Haematology Flashcards
Causes of the following blood film findings - Burr cells Target cells Tear drop Pencil poikilocytes Heinz bodies Howell Jolly bodies Reticulocytosis Schistocytes Sideroblasts Smudge cells Spherocytes
- Burr cells - uraemia
- Target cells – iron deficiency anaemia, post-splenectomy, sickle cell
- Tear drop poikilocytes - myelofibrosis
- Pencil poikilocytes: iron deficiency
- Heinz bodies – G6PD, alpha thalassaemia
- Howell-Jolly bodies – post-splenectomy, severe anaemia
- High number of reticulocytes – haemolytic anaemia
- Schistocytes – HUS, DIC, TTP, metallic heart valves, haemolytic anaemia
- Sideroblasts – myelodysplastic syndrome
- Smudge cells – chronic lymphocytic leukaemia
- Spherocytes – autoimmune haemolytic anaemia, hereditary spherocytosis
Causes of microcytic anaemia
TAILS Thalassaemia Anaemia of chronic disease Iron deficiency Lead poisoning Sideroblastic anaemia
Causes of normocytic anaemia
Acute blood loss
Anaemia of chronic disease (eg. renal failure)
Aplastic anaemia
Haemolytic anaemia
Hypothyroidism (can be normocytic or macrocytic)
Pregnancy
Causes of megaloblastic macrocytic anaemia (megaloblastic = impaired DNA synthesis)
Folate deficiency
B12 deficiency
Pernicious anaemia
Causes of normoblastic macrocytic anaemia
Alcohol Reticulocytosis Hypothyroidism Liver disease Drugs (eg. azathioprine)
Specific signs and symptoms caused by iron deficiency anaemia
Koilonychia – spoon shaped nails
Angular chelitis/stomatitis – inflammation of the corners of the mouth
Atrophic glossitis – smooth tongue due to atrophy of the papillae
Brittle hair and nails
Pica – dietary cravings to abnormal things (eg. dirt)
Hair loss
Investigations for anaemia
FBC: haemoglobin, MCV B12 Folate Ferritin Blood film Further Ix: OGD or colonoscopy to investigate for a GI cause of iron deficiency anaemia, bone marrow biopsy if cause is unclear
Causes of iron deficiency anaemia
Blood loss (eg. menorrhagia, oesophagitis, gastritis, GI cancer, IBD)
Dietary insufficiency
Increased requirements during pregnancy
Poor iron absorption: coeliac/Crohns cause inflamm of duodenum/jejunum which is where iron is absorbed. Stomach acid is required to keep iron in the ferrous form, reduced stomach acid changes iron into insoluble ferric form. Drugs which reduce stomach acid (eg. PPI) reduce iron absorption
Iron tests
Iron travels in blood as ferric irons (Fe3+), bound to a carrier protein called transferrin
Ferritin – reliable marker. Low in iron deficiency anaemia, high in inflammation/ infection/ cancer (released from cells)
Serum iron - unreliable to use on its own as it varies throughout the day
Total iron binding capacity (TIBC) is the total amount of space on a transferrin molecule for iron to bind to
TIBC – a marker for how much transferrin is in the blood. Increases in iron deficiency and decreases in iron overload
Transferrin saturation (%) = serum iron / TIBC
Transferrin saturation gives a good indication of the total iron in the body (30% is normal in adults, will be reduced in iron deficiency and raised in iron overload)
Management of iron deficiency anaemia
Oral ferrous sulphate TDS – slowly corrects iron deficiency (Hb rises by 10g/L every week). Causes constipation and black stools. Unsuitable in malabsorption.
Iron infusions – small risk of anaphylaxis but quickly corrects iron deficiency. Avoid during sepsis as it worsens sepsis.
Blood transfusion – immediately corrects the anaemia but carries risks
OGD and colonoscopy required for new iron deficiencies in adults without clear underlying cause to look for cancer of GI tract
Causes of B12 deficiency anaemia
Insufficient dietary intake of B12 (animal products) Pernicious anaemia (autoantibodies against parietal cells or intrinsic factor -> intrinsic factor deficiency -> unable to absorb vit B12 in ileum)
Clinical features of B12 deficiency anaemia
Peripheral neuropathy (numbness, paraesthesia) Loss of vibration sense or proprioception Visual changes Mood or cognitive changes
Investigations fo pernicious anaemia
FBC, B12 levels, Intrinsic factor antibody (first line for pernicious anaemia), gastric parietal cell antibody (less helpful)
Management of pernicious anaemia/ B12 deficiency
Dietary deficiency can be treated with oral replacement with cyanocobalamin
Pernicious anaemia can be treated with IM B12 (hydroxycobalamin)
If there is also folate deficiency, B12 deficiency must be treated before folate deficiency otherwise it can lead to subacute combined degeneration of the cord
Causes of haemolytic anaemia
Inherited: hereditary spherocytosis, hereditary elliptocytosis, thalassaemia, sickle cell disease, G6PD deficiency
Acquired: autoimmune haemolytic anaemia, alloimmune haemolytic anaemia, paroxysmal nocturnal haemoglobinuria, microangiopatic haemolytic anaemia, prosthetic valve related haemolysis, drugs (methyldopa, penicillin)
Features of haemolytic anaemia
Anaemia, due to reduction of circulating RBC: tiredness, SOB, headache, dizziness, palpitations, pallor
Splenomegaly as the spleen becomes filled with destroyed RBCs
Jaundice as bilirubin is released during RBC destruction
Intravascular vs extravascular haemolytic anaemia
Intrinsic – RBC destruction within the blood vessels due to abnormal RBCs
Extrinsic – RBC destroyed in spleen/ liver/ BM/ lymph
Investigations for haemolytic anaemia
FBC – normocytic anaemia, high reticulocytes, MCHC increased in autoimmune haemolytic anaemia and spherocytosis
LFTs – bilirubin high
LDH – high
Haptoglobin – low in intravascular haemolysis (haptoglobin binds to free Hb, so if there is increased Hb release from RBCs there will be more binding of haptoglobin to Hb and therefore less haptoglobin in the circulation)
Blood film – schistocytes (fragments of RBCs), spherocytes, reticulocytes
Direct Coombs test – positive in autoimmune haemolytic anaemia
Hereditary spherocytosis - Inheritance Presentation Ix Mx
Autosomal dominant -> causes sphere-shaped RBCs which are fragile and break down when passing through the spleen
Jaundice, gallstones, splenomegaly, aplastic crisis in the presence of parvovirus
Ix: family history, spherocytes on blood film, raised MCHC, raised reticulocytes
Mx: folate supplementation and splenectomy, cholecystectomy may be required if gallstones are troublesome
G6PD deficiency inheritance crisis triggers presentation investigations Mx
X-linked recessive
Crises triggered by infections, medications (primaquine, ciprofloxacin, sulphonylureas, sulfasalazine), broad beans
Jaundice (usually neonatal), gallstones, anaemia, splenomegaly
Ix: Heinz bodies on blood film, G6PD enzyme assay
Mx: avoid triggers, and transfuse if severe
Warm vs cold autoimmune haemolytic anaemia
Warm type AIHA – more common, haemolysis occurs at body temp, usually idiopathic, usually extravascular. Examples: SLE, lymphoma, CLL, methyldopa
Cold type AIHA – haemolysis at 4 degrees, haemolysis usually intravascular, often causes raynauds and acrocynaosis. Often secondary to lymphoma, leukaemia, SLE, mycoplasma, EBV, CMV and HIV. Responds less well to steorids.
Management of autoimmune haemolytic anaemia
Blood transfusions
Prednisolone
Rituximab
Splenectomy
Alpha thalassaemia inheritance defect presentation diagnosis management
Autosomal recessive
Defects in alpha globin chains
If all 4 alpha globin alleles are affected -> death in utero
Diagnosis: FBC (microcytic anaemia), haemoglobin electrophoresis, DNA testing
Management: monitor FBC, monitor complications, blood transfusions (risk of iron overload), splenectomy, BM transplant
Beta thalassaemia inheritance defect presentation diagnosis management
Autosomal recessive
Defects in beta globin chains (minor, intermedia or major depending on the type)
Beta thalassaemia major causes failure to thrive in first year of life, severe microcytic anaemia, splenomegaly and bone deformities (eg. pronounced forehead due to enlarging BM in order to produce more RBCs)
Diagnosis: FBC (microcytic anaemia), haemoglobin electrophoresis, DNA testing
Management: regular transfusions (risk of iron overload), iron chelation, splenectomy, BM transplant
Sickle cell disease - pathophysiology and relation to malaria
Autosomal recessive mutation of beta globin gene -> Haemoglobin S
One copy of mutated gene -> sickle-cell trait (asymptomatic)
Two copies of mutated gene -> sickle-cell disease
Sickle RBCs are fragile and easily destroyed -> haemolytic anaemia
Prone to sickle cell crises
Patients with a sickle cell trait aren’t affected by malaria as much as other people, so survive and pass on the gene, therefore there is a selective advantage to having sickle cell in areas of malaria
Complications of sickle cell disease
Anaemia Increased risk of infection Stroke Avascular necrosis Pulmonary hypertension Painful persistent erection CKD Sickle cell crises Acute chest syndrome
Management of sickle cell disease
Avoid dehydration and other triggers of crises
Ensure vaccines are up to date
Abx prophylaxis with pen V
Hydroxycarbamide stimulates production of foetal haemoglobin which does not leas to RBC sickling (protective effect against sickle cell crises)
Blood transfusions for severe anaemia
Bone marrow transplant
Types of sickle cell crises
Painful crisis – thrombi in capillaries -> distal ischaemia. Associated with dehydration and raised haematocrit
Splenic sequestration crisis – RBCs block blood flow within spleen-> acutely large painful spleen. Pooling of blood in spleen -> severe anaemia and hypovolaemic shock. Emergency -> transfusions, fluid, splenectomy if recurrent
Aplastic crisis – loss of RBC production due to parvovirus B19 -> significant anaemia
Acute chest syndrome – fever or resp symptoms with new infiltrates on CXR. Either due to infection or non-infective causes. Emergency -> supportive Mx, abx/antivirals, transfusions, incentive spirometry, NIV or intubation
Triggers of sickle cell crises
Infection, dehydration, cold, significant life events
Management of sickle cell crises
Hospital admission, treat any infection, do a septic screen, keep warm, oxygen if required, keep hydrated with IV fluids, appropriate analgesia, blood transfusion if required, treat underlying cause
Causes of neutropenia
Viral infections
Drugs: chemo, cytotoxics, carbimazole, sulphonamides
Severe sepsis
Neutrophil antibodies (SLE, haemolytic anaemia) -> increased destruction
Bone marrow failure (reduced production)
Causes of neutrophilia
Bacterial infections Inflammation Myeloproliferative disorders Drugs (eg. steroids) Disseminated malignancy Stress (eg. trauma, burns, haemorrhage, seizure)
Causes of lymphopenia
Steroid therapy (SLE, uraemia, HIV, marrow infiltration, chemo, radiotherapy)
Causes of lymphocytosis
Acute viral illness
Chronic infection (TB, hepatitis, syphilis)
Leukaemia (esp chronic lymphocytic leukaemia)
Lymphoma
Haemophilia A Inheritance Deficiency Presentation Ix Mx Complication of treatment
Factor VIII deficiency
X-linked recessive
Usually presents in neonates or early childhood -> intracranial haemorrhage, haematomas, cord bleeding
Bleeding into joints -> crippling arthropathy
Bleeding into muscles-> haematomas (neuropathy, compartment syndrome)
Ix: Increased APTT, reduced factor VIII assay
Mx: Avoid NSAIDs and IM injections. For minor bleeds can give pressure and elevation of body part, plus desmopressin to increase factor VIII levels. If more severe bleeding give recombinant factor VIII. Genetic counselling
Complications: some patients develop antibodies to factor VIII treatment making it ineffective
Haemophilia B deficiency inheritance presentation Ix Mx
Factor IX deficiency
X linked recessive
Presentation same as haemophilia A: haemorrhage (spontaneous or a result of minor trauma) -> into muscle (nerve compression, compartment syndrome), or into joints (crippling arthropathy). Often presents as neonate (ICH, bleeding into cord, haematomas)
Ix: raised APTT, reduced factor IX assay
Mx: recombinant factor IX. Avoid IM injections and NSAIDs
Immune thrombocytopenia
Autoantibodies against platelets
Acute or chronic
Acute - usually in children, 2wks after infection, self-limiting purpura
Chronic – usually in women, bleeding, purpura, epistaxis, menorrhagia
No splenomegaly
Ix: Increased megakaryocytes in BM, antiplatelet autoantibodies
Mx: aim to keep platelets >30. prednisolone if symptomatic or platelets <20, IV immunoglobulin (temp raises platelet levels), rituximab, splenectomy
Abnormal coagulation (effect on APTT, PT, bleeding time)
Haemophilia
vWF disease
Vit K deficiency
Haemophilia: APTT increased, PT normal, bleeding time normal
Von Willebrand disease: APTT increased, PT normal, bleeding time increased
Vit K deficiency: APTT increased, PT increased, bleeding time normal
Abnormal coagulation (factors affected) Heparin Warfarin DIC Liver disease
Heparin: prevents activation factors 2, 9, 10, 11
Warfarin: affects synthesis of factors 2, 7, 9, 10
DIC: factors 1, 2, 5, 8, 11
Liver disease: factors 1, 2, 5, 7, 9, 10, 11
What is APTT and what does it test
What is normal APTT
What causes prolonged APTT
Partial thromboplastin time
Tests clotting factors involved in the intrinsic and common pathways of coag cascade: fibrinogen (I), thrombin (II), X, XI, XII, co-factors V and VIII
A normal blood sample should clot in 30-40s
Prolonged APTT: deficiency in the tested factors, DIC, heparin
