Sickle Cell Disease Flashcards by Georgia Leggett

What is Sickle Cell Anaemia?

Homozygosity for HbS

HbSS

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What is Sickle Cell Disease?

Group of chronic conditions with sickling of RBCs caused by inheritance of haemoglobin S (HbS)

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What is the genotype in Sickle Cell trait? How does this present?

HbAS

Asymptomatic except in conditions that favour sickling (hypoxia, dehydration)

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What causes sickling of red blood cells?

Point mutation in B globin gene (Valine subs glutamic acid on position 6= non-polar so insoluble).
Results in formation of abnormal haemoglobin S

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Describe the pathophysiology of sickling cells

HbS polymerises when deoxygenated, causing sickling of RBCs
Sickling makes RBC’s more fragile + inflexible
Triggered by any event associated with reduced O2 tension

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Why are inflexible sickled cells pathological?

Lack elasticity + adhere to vascular endothelium

This disrupts microcirculation, causes vascular occlusion + subsequent tissue infarction.

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List 4 triggers precipitating sickling of RBCs

Infection
Hypoxia
Acidosis
Dehydration

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Describe the epidemiology of Sickle Cell disease

1 in 2000 births

African, Afro-Caribbean, Asian or Mediterranean

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What deficiency may arise in sickle cell disease? Why? What is done to restore this?

Folate deficiency
Haemolysis + subsequent increased turnover of RBCs increases demand for folate
Give Folic Acid: If severe haemolysis or in pregnancy

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Why is sickle cell disease more common in non UK populations?

Sickle cell trait confers resistance to Malaria, thus carrying HbS has a survival advantage

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When do symptoms of sickle cell disease start to present?

Coincides with switch from HbF to HbA synthesis

~3-6 months

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What are sickled red blood cells prone to?

Sequestration + destruction, leading to decreased RBC survival (20 days)
through Extravascular (Spleen) + intravascular haemolysis

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What are the acute manifestations of sickle cell anaemia?

Haemolytic crises
Infection
Vaso-occlusive events

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What 2 acute haemolytic crises can occur in sickle cell disease?

Splenic sequestration crisis

Aplastic crisis

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What is a splenic sequestration crisis?

Occlusion of blood flow out of spleen
Causes pooling of RBCs in spleen + splenomegaly
Results in anaemia + hypovolaemic shock

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List 4 features of a splenic sequestration crisis

Acute LUQ pain
Anemia
Reticulocytosis
Intravascular volume depletion: hypotension

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What 5 infections are those with sickle cell disease particularly susceptible to?

Pneumococcus
Meningococcus
Haemophilus Influenza
Osteomyelitis: Salmonella, Staph aureus 
Sepsis: Strep. pneumoniae

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What causes Aplastic Crises?

Infection by Parvovirus B19
infects developing red cells in BM + arrests maturation
With such reduced lifespan of RBC’s in SCD, results in dramatic fall in Hb

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Why are people with sickle cell disease more susceptible to infection?

Recurrent crises causes atrophy or infarction of the spleen

Increases risk of infection with encapsulated organisms

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List 5 vaso-occlusive crises in sickle cell disease

Acute chest syndrome 
Priapism 
Stroke (common in children) 
Infarctions of nearly any organ (esp. spleen)
Avascular necrosis

What are Vaso-occlusive crises ?

Ischaemia caused by obstruction of microcirculation by sickled RBCs

List 6 symptoms of vaso-occlusive crises

Swollen painful joints + bones
Abdo pain
Visual loss (proliferative retinopathy)
Loin pain
Neuro signs e.g. Hemiplegia (Stroke)
Tachypnoea

Which bones are commonly affected in adults and children by vaso-occlusion?

Adults: Ribs, Spine, Pelvis, Long bones
Children: Small bones of hand= Dactylitis

What symptom may indicate sequestration crises?

LUQ pain

Give 2 signs of sequestration crises on examination

Splenomegaly | Hypotension

Give 3 chronic features of sickle cell anaemia

Haemolytic anaemia: fatigue, weakness, pallor Pain Cholelithiasis (pigmented stones)

What may provoke vaso-occlusive crises?

Cold Infection Exertion Dehydration

List 4 signs of vaso-occlusion and infarction

Joint or muscle tenderness or swelling (due to avascular necrosis) Short digits: due to infarction in small bones of the hands Retina: cotton wool spots due to retinal ischaemia Jaundice (haemolysis)

What causes priapism in sickle cell anaemia?

Microvascular occlusion of the penis so blood can’t leave, it remains painful + erected for a long time

What characterises Acute Chest syndrome? What causes ACS?

New pulmonary infiltrate on CXR with: fever, cough, chest pain, tachypnoea. Vaso-occlusive crisis of the pulmonary vasculature

What investigations are performed in sickle cell disease?

Bloods: Anaemia Blood smear Sickle solubility test Haemoglobin electrophoresis / HPLC

What other investigations may be used in sickle cell disease? Why?

MRI or CT Head: neuro complications X-rays: identify avascular necrosis Bacterial cultures: to confirm infection CXR: if resp Sx

What is seen on a blood smear in sickle cell anaemia?

Sickle cells: crescent-shaped RBCs Target cells Howell-Jolly bodies Reticulocytosis

What is a sickle solubility test?

Dithionate added to blood smear | SCD: increased turbidity (no difference between SCA or trait so need to do HPLC to confirm)

What sign may be seen on skull x-ray in sickle cell anaemia?

"Hair on end"

Which investigation gives a definitive diagnosis of sickle cell disease?

Hb Electrophoresis Shows HbS Absence of HbA (if homozygous HbS) High HbF

How does reticulocyte count vary in sickle cell disease?

HIGH: in splenic sequestration crises LOW: in aplastic crises

List 3 prophylactic measures used in management of sickle cell anaemia

Pneumococcal vaccines Meningococcal vaccines Daily penicillin

Give 2 indications for treatment in sickle cell anaemia with hyroxyurea

Frequent, acute painful episodes or other vaso-occlusive events Severe symptomatic anaemia

Describe the mechanism of action of hydroxyurea in sickle cell anaemia. What adverse side effect may result from treatment with hydroxyurea?

``` Stimulates erythropoiesis + increases HbF HbS is proportionally reduced RBC polymerisation decreases Fewer vaso-occlusive episodes SE: Myelosuppression ```

What is used to prevent repeated admission due to septicaemia in febrile children?

Ceftriaxone

What drug can be used if patients are intolerant/ refractory to hydroxyurea?

L-glutamine

What treatment may be used in severe anaemia?

Red cell transfusion

When may an exchange transfusion be necessary in sickle cell patients?

Severe crises Pre-op Pregnancy

What advice is given to sickle cell patients?

Avoid precipitating factors Good hygiene + nutrition Genetic counselling Prenatal screening

What surgical treatment may be used in some patients?

BM transplant | Joint replacement for avascular necrosis

Describe the management of acute painful crises

Oxygen IV fluids Strong analgesia (IV opiates) Abx

List 9 complications of sickle cell anaemia

``` Cardiovascular manifestations Cholelithiasis Liver complications e.g. hepatomegaly, jaundice Leg ulcers Lung damage Poor growth in children Chronic renal failure Retinal disease Iron overload from repeated transfusion ```

What is the prognosis for those with sickle cell disease

Most survive to ~50 with good care | Major mortality results from pulmonary, neuro or infectious complications