Haematology Part 1 (p8-21- Blood film, anaemias, bleeding disorders + VTEs) Flashcards
In what conditions are acanthocytes found?
Abetalipoproteinaemia, liver disease, hyposplenism
In what conditions are basophilic RBC stippling found?
Lead poisoning, megaloblastic anaemia, myelodysplasia, liver disease, haemoglobinopathy
In what conditions are Burr cells found?
Uraemia, GI bleeding, stomach carcinoma
In what conditions are Heinz bodies found?
Glucose-6-phosphate dehydrogenase deficiency, chronic liver disease
In what conditions are Howell Jolly bodies found?
Post-splenectomy, hyposplenism (e.g. sickle cell disease), megaloblastic anaemia and hereditary spherocytosis
In what conditions are leucoerythroblastic anaemias found?
Marrow infiltration e.g. myelofibrosis
In what conditions are Pelger Huet cells found?
Congenital
Acquired (myelogenous leukaemia and myelodysplastic syndromes)
When is polychromasia found?
Premature/inappropriate release from BM
In what conditions are increased reticulocytes found?
Haemolytic anaemias
In what conditions are decreased reticulocytes found?
Aplastic anaemia
In what conditions is there right shift (hypermature white cells)?
Megaloblastic anaemia, uraemia, liver disease
When are rouleaux formations found?
Chronic inflammation, paraproteinaemia and myeloma
When are schistocytes found?
Microangiopathic anaemias e.g. DIC, haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura, pre-eclampsia
When are spherocytes found?
Hereditary spherocytosis, autoimmune haemolytic anaemia
When are stomatocytes found?
Hereditary stomatocytosis, high alcohol intake and liver disease
When are target cells found?
Liver disease, hyposplenism, thalassaemia and IDA
Clinical levels of anaemia in men and women?
Hb:
Men <135g/L
Women <115g/L
What are the general causes of anaemia?
Reduced production of RBCs
Increased loss of RBCs (haemolytic anaemia)
Increased plasma volume (pregnancy)
What are the symptoms and signs of anaemia?
Symptoms- fatigue, dyspnoea, faintness, palpitations, headache, tinnitus, anorexia
Signs- Pallor, Severe anaemia- hyperdynamic circulation e.g. tachycardia, flow murmurs
What are the causes of microcytic anaemia? (FAST)
Fe deficiency
Anaemia of chronic disease
Sideroblastic anaemia
Thalassaemia
What are the causes of normocytic anaemia?
Acute blood loss Anaemia of chronic disease Bone marrow failure Renal failure Hypothyroidism Haemolysis Pregnancy
What are the causes of macrocytic anaemia? (FATRBC)
Fetus (pregnancy) Antifolates (phenytoin) Thyroid (hypo) Reticulocytosis B12 or folate deficiency Cirrhosis (alcohol excess and liver disease) Myelodysplastic syndrome
What are the signs of Fe deficiency anaemia?
Koilonychia, atrophic glossitis, angular cheliosis (inflammation of corners of the mouth), post-cricoid webs (Plummer Vinson). brittle hair and nails
What do you see on the blood film for Fe deficiency anaemia?
Microcytic, hypochromic, anisocytosis (varying size), poikilocytosis (shape) and pencil cells
NICE guidelines for Fe deficiency anaemia with no obvious cause?
OGD + colonoscopy, urine dip and coeliac investigations
How do you treat Fe deficiency anaemia?
Treat the cause
Oral iron (SE- nausea, abdo discomfort, diarrhea/constipation, black stools)
IV if severe
Why is there anaemia of chronic disease?
Cytokine driven inhibition of red cell production
How do you diagnose sideroblastic anaemia?
Ring sideroblasts seen in the marrow (erythroid precursors with iron deposited in mitochondria in a ring around the nucleus)
What are the causes of sideroblastic anaemia?
Myelodysplastic disorders, following chemotherapy, irradiation, alcohol excess, lead excess, anti-TB drugs
How do you treat sideroblastic anaemia?
Remove the cause and give pyroxidine (Vit B6 promotes RBC production)
Plasma Iron Studies (Iron, TIBC + Ferritin):
What results would you see in iron deficiency?
Low iron, high TIBC + low ferritin
Plasma Iron Studies (Iron, TIBC + Ferritin):
What results would you see in ACD?
Low iron, low TIBC + high ferritin
Plasma Iron Studies (Iron, TIBC + Ferritin):
What results would you see in chronic haemolysis?
High iron, low TIBC, high ferritin
Plasma Iron Studies (Iron, TIBC + Ferritin):
What results would you see in haemochromatosis?
High iron, low or normal TIBC and high ferritin
Plasma Iron Studies (Iron, TIBC + Ferritin):
What results would you see in pregnancy?
High iron, high TIBC and normal ferritin
Plasma Iron Studies (Iron, TIBC + Ferritin):
What results would you see in sideroblastic anaemia?
High iron, normal TIBC and high ferritin
What are the sources of Vit B12 in human diet?
Meat and dairy products
What are the clinical features of Vit B12 deficiency?
Mouth- glossitis, angular cheilosis
Neuropsychiatric- irritability, depression, psychosis, dementia
Neurological- paraesthesia, peripheral neuropathy
What is the pathophysiology of pernicious anaemia?
Autoimmune atrophic gastritis -> achlorhydria and lack of intrinsic factor
What is most common cause of macrocytic anaemia in Western countries?
Pernicious anaemia (malabsorption leads to B12 deficiency)
Treatment of pernicious anaemia?
Replenish stores with IM hydroxocobalamin (B12)
What are the sources of Folate in human diet?
Green veg, nuts, yeast + liver
What are the causes of folate deficiency?
Poor diet
Increased demand (pregnancy or increased cell turnover e.g. haemolysis, malignancy, inflammatory disease and renal dialysis)
Malabsorption (coeliac disease)
Drugs (alcohol, anti-epileptics, methotrexate and trimethoprim)
What is the treatment for folate deficiency?
Oral folic acid
What would you see in haemolytic anaemia? (all, intravascular and extravascular)
All: Raised bilirubin (unconjugated), urobilinogen + LDH and reticulocytosis
Intravascular:
Increased free plasma Hb, low haptoglobin, haemoglobinuria (dark red urine)
Extravascular:
Splenomegaly
What are the inherited causes of haemolytic anaemia?
Membrane defects:
Hereditary spherocytosis
Hereditary eliptocytosis
Enzyme defects:
G6PD deficiency
Pyruvate kinase deficiency
Haemoglobinopathies:
SCD
Thalassaemias
What are the acquired causes of haemolytic anaemia?
Autoimmune- warm or cold Alloimmune- haemolytic transfusion reactions Mechanical- metal valves or trauma PNH, MAHA Infections Drugs
What is hereditary spherocytosis?
Autosomal dominant deficiency of spectrin or ankyrin (membrane proteins) leading to spherocyte formation
What are people with hereditary spherocytosis susceptible to?
Parvovirus B19 + often develop gallstones
Extravascular haemolysis also leads to splenomegaly
How do you treat hereditary spherocytosis?
Splenectomy and folic acid
What is hereditary elliptocytosis?
Autosomal dominant spectrin mutations (can lead to hydrops foetalis)
What is the commonest RBC enzyme defect?
G6PD deficiency
What is the inheritance route of G6PD deficiency?
X linked
In what areas is G6PD deficiency common?
Areas of malarial endemicity e.g. Africa, middle east etc
How does G6PD deficiency present?
Attacks- rapid anaemia and jaundice, with bite cells and Heinz bodies
Why do drugs, broad beans, acute stressors, moth balls and acute infection lead predispose G6PD deficiency attacks?
These things are oxidants as G6PD helps RBCs make glutathione which protects them from oxidant damage
How do you diagnose G6PD deficiency?
Enzyme assay ~2-3 months after a crisis
How do you treat G6PD deficiency?
Avoid precipitants, transfuse if severe
What is the inheritance route of pyruvate kinase deficiency?
Autosomal recessive
What are the symptoms of pyruvate kinase deficiency?
Severe neonatal jaundice, splenomegaly and haemolytic anaemia
What is the inheritance route for Sickle Cell Disease?
Autosomal recessive
What is the mutation in sickle cell disease?
Single base mutation- GAG -> GTG, Glu -> Val at codon 6 of beta chain -> HbS instead of HbA
What is the difference between Sickle cell disease, sickle cell anaemia and sickle cell trait?
Sickle cell disease- Umbrella term
Sickle cell anaemia- HbSS Severe
Sickle cell trait- HbAS (asymptomatic except under stress)
When does sickle cell anaemia manifest and why?
At 3-6 months as it coincides with decreasing fetal Hb (HbF)
What are the vaso-occlusive and infarction features of sickle cell anaemia (SICKLED)?
Stroke Infections (hyposplenism, CKD) Crises (spenic, chest and pain) Kidney (papillary necrosis, nephrotic) Liver (gallstones) Eyes (retinopathy) Dactilitis (impaired growth) Mesenteric ischaemia Priapism
How is sickle cell disease diagnosed?
Sickle cells and target cells on blood film
Sickle solubility test
Hb electrophoresis
Guthrie test (birth) to aid prompt pneumococcal prophylaxis
How do you treat sickle cell disease?
Acute:
Opioid analgesia for painful crises
Exchange transfusion in severe crises
Chronic:
All should be on penicillin V, pneumovax, HIB vaccine
What happens in beta thalassaemia?
Point mutations lead to reduced beta chain synthesis and excess alpha chains, which increases HbA2 and HbF
What signs are there in beta thalassaemia?
Skull bossing, maxillary hypertrophy, hairs on end skull X-ray + hepatosplenomegaly
How is beta thalassaemia diagnosed?
Hb electrophoresis (Guthrie test at birth)
How is beta thalassaemia treated?
Minor and some intermedia don’t need regular treatment
Blood transfusions with desferrioxamine to stop iron overload, plus folic acid
What happens in alpha thalassaemia?
Deletions- reduced alpha chain synthesis, excess beta chains
What is hydrops foetalis?
Form of alpha thalassaemia where all 4 chains are deleted- incompatible with life
What result for the Direct antiglobulin Test (DAT) or Coombs test would you get in an autoimmune acquired haemolytic anaemia?
Positive
What result for the Direct antiglobulin Test (DAT) or Coombs test would you get in a non-immune acquired haemolytic anaemia?
Negative
What are the differences between warm autoimmune haemolytic anaemia and cold agglutinin disease (features, causes and management)?
Warm:
Features- 37’C, IgG + Spherocytes
Causes- Idiopathic, Lymphoma, CLL, SLE, methyldopa
Management- Steroids, splenectomy and immunosuppression
Cold agglutinin disease:
Features- <37’, IgM, Raynaud’s
Causes- Idiopathic, lymphoma, infections, EBV, mycoplasma
Management- Treat, avoid cold and chlorambucil (chemo)
What haemolytic anaemias would have a negative coombs test?
Non-immune (simplified term)
Name some examples of MAHA?
Thrombotic thrombocytopenic purpura (TTP)
Haemolytic uraemic syndrome (HUS)
What happens in a microangiopathic haemolytic anaemia?
Mechanical RBC destruction (forced through fibrin/pit mesh in damaged vessels) -> schistocytes
What are the causes of MAHA?
HUS, TTP, DIC, Pre-eclampsia
How is MAHA treated?
Usually plasma exchange
What causes thrombotic thrombocytopenic purpura?
Autoimmune- antibodies against ADAMTS13 lead to long strands of VWF which act like cheese wire in the blood vessels, cutting up RBCs
What is the pentad of symptoms for TTP?
MAHA Fever Renal impairment Neuro abnormalities Thrombocytopenia
What causes haemolytic uraemic syndrome?
E.Coli leads to toxin damaging endothelial cells, which leads to fibrin mesh and RBC damage, subsequently causing impaired renal function and MAHA
What test is there to assess the intrinsic pathway?
Activated partial thromboplastin time (APTT)- to monitor heparin therapy
Starts with factor TWELVE
What test is there to assess the extrinsic pathway?
Prothrombin time (PT)- to monitor warfarin therapy (INR). Factor SEVEN
What test is there to assess the common pathway?
Thrombin time (TT)
What sort of bleeding is there in vascular defects or platelet disorders?
Superficial bleeding into skin, mucosal membranes
Bleeding immediate after injury
What sort of bleeding is there in coagulation disorders?
Bleeding into deep tissues, muscles and joints
Delayed but severe bleeding after injury
Bleeding often prolonged
Name some congenital vascular defects
Osler-Weber-Rendu syndrome
CTD (Ehlers-Danlos)
Name some acquired vascular defects
Senile purpura
Infection (meningococcal, measles, dengue)
Steroids
Scurvy
Name some features of acute idiopathic thrombocytopenia?
Children
Commonly preceded by infection
Lasts 2-6w
Commonly spontaneous remission
Name some features of chronic idiopathic thrombocytopenia?
Adults More common in F Rarely preceded by infection Long term Treated with IVIg, steroids and splenectomy
What is haemophilia A and what is its inheritance pattern?
Factor VIII deficiency (severity depends on level of factor VIII)
X-linked recessive
How is haemophilia A diagnosed?
Increased APTT, normal PT and decreased factor VIII assay
How is haemophilia A managed?
Avoid NSAIDs and IM injections, desmopressin, factor VIII concentrates as replacement
What is haemophilia B and how is it inherited?
Factor IX deficiency
X-linked recessive
How is haemophilia B treated?
Factor IX concentrates
Types of Von Willebrand Disease
VWD 1- Quantitative
VWD 2- Qualitative
VWD 3- Both (most severe)
What happens in VWD?
Decreased platelet function and factor VIII (as vWF carries factor VIII in circulation)
What is the presentation of VWD?
Often bleeding of a platelet disorder but also coagulation disorders
How is VWD diagnosed?
Increased APTT and bleeding time, decreased factor VIII and vWF Ag, normal INR
How is VWD managed?
Desmopressin, VWF and Factor VIII concentrates
What happens in disseminated intravascular coagulation?
Widespread activation of coagulation where clotting factors and platelets are consumed, leading to increased risk of bleeding
Causes of DIC
Malignancy Sepsis Trauma Obstetric complications Toxins
Treatment for DIC
Cause and give transfusions, FFP, platelets, cryo etc
How does liver disease lead to coagulation problems?
Decreased synthesis of II, V, VII, IX, X, XI and fibrinogen
Decreased absorption of vit K
How does vit K deficiency lead to coagulation problems?
Vit K is needed for synthesis of Factors II, VII, IX and X and protein C/S
What are the causes of vit K deficiency?
Warfarin, vit K malabsorption/malnutrition, Abx therapy, biliary obstruction
What is the treatment of vit k deficiency?
IV Vit K or FFP for acute haemorrhage
What is Virchow’s triad?
Three factors leading to venous thrombosis:
Vessel wall
Blood
Flow
Name some inherited coagulopathies?
Antithrombin deficiency Protein C deficiency Protein S deficiency Factor V Leiden Prothrombin G20210A Lupus anticoagulant
What are the RFs for VTE?
Age, Obesity Previous DVT or PE Immobilisation Major surgery- esp ortho, >30 mins, plaster cast immobilisation Long distance travel Malignancy- esp pancreas Pregnancy, COCP, HRT Antiphospholipid syndrome Polycythaemia Thrombocythaemia
What is the treatment for a DVT or PE?
LMWH (treatment dose SC) followed by warfarin or apixaban/rivaroxaban (DOACs)
Why do you continue LMWH after starting warfarin when treating a DVT/PE?
Warfarin affects protein C/S and often leads to a procoagulant state in first few days before anticoagulant effect
How does heparin work?
Potentiates antithrombin III which inactivates thrombin and factors 9, 10 and 11
What is the antidote for heparin?
Protamine sulphate
Side effects of heparin?
Bleeding and heparin induced thrombocytopenia (HIT) -> Osteoporosis with long term use
How does warfarin work?
Inhibits the reductase enzyme responsible for regenerating the active form of vit K and therefore inhibits synthesis of factors 2, 7, 9, 10 and proteins C, S and Z
How is the effect of warfarin reversed?
IV vit K/factor concentrates
What is the target INR for someone following a 1st DVT or PE?
2.5
What is the target INR for someone following a recurrent DVT or PE?
3.5
