Haematology and Immunology Flashcards
Polycythaemia
Increased rbc
- JAK2 gene (myeloid malignancies)
Thrombocytosis
Increased platelets
- Infection
- Trauma
- Myeloid malignancy (myeloproliferative disorders)
- Iron deficiency
- Inflammation
Thrombocytopenia
Reduced platelets: decreased production (Tx: thrombopoietin analogues), increased consumption
- Acquired: Marrow failure, DIC
- Autoimmune (high dose steroids)
- Hypersplenism (splenectomy)
- Normal blood except reduced platelet count
Hormones controlling blood cell production
- Thrombopoietin (liver) - platelets
- Erythropoietin (kidneys)
- Cytokine granulocyte colony-stimulating factor
Normal Hb (male)
140-180 g/L
Normal Hb (female)
120-160 g/L
Normal platelets
150-400 x10^9/L
Normal WBC
4-10 x10^9/L
Donor/recipient compatibility
- ABO group
- Rhesus
- Serum alloantibodies
Anaemia
- and morphological description
Reduced levels of rbc’s or Hb
- Bone marrow (cellularity, stroma, nutrients)
- Red cell (membrane, Hb, enzymes)
- Destruction/loss (haemorrhage, haemolysis, hypersplenism)
- Hypochromic, microcytic
- Normochromic, normocytic
- Macrocytic
Anaemia presentation
- Tiredness/fatigue
- Pallor
- Peripheral oedema
- Dizziness
- Chest pain
Symptoms relating to underlying cause
Hypochromic microcytic anaemia
Do serum ferritin
- Iron deficiency (low)
- Thalassaemia (normal)
- Secondary anaemia - infection, inflammation, malignancy
Normochromic normocytic anaemia
Do reticulocyte count
- Blood loss/haemolysis (increased)
- Secondary anaemia (normal)
Macrocytic anaemia
Do B12/folate
- Megaloblastic (low) -> pernicious anaemia
- Normal -> non-megaloblastic anaemia (alcohol, drugs, liver)
Iron deficiency anaemia
Increased iron loss (bleeding, diet, malabsorption) or requirement (pregnancy)
Physiology: Ferroportin (Hepcidin inhibits - inflammation) -> Transferrin (plasma) -> Ferritin
Examination: koilonychia, atrophic tongue, angular cheilitis
Investigation: blood film (hypochromic, microcytic), low serum ferritin
Management: iron supplementation, blood transfusion, correct cause
Haemolytic anaemia
Accelerated red cell destruction
- Congenital: HS, G6PD deficiency, SSD
- Autoimmune (positive DGAT)
- Non-immune: mechanical, infection (negative DGAT)
Investigation:
- Reticulocyte count (increased)
- Low haptoglobin (free Hb)
- DGAT
- Increased conjugated bilirubin
Management:
- Folic acid
- Correct cause - immunosuppression, splenectomy etc
- Transfusion
Macrocytic anaemia
Large red blood cells.
Megaloblastic:
- B12 deficiency (pernicious anaemia)
- Folate deficiency
- Neurological symptoms
- Yellow tinge
Non-megaloblastic: alcohol, marrow infiltration, drugs, disordered liver, hypothyroidism
Pernicious anaemia
Autoimmune disease
- Low B12 and macrocytic blood film
- Anti-intrinsic factor antibodies
- IM vitamin B12
Hereditary spherocytosis
Spherical RBCs
- Autosomal dominant
- 5 structural protein defects
- Anaemia, jaundice, splenomegaly, pigment gallstones
- Negative DAGT
- Folic acid, transfusion, splenectomy
G6PD deficiency
Cells vulnerable to oxidative damage
- X-linked and precipitated by infection, acute illness, drugs
- Anaemia, jaundice, splenomegaly, pigment gallstones
- Haemoglobinuria and low haptoglobin
Thalassaemia
Reduced/absent globin chain production
- X-linked
- Hypochromic, microcytic blood film
- Normal ferritin
- Severe anaemia, bone deformities, splenomegaly
Sickle cell disease
Structurally abnormal globin chain
- X-linked
- Symptoms occur due to vaso-occlusion: bone crisis, chest crisis, stroke, infection, chronic haemolytic anaemia, sequestration crisis
- Reticulocyte count, bilirubin, LDH, haemoglobinopathy screen
- Lifelong prophylaxis - folic acid, vaccines, penicillin
Haemophilia A and B
A: CFVIII deficiency
B: CFIX deficiency
- X-linked
- Coagulation factor pattern of bleeding: haemarthrosis, muscle haematoma, CNS bleeding, retroperitoneal bleeding
- Coagulation tests and assays: prolonged aptt, normal pt
- Coagulation factor replacement: recombinant, transfision, DDAVP, tranexamic acid, emicizumab
Von Willebrand disease
vWF
Type 1: quantitative deficiency
Type 2: qualitative deficiency
Type 3: severe deficiency
- Autosomal dominant
- Platelet-type pattern of bleeding: epistaxis, purpura, menorrhagia, GI
- Coagulation tests
- vWF concentrate, DDAVP, tranexamic acid, combined OCP
Causes of bleeding
- Haemophilia (FVIII, IX)
- vWD
- Thrombocytopenia
- Liver failure (prolonged PT, APTT, reduced fibrinogen)
- Vitamin K deficiency (haemorrhagic disease of newborn)
Leukaemia
Progressive, malignant disease of the blood-forming organs (leukocytes and precursors in blood and bone marrow)
- Myeloid or lymphoid
- Acute or chronic
Acquired genetic and environmental
Leukaemia presentation
- Fatigue
- Weight loss
- Fever
- Pallor
- Bruising
- Petechiae
- Sweats
- Anaemia: SOB, dizziness, palpitations
Leukaemia investigations
Blood analysis
- FBC, blood film
- Coagulation screen
- B12, folate, ferritin
- U&Es, LFTs, CRP, ESR
- Reticulocyte count
Bone marrow biopsy
Acute myeloid leukaemia (AML)
Blast myeloid cells have ability to proliferate but cannot differentiate.
- Myelodysplastic syndrome can progress to AML.
Presentation: bone marrow failure
- Anaemia
- Thrombocytopenic bleeding
- Infection
- Gum hypertrophy
Investigation
- Bone marrow biopsy
- Reduced erythrocytes
Management
- Supportive
- Anti-leukaemic chemotherapy
Chronic myeloid leukaemia (CML)
Myeloid cells have ability to proliferate and differentiate
- Philadelphia chromosome T(9;22)
Presentation
- Anaemia of chronic disease
- Splenomegaly
- Weight loss
- Hyperleukostasis
- Gout
- Thrombocytopenia
Investigation
- High WCC/platelets, film
- Bone marrow biopsy (hypercellular)
Management
- Tyrosine Kinase Inhibitors
- BCR-ABL inhibitors
- Allogeneic transplantation
- Folic acid
- Steroids
Myeloproliferative neoplasms (MPN)
Polycythaemia vera (PV) Essential thrombocythemia (ET) - JAK2 V617F/CALR mutation
Presentation
- Headaches
- Itch
- Vascular occlusion
- Thrombosis
- TIA, stroke
- Splenomegaly
- Plethora
- Myelofibrosis: extensive scarring in bone marrow leading to severe anaemia
Investigations
- Mutation screening
Polycythaemia vera (PV)
Myeloproliferative neoplasms (MPN)
- Raised Hb and haematocrit
- Raised uric acid
- Low (iron-deficient PV)
Management:
- Venesection
- Aspirin
- Cytoreduction
- JAK2 inhibitor
Essential thrombocythemia (ET)
Myeloproliferative neoplasms (MPN) - Raised platelets
Management:
- Aspirin
- Cytoreduction
Acute lymphoblastic leukaemia (ALL)
Lymphoid (blast) cells can proliferate but not differentiate
Presentation:
- Bone marrow failure - anaemia, thrombocytopenia
- Bone/joint pain
- Infection
- Sweats
Investigation:
- Low Hb, platelets
- High WBC
- Spherocytes
- High reticulocyte count
Bone marrow biopsy
- CD-20: mature
- CD-34, TDT: immature
Management:
- Chemotherapy
Chronic lymphocytic leukaemia (CLL)
Lymphoid (blast) cells have ability to proliferate and differentiate.
Presentation
- Asymptomatic
- Bone marrow failure
- Lymphadenopathy
- Splenomegaly
- Systemic features
- Hepatomegaly
- Infections
Investigation
- High WBC
- Flow cytometry
Staging (Binet)
a) <3 lymph nodes
b) 3+ nodes
c) 3+ nodes + bone marrow failure
Management
- Observe
- Chemotherapy
- Monoclonal antibodies
- Novel agents
Lymphoma
Cancer originating in lymphoid tissue (lymphocytic differentiation in germinal centre of lymph nodes)
- Lymph nodes, spleen, thymus, bone marrow
Presentation
- Lymphadenopathy (painless)
- Hepato/splenomegaly
- Systemic (B) symptoms
- Bone marrow involvement
Investigations
- High WBC
- Lymph node biopsy
- PET-CT scan
- Bone marrow aspirate
- Virology and FNA (rule out)
Staging (look at table)
Combination chemotherapy
Non-Hodgkin lymphoma
Lineage (B or T-cell)
Grade
- High: diffuse large B-cell (aggressive), curable
- Low: follicular, marginal zone, often asymptomatic, incurable
Hodgkin lymphoma
Presence of Reed-Sternberg cells
Associations:
- Epstein Barr virus
- Familial
- Geographical
- Young
Management
- +/- radiotherapy
- Monoclonal antibodies (anti-30)
- Immunotherapy
IgM paraproteins present
Lymphoma
IgG, IgA paraproteins present
Myeloma
Myeloma
Neoplastic disorder of plasma cells
- IgG, IgA paraprotein present
Paraproteins or plasma cells -> symptoms: CRAB - Hypercalcaemia - Renal failure - Anaemia - Bone disease/failure
- Infections: leukopenia
Serum total electrophoresis and protein, ESR
Management: Asymptomatic -> don't treat - Chemotherapy - Biphosphonate therapy - Radiotherapy - Steroids - Surgery (stabilise bones) - SCT
Infection in neutropenia
Bacterial
Fungal
Infection in monocytopenia
Fungal (deep-seated)
- Candida
- Aspergillus
Infection in low eosinophils (Cushing’s)
Parasitic
Infection in lymphopenia
T-cell: fungal and viral infection, PJP (pneumocystis jirovecii)
B-cell: bacterial
