Haematology Flashcards
In the UK what cancer screening programmes are in place?
Cervical, colon, breast
What are serum tumour markers and what are they used for?
Intracellular proteins or cell surface glycoproteins that may be released into the circulation, and are in higher than usual concentrations in patients with cancer
Used for monitoring treatment effectiveness
What is the difference between adjuvant and neoadjuvant therapy?
Adjuvant = chemo,radio, hormone given after surgery to lower risk of micrometastasis
Neoadjuvant = chemo, radio, hormone given before surgery to shrink tumour
How does chemotherapy work and what other cells does it affect and why?
Chemo damages DNA and RNA, promotes apoptosis
Damages all rapidly dividing cells, e.g. bone marrow, gastrointestinal tract and germinal epithelium
Side effects of chemotherapy?
- Bone marrow supression –> anaemia, thrombocytopenia, neutropenia
- Mucositis
- Alopecia
- Sterility
- Nausea and vomiting
Examples of antiemetics?
- Metaclopramide and domperidone
or for severe
5-HT3 antagonists (ondansetron and granisetron) with dexamethosone
How does radiotherapy work?
Causes strand breaks in DNA and apoptosis
Side effects of radiotherapy?
- Damage to the skin (erythema and desquamation)
- Damage to the gut (ulceration, nausea and diarrhoea)
- Damage to testis
- Damage to bone marrow (anaemia, leucopenia)
- General lethargy
What cancers are endocrine therapies used in?
Breast and prostate
Agonist and antagonist of oestrogen used in breast cancer as an adjuvant therapy?
Tamoxifen
What drug type is rituximab and what conditions could it be used in?
Monoclonal antibody - destroys cells with CD20 on their surface (B cells), could be used in rheumatoid arthritis, leukaemia, lymphoma
What is myeloablative therapy?
High dose chemotherapy or chemo plus radiation with the aim to clear the bone marrow completely of both benign and malignant cells
What are the 2 main methods of bone marrow transplantation post myeloablative therapy?
- Allogeneic - bone marrow or peripheral blood stem cells from another individual - usually HLA-identical sibling.
- Autologous - patient acts as his or her own source of stem cells. Collected from bone marrow or peripheral blood before myeloablative therapy
What are the main symptoms of graft-versus host disease and how are they caused?
T cells infiltrate the skin, gut, and liver - causing maculopapular rash, diarrhoea and liver necrosis.
What are the normal ranges for haemoglobin levels in both males and females?
Males 13.5-17.5g/dL
Females 11.5-16g/dL
What are the normal ranges for WBC count in both males and females?
4-11 x 10^9 /L
What is the normal platelet count?
150-400 x 10^9 /L
What is the normal range for MCV (mean corpuscular volume)?
80-96fL
What is anaemia?
Reduced red cell mass, and therefore reduced haemoglobin.
In anaemia what values decrease?
RCC, PCV, haemoglobin
What is dilutional anaemia and give an example
If the plasma volume increases, but the RCC/PCV remain the same then they appear smaller per volume plasma, e.g. in pregnancy or in massive splenomegaly
How does anaemia often present?
If acute - fatigue, faintness, breathlessness. Will also often see pale mucous membranes, and tachycardia
What are reticulocytes and what 3 things will cause their levels to be increased?
Young red cells, still contain RNA. Are larger than mature cells.
Will be increased in haemorrage, haemolysis, treatment with specific haemanitics (iron, B12, folate) in deficiency states
What are the main 3 causes of microcytic anaemia?
- Iron deficiency
- Chronic disease
- Thalassemia
Why can a diagnosis of anaemia not always be based around ferritin levels?
Ferritin can be falsely elevated in inflammation
What are the main causes of iron deficiency in anaemia?
In most men and post menopausal women = GI bleeding
In most pre-menopausal women = menorrhagia
Other potential causes: Hookworm, cancer, breast feeding, pregnancy, decreased absorption (small bowel disease/ post gastrectomy) or poor intake (but this is rare)
Most common cause of anaemia world wide?
Iron deficiency
Factors that promote intestinal absorption of iron?
Gastric acid, iron deficiency, increased erythropoietic activity
What are the signs and symptoms of iron deficiency (not including normal signs of anaemia)?
- Brittle hair and nails
- Atrophic glossitis
- Angular stomatitis
What tests would be done to confirm and try to work out the cause of suspected iron deficiency anaemia?
Confirm - blood count and film - microcytic and hypochromic RBC’s. Serum ferritin low.
To work out cause would do colonoscopy
What chronic diseases can cause microcytic anaemia?
- Inflammatory diseases - Crohn’s, RA
- Chronic infections - TB, malignancy, CKD
In kidney problem= decrease EPO
What are the 3 main causes of normocytic anaemia?
- Acute blood loss
- Anaemia of chronic disease
- Combined haematinic deficiency
What are the 4 main causes of macrocytic anaemia?
- B12/folate deficiency
- Alcohol excess/liver disease
- Hypothyroid
- HAEMATOLOGICAL (chemo drugs, haemolysis (more reticulocytes) bone marrow failure, bone marrow infiltration)
What would be the initial investigation done to determine the cause of macrocytic anaemia?
Serum B12 and red cell folate measurement (B12 is necessary to convert serum folate to active intracellular form)
Where do we get our B12/ folate?
B12- animal products (meat and dairy)
Folate - green vegetables and offal
What is megaloblastic anaemia and what is the main cause?
Developing red blood cells in the bone marrow with delayed nuclear maturation in comparison to cytoplasm (macrocytic). Main cause is due to defective DNA synthesis due to deficiency of vitamin B12 or folate
How is vitamin B12 absorbed?
Parietal cells in the stomach secrete both instrinsic factor and H+. Instrinsic factor bind to B12 and it is absorbed in the terminal ileum. Stored in the liver
What is pernicious anaemia, and what is it a cause of ?
Autoimmune condition in which there is atrophic gastritis (infiltration of fundus with plasma cells and lymphoid cells) causing loss of parietal cells, and so lack of B12 absorption
What are the main causes of B12 deficiency?
- Low dietary intake (vegan)
- Impaired absorption- pernicious anaemia, gastrectomy, ileal disease (e.g. Crohns), coeliac disease
- Abnormal utilization - nitrous oxide inactivates B12
What clinical features are seen in B12 deficiency?
- Symptoms of anaemia - glossitis, angular, stomatitis, and mild jaundice
- Neurological features - polyneuropathy, subacute combined degeneration of the cord (posterior and lateral columns) which leads to progressive weakness, ataxia and paralplegia
Prophylactic folic acid is given to who?
- Individuals with chronic haemolysis
2. Pregnant women
How is alcohol excess thought to cause macrocytic anaemia?
Altered or excess lipid deposition on red cell membranes
Why does vitamin B12/folate deficiency cause macrocytic anaemia?
Not enough B12 to divide between all cells so do 1 fewer divisions
How does Haemoglobin S occur in sickle cell anaemia?
Point mutation in B globin gene (chromosome 11)
What type of inheritance does sickle cell disease have?
Autosomal recessive
What are the two types of haemoglobinopathy and give examples of both
- Disorders of quality (abnormal chain structure) e.g. sickle cell anaemia
- Disorders of quantity (abnormal chain production) e.g. Thalassaemia