Haematology Flashcards
Define macrocytic anaemia.
Anaemia associated with a high MCV of erythrocytes (> 100 fl in adults).
What are the causes of macrocytic anaemia?
o Megaloblastic - deficiency of B12 or folate required for the conversion of deoxyuridate to thymidylate, DNA synthesis and nuclear maturation
- Vitamin B12 Deficiency = reduced absorption (e.g. post-gastrectomy, pernicious anaemia, terminal ileal resection or disease), Reduced intake, Abnormal metabolism (congenital transcobalamin II deficiency)
- Causes of Folate Deficiency = Reduced intake, Increased demand (pregnancy, lactation, malignancy, chronic inflammation), Reduced absorption, Jejunal disease (e.g. coeliac disease), Drugs (e.g. phenytoin)
o Drugs = Methotrexate (dihydrofolate reductase inhibitor), Hydroxyurea, Azathioprine, Zidovudine
o Non-Megaloblastic = Alcohol excess, Liver disease, Myelodysplasia, Multiple myeloma, Hypothyroidism, Haemolysis, Drugs (e.g. tyrosine kinase inhibitor)
What are presenting symptoms of macrocytic anaemia?
o Non-specific symptoms of anaemia = Tiredness, Lethargy, Dyspnoea
o Family history of autoimmune disease
o Previous GI surgery
o Symptoms of the CAUSE (e.g. weight loss, diarrhoea)
What are the clinical signs of macrocytic anaemia on examination?
o Signs of Anaemia = Pallor, Tachycardia, Breathlessness
o Signs of Pernicious Anaemia = Mild jaundice, Glossitis, Angular stomatitis, Weight loss
Signs of B12 Deficiency = Peripheral neuropathy, Ataxia, Subacute combined degeneration of the spinal cord, Optic atrophy, Dementia
What are the appropriate investigations for macrocytic anaemia?
o Bloods = FBC, (high MCV, low Hb), LFT s (high bilirubin (due to ineffective erythropoiesis or haemolysis)), ESR, TFT, Serum vitamin B12, Red cell folate, Serum protein electrophoresis
o Antibodies = Anti-parietal cell and anti-intrinsic factor antibodies
o Blood Film = Large erythrocytes, Megaloblasts, Hypersegmented neutrophil nuclei
o Schilling Test
o Bone Marrow Biopsy (rarely needed)
o Investigations for the cause
What is the management of macrocytic anaemia?
o Pernicious Anaemia = IM hydroxycobalamin for life
o B12 Deficiency = Oral B12 with intrinsic factor (if pernicious) - treated before folate
o Folate Deficiency = Oral folic acid
What are the possible complications of macrocytic anaemia?
o Pernicious anaemia = increased risk of gastric cancer
o Pregnancy -> folate deficiency increases the risk of neural tube defects
Define microcytic anaemia.
Anaemia associated with a low MCV (< 80 fl).
What are the causes of microcytic anaemia?
o Iron Deficiency (most common) = Blood loss, Reduced absorption (e.g. small bowel disease), Increased demands (e.g. growth, pregnancy), Reduced intake
o Anaemia of Chronic Disease
o Thalassemia
o Sideroblastic Anaemia (abnormality of haem synthesis) = Inherited or secondary (e.g. to alcohol, drugs)
What are the presenting symptoms of microcytic anaemia?
o Non-Specific = Tiredness, Lethargy, Malaise, Dyspnoea, Pallor, Exacerbation of ischaemic conditions (e.g. angina, intermittent claudication)
o Lead Poisoning (can cause microcytic anaemia) = Anorexia, Nausea/Vomiting, Abdominal pain, Constipation, Peripheral nerve lesions
What are the clinical signs of microcytic anaemia on examination?
o Signs of anaemia = Pallor, Brittle nails and hair, Koilonychia, Glossitis, Angular stomatitis
o Signs of thalassaemia
o Lead poisoning signs = Blue gumline, Peripheral nerve lesions (causing wrist or foot drop), Encephalopathy, Convulsions, Reduced consciousness
What are the appropriate investigations for microcytic anaemia?
o Bloods = FBC (low Hb, low MCV), Serum iron (low in iron deficiency), Total iron binding capacity (high in iron deficiency), Serum ferritin (low in iron deficiency), Serum lead
o Blood Film
- Iron deficiency anaemia = Microcytic, Hypochromic, Anisocytosis, Poikilocytosis
- Sideroblastic anaemia = Dimorphic blood film, Hypochromic microcytic cells
o Lead poisoning = Basophilic stippling
o Hb Electrophoresis = Checking for haemoglobin variants and thalassemia
o Sideroblastic Anaemia = Ring sideroblasts in the bone marrow
o No obvious cause of blood loss is identified = Upper GI endoscopy, Colonoscopy, Haematuria
What is the management plan for microcytic anaemia?
o Iron Deficiency = Oral iron supplements
o Sideroblastic Anaemia = Treat the cause - Pyridoxine used in inherited forms with blood transfusion and iron chelation considered if there is no response to other treatments
o Lead Poisoning = Remove the source, Dimercaprol, D-penicillinamine
What are the possible complications of microcytic anaemia?
o High-output cardiac failure
o Complications related to the cause
Define normocytic anaemia.
Anaemia with normal MCV (80-100 fl).
What are the causes of normocytic anaemia?
o Decreased production of normal-sized blood cells (e.g. anaemic of chronic disease, aplastic anaemia)
o Increased production of HbS (sickle cell disease)
o Increased destruction of red blood cells (e.g. haemolysis, post-haemorrhagic anaemia)
o Uncompensated increase in plasma volume (e.g. pregnancy, fluid overload)
o Vitamin B2 deficiency
o Vitamin B6 deficiency
Define aplastic anaemia.
Characterised by diminished haematopoietic precursors in the bone marrow and deficiency of all blood cell elements (pancytopaenia).
What are the causes of aplastic anaemia?
o Idiopathic (> 40%) = May be due to destruction or suppression of stem cells via autoimmune mechanisms
o Acquired = Drugs (e.g. chloramphenicol, sulphonamides, methotrexate), Chemicals (e.g. benzene, DDT), Radiation, Viral infection (e.g. parvovirus B19), Paroxysmal nocturnal haemoglobinuria
o Inherited = Fanconi’s anaemia (bone marrow failure), Dyskeratosis congenita (a rare, progressive bone marrow failure syndrome)
What are the presenting symptoms of aplastic anaemia?
o Can be both slow-onset (months) or rapid-onset (days)
o Anaemia Symptoms = Tiredness, Lethargy, Dyspnoea
o Thrombocytopaenia Symptoms = Easy bruising, Bleeding gums, Epistaxis
o Leukopaenia Symptoms = Increased frequency and severity of infections
What are the appropriate investigations for aplastic anaemia?
o Bloods = FBC (low Hb, low platelets, low WCC, normal MCV, low or absent reticulocytes)
o Blood Film = Exclude leukaemia (check for abnormal circulating white blood cells)
o Bone Marrow Trephine Biopsy
o Fanconi’s Anaemia = Check for presence of increased chromosomal breakage in lymphocytes cultures in the presence of DNA cross-linking agents
Define anti-phospholipid syndrome.
A disease characterised by the presence of antiphospholipid antibodies (APL) in the plasma, venous and arterial thrombosis, recurrent foetal loss and thrombocytopaenia.
What are the presenting symptoms of anti-phospholipid syndrome?
o Recurrent miscarriages
o History of = Arterial thromboses (stroke), Venous thromboses (DVT, PE)
o Headaches (migraine)
o Chorea
o Epilepsy
What are the clinical signs of anti-phospholipid syndrome on examination?
o Livedo reticularis = mottled reticulated vascular pattern that appears as a lace-like purplish discolouration of the skin
o Signs of SLE (e.g. malar rash, discoid lesions)
o Signs of valvular heart disease
What are the appropriate investigations for anti-phospholipid syndrome?
o Bloods = FBC (low platelets, ESR (usually normal), U&Es -(can get nephropathy), Clotting screen (high APTT)
o Antibodies = Presence of antiphospholipid antibodies may be demonstrated - ELISA testing for anticardiolipin antibodies, Lupus anticoagulant assays
What are the indications for blood transfusions?
o Major surgery (less than 50x103 per uL)
o Ocular and neurosurgery (less than 100x103 per uL)
o Surgery with active bleeding (less than 50x103 per uL)
o Stable, non-bleeding (less than 10x103 per uL)
o Stable, non-bleeding with temperature of 38 degrees (less than 20x103 per uL)
What are the complications of blood transfusions?
o Acute kidney failure
o Anaemia
o Lung problems
o Shock
o Viral infections
Define haemolytic anaemia.
Premature erythrocyte breakdown causing shortened erythrocyte life span (< 120 days) with anaemia.
What are the hereditary causes of haemolytic anaemia?
o Membrane Defects = Hereditary spherocytosis, Elliptocytosis
o Metabolic Defects = G6PD deficiency, Pyruvate kinase deficiency
o Haemoglobinopathies = Sickle cell disease, Thalassemia
What are the acquired causes of haemolytic anaemia?
o Autoimmune = Antibodies attach to erythrocytes causing intravascular and extravascular haemolysis
o Isoimmune = Transfusion reaction, Haemolytic disease of the newborn
o Drugs = Penicillin, Quinine
o Trauma = Microangiopathic haemolytic anaemia - e.g. haemolytic uraemic syndrome, DIC, malignant hypertension
o Infection = Malaria, Sepsis
o Paroxysmal nocturnal haemoglobinuria
What are the presenting symptoms of haemolytic anaemia?
o Jaundice
o Haematuria
o Anaemia
What are the clinical signs of haemolytic anaemia?
o Pallor
o Jaundice
o Hepatosplenomegaly
What are the appropriate investigations for haemolytic anaemia?
o Bloods = FBC (low Hb, high reticulocytes, high MCV), High unconjugated bilirubin, Low haptoglobin, U&Es, Folate
o Blood Film = Leucoerythroblastic, Macrocytosis, Nucleated erythrocytes or reticulocytes, Polychromasia, Spherocytes, Elliptocytes, Sickle cells, Schistocytes, Malarial parasites
o Urine = High urobilinogen, Haemoglobinuria, Haemosiderinuria
o Direct Coombs’ Test = Tests for autoimmune haemolytic anaemia and identifies erythrocytes coated with antibodies
o Osmotic fragility test or Spectrin mutation analysis = Identifies membrane abnormalities
o Ham’s Test = Lysis of erythrocytes in acidified serum in paroxysmal nocturnal haemoglobinuria
o Hb Electrophoresis or Enzyme Assays = To exclude other causes
o Bone Marrow Biopsy (rarely performed)
Define haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopaenic purpura (TTP).
Triad of microangiopathic haemolytic anaemia (MAHA), acute renal failure, thrombocytopaenia.
o 2 forms:
- D+ = diarrhoea-associated form
- D- = no prodromal illness identified
What are the causes of HUS and TTP
o Infection = E coli, Shigella, Neuraminidase-producing infections, HIV
o Drugs = COCP, Ciclosporin, Mitomicin, 5-fluorouracil
o Others = Malignant hypertension, Malignancy, Pregnancy, SLE, Scleroderma
What are the presenting symptoms of HUS and TTP?
o GI = Severe abdominal colic, Watery diarrhoea that becomes bloodstained
o General = Malaise, Fatigue, Nausea, Fever < 38 degrees (D+)
o Renal = Oliguria or anuria, Haematuria
What are the clinical signs of HUS and TTP on examination?
o General = Pallor, Slight jaundice, Bruising, Generalise oedema, Hypertension, Retinopathy
o GI = Abdominal tenderness
o CNS Signs = Occurs in TTP, Weakness, Reduced vision, Fits, Reduced consciousness
WHat are the appropriate investigations for HUS and TTP?
o FBC = Normocytic anaemia, High neutrophils, Very low platelets
o U&Es = High urea, High creatinine, High K+, Low Na+
o Clotting = Normal APTT and fibrinogen levels (abnormality may indicate DIC)
o LFTs = High unconjugated bilirubin, High LDH from haemolysis
o Blood cultures
o ABG = Low pH, Low bicarbonate, Low PaCO2, Normal anion gap
o Blood Film = Schistocytes, High reticulocytes and spherocytes
o Urine = 1+ g protein/24 hrs, Haematuria
o Stool Samples = MC&S
o Renal Biopsy = Can distinguish between D+ and D- HUS
Define haemophilia.
o Bleeding diatheses resulting from an inherited deficiency of a clotting factor.
o 3 subtypes:
- Haemophilia A (most common) = deficiency in factor 8
- Haemophilia B = deficiency in factor 9
- Haemophilia C = RARE - deficiency in factor 11
What are the risk factors for haemophilia?
o X-linked so mainly seen in males
What are the presenting symptoms of haemophilia?
o Symptoms usually begin in early childhood
o Swollen painful joints occurring spontaneously or with minimal trauma (haemarthroses)
o Painful bleeding into muscles
o Haematuria
o Excessive bruising or bleeding after surgery or trauma
o Female carriers are usually asymptomatic, but may experience excessive bleeding after trauma
Generally speaking, bleeding in haemophilia is DEEP (into muscles and joints)
What are the clinical signs of haemophilia on examination?
o Multiple bruises
o Muscle haematomas
o Haemarthroses
o Joint deformity
o Nerve palsies (due to nerve compression by haematomas)
Signs of iron deficiency anaemia
What are the appropriate investigations for haemophilia?
o Clotting screen (high APTT)
o Coagulation factor assays (low factor 8, 9 or 11 (depending on type of haemophilia))
o Other investigations may be performed if there are complications (e.g. arthroscopy)
Define immune thrombocytopaenic purpura (ITP).
Syndrome characterised by immune destruction of platelets resulting in bruising or a bleeding tendency.
What are the causes of ITP?
o Often Idiopathic
o Acute ITP is often seen after viral infection in children
o Chronic ITP is more common in adults
o Associated with: Infections (e.g. malaria, EBV, HIV), Autoimmune diseases (e.g. SLE, thyroid disease), Malignancies, Drugs (e.g. quinine)
o Autoantibodies are generated, which bind to platelet membrane proteins (e.g. GlpIIb/IIIa) resulting in thrombocytopaenia
What are the presenting symptoms of ITP?
o Easy bruising
o Mucosal bleeding
o Menorrhagia
o Epistaxis
What are the clinical signs of ITP on examination?
o Visible petechiae and bruises
o Signs of other illness (e.g. infections, wasting, splenomegaly) would suggest that other causes
What are the appropriate investigations for ITP?
o Diagnosis of exclusion -> must exclude = Myelodysplasia, Acute leukaemia, Marrow infiltration
o Bloods = FBC (low platelets), Clotting screen (normal PT, APTT and fibrinogen)
o Autoantibodies (e.g. antiplatelet antibody)
o Blood Film = rule out pseudothrombocytopaenia (which is caused by platelets clumping together and giving falsely low counts)
o Bone Marrow = exclude other pathology
Define myelodysplasia.
A series of haematological conditions characterised by chronic cytopaenia (anaemia, neutropaenia, thrombocytopaenia) and abnormal cellular maturation.
- o There are FIVE subgroups:*
- Refractory anaemia (RA)*
- RA with ringed sideroblasts (RARS)*
- RA with excess blasts (RAEB)*
- Chronic myelomonocytic leukaemia (CMML)*
- RAEB in transformation (RAEB-t)*
What are the presenting symptoms of myelodysplasia?
o May be ASYMPTOMATIC and diagnosed on routine blood counts
o Symptoms of Bone Marrow Failure = Anaemia (fatigue, dizziness), Neutropaenia (recurrent infections), Thrombocytopaenia (easy bruising, epistaxis)
o Check risk factors = Occupational exposure to toxic chemicals, Prior chemotherapy or radiotherapy
What are the clinical signs of myelodysplasia on examination?
o Signs of bone marrow failure
- Anaemia (pallor, cardiac flow murmur)
- Neutropaenia (infections)
- Thrombocytopaenia (purpura or ecchymoses)
- Gum hypertrophy
Lymphadenopathy
What are the appropriate investigations for myelodysplasia?
Bloods = FBC (pancytopaenia)
o Blood Film = Normocytic or macrocytic red cells, Variable microcytic red cells in RARS, Low granulocytes, Granulocytes are not granulated
o Bone marrow aspire or biopsy = Hypercellularity, Ringed sideroblasts , Abnormal granulocyte precursors, 10% show marrow fibrosis
Define myelofibrosis.
Disorder of haematopoietic stem cells characterised by progressive bone marrow fibrosis in association with extramedullary haematopoiesis and splenomegaly.
What are the presenting symptoms of myelofibrosis?
o Asymptomatic = diagnosed after routine blood count
o Common = Weight loss, Anorexia, Fever, Night sweats, Pruritis
o Uncommon = LUQ pain, Indigestion (due to massive splenomegaly), Bleeding, Bone pain, Gout
What are the clinical signs of myelofibrosis on examination?
o Splenomegaly
o Hepatomegaly (present in 50-60%)
What are the appropriate investigations for myelofibrosis?
o Bloods = FBC (initially variable Hb, WCC and platelets but later anaemia, leukopaenia, thrombocytopaenia), LFTs (abnormal)
o Blood Film = Leucoerythroblastic changes (red and white cell precursors in the peripheral blood), ‘Tear drop’ poikilocytes
o Bone Marrow Aspirate or Biopsy = Aspiration usually unsuccessful - ‘dry tap’ (due to fibrosis) but trephine biopsy shows fibrotic hypercellular marrow, with dense reticulin fibres on silver staining
Define polycythaemia.
An increase in haemoglobin concentration above the upper limit of normal for a person’s age and sex.
o Classified into:
- Relative Polycythaemia = normal red cell mass but low plasma volume
- Absolute (True) Polycythaemia = increased red cell mass
What are the causes of polycythaemia?
o Polycythaemia Rubra Vera = Genetics (mutations in JAK2 tyrosine kinase)
o Secondary Polycythaemia
- Appropriate increase in erythropoietin = Chronic hypoxia (e.g. chronic lung disease, living at high altitude)
- Inappropriate increase in erythropoietin = Renal (carcinoma, cysts, hydronephrosis), Hepatocellular carcinoma, Fibroids, Cerebellar haemangioblastoma, Erythropoietin doping
o Relative Polycythaemia = Dehydration (e.g. diuretics, burns, enteropathy), Gaisbock’s syndrome (occurs in young male smokers with hypertension, which results in a decrease in plasma volume and an apparent increase in red cell count)
What are the presenting symtpoms of polycythaemia?
o Headaches
o Dyspnoea
o Tinnitus
o Blurred vision
o Pruritis after hot bath
o Night sweats
o Thrombosis (DVT, stroke)
o Pain from peptic ulcer disease
o Angina
o Gout
o Choreiform movements
What are the signs of polycythaemia on examination?
o Plethoric complexion = Red, ruddy skin
o Scratch marks from itching
o Conjunctival suffusion (redness of the conjunctiva)
o Retinal venous engorgement
o Hypertension
o Splenomegaly (in 75% of cases)
o Signs of underlying aetiology in secondary polycythaemia
What are the appropriate investigations for polycythaemia?
o Required for Diagnosis = FBC - High Hb, High haematocrit, Low MCV
o Isotope Dilution Techniques = allows confirmation of plasma volume and red cell mass to distinguish between relative and absolute polycythaemia
o Polycythaemia Rubra Vera = High WCC, High platelets, Low serum EPO, JAK2 mutation, Bone marrow trephine and biopsy shows erythroid hyperplasia and raised megakaryocytes
o Secondary Polycythaemia = High serum EPO, Exclude chronic lung disease/hypoxia, Check for EPO-secreting tumours
Define sickle cell disease.
A chronic condition with sickling of red blood cells caused by inheritance of haemoglobin S (HbS).
o Sickle Cell Anaemia = Homozygous HbS
o Sickle Cell Trait = Carrier of one copy of HbS
o Sickle Cell Disease = includes compound heterozygosity for HbS and:
- HbC (abnormal haemoglobin in which glutamic acid is replaced by lysine at the 6th position in the beta-globin chain)
- Beta-thalassemia
What other factors can cause red blood cell sickling?
o Infection
o Dehydration
o Hypoxia
o Acidosis
What are the presenting symptoms of sickle cell disease?
o Symptoms secondary to vaso-occlusion or infarction
- Autosplenectomy = increased risk of infections with encapsulated organisms
- Abdominal Pain
- Bones = painful crises affect small bones of the hands and feet causing dactylitis in children and ribs, spine, pelvis and long bones in adults
- Myalgia and Arthralgia
- CNS = fits and strokes
- Retina = visual loss (proliferative retinopathy)
o Symptoms of sequestration crisis = occur due to pooling of red cells in various organs (mainly the spleen)
- Liver = exacerbation of anaemia
- Lungs = acute chest syndrome
- Breathlessness
- Cough
- Pain
Fever
Corpora cavernosa
Persistent painful erection (priapism)
Impotence
What are the clinical signs of sickle cell disease on examination?
o Signs secondary to vaso-occlusion, ischaemia or infarction
- Bone = joint or muscle tenderness or swelling (due to avascular necrosis)
- Short digits
- Retina = cotton wool spots due to retinal ischaemia
o Signs secondary to sequestration crisis
- Organomegaly - spleen is enlargedin early disease
- Priapism
o Signs of anaemia
What are the appropriate investigations for sickle cell disease?
o Bloods = FBC (low Hb, reticulocytes - high in haemolytic crises but low in aplastic crises), U&Es
o Blood Film = Sickle cells, Anisocytosis (variation in size of red cells), Features of Hyposplenism (target cells, Howell-Jolly bodies)
o Sickle Solubility Test = Dithionate is added to the blood - in sickle cell disease you get increased turbidity
o Haemoglobin Electrophoresis = Shows HbS, Absence of HbA (if homozygous HbS), High HbF
o Hip X-Ray = Femoral head is a common site of avascular necrosis
o MRI or CT Head - if there are neurological complications
What is the management plan for sickle cell disease - painful crisis?
o Oxygen
o IV Fluids
o Strong analgesia (IV opiates)
o Antibiotics
What is the management plan for sickle cell disease?
o Infection Prophylaxis = penicillin V and regular vaccinations (particularly against capsulated bacteria e.g. pneumococcus)
o Folic Acid = if severe haemolysis or in pregnancy
o Hydroxyurea/Hydroxycarbamide = increases HbF levels and therefore reduces the frequency and duration of sickle cell crisis
o Red Cell Transfusion = severe anaemia or repeated transfusions (with iron chelators) may be required in patients suffering from repeated crises
o Advice = avoid precipitating factors, good hygiene and nutrition, genetic counselling, prenatal screening
o Surgical = bone marrow transplantation, joint replacement in cases with avascular necrosis
What are the possible complications of sickle cell disease?
o Aplastic crises = Infection with Parvovirus B19 can lead to a temporary cessation of erythropoiesis -> RCC plummets in sickle cell patients because their RBCs have a shortened life span and can’t tolerate a cessation of erythropoiesis)
o Haemolytic crises
o Pigment gallstones
o Cholecystitis
o Renal papillary necrosis
o Leg ulcers
o Cardiomyopathy
o Death (usually around 50) - infection in children and pulmonary or neurological complications in adults
Define thalassaemia.
A group of genetic disorders characterised by reduced globin chain synthesis.
- Alpha thalassaemia
- Beta thalassaemia major = no beta-chain synthesis
- Beta thalassaemia intermedia = mild defect in beta-chain synthesis
- Beta thalassaemia trait
What are the presenting symptoms of beta thalassaemia?
o Presenting at 3-6 months - when the change from HbF to HbA takes place
o Anaemia
o Failure to thrive
o Prone to infection
What are the presenting symptoms of alpha or beta thalassaemia trait?
o Asymptomatic
o Detected during routine blood tests or due to family history
What are the clinical signs of beta thalassaemia on examination?
o Pallor
o Malaise
o Dyspnoea
o Mild jaundice
o Frontal bossing
o Thalassaemia facies (facial features caused by marrow hyperplasia)
o Hepatosplenomegaly (due to erythrocyte pooling and extramedullary haematopoiesis)
o Patients with beta-thalassemia intermedia may also have these signs
What are the appropriate investigations for thalassaemia?
o Bloods = FBC (low Hb, low MCV, low MCH)
o Blood Film = hypochromic microcytic anaemia, target cells, nucleated red cells, high reticulocyte count
o Hb Electrophoresis = Absent or reduced HbA, high HbF
o Bone Marrow = hypercellular, erythroid hyperplasia
o Genetic Testing (rarely used)
o Skull X-Ray = ‘Hair on end’ appearance in beta thalassemia major - caused by expansion of marrow into the cortex
What are the causes of B12 deficiency?
o Pernicious anaemia = lack of intrinsic factor
o Gastric = gastrectomy, atrophic gastritis
o Inadequate intake - vegan
o Intestinal = malabsorption, ileal resection, Crohn’s, tropical sprue
o Drugs = colchicine, metformin
What are the presenting symptoms of B12 deficiency?
o Typical anaemia symptoms = Fatigue, Lethargy, Dyspnoea, Faintness, Palpitations, Headache
o Neurological Symptoms = Paraesthesia, Numbness, Cognitive changes, Visual disturbances
What are the clinical signs of B12 deficiency on examination?
o Typical anaemia = Pallor, Glossitis, Angular stomatitis
o Heart failure (can occur with severe anaemia)
o Neuropsychiatric = Irritability, Dementia, Depression
o Neurological = Subacute combined degeneration of the spinal cord, Peripheral neuropathy
What are the appropriate investigations for B12 deficiency?
o FBC and blood film = Hypersegmented neutrophils, Oval macrocytes, Circulating megaloblasts
o Pernicious Anaemia Tests = Anti-intrinsic factor antibodies, Anti-parietal cell antibodies, Schilling test
- Serum B12 is not very accurate or reliable
Define von Willebrand disease.
Bleeding disorder which may present with mucocutaneous bleeding (mouth, epistaxis, menorrhagia), increased bleeding after trauma and easy bruising.
o Type 1 = the von Willebrand factor works well but there isn’t enough of it
o Type 2 = normal levels of von Willebrand factor but it is abnormal and doesn’t function correctly
o Type 3 = no von Willebrand factor
What are the presenting signs and symptoms of von Willebrand disease?
o Easy bruising
o Epistaxis - hard to stop
o Prolonged bleeding from gums after dental procedures
o Heavy or prolonged menstrual bleeding
o Blood in stools
o Blood in urine
o Heavy bleeding from a cut or other accident
What are the appropriate investigations for von Willebrand disease?
o Bleeding time = High
o APTT = High
o Factor VIII = High
o vWF = Low in type 1 and 3 but normal in 2
o Ristocetin cofactor = reduced platelet aggregation by vWF in the presence of ristocetin
