Sickle Cell Flashcards
What are modifiers of sickle cell disease?
Factors influencing clinical severity and manifestations
Modifiers include haplotypes, co-inheritance with alpha thalassemia, and levels of Hb F.
What causes gradual decrease in haematocrit in sickle cell disease?
Folate deficiency and chronic renal insufficiency
Chronic renal insufficiency affects erythropoietin production.
What are acute exacerbations in sickle cell disease?
Aplastic crisis, splenic sequestration
These can lead to severe complications in patients.
At what age do infants with sickle cell disease show a decline in haematocrit?
12 to 15 months
Infants have lower than normal haematocrit after the neonatal period.
What is the relationship between haematocrit levels and stroke risk in sickle cell disease?
Lower haematocrit increases stroke risk; higher haematocrit increases painful episodes
Patients with lower baseline haematocrit are at greater risk for stroke and renal dysfunction.
What are the two major pathophysiologic mechanisms of clinical features in sickle cell disease?
Haemolytic and vasoocclusive
These mechanisms explain the clinical manifestations observed in patients.
What characterizes a haemolytic crisis in sickle cell disease?
Pronounced haemolysis and laboratory findings of haemolysis
Caused by infections, transfusion reactions, or sepsis.
What is a sequestration crisis?
Massive pooling of red cells in the spleen
Typically seen in children under 5 years and can recur in about half of survivors.
What causes an aplastic crisis in sickle cell disease?
ParvoB19 virus infection
This virus attaches to P-antigen on erythroid progenitor cells, leading to temporary erythropoiesis arrest.
What is a vasoocclusive crisis?
Acute painful crisis common in young adults
Often precipitated by cold, dehydration, or stress.
Which pathogens are commonly associated with infections in sickle cell disease patients in Africa?
Salmonella spp, Klebsiella spp, E. coli, Staphylococcus spp
These organisms are responsible for various infections in this population.
What is the most common organism causing pneumonia in sickle cell disease patients?
Streptococcus pneumoniae
Other common causes include Mycoplasma pneumoniae and Chlamydia pneumoniae.
What is the risk of stroke in patients with sickle cell disease?
Approximately 11% of patients younger than 20 years
Stroke types vary with age; ischaemic stroke is most common in children.
What is the effect of anaemia on cardiac output in sickle cell disease?
Increased cardiac output due to elevated stroke volume
Hyperdynamic circulation may lead to clinical manifestations like murmurs and tachycardia.
What percentage of sickle cell disease patients experience pulmonary hypertension?
6 to 11%
Contributing factors include abnormalities in nitric oxide metabolism and inflammation.
What defines acute chest syndrome in sickle cell disease?
New infiltrate on chest radiograph, chest pain, fever, tachypnoea
It is the leading cause of death among sickle cell anaemic patients.
What is the best predictor of stroke risk in sickle cell disease?
Increased blood flow velocity in intracranial arteries
Velocities greater than 200 cm/s are associated with a higher stroke risk.
What are the four major crises identified in sickle cell disease?
Vasoocclusive, aplastic, haemolytic, sequestration
Each crisis has distinct features and management strategies.
What role do environmental and genetic factors play in the clinical course of sickle cell disease?
They influence the severity and frequency of complications
Some patients may live a normal life while others face frequent hospitalizations.
What is the role of nitric oxide in the vascular endothelium?
Vasodilatory, anti-inflammatory, and antiplatelet properties
Nitric oxide is synthesized from L-arginine by endothelial nitric oxide synthase.
What happens to nitric oxide synthesis during haemolysis in sickle cell disease?
It decreases due to the release of L-arginase
This reduces the available L-arginine for nitric oxide production.
How does sickle cell dehydration occur?
Impaired cation homeostasis and loss of intracellular potassium
This leads to increased red cell haemoglobin concentration and promotes sickling.
What factors influence the polymerization of Hb S?
Oxygenation status, intracellular haemoglobin concentration, presence of non-sickle haemoglobins
Acidosis and elevated 2,3-DPG levels promote polymer formation.
What is the laboratory profile of sickle cell anaemia?
Evidence of haemolysis, increased LDH, indirect bilirubin, high reticulocyte count
Decreased serum haptoglobin is also observed.
What causes susceptibility to infections in sickle cell anaemic patients?
Hyposplenism and defects in the alternative complement pathway
These factors increase the risk of severe infections.
What is natriuretic peptide associated with?
Pulmonary Hypertension and Congestive Heart failure
Natriuretic peptide levels increase in these conditions.
What laboratory features characterize sickle cell anaemia?
- Increase Lactate dehydrogenase
- Increase Indirect bilirubin
- High reticulocyte count
- Decrease Serum haptoglobin
Why are sickle cell anaemic patients susceptible to infection?
- Hyposplenism
- Defect in the alternative complement pathway
- Reduced ability of neutrophils to kill organisms
What adverse outcomes are associated with the upregulation of endothelin-1 in sickle cell disease?
It is a potent vasoconstrictor leading to complications.
Which proinflammatory mediators are increased in sickle cell anaemia?
- TNF-alpha
- IL-6
- IL-1β
What is the role of Placental growth factor (PGF) in sickle cell disease?
Activates monocytes to produce inflammatory cytokines and upregulates endothelin-1 signaling.
What is recognized as an adverse prognostic factor in sickle cell anaemia?
Neutrophilia
Which haplotypes are associated with severe clinical presentation of sickle cell disease?
- Bantu
- Benin
What is the most common cause of acute renal failure in sickle cell disease?
Dehydration
What is isosthenuria?
A condition prevalent in sickle cell disease that increases glomerular hyperfiltration.
What is priapism?
Painful, persistent penile erection that occurs with or without sexual stimulation.
What percentage of male sickle cell disease patients report priapism?
About 35%
What are the two types of priapism?
- Ischaemic (Low flow)
- Non-Ischaemic
What is the prevalence of sickle cell trait in West Africa?
25–30% of the population
What is the genetic inheritance pattern of sickle cell disorders?
Autosomal codominant
Which variant of sickle cell syndrome is associated with milder disease and higher Hb F?
Saudi-Indian (Arab-Indian) haplotype
What does the sickle cell trait (Hb AS) indicate?
A benign condition with no haematological manifestations.
What is the typical haemoglobin ratio in sickle cell trait?
60:40 (Hb A to Hb S)
What is the incidence of microalbuminuria among SCD patients over the age of 35?
Greater than 60%
What major discovery did Linus Pauling make in 1949?
Electrophoretic difference between Hemoglobins from normal, sickle cell trait, and sickle cell anaemia.
What is chronic leg ulcer and its prevalence among sickle cell disease patients?
Common among adults, affecting 2-40% of patients.
What is the typical presentation of avascular necrosis (AVN) in sickle cell disease?
Chronic joint pain with progressive reduction in motion range.
What are the risk factors for avascular necrosis?
- History of frequent vasoocclusive episodes
- Male gender
- Higher baseline Haemoglobin concentration
- Low Hb F
- Vitamin D deficiency
What are the common bacteria colonizing chronic leg ulcers in sickle cell disease?
- Pseudomonas aeruginosa
- S. aureus
- Streptococcus spp
What is the typical treatment for priapism?
- Cold bath
- Brisk walks
- Exchange blood transfusion
- Alpha and beta adrenergic agonist
- Shunts (Winter’s)
- Penile prosthesis
What is the significance of the ratio of Hb A to Hb S in sickle cell trait?
It indicates the greater affinity of α-globin chains for β-globin chains.
What is the impact of sickle cell trait on malaria?
Reduces the risk of severe falciparum malaria but not the prevalence of parasitaemia.
What major change in the β-globin gene was identified in 1977?
Change in codon 6 from GAG to GTG (Adenine to Guanine).
What condition is associated with Sickle Cell Disease (SCD) regarding anaemia?
Less severe anaemia, hypochromia, and microcytosis
SCD patients with a normal complement of α-globin genes show clinical severity similar to HbSS patients.
What is a haplotype?
A set of DNA variants along a single chromosome that tend to be inherited together
List some populations with different haplotypes of the beta S gene.
- Bantu
- Benin
- Cameroon
- Senegalese
- Saudi-Indian (Arab-Indian)
What are some hepatobiliary complications of sickle cell disease?
- Intrahepatic trapping of sickled red cells
- Transfusion-acquired infections like Hepatitis
- Transfusional haemosiderosis
- Cholelithiasis (gall stones)
What is the management for cholelithiasis in sickle cell disease patients?
Cholecystectomy
Cholelithiasis is seen in 2/3rds of patients.
Which investigations can be employed to diagnose sickle cell disease?
- Peripheral blood film
- Haemoglobin electrophoresis (cellulose acetate at pH 8.4 or Agar gel at pH 6.5)
- High performance liquid chromatography
- Newborn screening (Population study)
What are some routine drugs used in the treatment of sickle cell disease?
- Folic acid
- Vitamin Bco
- Paludrine
What types of blood transfusions are used in sickle cell disease treatment?
- Top-up
- Exchange blood transfusion
What analgesics are recommended for sickle cell disease?
- Acetaminophen
- NSAIDS (Diclofenac, Naxen)
- COX 2 inhibitors (Celecoxib)
- Opioids (Pentazocine, Morphine)
What is a key component of the treatment regimen for sickle cell disease?
Adequate rehydration
What does Hydroxycarbamide (Hydroxyurea) do in sickle cell disease treatment?
- Increases Haemoglobin F concentration
- Increases water content
- Reduces deformability
What advanced treatments are available for sickle cell disease?
- Haemopoietic stem cell transplant
- Gene therapy
