Ella Kulman Haematology

What is myeloma?

malignancy of plasma cells leading to progressive bone marrow failure

In order to make a diagnosis of myeloma, there must be evidence of mono-clonality. What is this?

abnormal proliferation of a single clone of plasma cell leading to immunoglobulin secretion and causing organ dysfunction especially to the kidney

Give 3 symptoms of myeloma

1. Tiredness
2. Bone/back pain
3. Infections

Give 4 signs of myeloma

CRAB!
1. Calcium is elevated
2. Renal failure
3. Anaemia
4. Bone lesions

Why is calcium elevated in myeloma?

There is increased bone resorption and decreased formation, so there is more calcium in the blood

Why might someone with myeloma have anaemia?

bone marrow is infiltrated with plasma cells - consequences of this are anaemia, infections and bleeding

Why might someone with myeloma have renal failure?

due to light chain deposition

What investigations might you do in someone who you suspect has myeloma?

1. Blood film
2. Bone marrow aspirate and trephine biopsy
3. Electrophoresis
4. x-ray
5. CT scan
6. MRI scan
7. Chromosomal abnormalities

What would you expect to see on the blood film taken from someone with myeloma?

aggregation of RBC's - Rouleaux formation

what are you looking for on a bone marrow biopsy taken from someone with myeloma?

Increased plasma calls

what are you for on an X-ray taken from someone with myeloma?

Bone lesions

what is the treatment for asymptomatic myeloma?

active watch + wait

Describe the treatment for symptomatic myeloma

Chemo, analgesia and bisphosphonates.

radiotherapy and bone marrow transplant can also be done

What is a lymphoma?

malignant growth of WBC's predominantly in the lymph nodes

Athough predominantly in the lymph modes, lymphoma is systemic. What other organs might it effect?

1. Blood
2. Liver
3. Spleen
4. Bone marrow

Give 4 risk factors for lymphoma

1. Primary immunodeficiency (syndromes)
2. Secondary immunodeficiency (e g. HIV)
3. Infection
4. Autoimmune disorders e.g. RA

Give 4 symptoms of lymphoma

1. Enlarged lymph nodes in arm/neck
2. Symptoms of compression symptoms
3. General systemic 'B' symptoms - weight loss, night sweats, fever
4. Liver and spleen enlargement

What investigations might you do in someone who you suspect has lymphoma?

1. Blood film
2. Bone marrow biopsy
3. Lymph node biopsy
4. Immunophenotyping
5. Cytogenetics

What are the 2 sub-types of lymphoma?

Non/Hodgkins

What are the symptoms of Hodgkins lymphoma?

1. Painless lymphadenopathy
2. Presence of 'B' symptoms - fever, night sweats, weight loss

What is needed for a diagnosis of Hodgkins lymphoma?

Presence of Reed-sternberg cells

What are the possible complications of treatment for Hodgkins lymphoma?

1. Secondary malignancies
2. IHD
3. Infertility
4. Nausea
5. Alopecia

Describe low grade/indolent non-hodgkins lymphoma

slow growing, advanced at presentation, often incurable - median survival 10 years

Describe high grade non-hodgkins lymphoma

aggressive. Nodal presentation, patient unwell. Often incurable

What is leukaemia?

malignant proliferation of haemopoietic stem calls

4 sub-types of leukaemia

1. AML- acute myeloid leukaemia
2. CML - chronic myeloid leukaemia
3. ALL- acute lymphoblastic leukaemia
4. CLL- chronic lymphoblastic leukaemia

What is acute lymphoblastic leukaemia?

Neoplastic proliferation of blast cells

What can increase the risk of developing AML?

1. Preceding haematological disorders
2. Prior chemotherapy
3. Exposure to ionising radiation

Give 5 symptoms of leukaemia

1. Anaemia
2. Infection
3. Bleeding
4. Hepatomegaly
5. Splenomegaly

Why are anaemia, infection and bleeding symptoms of Leukaemia?

due to bone marrow failure

Why are hepatomegaly and splenomegaly symptoms of leukaemia?

because of tissue infiltration

What investigations might you do on someone you suspect has Leukaemia?

1. Blood film
2. Bone marrow biopsy
3. Lymph node biopsy
4. Immunophenotyping
5. Cytogenetics

Treatment for AML

1. Supportive care
2. Chemotherapy (palliative - local)
3. Bone marrow transplant

What is CML?

chronic myeloid leukemia - uncontrolled clonal proliferation of basophils, eosinophils and neutrophils

what would the FBC from someone with CML look like?

High WBC's

What is ALL?

acute lymphoid leukemia - uncontrolled proliferation of immature lymphoblast calls

What is the treatment for ALL?

CNS directed therapy and stem cell transplant

What is CLL?

chronic lymphoid leukemia - proliferation of B lymphocytes leads to accumulation of mature B calls that have escaped apoptosis

3 broad categories of RBC disorders

1. Haemoglobinopathies
2. Membranopathies
3. Enzymopathies

What is normal adult Hb made of?

2 alpha and 2 beta chains

What is foetal Hb made of?

2 alpha and 2 gamma chains

What is sickle cell disease?

A haemoglobin disorder of quality - HbS polymerises → sickle shaped RBC

What is an advantage of being a carrier of sickle cell?

offers protection against falciparum malaria

Inheritance pattern of sickle cell

autosomal recessive -homozygous SS

Offspring have 25% chance of affectation, 50% chance of carrier

How long do sickle cells last for?

5-10 days → hence why it is described as haemolytic

Give 4 acute complications of sickle cell disease

1. Very painful crisis
2. stroke in children
3. Cognitive impairment
4. Infections

Treatment for sickle cell

1. Transfusion
2. Hydroxycarbamide
3. Stem cell transplant

what is thalassaemia?

Hb disorder of quantity. Reduced synthesis of one or more globin chains leading to a reduction in Hb → anaemia

What is the significance of parvovirus for someone with sickle cell?

common infection in childen, leads to deceased RBC production → bad as they already have reduced RBC lifespan

What forms the differential diagnosis for a DVT?

Cellulitis

What are enzymopathies?

enzyme deficiencies lead to a shortened RBC Lifespan

What is anaemia?

decrease in the amount of Hb in the blood below the reference range

What organs are responsible for removal of RBC's?

1. Spleen
2. Liver
3. Bone marrow
4. Blood loss

What is microcytic anaemia?

Any type of anaemia characterised by abnormally small erythrocytes, because they don't have enough Hb

Give 3 causes of microcytic anaemia

1. Iron deficiency
2. Anaemia of chronic disease
3. Thalassaemia

What is thalassaemia?

inherited blood disorders characterised by deceased Hb production

what is normocytic anaemia?

fewer RBC than normal, and they don't have the normal amount of Hb

Give 3 causes of normocytic anaemia

1. Acute blood loss
2. Anaemia of chronic disease
3. Combined haematinic deficiency

What is macrocytic anaemia?

bone marrow produces abnormally large RBC

Give 3 causes of macrocytic anaemia

1. B12/ folate deficiency
2. Alcohol excess /liver disease
3. Hypothyroid

Give 5 potential causes of iron deficiency

1. Blood loss
2. Poor absorption
3. Decreased intake in diet
4. Hook worm!
5. Breastfeeding, low iron in breast milk

Treatment for anaemia

treat the underlying cause

What is polycythaemia?

too many RBCs - increase in Hb

What hormone is responsible for regulating RBC production?

erythropoietin

Name a primary cause of polycythaemia

polycythaemia rubra vera- over reactive bone marrow

Give 3 secondary causes of polycythaemia

1. Heavy smoking
2. Lung disease
3. cyanotic heart disease
4. High altitude

What is neutrophilia?

too many neutrophilia

Give 3 causes of neutrophilia

1. Infection
2. Inflammation
3. CML
4. Cancer

What is lymphocytosis?

too many lymphocytes

Give 3 causes of lymphocytosis

1. Viral infections
2. Inflammation
3. Malignancy
4. CLL

What is thrombocytopenia?

not enough platelets

What is thrombocytosis?

too many platelets

What is neutropenia?

not enough neutrophils

What is the major risk associated with being neutropenic?

susceptible to infection

Give 3 causes of neutropenia

1. Marrow failure
2. Marrow infiltration
3. Marrow toxicity

Where are platelets produced?

bone marrow

What hormone regulates platelet production?

thrombopoietin - produced mainly in the liver

platelet lifespan

7-10 days

Organ responsible for platelet removal?

spleen

what can cause deceased platelet production?

1. congenital causes
2. Infiltration of bone marrow e.g. leukaemia
3. Alcohol
4. Infection e.g. HIV/TB

Give 3 symptoms of platelet dysfunction

1. Mucosal bleeding
2. Easy bruising
3. Petechiae/purpura

Describe the presentation of spinal cord compression

1. Back pain
2. Weakness in legs
3. Inability to control bladder
4. Spastic paresis
5. Sensory level

What is tumour lysis syndrome?

breakdown of malignant calls→ content release can cause electrolyte disturbances

What is hyperviscosity syndrome?

increase in blood viscosity usually due to high levels of immunoglobulins

Describe the presentation of hyperviscosity syndrome

1. Mucosal bleeding
2. Visual change
3. Neurological disorders
4. Breathlessness
5. Fatigue

What do you avoid in the treatment of hyperviscosity syndrome?

blood transfusion - do so cautiously as it could increase serum viscosity

Give 5 signs/symptoms of hypercalcaemia

1. Confusion
2. Bone pain
3. Constipation
4. Nausea
5. Abdominal pain

What might you see on an ECG taken from someone with hypercalcaemia?

shortened QT interval

hypercalcaemia= risk of MI

Treatment for hypercalcaemia

IV hydration and bisphosphonates

How is myeloma bone disease usually assessed?

X-ray

What clotting factors depend on vitamin k?

2, 7, 9, 10

Give 4 symptoms of ALL

1. Bone pain
2. Recurrent infections (neutropenia)
3. Pale and tired (anaemia)
4. Bruising (low platelets)

Is ALL more common in adults or children?

children

Give 3 signs of haemolytic anaemia

1. Pallor
2. Jaundice
3. Splenomegaly

Give 3 things that can cause coagulation disorders

1. Vitamin K deficiency
2. Liver disease
3. Congenital e.g. haemophilia

How does warfarin work?

antagonises vitamin k and so you get a reduction in clotting factors 2,7,9 and 10

How does Heparin work?

activates antithrombin which then inhibits thrombin and factor Xa

Give 7 risk factors for DVT

1. Increasing age
2. Obesity
3. Pregnancy
4. OCP (hyper-coagulability)
5. Major surgery
6. Immobility
7. Past DVT

Give 3 symptoms of DVT

unilateral warm, tender, painful swollen leg

Where would you normally take a bone marrow biopsy from?

posterior iliac crest