Despite the widespread principle of selective mating being propagated by religious bodies, media and various NGOs, increasing awareness of the disease and widespread stigmatization against the affected populace, sickle cell disease has continued to flourish in Africa.
Nigeria’s large population and genetic co-operation between malaria and the sickle cell carrier state. Carriers (HbAs) have flourish in Africa because their carrier state prevent them from yielding to the fatal falciparum malaria prevalent in the region has ensured over 40 million Nigerians are healthy carrier of the S genome. Consequently, about 150000 Nigerian children are born each year with sickle cell anaemia (HbSS).
The term sickle cell disorder refer to a group of haemoglobinopathies arising from the inheritance of the single gene in a homozygous state (SS)- single cell anaemia or as a double heterozygous state in combination with other abnormal genes that is haemoglobin C. In simple form, it takes two people with the abnormal haemoglobin (HbS) to produce offsprings with HbSS (sickle cell anaemia).
Sickle cell crisis
Individuals with sickle cell disease run an extremely variable clinical course characterized by asymptomatic steady state at one end and crippling severe crisis at the other end of the spectrum. Sickle cell crisis refers to any new event that develops rapidly and incapacitates individuals with sickle cell disease and is not due to any other pathology. Sickle cell crisis is often acute and sometimes life threatening. These include vaso-occlusive crisis (VOC characterized by vascular occlusion and tissue infarction) and acute-on-chronic haemolysis that results from increased red cell destruction with a fall in haemoglobin level. Also, sequestration into the spleen (commonly), liver or splanchnic bed (Girdle syndrome) may occur, engorged with sickle erythrocytes. The aplastic crisis is characterized by period of marrow failure resulting from intercurrent infection particularly due to parvovirus B19 infection.Also, accelerated erythropoiesis follow increased demand for folate may result in megaloblastic crisis. Vaso-occlusive crisis is the most common event that brings most sickle cell disease patients to the hospital. It causes pain in the bones, joints, chest and abdomen. Other acute events related to the HbS include stroke, acute chest syndrome, priapism, avascular necrosis of the femoral head which often becomes chronic.
Evaluation of the sickle cell disease patient
The work-up of patient with a crisis should include a complete history, a thorough physical examination and selected laboratory tests based on the clinical assessment of the patient. The physician should look for reversible conditions known to precipitate crisis especially in those with vaso-occlusive crisis and haemolytic crisis. Malaria and other forms of infections must be excluded. In patients with very severe crisis requiring hospital admission, laboratory investigation should include blood film for malaria parasites, microscopy, culture and sensitivity (MCS) of spectrum, urine and blood especially in those with prolonged fever. Full chemistry profile and a creatinine clearance may be required in patients with mandatory in those with chest symptoms or acute chest syndrome. The brain computed tomography scan and MRI is indicated in patients with stroke. The list of investigations is not limited and should be individualized.
Specific management
Optimal care for patients with sickle cell disease requires a multidisciplinary approach which includes the haematologist, paediatrician, anaesthetist, nurses, psychiatrist, family physician and social workers. The aim is to provide consistent longitude care for the patient. However, the extent of therapy is dictated by the type of crisis.
Pain management
The initial management should be aimed at providing rapid pain control. Assess pain severity by using subjective patient feelings complimented by objective parameters, example the usual analogue scale or categorical pain scale. Mild to moderate pain can be treated at home or a primary health care centre. Parental education on the appropriate use of non-narcotic analgesic (for example paracetamol), antimalarials and the liberal use of oral fluids are crucial. Severe acute pain requiring opiates should be treated in a hospital. The World Health Organization three step ladder pharmacological management of pain is usually adequate for patients with sickle cell disease:Step 1: Mild pain: non-opioid adjuvant
Step 2: Moderate pain: weak opioid (or low dose of undiluted opioid) non-opioid adjuvant.
Step 3: Severe/acute pain: strong opioid non—opioid adjuvant.
Non-opioid includes non-steroidal anti-inflammatory drugs and paracetamol.
Weak opioids include codeine, dihydrocodeine (DF 118), pentazocine and tramadol while the strong opioids include morphine and pethidine.
Adjuvant drugs are also known as the co-analgesic, they are used for the control of nausea and or vomiting, pain related anxiety and muscle spasm, and to control opiate induced constipation. They include antiemetics (metoclopramide and prochloperazine); benzodiazepines (diazepam) and laxatives. Treatment should be aggressive in patients requiring hospital admission. The following is recommended:
Malaria and any other precipitating factor must be treated.
Start patient on parental opioid analgesics, tailoring the choice and dose to the individual patient until pain is controlled. Give drug regularly every 3-4 hours.
Administer rescue dose of 25%-50% of the initial dose of opioids for breakthrough pain if adequate relief is not achieved.
Start patient on intravenous fluid to correct volume deficits (0.9% saline; and for further fluid replacement, use 5% dextrose). Give 3l/m/24 hours.
Administer adjuvant non-opioid analgesics: paracetamol, NSAID. Prescribe laxatives routinely and other adjuvants as necessary.
Monitor pulse rate, pain, vital signs, respiratory rate, sedation and oxygen saturation every 30 minutes until pain is controlled and stable, and then every 2 hours. Skip the rescue dose if the respiratory rate is less than 10 cycles/minutes or the patient is heavily sedated.
Consider reducing analgesia after 2-3 days and replacing injections with equivalent dose of oral opiates.
Discharge patient when pain is controlled on oral drug for 2-3 days, to continue follow-up on outpatient basis.
Previous trials have shown no clinical benefit for routine oxygen administration. The availability of haematology day-care facilities is particularly helpful in the management of sickle cell pain crisis. It enhances the coordinated management of the patient by specialized physicians and dedicated day-care nurses.
Acute chest syndrome
Acute chest syndrome is defined as a new infiltrate on the chest radiograph and may be associated with fever or respiratory symptoms. It affects 40% of all people with sickle cell disease and is a common reason for early mortality. Patients are often hypoxaemic and can deteriorate rapidly. Important aspects of therapy include:Oxygen is given to maintain partial pressure of arterial oxygen >75mmHg and oxygen saturation >95%, prolonged use of oxygen may depress erythropoiesis.
Close monitoring of fluid balance: dehydration promotes sickling while over-hydration can add a component of pulmonary edema and worsening acute chest syndrome.
Adequate pain: control and appropriate antibiotics ; macrolides are recommended because of frequent involvement of a typical bacteria.
Exchange transfusion may be necessary in those with rapidly progressive disease.
Incentive spirometry helps reduce atelectasis and has been shown to reduce the incidence of acute chest syndrome in those with thoracic bone pains.
In general, a high index of clinical suspicion is important to make a diagnosis, as there is no specific management for this problem.
Priapism
The goals of management are to help with the emptying of the corpora carvenosa, relieve patients’ pain and prevent impotence. Patients with mild acute priapism can be managed at home with increased oral fluid intake, frequent bladder emptying, exercise, warm baths and simple non-opioid analgesics. Non-resolution after 3 hours should prompt urgent medical intervention. The management of acute prolonged priapism includes exclusion of possible etiology (recent trauma, infections etc).Initial treatment include generous intravenous hydration, parenteral analgesics using opioids, insertion of Foley’s catheter to promote bladder emptying and exchange blood transfusion to decrease the percentage of sickled cells to <25%. Studies have suggested that if after 24 hours of completing exchange transfusion detumescence has not begun, surgical interventions (penile aspiration, spongiosum carvenum shunts Winter’s procedure or Hashmat shunt) are recommended. Impotence remains a frequent complication of priapism.
Blood transfusion
Most sickle cell disease patients have haemoglobin values of 6-10g/dl haemoglobin of 5g/dl or less or a declining haemoglobin value of 2g/dl from the patient baseline level have been used as a guide for simple transfusion therapy. Individuals with uncomplicated haemolytic crisis and/or aplastic crisis are adequately managed with simple transfusion therapy. Any underlying precipitating factor must be sought and treated. Where possible, patients should be transfused to their baseline (steady-state) haemoglobin. Exchange transfusion is aimed at reducing the HbS levels to <25% and may be indicated in acute chest syndrome refractory vaso-occlusive crisis, during surgery and in (complicated)pregnancy/peuperium, cerebrovascular events and multiple organ failure.
Splenic sequestration
This presents a range from mild splenic enlargement with a slight fall in haemoglobin to gross, rapidly developing and life-threatening episode. The etiology is uncertain. It is common in childhood and may complicate pregnancy. The treatment of acute episode requires immediate packed cells transfusion with a good prognosis is diagnosed early. Recurrences may be prevented by chronic transfusion which helps to improve splenic function. Splenectomy has been recommended for recurrent episodes.
Newer trends
Hydroxyurea increases the production of HbF and thus reduces the severity of sickle cell disorder by preventing the formation of HbS polymers. At present, hydroxyurea, is considered in patients with severe disease, it has been shown to reduce the frequency of painful crisis and decrease the frequency of acute chest syndrome. Regular blood count and strict monitoring of patient is mandatory. Also, studies have shown that the inhalation of low doses of nitric oxide,(NO) reduce the P of the oxygen saturation curve which reduces deoxyhaemoglobin S concentration and consequently the tendency to polymer formation. NO has preferential vasodilatory effect on pulmonary vasculature by an ill-understood allosteric mechanism and may improve outcome in acute chest syndrome.
Conclusion
The understanding of the various steps involved in the sickling process has improved the approach to the management of sickle cell crisis. Dedicated day-care centres, prompt diagnosis, adequate use of analgesia and judicious use of blood transfusion have improved patient’s outcome.