Haematology - Sickle Cell Disease Flashcards
Definition
SCD incorporates sickle cell anemia (HbSS) + compound heterozygous states that lead to a disease syndrome due to sickling (ie HbSC, HbS beta thalassemia)
UK stats
12000-15000 ppl; 70% in Greater London; 350 new births per annum (most common monogenic disorder); National Hemoglobinopathy Register
Pathogenesis
HAEMOLYSIS OF SICKLED RBCs:
shortened RBC lifespan (20 days vs normal 120) = anemia (baseline [Hb] in HbSS ~ 60-80 g/L, cf (vs) 125-160 in HbA); increased hemolysis = more RBC waste products = gallstones (increased release of bilirubin); aplastic crisis (parvovirus B19 - bone marrow erythropoiesis shuts down); vaso-occlusion (blockage to microvascular circulation) = tissue damage and necrosis (infarction), pain and dysfunction, consequence of polymerisation of abnormal haemoglobin in low O2 conditions, sickle cells (sticky and rigid) can get stuck in capillaries -> low/no O2 supply to tissues
O2 curve
even though baseline [Hb] in HbSS individuals is lower, there are no anemia symptoms because HbS is a low affinity Hb (curve shifts to right -> gives O2 off more readily to tissues); erythropoietin synthesized in kidneys in response to hypoxia
Pathophyisology
Hypoxia -> polymerisation HbS -> rigid sickling of RBCs (= haemolysis, reduced RBC survival -> anemia, jaundice, gallstones) -> vaso-occlusion (in early childhood = susceptibility to encapsulated bacteria) -> chronically impact bone, kidney, cerebral, retina, lung & spleen tissues
Early presentation
Irate before 4-6 months of a*e; onset coincides with switch from foetal to adult Hb synthesis; dactylitis (digit (toe/finger) inflammation), pooling of RBCs in spleen (splenic sequestration, life-threatening unpredictable complication in young children); infection
Spleen + effects on it
Immune defence + breakdown & removal of old, malformed, damaged RBCs; repeated splenic vaso-occlusion (typically with no symptoms) in HbSS = spleen no longer working by 5 yrs old (functional hysosplenism)
Functional hysosplenism
Increased susceptibility to encapsulated bacteria (ie those for meningitis & pneumonia (pneumococcus streptococcus pneumoniae & meningococcus Neisseria meningitidis); immunizations + prophylactic (preventative) antibiotics daily
Acute chest syndrome
caused by vaso-occlusion in chest; pulmonary infiltrate on x-ray with fever, cough, chest pain, tachypnaea; diagnosis often delayed; mechanical ventilation for 15%; mortality >18 = 9%; patients usually require exchange of RBCs to halt sickling
Stroke
8% HbSS patients; most common in childhood; involves major cerebral vessels; identifiable by bright white areas in angiograph, in CT/MRI -> white spot; children monitored and blood exchange set up for those at risk
A vascular necrosis of femoral head on RX
White
Osteomyelitis due to salmonella on RX
Areas less dense
Gallstones
Prevalence of 50% by age 25 in HbSS individuals; gallbladder removal (cholecystectomy); due to increase in bilirubin as result of RBC breakdown due to enhanced turnover
Lab features
Low Hb (60-80 g/L); reticulocytes (RBC precursors) high (reflects high cell turnover)
Blood film
Target cells (darker at centre and outer edge, feature of hyposplenism), sickled cells, boat cells (pointed at both ends but not curved); Howell Jolly bodies (blue dots, feature of hyposplenism, DNA remnants, from nuclei that haven’t been fully expelled by late erythrocytes during bone marrow maturation, would usually be removed by spleen as part of quality control process)
