Sickle Cell Disease

The curriculum asks for knowledge of 'abnormal haemoglobins e.g. HbS'.

This topic was the subject of a CRQ in March 2021 (65% pass rate), with marks lost on 'the systemic effects of sickle cell disease' and 'the peri-operative factors that may precipitate sickling'.

Resources

Anaesthetic management of patients with sickle cell disease in obstetrics (BJA Education, 2022)
Standards for Clinical Care of Adults with Sickle Cell Disease in the UK (Sickle Cell Society, 2018)
Haemoglobinopathy and sickle cell disease (BJA Education, 2009)
Anaesthetic management of children with sickle cell disease (BJA Education, 2018)
Peri-operative management of patients with sickle cell disease (Anaesthesia, 2021)

Sickle cell disease is a haemoglobinopathy characterised by abnormal function of the β-globin chain
Common in Africa, South Europe, Asia and Middle East due to conference of malarial resistance by HbAS carrier state

Caused by a single genetic base mutation (A → T) in the β-globin chain gene on chromosome 11
The mutation causes a valine (abnormal) to be substituted in for a glutamic acid (normal) at position 6 of the β-globin chain

Is an autosomal recessive disease:

HbAA - normal

HbAS - carrier ('trait')

No increase in perioperative morbidity or mortality
Usually 30-40% HbS levels
Cells only sickle under extreme physiological conditions

HbSS - sickle cell anaemia

Associated perioperative mortality 1%
The P₅₀ of Hb is much higher (i.e. rightward shift of Oxy-Hb dissociation curve)
Survival rare beyond the fifth decade

Detecting HbS

Sickle solubility test detects presence of HbS but not other Hb subtypes
E.g. the SickleDex test, which will detect HbS concentrations >10%, but does not differentiate between HbSS (disease) and HbAS (carrier) states

Hb electrophoresis

Should postpone elective surgery until electrophoresis performed to determine extent of disease in suspected cases

Genetic testing

Other investigations

Microcytic anaemia
Symptoms of anaemia less severe than expected for [Hb] due to rightward shift of Oxy-Hb dissociation curve

Blood film

Normal in HbAS
HbSS: sickle cells, target cells, Howell-Jolly bodies
Raised reticulocyte count due to haemolysis

Raised bilirubin and LDH due to haemolysis

Airway

Frontal bossing and prominent maxilla due to extramedullary haemopoiesis

Respiratory

Restrictive lung disease (70%)
Acute chest syndrome: dyspnoea, cough, haemoptysis, pleuritic chest pain due to pulmonary infarction
OSA from proliferation of lymphoid tissue in adenoid and tonsillar glands

Cardiovascular

Leg ulcers
Proliferative retinopathy
Multiple organ damage due to recurrent vaso-occlusive crises may precipitate cardiac failure
Pulmonary HTN (6%) due to recurrent pulmonary infarction
Fluid overload states from repeated transfusions or cardiac failure

Neurological

Delayed growth
Increased risk of TIA/stroke and haemorrhagic events
Dactylitis

Genitourinary

Nephropathy/chronic renal failure (20%)
Proteinuria (40%)
Painful priapism

Gastrointestinal

Acute abdomen due to vaso-occlusive crisis or visceral sequestration in the spleen
Gallstones from haemolytic anaemic
Hepatosplenomegaly

Haematological

Haemolytic anaemia
RBC lifespan only 12 days in HbSS cells vs. 120 days normally

Anaemia may be worsened by aplastic crises:

Infection-induced marrow suppression e.g. B₁₉ parvovirus
Acute splenic sequestration
Folate deficiency

Iron overload from repeated transfusions
Splenic infarction

Immunological

Susceptible to Gram-negative sepsis from urinary tract and biliary tree
Auto-infarction of the spleen
Splenomegaly in childhood then functional hyposplenism in adults with susceptibility to infections
May be proliferation of other lymphoid tissue, e.g. adeno-tonsillar hypertrophy and OSA
Haemolytic transfusion reactions due to secondary alloimmunisation

Metabolic

Osteonecrosis / avascular necrosis
Osteomyelitis

Deoxygenated HbS polymerises into large intracellular aggregates, which causes the classical sickled shape

Triggers for sickling

Cold / hypothermia

Hypoxia (see below)

Dehydration inc. alcohol consumption

Venous stasis

Infection

Pain

Acidosis

Strenuous exercise (& lactic acidosis)

HbSS-containing RBC's sickle at higher oxygen levels

Sats 85%
PO₂ 5.2-6.5kPa

HbAS-containing RBC's sickle at lower oxygen levels

Sats 40%
PO₂ 3.2-4kPa

Occur due to vascular endothelial damage and inflammation, thrombus formation and impaired blood flow/DO₂

Vaso-occlusive crises

Vaso-occlusive crises are the most frequent cause of morbidity and mortality, manifesting as:

Acute chest syndrome
Acute abdomen
Splenic infarcts
Cerebral infarcts/stroke
Acute bony pain due to avascular necrosis
Priapism
Dactylitis

Aplastic crises

Triggered by parvovirus infection or folate deficiency
Sudden, precipitous drop in Hb
↓ or absent reticulocytes

Splenic sequestration crises

Occurs mainly in infants
Massive pooling of RBC's in spleen leads to anaemia, splenomegaly and abdominal pain
May lead to hypotension

Haemolytic crises

Fall in red cell Hb
↑ reticulocytes differentiates it from aplastic crisis
Rise in bilirubin
May be a rise in free haemoglobin concentration
Can itself trigger a vaso-occlusive crisis

Non-pharmacological

Education re: disease, avoiding triggers, genetics etc.

Pharmacological

Manage splenic dysfunction

Vaccines (pneumococcal, meningococcal C, Hib)
Penicillin prophylaxis (or clarithromycin if penicillin allergic)
Folate supplements

Hydroxyurea to stimulate HbF production

Management of acute crises

Analgesia
Hydration
Blood transfusion
Cultures and treatment of infection

Interventional

Allogenic bone marrow transplant (if <16yrs)

Perioperative management of the patient with sickle cell disease

History and examination

Assess disease severity: number and timing of crises, hospital admissions
Presence of end-organ disease, especially cardio-respiratory

Investigations

Bloods: FBC | U&E | LFT's | clotting
Repeat G&XM, especially as may have received transfused blood since last sample
Targeted investigation of end-organ disease
CXR
ECG
Consider lung function testing - may have restrictive lung deficit
Consider TTE - may have evidence of volume overload or RWMA from repeated vaso-occlusive crises

Optimisation

Consider pre-admission for IV fluid hydration
Pre-operative chest physiotherapy
Seek expert advice from Haematology on peri-operative management

Pre-operative transfusions:

Aim Hb >100g/L
May need aggressive transfusion to reduce HbS to <30% if major surgery
In children undergoing low - or medium - risk surgery, there are fewer complications if the targets are Hb>100g/L and HbS <60%

First on list; minimise starvation/dehydration time

Monitoring and access

AAGBI
Consider A-line

Anaesthetic technique

No anaesthetic technique superior to another

Regional techniques may be:

Beneficial as they are analgesic, preclude need for intubation/ventilation (and sequelae of this) and improve peripheral blood flow
Detrimental as they can cause hypotension, hypoperfusion and the need for vasoconstricting drugs

If GA used, controlled ventilation to maintain normocarbia and avoid acidosis

Avoid factors precipitating crises

Meticulous approach to:

Normoxia inc. preoxygenation, mandatory ventilation
Euthermia inc. warmed fluids, forced air blankets
Normotension and maintaining normal perfusion inc. replacing fluid losses

Caution with pneumoperitoneum, which may impair portal vein flow and cause liver ischaemia

Other

Avoid use of adrenaline-containing LA
Use of tourniquets controversial; make a risk - benefit decision
Cell salvage not recommended by manufacturers but has been used

Aim sats >96%

Analgesia

Take into account patients may have higher opioid tolerances due to pre-existing consumption
Avoid NSAIDs in those with renal impairment

Meticulous approach to ensuring appropriate oxygenation, hydration, temperature control and analgesia
Lower threshold for post-operative care in an HDU setting for closer observation
Day surgery may be advisable