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Haematology, The link between deoxygenation and sickle cells,…

- - - - History:
        
        Family history
        
        Jaundice
        
        Gallstones
    - - Investigations:
        
        Increased reticulocytes
        
        Increased LDH
        
        Increased unconjugated bilirubin
        
        Reduced haptoglobin
        
        Haemolytic anaemia
        
        Haemolytic markers
    - - Genetic mutation which results in defective red cell membrane
      - Usually hypochromic microcytic
      - Increased destruction of RBCs
    - - Spherocytes
        
        Lacking pallor
  - - - i
        
        Hypochromic, microcytic anaemia
        
        Reduced MCV
        
        Increases TIBC
        
        Reduced Transferrin saturation
      - Blood film
        
        Pencil Cells
        
        Anisocytosis
        
        Poikilocytosis
        
        Microcytic
        
        Hypochromic
      - Treatment
        
        IV
        
        Orally
      - Clinical Signs:
        
        pallor
        
        Angular stomatitis
        
        Koilonychia
    - - Vitamin B12 Deficiency
        
        Macrocytic
        
        Inefficient erythropoiesis
        
        Intrinsic factor antibodies
        
        Clinical Signs:
        
        Pallor
        
        Glossitis
        
        Rarely paraesthesia
        
        Peripheral neuropathy
        
        Ataxia
        
        Loss of vibration
        
        Increased MCV
        
        Increased MMA
        
        Reduced B12
        
        Blood Film:
        
        Macrocytosis
        
        Poikilocytosis
        
        Anisocytosis
        
        Large ovalocytes
        
        Hypersegmented neutrophils
        
        Reticulocytopenia
        
        Treatment:
        
        Replacement of B12 either orally or IM
  - - - autoimmune antibodies
      - LPD
      - Infections
      - Family history
    - - Raised reticulocytes, raised LDH, raised unconjugated, decreased haptoglobin
    - - Spherocytes lacking central pallor
    - - Steroids
      - Immunosupression
  - - - Chronic non-spherocytic haemolytic anaemia
      - There are three forms:
      - o Acute intermittent haemolytic anaemia
      - o Chronic haemolytic anaemia
      - o No risk of haemolytic anaemia
    - - Drugs
        
        Infection
        
        Favism (fava beans)
        
        Neonatal jaundice
    - - G6PD assay
        
        Increased reticulocytes
        
        Increased LDH
        
        Increased unconjugated bilirubin
        
        Reduced haptoglobin (haemolytic markers)
        
        Heinz bodies in drug-induced haemolysis
    - - Usually supportive
        
        o Folic acid
        
        o Transfusion
        
        o Exchange transfusion in infants
  - - - Previous radiation
      - Family history
      - Infection
      - Drugs
    - - Bleeding
      - Purpura
      - Ecchymoses (bruising)
    - - Reticulocytes ( ↓ or absent)
      - MCV ↑
      - Bone marrow biobsy
    - - Oxidative damage
      - Denatured Hb
      - Methaemoglobin
      - Heinz Bodies
      - RBC less deformable
      - Destroyed by spleen
      - G6PD is the first step in the pentose phosphate pathway which converts glucose-6-phopshate to 6 phosphogluconolactone. This reaction also results in nicotinamide adenine dinucleotide phosphate NADP and NADPH. NADPH is important for converting oxidised glutathione back to its reduced forms. Reduced glutathione protects the blood cells from oxidative damage by oxidants such as superoxide anion (O2-) and hydrogen peroxide. Therefore, reduced G6PD results in a reduced NADPH which reduces the level of reduced glutathione, increasing red cell susceptibility to oxidative stress :warning:
    - - Supportive
      - Transfusions
      - Immunosupression
      - Bone marrow transplant
- - - - Normal haemoglobin with the sickle cell trait is HbAS
      - Homozygous sickle cell disease
        
        HbSS
        
        Some patients inherit just one HbS and another abnormal haemoglobin (HbC) which results in a milder form of sickle cell disease (HbSC)
      - Polar amino acid glutamate is substituted by non-polar valine in each of the beta chains (codon 6). This decreases the water solubility of deoxy-Hb.
    - - Acute chest syndrome
        
        All ages; commonest cause of death in adults (25% of all deaths)
        
        2nd most common cause of hospitilisation
        
        Definitions
        
        Acute illness
        
        New infiltrate on CXR
        
        Respiratory Syndrome
        
        Risks
        
        Surgery/anaesthesia, pregnancy
        
        increased risk of chronic disease
        
        increased risk of death
        
        acute management
        
        adequate analgesia
        
        incentive spirometry
        
        reduces ACS in patients admitted with VOC
        
        O2 therapy
        
        Value of NIV even in the absence of severe hypoxia
        
        fluid management
        
        Antibotics
        
        Transfusion
      - Hyposplenic sepsis
        
        Pathophysiology
        
        Auto-infarction from young age (<3) leads to functional asplenia
        
        Causative organisms
        
        Pneumococcal, Meningococcal &
        Haemophilus influenzae
        
        Symptoms
        
        Coma
        
        Altered sensorium
        
        Seizures
        
        Febrile
        
        Treatment
        
        Urgent ABx
        
        Prophylactic pen V
        
        Vaccination
      - Painful crises
        
        Systemic vasculopathy
        
        End-organ damage
        
        Reduced life expectancy
      - Aplastic crisis
        
        Cause
        
        Infection- HPV B19
        
        (5th disease)
        
        Pathophysiology
        
        Infection of RBC precursors in bone marrow leads to pure RBC aplasia
        
        ↓ reticulocytes
        
        Management
        
        Urgent blood transfusion
      - Sequestration
        
        Symptoms
        
        Painful splenomegaly
        
        ↓ Hb
        
        ↑ reticulocytes
        
        78% <2 yrs old
        
        Management
        
        Splenectomy
        
        Urgent blood transfusion
        
        Parental education
        
        Early detection
    - - Clinical
        
        o Family history
        
        o Recurrent pain
      - Laboratory
        
        o Anaemia
        
        o Haemolysis
        
         High bilirubin
        
         High LDH
        
         Raised reticulocytes
        
         Undetectable haptoglobin
        
        o Blood film
        
        o Haemoglobin electrophoresis/Sickle solubility test
    - - Pain/acute painful crisis
        
        Overwhelming sepsis
        
        Acute chest syndrome
      - Stroke
        
        Fat embolism syndrome/Mulit-organ failure
        
        Renal impairment
        
        Priapism
        
        Acute visual loss
    - - Rapid onset of bone pain; bone marrow infarction
        
        Variable severity and duration; hours to weeks
        
        Fever, bone tenderness +/- swelling, hypertension, tachycardia, tachypnoea
      - Management:
        
        Deliver analgesia within 30 mins from presentation
        
        Parenteral opiate analgesia often required
        
        Re-assess and repeat as necessary
        
        Anticipate and treat pre-emptively
        
        Nausea/vomiting- antiemetics
        
        Pruritis- antihistamines
        
        Constipation – laxatives
      - Monitor
        
        Vital signs
        
        Temperature
        
        Fluid intake
        
        Analgesia use and pain score (10 point score)
        
        Sedation/urinary retention/restlessness
    - - FBC and reticulocytes
        
        U&E/LFT
        
        LDH
        
        CRP
        
        Group and Save
        
        Blood cultures
        
        Chest X-RAY
  - - - Alpha Thalassemia
        
        Haemoglobin H disease (α-/--)
        
        Tendency for iron overload
        
        HbH inclusion bodies
        
        Microcytic / hypochromic anaemia of variable
        severity
        
        Homozygous α 0 thalassemia (--/--)
        
        Incompa
        
        Hydrops Fetalis
      - Beta Thalassemia
        
        Assessment of iron status
        
        Gold Standard - cardiac/liver MRI
        
        serum ferritin
        
        acute phase protein - non specific
        
        quick, cheap, readily available
        
        liver biopsy
        
        risk
        
        invasive
        
        Transfusional iron overload
        
        Iron chelation
        
        available chelating agents
        
        Combination
        
        Defrassirox
        
        Deferiprone
        
        Desferoxamine
        
        in B thal major without chelation, effects of hemosiderosis appear at the end of the first decade
        
        Bone marrow expansion
        
        death in first - second decade without transfusion
        
        extramedullary haemopoiesis
        
        bone disease
        
        poor detention
        
        Thalassemic facies
        
        severe anaemia
        
        plasma volume expansion
        
        heart failure
        
        worsening of anaemia
        
        Growth Failure
      - effects of iron overload in transfused patients
      - effects of anaemia
      - imbalance => ineffective erythropoiesis
      - reduced/ absent production of beta or alpha chains

Precipitating Factors:

HbS- substitution of glutamate by valine in position 8 of the beta globin gene