types of cancer can also cause secondary polycythemia?

Answer 3

Renal cell cancer and liver cancer

Question 4

What is the most common cause of Fe deficiency anaemia?

Answer 4

Occult blood loss e.g. GI cancers, urinary tract cancers

Question 5

What are the laboratory findings for Fe deficiency anaemia?

Answer 5

• Reduced ferritin - Transferrin saturation - Low Hb - Low MCV

Question 6

What is leuco-erythroblastic anemia?

Answer 6

Red cell and white cell precursor anaemia. Causes a variable degree of anaemia

Question 7

What the morphological features of leuco-erythroblastic anaemia on a blood film?

Answer 7

• Tear drop red blood cells (aniso and poikilocytosis)
• Nucleated RBCs
• Immature myeloid cells

Question 8

What does this blood film show?

Answer 8

Leuco-erythroblastic anaemia

• tear drop poikilocytes
• Nucleated red blood cells
• myelocytes

Question 9

What are the 3 main causes of bone marrow infiltration that causes a leucoerythroblastic film?

Answer 9

• Cancer - haemopoietic e.g leukemia/lymphoma/myeloma. Or non-haempoitetic e.g. breast/bronchus/prostate
• severe infection e.g. miliary TB, severe fungal infection
• myleofibrosis - massive splenomegaly, dry tap on BM aspirate

Question 10

What are the most common distinguishing features of haemolysis? (any aetiology)

Answer 10

• anaemia - though may be compensated
• reticulocytosis
• raised bilirubin (unconjugated)
• raised LDH - intracellular enzyme
• Reduced haptoglobins

Question 11

What are the two pathogenic groups of haemolytic anaemias?

Answer 11

• Inherited - defects of the red cell
• Acquired - defects of the environment in which the red cell finds itself. Can be immune or non-immune

Question 12

What test can distinguish between immune and non-immune types of acquired haemolytic anaemias?

Answer 12

Direct Antiglobulin (DAT or Coombs test)

Question 13

1. What are findings on haematological studies are associated with auto-immune haemolysis?
2. What can be the underlying cause of auto-immune haemoloysis?

Answer 13

1. Anaemia, reticulocytosis, raised unconjugated bilirubin, raised LDH, Positive DAT
2. Idiopathic or underlying lymphoma/CLL/SLE

Question 14

What are the two main causes of acquired haemolytic anaemia/non-immune/DAT negative?

Answer 14

• Infection - malaria
• Micro-angiopathic Haemolytic anaemia (MAHA)

Question 15

1. What are the main findings in blood studies for MAHA?
2. What conditions are MAHA associated with?

Answer 15

1. Red cell fragments, low platelets, DIC/bleeding
2. Underlying adenocarcinoma and Haemolytic Uremic syndrome (E.coli infection)

Question 16

What does this blood film show?

Answer 16

MAHA - Micro-angio-pathic haemolytic anaemia

• red cell fragments
• thrombocytopenia

Question 17

Micro angiopathy can happen because of malignancy e.g. adenocarcinomas.

Describe the underlying mechanism

Answer 17

• Adenocarcinoma, low grade DIC
• Platelet consumption occurs
• Leading to fibrin deposition and degradation
• Red cell fragmentation occurs - microangiopat
• Bleeding occurs

Question 18

What are the two main causes of true polycythemia in cancer?

Answer 18

True polycythemia is raised red cell mass

1. Secondary raised EPO appropriate/inappropriate e.g. hepatocellular cancer, bronchial cancer, renal cancer
2. Polycythemia vera (PV) e.g. Clonal myleoproliferative disorder acquired mutations in JAK2

Question 19

What types of white blood cells are there?

Answer 19

1. Normal mature phagocytes - neutrophils, eosinophils and basophils
2. monocytes
3. immunocytes - T and B lymphocytes, NK cells

Immature - blasts present in a small percentage. Many immature cells are not normal

Question 20

What does this blood film show?

Answer 20

Chronic lymphocytic leukemia

• WBC increased mature cells

Question 21

What does this blood film show?

Answer 21

Acute myeloid leukemia

• WBC increased immature cells

Question 22

What can cause neutrophilia?

Answer 22

• Corticosteroids
• Underlying neoplasia
• Tissue inflammation e.g. colitis, pancreatitis
• myeloproliferative/leukaemic disorders
• infection

Question 23

Most localised and systemic infections cause a neutrophilia. Which infections characteristically do not cause a neutrophilia?

Answer 23

• Brucella
• Typhoid
• many viral infections

Question 24

What are the differences between

1. Reactive neutrophilia
2. Malignant neutrophilia?

Answer 24

1. Reactive neutrophilia - reaction and increase in neutrophils in response to infection/inflammation. Presence bands and toxic granulation
2. Malignant neutrophilia - neutrophilia, basophilia, plus immature cells myleocytes, and splenomegaly. This suggests a myleoproliferative (CML)

*neutroPENIA plus myeloblasts - AML - Acute Myeloid Leukemia

Question 25

What does this show?

Answer 25

Reactive neutrophilia * Nuclear polymorphs * neutrophilia * toxic granulation

Question 26

What does this blood film show?

Answer 26

Chronic Myeloid Leukemia * Neutrophilia * Basophilia * Immature cells such as myleocytes * splenomegaly

Question 27

What can cause a reactive eosinophilia?

Answer 27

* Parasitic infection * Allergic diseases e.g. asthma, rheumatoid * Underlying neoplasms esp. Hodgkin's, T-cell NHL * Drugs - reaction erythema multiforme

Question 28

What are the underlying cause of Chronic Eosinophilic leukemia?

Answer 28

Eosinophils form part of the 'clone'. FIP1L1-PDGFRa fusion gene

Question 29

What conditions/chronic infections/ haematological disorders can moncytosis be seen?

Answer 29

* TB, Brucella, typhoid * Viral, CMV, Varicella zoster * Sarcoidosis * Chronic myelomonocytic leukemia (MDS)

Question 30

What in the following categories causes an elevated neutropil count? 1. Infection 2. Inflammation 3. Neoplasia 4. Myeloproliferative

Answer 30

1. Bacterial infections 2. Auto-immune and Tissue necrosis 3. All types 4. CML

Question 31

What in the following categories causes an elevated eosinophil count? 1. Infection 2. Inflammation 3. Neoplasia 4. Myeloproliferative

Answer 31

1. Parasitic infections 2. Allergic e.g. asthma, atopy, drug reactions 3. Hodgkin's and NHL 4. N/A

Question 32

What in the following categories causes an elevated Basophil count? 1. Infection 2. Inflammation 3. Neoplasia 4. Myeloproliferative

Answer 32

1. Pox viruses 2. N/A 3. N/A 4. CML

Question 33

What in the following categories causes an elevated monocyte count? 1. Infection 2. Inflammation 3. Neoplasia 4. Myeloproliferative

Answer 33

1. Chronic e.g. TB, Brucella 2. N/A 3. N/A 4. CMML

Question 34

What is the difference between a secondary and primary lymphocytosis?

Answer 34

SECONDARY lymphocytosis - is reactive, and is a polyclonal response to an infection or chronic inflammation PRIMARY lymphocytosis - is a monoclonal lymphoid proliferation, as seen in CLL, NHL

Question 35

What are the causes of a reactive lymphocytosis?

Answer 35

* EBV, CMV, Toxoplasma * Infectious hepatitis, rubella, herpes infections * Autoimmune disorders * Sarcoidosis

Question 36

What conditions has the following lymphocytes? 1. Normal blood film 2. Infective mononucleosis 3. CLL and NHL 4. Acute lymphoblastic leukemia

Answer 36

1. Normal blood - mature lymphocytes 2. IM - Recactive/atypical lymphocytes 3. CLL and NHL - small lymphocytes and smear cells 4. ALL - Lymphoblasts

Question 37

1. What does this blood film show? 2. What could this be a sign of?

Answer 37

1. Lymphocytosis 2. Could be EBV infection or early CLL

Question 38

What does this blood film show?

Answer 38

CLL - Chronic lymphocytic leukemia

Question 39

What does this blood film show?

Answer 39

Acute lymphoblastic leukemia presence of lymphoblasts

Question 40

What does flow cytometry show?

Answer 40

Known as immunophenotyping - flow cytometry looks at the antigens expressed on the cells. Blue - CD4 Green - CD34 Purple - CD7

Question 41

Is EBV monoclonal or polyclonal?

Answer 41

Polyclonal, and B cells so amount of kappa and lambda light chains are normal, and in usual proportions

Question 42

What are the 2 different light chains that B cells can have?

Answer 42

Kappa and Lambda

Question 43

Is CLL monoclonal or polyclonal?

Answer 43

CLL is monoclonal. One mother B cell with the mutation will proliferate meaning only one of the light chains, either kappa or lambda will be produced. This means that one light chain is measured to be a lot higher than the other. This is usually a sign of a worse prognosis.

Question 44

What is the diagnosis? 39 year old woman Had breast cancer over 4 years ago Presents with jaundice and hepatomegaly Hb = 87 Bilirubin = 50, conjugated (elevated) DAT negative Blood film - nucleated red blood cells

Answer 44

Bone marrow metastases from breast cancer

Question 45

What is the diagnosis? ## Footnote 45 year old male 3 week history of sore throat Recent episode of shingles EBV IgG serology positive FBC: Raised lymphocytes, normal neutrophils Blood film: Reactive lymphocytes, no abnormal cells Monoclonal

Answer 45

Mature B cells, monoclonal CLL