Haematology Flashcards
What is iron deficiency anaemia?
What the the main groups of causes? (4)
- Most common anaemia worldwide.
- Bone marrow needs iron to make the haemoglobin in red blood cells, therefore a deficiency of iron leads to a reduction in red blood cells/haemoglobin production
- Excessive blood loss –> Most common cause in adults. Blood loss due to menorrhagia is the most common cause in pre-menopausal women, whereas gastrointestinal bleeding is the most common cause in men (always suspect colon cancer e.g w slow bleeding) and post-menopausal women.
- Inadequate dietary intake –> Most common cause in growing children. as meat is a good source of iron, vegans and vegetarians are more likely to develop iron deficiency anaemia due to a lack of meat in their diet.
- Poor intestinal absorption –> conditions which affect the small intestine, such as coeliac disease, can prevent sufficient iron being absorbed.
- Increased iron requirements –> children have increased iron demands during periods of rapid growth. Women also have increased demands during pregnancy as the baby will receive their iron supply from the mother.
What are the main symptoms of iron deficiency anaemia?
- Pallor, fatigue, palpitations, SOB.
- Kolionchyia (spoon shape nails), hair loss, glossitis, angular stomatitis
What are the investigations for iron deficiency anaemia?
-Hx –> most important step in looking for potential causes –> ask about changes in diet, medication history, menstrual history, weight loss, change in bowel habit
- FBC –> hypochromic microcytic anaemia
- Serum ferritin –> likely low, as serum ferritin correlates with iron stores. <15 micrograms/litre confirms diagnosis. But ferritin can be raised during states of inflammation/infection and is also less reliable in pregnancy –> so a raised ferritin does not necessarily rule out iron deficiency anaemia.
- Total iron-binding capacity (TIBC)/transferrin high. A high TIBC reflects low iron stores. . Note that the transferrin saturation will however be low
- Blood film –> anisopoikilocytosis (red blood cells of different sizes and shapes), poikilocytes (abnormally shaped RBCs ?pencil)
- INVESTIGATE CAUSE when not known e.g endoscopy.
- New iron deficiency w/o clear underlying cause e.g heavy menstruation should be investigated w suspicion. –> OGD and colonoscopy looking for cancer of GI tract.
When is endoscopy indicated when iron deficiency anaemia?
- New iron deficiency anaemia without clear underlying cause.
- Endoscopy to rule out malignancy, males and post-menopausal females who present with unexplained iron-deficiency anaemia should be considered for further gastrointestinal investigations. Post-menopausal women with a haemoglobin level ≤10 and men with a haemoglobin level ≤11 should be referred to a gastroenterologist within 2 weeks.
- Referral for 2ww when –> aged over 60 years with iron deficiency anaemia or women aged over 55 years with postmenopausal bleeding.
- Urgent referral should be considered for people aged under 50 years with rectal bleeding.
What is the management for iron deficiency anaemia?
Management
- Tx underlying cause and manage.
- Can be Tx depending on severity and symptoms.
- Pre menopausal women or pregnant –> consider trial iron Tx.
- Men and post menopausal women –> r/o GI bleeding causes.
- Oral ferrous sulfate –> 200mg x3 daily. Patients should continue taking iron for 3 months after the iron deficiency has been corrected in order to replenish iron stores.
- Haemoglobin (FBC) levels should be check after 2-4 weeks to assess response Tx.
- Specialist assessment when lack response increase <20g/L after 2-4 weeks.
- Common side effects of iron supplementation include nausea, abdominal pain, constipation, diarrhoea, black colured stools. Unsuitable where malabsorption is cause of anaemia.
- When correcting iron deficiency anaemia with iron you can expect the haemoglobin to rise by around 10 grams/litre per week.
-Conservative –> Iron-rich diet –> dark-green leafy vegetables, meat, iron-fortified bread
- Possible blood transfusion which will correct anaemia but not underlying deficiency.
- Or iron infusion e.g cosmofer, small risk anaphylaxis, avoid during sepsis as iron feeds bacteria. Indications –> failrue of oral therapy, impaired GI absorption e.g IBDm gastrectomy
What is vitamin B12 anaemia?
What is the most common cause?
What are the other causes?
- A common cause of megaloblastic anaemia.
- Megaloblastic anaemia à characterised by the development of larger than normal red blood cells (macrocytosis), red cells with a mean cell volume (MCV) above the normal range (greater than 100 femtolitres).
-More common in females, typically develops middle – old age. Associated w other autoimmune disorders –> thyroid, T1DM, addisions, rheumatoid, vitiligo.
Causes
- Pernicious anaemia –> most common cause of B12 deficiency anaemia.
- Other causes B12 deficiency anaemia –> insufficient dietary intake (malnutrition e.g alcoholism or vegan), atrophic gastritis (secondary to H pylori infection), impaired absorption e.g crohns, ileal resection, gastrectomy, Zollinger-Ellison syndrome, drugs e.g PPIs, alcohol.
What is pernicious anaemia?
The parietal cells of the stomach produce a protein intrinsic factor –> is essential for the absorption of vitamin B12 in the ileum. Absorbed in leum, B12 bilnds IF in duodenum.
- Pernicious anaemia is an autoimmune condition affecting gastric mucosa.
- Antibodies form against the parietal cells or intrinsic factor.
- Intrinsic factor Ab –> bind to intrinsic factor blocking vit B12 binding site.
- Gastric parietal cell Ab –> reduce acid production and atrophic gastritis.
- A lack of intrinsic factor production prevents the absorption of vitamin B12 –> vit B12 deficient.
- Vit B12 important in production RBC and myelination of nerves –> megaloblastic anaemia and neuropathy.
What is the presentation of vit B12 deficiency?
-Symptoms often subtle and often slow diagnosis –> can develop slowly over years.
Anaemia
- Pallor, lethargy, dyspnoea
- Glossitis, angular chelitis.
Neurological
- Peripheral neuropathy –> pins and needles. Numbness or parasethesia.. Typically symmetrical and affects legs > arms. Loss of vibration sense of propioception.
- Cognitive/mood changes –> memory loss, poor concn, confusion, depression, irritability.
- Subacute combined degenration spinal cord –> progressive weakness, ataxia, paresthesias that can progress to spasticity and paraplegia. Visual changes.
- Other –> mild jaundice (w pallor get lemon tinge)
-TEST WHEN PRESENTING W PERIPHERAL NEUROPATHY
What are the investigations for vit B12 deficiency?
- FBC –> decrease Hb w increase MCV –> macrocytosis may be absent in around of 30% of patients. Hypersegmented polymorphs on blood film. Low WCC and platelets may also be seen
- Vitamin B12 and folate levels –>B12 of >= 200 nh/L is generally considered to be normal
- Vit B12 deficiency found –> serum anti IF Ab checked. If not found but strong features then also check.
- Antibodies –> anti intrinsic factor antibodies: sensivity is only 50% but highly specific for pernicious anaemia (95-100%) therefore 1st line pernicious. Anti gastric parietal cell antibodies in 90% but low specificity so often not useful clinically
- Schilling test is no longer routinely done –> radiolabelled B12 given on two occasions, firstly on its own, secondly with oral IF. Urine B12 levels are then measured
What is the management for vit B12 anaemia?
-Neurologic involvement –> urgent specialist advice from haematologist. If advice not available then Tx w hydroxocobalamin 1mg IM on alternate days until no further improvement, then IM every 2 months.
No neurologic involvement
-Hydroxocobalamin 1mg IM x3 week for 2 weeks.
-Maintenance –> IM hydroxocobalamin 1mg every 3 months = when deficiency not diet related.
-Maintenance when diet related deficiency –> oral cyanocobalamin tablets or twice yearly hydroxocobalamin 1mg injection.
-If there is also folate deficiency it is important to treat the B12 deficiency first before correcting the folate deficiency. Treating patients with folic acid when they have a B12 deficiency can lead to subacute combined degeneration of the cord.
What is multiple myeloma?
What are the RF?
- A cancer of bone marrow plasma cells –> haematological malignancy characterised by plasma cell proliferation.
- Plasma cells –> type of B lymphocyte that produces antibodies.
- It arises due to genetic mutations which occur as B-lymphocytes differentiate into mature plasma cells.
- MM second most common haematological malignancy.
- RF –> older age, male, black african, FH, obesity.
- Peak incidence 60-70 years old.
What is the typical presentation of MM?
6 key areas
CRABBI
- Hypercalcaemia occurs as a result of increased osteoclast activity within the bones
- This leads to constipation, nausea, anorexia and confusion
Renal
- Monoclonal production of immunoglobulins results in light chain deposition within the renal tubules
- This causes renal damage which presents as dehydration and increasing thirst
Anaemia
-Bone marrow crowding suppresses erythropoiesis leading to anaemia
-This causes fatigue, pallor, lethargy
Bleeding
-Bone marrow crowding also results in thrombocytopenia which puts patients at increased risk of bleeding and bruising
Bones
-Bone marrow infiltration by plasma cells and cytokine-mediated osteoclast overactivity creates lytic bone lesions
-Bone presents as –> bone pain (especially in the back), osteoporosis and pathological fractures (typically vertebral).
Infection
-A reduction in the production of normal immunoglobulins results in increased susceptibility to infection
What are the initial investigations in MM and what do you expect them to show?
- FBC (low white blood cell count in myeloma), normocytic anaemia (80%), raised urea and creatinine
- Calcium (raised in myeloma)
- ESR (raised in myeloma)
- Plasma viscosity (raised in myeloma)
If any of these are positive or myeloma is still suspected do an urgent serum protein electrophoresis and a urine Bence-Jones protein test.
What are the diagnostic investigations for MM? (4+2)
NICE recommend the following when myeloma is suspected.
“BLIP”.
B – Bence–Jones protein (request urine electrophoresis)
L – Serumfree Lightchain assay
I – Serum Immunoglobulins
P – Serum Protein electrophoresis
-Serum and urine protein electrophoresis –> raised concentrations of monoclonal IgA/IgG proteins will be present in the serum. In the urine, they are known as Bence Jones proteins
-Random ?Peripheral blood film when done show –> rouleaux formation –> stacked RBCs
-Bone marrow biopsy is necessary to confirm the diagnosis of myeloma and get more information on the disease.
Imaging is required to assess for bone lesions
-1st line –> Whole body MRI. If not suitable then CT. If not either then skeletal survey.
-X ray sings à Punched out lesions, Lytic lesions. “Raindrop skull” caused by many punched out (lytic) lesions throughout the skull that give the appearance of raindrops splashing on a surface. NOT pepperpot skull seen in primary hyperparathyroidism.
What is the management for MM?
What is the management for the associated symptoms?
- A chronic relapsing-remitting course which is incurable.
- Management to improve quality and quantity of life. Control symptoms, reduce complications, prolong survival.
CHEMO
- 1st line à combination of chemotherapy with à Bortezomid, Thalidomide, Dexamethasone
- Autologous stem cell transplantation can be used as part of a clinical trial where patients are suitable. Typically younger, healthier patients who are suitable for stem cell transplantation and rigorous chemotherapy regimes.
- Pain –> treat with analgesia (using the WHO analgesic ladder)
- Pathological fracture –> Zoledronic acid is given to prevent and manage osteoporosis and fragility fractures as these are a large cause of morbidity and mortality, particularly in the elderly.
- Infection –> patients receive annual influenza vaccinations. They may also receive Immunoglobulin replacement therapy.
- VTE prophylaxis à aspirin or LWMH when on certain chemo regimes.
- Fatigue–> treat all possible underlying causes. If symptoms persist consider an erythropoietin analogue.
