Dr K Henderson,
Senior Registrar in Anaesthesia, Birmingham. (formerly: Lecturer in Anaesthesia, Accra, Ghana)

Introduction		Regional anaesthesia
Pathophysiology		Emergency Anaesthesia
Clinical Features		Postoperative period
Preoperative assessment		Summary
Investigations		Note
Anaesthesia planning

Introduction

Haemoglobin (Hb) is contained in red blood cells and is capable of combining with oxygen in the lungs, transporting it to the tissues and releasing it there. Normally it is composed of 4 polypeptide chains combined with 4 haem radicals (see Table 1). When the haemoglobin is combined with oxygen it is said to be oxygenated. When it is not combined with oxygen it is deoxygenated (sometimes also called "reduced").

Sickle cell disease is a genetically inherited abnormality of haemoglobin in which valine (an amino acid) replaces glutamine at the sixth position on the beta chains of the haemoglobin molecule. This haemoglobin is termed Haemoglobin S (usually written HbS). Unfortunately when HbS becomes deoxygenated it comes out of solution forming long crystals called "tactoids" which distort the red cell.

Two types of sickle cell illness are described depending on the genetic make-up. Everyone has 2 genes responsible for haemoglobin synthesis. When a person has one normal (HbA) gene and one sickle (HbS) gene they make a mixture of HbA and HbS. They are called heterozygous patients (meaning that they have both genes present) and are said to have Sickle cell trait. The mixed haemoglobin is described as HbAS; their blood contains around 20-45% HbS, the rest being HbA. Because their HbS is mixed with normal HbA, they are much less susceptible to the problems of sickle cell disorders described below.

 
Pathophysiology

Deoxygenated HbS is 50 times less soluble in blood than deoxygenated HbA. When HbS becomes deoxygenated it comes out of solution forming long crystals called "tactoids" which distort the red cell and cause it to become crescent shaped. Initially this is reversible with oxygenation but repeated sickling in the low oxygen tension of the microcirculation causes membrane damage. The cell wall becomes brittle and permanently deformed or "sickled". These cells are then susceptible to premature destruction resulting in a lifespan of only 10-20 days as opposed to a normal 120 days. This causes a chronic haemolytic anaemia with a haemoglobin of around 5-8g/dl.

The structural change and associated increase in blood viscosity promotes venous stasis. A vicious cycle is initiated with local blood vessel obstruction leading to tissue hypoxia producing further deoxygenation which promotes further sickling. This leads to cell death and tissue infarction at the site of obstruction. This is termed a sickle cell crisis.

These vaso-occlusive episodes commence from about 6 months of age after the reduction in fetal haemoglobin (HbF) which initially acts as a protective mechanism. Some sufferers are fortunate to maintain a higher that normal HbF production throughout their lives which improves their condition.

Many episodes of sickling occur spontaneously although certain factors may increase the risk. Apart from hypoxia, acidosis (irrespective of the prevailing oxygen tension) is important and is the principle reason for most sickling occurring in the venous circulation.

Infections (bacterial or viral) are potent inducers. Hypothermia and dehydration are also important causing venous stasis and hypoxia via vasoconstriction.

 
Clinical Features

Patients with sickle trait are usually fit and healthy. However patients with sickle cell disease will usually demonstrate multiple organ damage through repeated veno-occlusive episodes superimposed on a history of poor development and failure to thrive.

Haematological. An acute fall in Hb is usually secondary to infection induced haemolysis or an acute sequestration syndrome in the spleen (infants and children) or liver (children and adults). Blood transfusion is often essential. Bone marrow failure (aplastic crisis) also occurs with a high mortality. Damage to the spleen with increased susceptibility to infections occurs with age.

Respiratory. Dyspnoea, cough , haemoptysis and pleuritic chest pain are classical features of the "acute chest syndrome". Repeated episodes can lead to compromised lung function, pulmonary hypertension and respiratory failure.

Genitourinary. The relative hypoxia and hyperosmolarity of the renal medulla creates an environment for sickling in the vasa recta. The long Loops of Henle are destroyed causing renal failure as the kidney loses its ability to concentrate urine. Haematuria is also a complicating feature. Priapism (prolonged painful penile erection due to venous occlusion) is common, often requiring surgical decompression.

Liver. Jaundice and gallstone formation are a consequence of chronic haemolysis. Liver failure may supervene as a result of multiple infarcts or haemosiderosis from frequent blood transfusions.

Skeletal. Sickling and microvascular occlusion within bones and epiphyseal plates often leads to shortening of the limbs and gross deformity of joints. Osteomyelitis may occur.

Skin. Leg ulcers following skin infarcts are common and often complicated by trauma and poor hygiene.

Neurological. "Acute brain syndrome" is rare but serious. It is characterised by confusion with variable neurological defects. Whilst most resolve spontaneously permanent damage can occur. There is an increased incidence of subarachnoid haemorrhage, blindness and deafness.

Many patients with sickle cell anaemia have frequent hospital admissions for exacerbations of the disease. This can alter their mental health to an extent that considerable psychological, as well as physical, support is essential to their well being.

 
Preoperative Assessment

1. A careful medical history and examination should be performed in susceptible patients as not all patients have obvious symptoms or signs of the disease.

2. If improvements can be made to the function of the cardiovascular or respiratory systems then the operation should be deferred if possible until this has been achieved.

3. In patients with haemoglobinopathy the need for an operation should be considered very carefully, as sickle cell crises can mimic acute surgical events eg an acute abdomen.

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