Haematology - Haematology of systemic disease

Question 1

which anaemias can cancer present with?

Answer 1

• iron def
• anaemia of chronic disease
• leucoerythroblastic anaemia
• haemolytic anaemia

Question 2

how could cancer cause a secondary polycythaemia?

Answer 2

• renal cell cancers and liver cancers can secrete EPO

Question 3

what is the most common cause of iron def anaemia?

Answer 3

occult blood loss

• GI cancers (gastric, colon)
• Urinary tract cancers (renal cell carcinoma, bladder cancer)

Question 4

Laboratory findings of iron def anaemia

Answer 4

• low ferritin
• low transferrin saturation
• high TIBC

Question 5

what is leucoerythroblastic anaemia?

Answer 5

red and white cell precursor anaemia

Question 6

what are the morphological features on blood film of leucoerythroblastic anaemia?

Answer 6

• teardrop red blood cells (aniso and poikilocytosis)
• nucleated RBCs (normally have no nucleus)
• immature myeloid cells

Question 7

what tends to cause leucoerythroblastic anaemia?

Answer 7

bone marrow infiltration

Question 8

causes of bone marrow infiltration and so leucoerythroblastic anaemia

Answer 8

1. CANCER (haemopoietic = leukaemia/ lymphoma/ myeloma, non haemopoietic = breast/bronchus/prostate)
2. SEVERE INFECTION (miliary TB, severe fungal infection)
3. MYELOFIBROSIS (massive splenomegaly, dry tap on BM aspirate)

Question 9

what is haemolytic anaemia?

Answer 9

shortened red cell survival

Question 10

what are the distinguishing features of haemolytic anaemia?

Answer 10

• anaemia
• reticulocytosis
• raised unconjugated bilirubin
• raised LDH (intracellular enzyme, released when cells break down)
• reduced haptoglobins

Question 11

what are the 2 main groups of haemolytic anaemia?

Answer 11

• inherited (defects of red cell)

- acquired (defects of the environment)

Question 12

what are the inherited haemolytic anaemias?

Answer 12

• membrane: hereditary spherocytosis
• cytoplasm/enzymes: G6PD def
• haemoglobin: sickle cell disease, thalassemia

Question 13

what are the acquired haemolytic anaemias?

Answer 13

• immune mediated

- non-immune mediated

Question 14

what is the test to distinguish immune mediated and non-immune mediated haemolytic anaemia?

Answer 14

DAT or Coombs’ test

Question 15

what does DAT +ve mean?

Answer 15

acquired haemolytic anaemia is mediated through immune destruction of RBCs

Question 16

how can AI haemolytic anaemia appear on blood film?

Answer 16

formation of spherocytes

Question 17

what systemic disorders is AI haemolytic anaemia associated with?

Answer 17

• cancers of immune system (lymphoma)
• disease of immune system (SLE)
• infection (disturbs immune system)

Question 18

What is non-immune haemolytic anaemia?

Answer 18

red cell breakdown not caused by immune system

DAT negative

Question 19

causes of non-immune haemolytic anaemia?

Answer 19

infection e.g. malaria

can be caused by microangiopathic haemolytic anaemia (MAHA)

Question 20

what are the key features of MAHA?

Answer 20

• RBC fragments
• thrombocytopenia
• DIC/bleeding
• usually caused by underlying carcinoma

Question 21

what is mechanism of MAHA?

Answer 21

• underlying carcinoma release lots of procoagulant cytokines
• activate coagulation cascade
• erratic cytokine release = DIC
• activation of coagulation cascade in parts of microvasculature = fibrin strands
• RBCs pushed through fibrin strands by BP
• causes RBCs to fragment

Question 22

what is true polycythaemia? causes?

Answer 22

raised red cell mass

1. polycythemia vera (PV)
2. secondary (raised EPO)

Question 23

What is PV?

Answer 23

clonal myeloproliferative disorder

acquired mutation in JAK 2

Question 24

what can cause a secondary polycythaemia?

Answer 24

raised EPO

• appropriate (high altitude, hypoxic lung injury, cyanotic heart disease)
• inappropriate (hepatocellular carcinoma, bronchial carcinoma, renal cancer)

Question 25

what are the normal mature white blood cells?

Answer 25

``` Phagocytes - granulocytes (neutrophils, eosinophils, basophils) - monocytes Immunocytes - T lymphocytes - B lymphocytes - NK cells ```

Question 26

what are the immature WBCs and where should you find these?

Answer 26

- blasts - promyelocytes - myelocytes - normal in BM not normal in peripheral blood

Question 27

difference between acute and chronic leukaemia?

Answer 27

- mature white cells raised in CHRONIC | - immature blast cells raised in ACUTE

Question 28

what are the causes of neutrophilia?

Answer 28

- corticosteroids (due to demargination) - underlying neoplasia - tissue inflammation (e.g. colitis, pancreatitis) - myeloproliferative/leukaemia disorders - infection

Question 29

which diseases DO NOT cause a neutrophilia?

Answer 29

- brucella - typhoid - many viral infections

Question 30

how would a reactive neutrophilia appear on blood smear?

Answer 30

- band cells (stage in neutrophil maturation, sign that bone marrow is releasing more WBCs) - toxic granulation - signs of infection/ inflammation

Question 31

how does malignant neutrophilia appear?

Answer 31

- neutrophilia + basophilia + immature myelocytes + splenomegaly = myeloproliferative disorder (CML) - neutrophilia + myeloblasts = AML

Question 32

when do you see a monocytosis?

Answer 32

``` RARE seen in some chronic infections/ primary haematological disorders - TB, brucella, typhoid - Viral: CMV, VZV - Sarcoidosis - chronic myelomonocytic leukaemia ```

Question 33

what causes a reactive eosinophilia?

Answer 33

- parasitic infection - allergic diseases (e.g. asthma, RA) - underlying neoplasma (Hodgkin's, T cell lymphoma, NHL) - drug reaction (e.g, erythema mutliforme)

Question 34

how do you interpret a lymphocytosis?

Answer 34

- secondary (reactive): more common, response to infection/ chronic inflammation - primary (monoclonal lymphoid proliferation e.g. CLL, NHL)

Question 35

causes of a reactive lymphocytosis?

Answer 35

- infection (EBV, CMV, Rubella, Herpes) - AI disorders - Sarcoidosis

Question 36

how is immunophenotyping carried out?

Answer 36

- monoclonal antibodies targeted at different antigens - antibodies fluorescently labelled - passed through flow cytometer - can determine stage of maturation by antigens present

Question 37

how can immunophenotyping be used to find lymphoproliferative disorders?

Answer 37

- raised lymphocyte count with even mix of kappa and lambda = reactive lymphocytosis - lymphoproliferative disorders = overwhelming majority of either kappa or lamdba