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Sickle Cell Disease is lifelong and can be life limiting. The condition is characterised by anaemia, episodes of acute painful crisis and an increased risk of infection. Clinical presentation and severity can be wide ranging.
Authorised personnel / specific staff competencies:
Inform on call haematology registrar of admission as soon as possible
During normal working hours patients can be assessed and treated on the Ward 2B Day Care unit with admission to the ward as needed. Out of hours - see flow chart below. The Haematology Middle Grade On Call should be informed of their attendance and will arrange admission to the ward where necessary.
CLINICAL ASSESSMENT:
A full history and examination must be carried out, paying particular attention to symptoms/signs of life-threatening complications, including acute chest syndrome, sequestration of aplastic crisis, or septicaemia. Extreme pallor, weakness, lethargy, breathlessness, headaches, fits, and priapism require urgent attention.
Note:
DISCHARGE FROM CASUALTY OR WARD:
If there are no other indications for admission, following discussion with the Haematology Specialist Registrar, a child can be discharged from Casualty or from Day Care with:
ROUTINE INVESTIGATIONS (ALL CASES):
Blood Tests
HbS % (only if on regular transfusion programme)
Microbiological Screen
Other Tests
ADDITIONAL INVESTIGATIONS:
Certain tests are done if indicated, as follows:
Test |
Indication |
Capillary or Arterial Blood Gases |
If deteriorating O2 sats in air |
Serum amylase Abdominal ultrasound |
Abdominal symptoms/signs Symptoms suggestive of cholecystitis |
Screen stool for Yersinia. Serum for Yersinia antibodies |
Patients on desferrioxamine (DFO) with diarrhoea/abdominal pain (STOP DFO) |
Erythrovirus B19 (Parvovirus) IgM serology and PCR |
Fall in Hb with low retics |
CT scan of head |
See stroke and other CNS complications |
X-rays of painful joints/limbs* |
Generally not helpful. See below |
ECG |
If possible arrhythmia or cardiac pain |
Throat, nose, sputum, stool, wound, CSF cultures etc |
As clinically indicated |
*X-rays of bones and joints show little or no change in the first week of an acute illness and rarely differentiate between infarction and infection. Ultrasound should be considered for suspected osteomyelitis. X-rays can be useful in confirming avascular necrosis as a cause of chronic or intermittent pain
INVESTIGATIONS (IF NEW TO THE HOSPITAL):
New patients to the hospital require all the routine investigations.
Additional Blood Tests
Consider HIV serology
Management is supportive unless there are indications for exchange transfusion. The aim of treatment is to break the cycle of: sickling, hypoxia and acidosis - all exacerbated by dehydration.
GENERAL MANAGEMENT INCLUDES:
ANALGESIA – SEE FLOW CHART BELOW
Monitoring
The following should be monitored in all patients on analgesia:
These observations should be performed at least every 30 minutes until the pain has been controlled and observations are stable, then according to local pain management protocols, or at least every 2 hours whilst the patient is on opiate analgesia. If the respiratory rate falls below 10/minute then any opiate infusion should be discontinued and consider the use of naloxone.
FIRST DOSE ANALGESIA SHOULD BE ADMINISTERED WITHIN 30 MINUTES
(FOR DOSES OF DRUGS REFER TO INFORMATION BELOW)
SEVERE PAIN
Intra nasal Diamorphine (IND) – if patient presents in ED –see below:
(For full guideline refer to Pain in children, management in the ED- “Guideline for using Intra nasal Diamorphine” 2015: Author Joanne Stirling).
It should be noted that IND and 1st dose of Oramorph should be given simultaneously. If IND contraindicated/unavailable, Oramorph or IV morphine should continue to be administered as per protocol.
Indications:
To be included as part of the first-line treatment of severe pain in a child (without IV access). For example, in children with pain secondary to:
Contraindications:
Protocol:
Dilute 5mg of diamorphine powder with specific volume of sterile water
Weight (kg) |
Volume of sterile water to be added | Final dose in mg (in 0.2mls) |
10 |
1ml | 1mg |
11 |
0.9ml | 1.11mg |
12 |
0.85ml | 1.18mg |
14 |
0.7ml | 1.43mg |
16 |
0.6ml | 1.67mg |
18 |
0.55ml | 1.82mg |
20 |
0.5ml | 2mg |
25 |
0.4ml | 2.5mg |
30 |
0.35ml | 2.86mg |
35 |
0.3ml | 3.33mg |
40 |
0.25ml | 4mg |
≥50 |
0.2ml | 5mg |
Oral morphine:
From |
From |
Dose |
1 months |
2 months |
50 - 100 micrograms/kg every 4 hours, adjusted according to response |
3 months |
5 months |
100 - 150 micrograms/kg every 4 hours, adjusted according to response |
6 months |
11 months |
200 micrograms/kg every 4 hours, adjusted according to response |
1 years |
1 years |
200 - 300 micrograms/kg every 4 hours, adjusted according to response |
2 years |
11 years |
200 - 300 micrograms/kg (maximum 10mg) every 4 hours, adjusted according to response |
12 years |
17 years |
Initially 5-10mg every 4 hours, adjusted according to response |
Stat IV bolus of morphine (if required) once access established. This will take 5-20 minutes to take effect. Dose should be given by titration over at least 5 minutes to assess efficacy of dose.
From |
To |
Dose |
1 year |
18 years |
100 micrograms/kg/dose (max 5mg initially) |
When pain control is established consider continuous infusion. If PCA/NCA is felt to be more appropriate then the pain team should be contacted (where available). MST may also be considered – see local pain management protocols. Efficacy of analgesia should be assessed repeatedly over the first few hours and adjusted if necessary. Patients will vary in their analgesic requirements.
Morphine infusion:
Set up values |
|
Concentration (mg/ml) |
20 micrograms/kg/ml (weight in kg = dose of morphine in mg; made up to 50mls with 0.9 saline). Maximum 50mg/50mls. |
Continuous infusion |
10 - 40 micrograms /kg/hour = |
To reverse opiate-induced hypoventilation: Naloxone should always be available
(see BNFc for dosing recommendations).
MODERATE PAIN
MILD PAIN
Oral Paracetamol:
From |
To |
Dose |
Neonate (32 weeks corrected gestational age and above) |
20 mg/kg for 1 dose, then 10-15 mg/kg every 6-8 hours as required. Maximum daily dose to be given in divided doses (maximum 60mg/kg/day) |
|
1 month |
2 months |
30-60 mg every 8 hours as required. Maximum daily dose to be given in divided doses (maximum 60mg/kg/day) |
3 months |
5 months |
60 mg every 4-6 hours as required. Maximum 4 doses per day |
6 months |
1 year |
120 mg every 4-6 hours as required. Maximum 4 doses per day |
2 years |
3 years |
180 mg every 4-6 hours as required. Maximum 4 doses per day |
4 years |
5 years |
240 mg every 4-6 hours as required. Maximum 4 doses per day |
6 years |
7 years |
240 - 250 mg every 4-6 hours as required. Maximum 4 doses per day |
8 years |
9 years |
360 - 375 mg every 4-6 hours as required. Maximum 4 doses per day |
10 years |
11 years |
480 - 500 mg every 4-6 hours as required. Maximum 4 doses per day |
12 years |
15 years |
480 - 750 mg every 4-6 hours as required. Maximum 4 doses per day |
16 years |
17 years |
0.5 - 1 g every 4-6 hours as required. Maximum 4 doses per day |
Oral Ibuprofen:
From |
To |
Dose |
1 months |
2 months |
5mg/kg 3-4 times daily |
3 months |
5 months |
50mg 3 times daily |
6 months |
11 months |
50mg 3 - 4 times daily |
1 years |
3 years |
100mg 3 times daily |
4 years |
6 years |
150mg 3 times daily |
7 years |
9 years |
200mg 3 times daily |
10 years |
11 years |
300mg 3 times daily |
12 years |
17 years |
300 - 400mg 3 - 4 times daily |
FLUIDS:
Dehydration occurs readily in children with sickle cell disease due to impairment of renal concentrating power (hyposthenuria). Diarrhoea and vomiting are thus of particular concern. An IV line should be established whenever parenteral opiates have been given, or if the patient is not taking oral fluids well. In the less ill patient who is able to drink the required amount, hydration can be given orally. As an alternative, consider a nasogastric tube in an alert patient.
A fluid chart should be commenced and careful monitoring of both input and output.
The ill child should be assessed for the degree of dehydration by the history; the duration of the illness; by clinical examination; and (if known) weight loss. Hb and PCV (Hct) may be elevated as compared with the child's steady state values.
Hyperhydration (150%) of normal requirements should be commenced on admission, as follows; fluid balance must be reviewed regularly; avoid fluid overload especially in those with respiratory or cardiac compromise.
Body weight (kg) |
Fluids (ml/kg/day) |
First 10 kg |
150 |
11- 20 kg |
75 |
subsequent kilograms over 20 |
30 |
For example:
An 8kg infant will require 150 x 8 = 1200ml per 24hrs (50ml/hr)
A 16kg child will require (150 x 10) + (75 x 6) = 1950ml per 24hrs (81ml/hr)
A 36 kg child will require (150 x 10) + (75 x 10) + (30 x 16) = 2730ml/24hrs (114ml/hr
OXYGEN:
This is of doubtful use if the patient has only limb pain, but may be given if requested by the patient. The patient’s oxygen saturation (SaO2) should be monitored by pulse oximetry with regular readings in air (minimum 4 hourly)
PHYSIOTHERAPY:
All children with acute chest or back pain and those requiring opiate analgesia should be referred to physiotherapy with a view to incentive spirometry or other measures as appropriate for age. Contact the Resp physio team by telephone in the first instance. Follow up with trakcare referral.
ANTIBIOTICS:
Infection is a common precipitating factor of painful or other types of sickle crises. These children are immunocompromised. Functional asplenia or hyposplenia occurs, irrespective of spleen size, resulting in an increased susceptibility to infection, in particular with capsulated organisms such as pneumococcus, neisseria, Haemophilus influenzae and salmonella – all of which can cause life-threatening sepsis.
OTHER DRUGS:
Please prescribe:
a) Folic Acid (oral)
From |
To |
Dose |
Birth |
1 month |
0.5mg once daily |
1 month |
12 years |
2.5mg – 5mgs once daily |
12 years |
18 years |
5mg – 10mgs once daily |
b) Antiemetic: eg Cyclizine (if required with opiate analgesia)
From |
To |
Dose |
1 month |
6 years |
0.5-1.0 mg/kg 3 times daily |
6 years |
12 years |
25 mg 3 times daily |
12 years |
18 years |
50 mg 3 times daily |
c) Laxatives, if receiving opiate analgesia e.g. Lactulose, Senna, Macrogols - doses adjusted according to response
Lactulose:
From |
To |
Starting Dose |
1 month |
1 year |
2.5 mls 12 hourly |
1 year |
5 years |
5 mls 12 hourly |
5 years |
10 years |
10 mls 12 hourly |
over 12 years |
|
15 mls 12 hourly |
Senokot liquid (5mls=7.5mg):
From |
To |
Starting Dose |
1 month |
2 years |
0.5ml/kg/dose at night |
2 years |
6 years |
2.5-5mls at night |
6 years |
12 years |
5-10 mls at night |
over 12 years |
|
10-20 mls at night |
d) Macrogols:
From |
To |
Dose |
Product |
1 month |
1 year |
1/2 – 1 sachet |
Laxido Paediatric |
1 year |
6 years |
1 sachet |
Laxido Paediatric |
6 years |
12 years |
2 sachets |
Laxido Paediatric |
12 years |
adult |
1 – 3 sachets |
Laxido |
e) Antipruritic (if receiving opiate analgesia)
Oral Chlorphenamine Maleate (Piriton):
From |
To |
Dose |
1 month |
2 years |
1 mg twice daily |
2 years |
5 years |
1 mg 4-6 hourly |
6 years |
12 years |
2 mg 4-6 hourly |
12 years |
adult |
4 mg 4-6 hourly |
Consider non-sedating antihistamines if sedated with piriton
f) Iron chelation therapy – e.g. Desferrioxamine (if they would receive this normally)
g) Thromboprophylaxis - LMWH (Clexane): consider in those ≥13yrs of age.
Please refer to Appendix 1 and also section 5.10 of the Anti thrombotic protocol (HAEM-007)
ABDOMINAL CRISIS AND GIRDLE SYNDROME:
Abdominal crises often start insidiously with non-specific abdominal pain, anorexia and abdominal distension. As abdominal pain is not an infrequent symptom in children, it can be difficult to diagnose. Constipation may often co-exist, especially if codeine or other opiates have been used as analgesia. In an abdominal crisis, bowel sounds are diminished, and there is often generalised abdominal tenderness; rebound tenderness absent. The abdomen is not rigid and moves on respiration. Vomiting and diarrhoea are less common.
Girdle (or mesenteric) syndrome may be said to be present when there is an established ileus, with vomiting, a silent distended abdomen, and distended bowel loops and fluid levels on abdominal x-ray. Some hepatic enlargement is common, and it is often associated with bilateral basal lung consolidation (early chest syndrome).
Differential diagnosis
Consider the possibility of surgical pathology such as acute appendicitis, pancreatitis, cholecystitis, biliary colic, splenic abscess, ischaemic colitis, peptic ulcer etc. Well localised or rebound tenderness, board-like rigidity or lack of movement on respiration are suggestive of these diagnoses. Ultrasound may be helpful. If surgical intervention is contemplated, exchange transfusion should be performed prior to laparotomy: this can be started pending clarification of the diagnosis.
Investigations
Management
Girdle syndrome may be an indication for top up or exchange transfusion – see ACS management.
ACUTE CHEST SYNDROME (ACS):
Acute sickle chest syndrome is an acute illness characterised by fever and/or respiratory symptoms accompanied by new infiltrates on chest x-ray.
It is likely to be multifactorial in origin. Sickling within the pulmonary vasculature leads to infarction and sequestration. Infection can precipitate or complicate ACS. The distinction between infection and sickling is difficult and management principles should be the same for the two conditions. Commonly pain in the thorax, upper abdomen or spine leads to hypoventilation, which may be exacerbated by opiate analgesia reducing respiratory drive. Basal hypoventilation leads to regional hypoxia, which triggers localised sickling with subsequent infarction and consolidation. Thus, a vicious circle is set up with sickling, leading to progressive hypoxia and in turn to further sickling.
Acute chest syndrome is one of the major causes of death from sickle cell disease. A high index of suspicion is needed to detect and treat early. Patients should be treated aggressively irrespective of disease phenotype.
Triggers
Symptoms
Signs
Differential Diagnosis
Sickle lung and pneumonia are often clinically and radiologically indistinguishable. However, consolidation in the upper and/or middle lobes, without basal changes, is suggestive of chest infection rather than sickle chest syndrome. Bilateral disease is most likely due to sickling, but atypical pneumonia should be considered. Pleuritic pain may also be due to spinal/rib/sternal infarction, or from subdiaphragmatic inflammation.
Investigations
Management - General Measures
Management - Transfusion
APLASTIC CRISIS:
A temporary red cell aplasia caused by B19 (Parvovirus) can lead to a sudden severe worsening of the patient’s anaemia. A viral prodromal illness may have occurred, but classical erythema infectiosum (‘slapped cheek syndrome’) is uncommon.
The main differential diagnosis is splenic sequestration. Aplastic crisis may affect multiple members of a family concurrently or consecutively.
Diagnosis
Management
STROKE:
Stroke is a potentially devastating complication of sickle cell disease, most commonly occurring in individuals with homozygous disease (HbSS). Vaso occlusion of the cerebral vessels leads to infarction, generally in the territory of the middle cerebral artery, and untreated the majority of patients will have a recurrence.
Predictive factors for stroke include those with a history of transient ischaemic attacks, chest syndrome, hypertension, a family history of sickle related stroke, or those with a low Hb F and/or a low total haemoglobin. The Stroke Prevention Trial (STOP) showed that children with trans-cranial Doppler (TCD) velocities of >200cm/sec are also at significant risk.
Investigations
Lumbar puncture may be necessary to exclude infection or subarachnoid haemorrhage.
Management
SUBARACHNOID HAEMORRHAGE:
Investigation
Management
CONVULSIONS
Febrile convulsions may occur with high fevers, including after vaccination, however it is important to distinguish these from convulsions due to cerebral sickling.
Convulsions are not uncommon following stroke, and may occur following administration of intravenous pethadine.
Investigations
Management
Immediate:
Definitive:
SPLENIC SEQUESTRATION:
Splenic sequestration is more common in infants and young children (< 3 years old).
It may be precipitated by fever, dehydration or hypoxia. Rapid sequestration of red cells can lead to sudden anaemia and even death from hypoxic cardiac failure with pulmonary oedema. In some patients it may have a more insidious onset and can be recurrent.
Symptoms
Signs
Investigations
Management
HEPATIC SEQUESTRATION
Symptoms
Signs
Investigations
Management
Priapism is defined as a sustained painful erection and is one of the vaso-occlusive complications of sickle cell anaemia. The prevalence of severe priapism in sickle cell is unknown, but a survey in young males suggested that 89% will experience priapism by 20 years of age and 25% of children with sickle cell disease related priapism are pre-pubertal.
Priapism can be acute/fulminant or stuttering:
ACUTE/FULMINANT PRIAPISM
STUTTERING PRIAPISM
The optimal management of priapism is still a subject of debate. This protocol is based on a recent review of the literature.
Aims of Treatment
The aim of treatment is threefold:
Outcome is dependent on the pubertal status of the patient and length of time to detumescence. Poor long term outcome in terms of impotence is associated with post-pubertal males and a long duration of erection. The likelihood of responding to intervention is also related to duration of erection with most procedures being most effective in the first 6 hours and relatively ineffective after 24-48 hours.
Hence PRIAPISM IS A UROLOGICAL EMERGENCY requiring rapid assessment and treatment to prevent irreversible ischaemic penile injury, corporal fibrosis and impotence.
Patient Education
Male sickle cell patients and their families should be educated about priapism early after diagnosis or transfer to the service and written information should be given. Specific enquiry should be made about this symptom at follow-up. They should be instructed to present to hospital immediately if an episode of priapism does not resolve within 2 hours.
History and examination
Investigations
General Principles of Early Management
Management Plan For Acute/Fulminant Priapism
If the patient has had previous episodes of priapism then medium to long term prophylaxis should be discussed (see stuttering priapism below).
Procedure for Aspiration and Irrigation
Table 1 (adapted from Donaldson et al 2014)
Drug |
Available Preparations |
Concentration |
Age and aliquot |
Further doses |
Epinephrine |
1 in 10,000 |
1 mL + 99 mL 0.9% saline (1 in 1 000 000 or 1 μg/ml) |
≥ 11 yrs: 15 mL 3-11 yrs: 10 mL <2 yrs: 2.5-5 mL |
≤4 doses at 10 min intervals |
1 in 1000 |
1 mL + 1000 mL 0.9% saline (1 in 1 000 000 or 1 μg/ml) |
|||
Etilefrine |
10 mg/mL |
None |
0-18 yrs: 0.5 mL |
≤2 doses at 10 min |
Phenylephrine |
10 mg/mL |
0.1 mL + 4.9 mL 0.9% saline (200 μg/ml) |
≥ 11 yrs: 0.5 mL |
≤10 doses at 5-10 min (max 1 mg) |
Suggested sympathomimetic preparation for intracorporal injection (ICI). This is an unlicensed indication and route of administration. When available Phenylephrine should be used in boys aged ≥11 years; Epinephrine should be used in boys ≤10 years. There are no reliable data on ICI ≤2 years; we recommend using a reduced dose of Epinephrine (Adrenaline).
Management of Stuttering Priapism
An exchange transfusion programme has the disadvantages of potential iron overload, alloimmunisation, difficulties with venous access and repeated hospital visits but has the advantages of reducing other sickle related morbidity during the period of transfusion.
Etilefrine is a direct acting alpha-adrenergic agonist. In normal physiological circumstances adrenergic impulses keep the penis flaccid in the absence of sexual stimulation.
Etilefrine has advantages over other alpha agonists such as epinephrine and phenylepinephrine in that it is rapidly absorbed orally and has a short half life (150 minutes) and it may have a lower risk of systemic hypertension. It appears effective in small trials but there is only limited experience in children. Systemic hypertension has not been seen in paediatric patients reported in the literature but should be assessed regularly on treatment.
Etilefrine is given in a dose of 0.5mg/kg daily. This can be given as one dose of 0.5mg/kg in the evening for patients with nocturnal priapism or 0.25mg/kg twice daily in other patients. It will not reduce other sickle cell related symptoms.
Hydroxycarbamide has been shown to be effective in reducing sickle related complications in children. There are case reports documenting its efficacy in treatment of recurrent priapism but this outcome was not studied in the large scale trials reported to date. It has the advantage of preventing other sickle related morbidity and reducing need for transfusion. Regular blood count monitoring is required throughout treatment and potential long term adverse effects are unknown.
HAEMATURIA:
Microscopic haematuria is common in sickle cell disease; macroscopic haematuria may be due to urinary infection or papillary necrosis. Passing of renal papillae may cause renal colic and ureteric blockage. Haematuria can also occur in patients with sickle trait.
Investigations
NOCTURIA AND ENURESIS:
Nocturia and enuresis are common in part due to obligatory high fluid intake, coupled with reduced urinary concentrating capacity. Cultural and familial influences may also play a part.
Reassurance, patience, and measures such as reward systems, bell and pad training, etc may be required. Referral to a local Enuresis Clinic or to the clinical psychologist may be appropriate.
URINARY TRACT INFECTIONS:
Not uncommon in sickle cell disease, in both sexes. It should be vigorously investigated and treated to prevent serious renal pathology. Haematuria, secondary to papillary necrosis, can precipitate UTI, but other factors must be excluded.
CHRONIC RENAL FAILURE:
Uncommon in children. Predictors include increasingly severe anaemia, hypertension, proteinuria, the nephrotic syndrome, and microscopic haematuria.
Investigations
Management
The ocular complications due to sickle cell disease are uncommon in children, however retinal vessel occlusion may begin in adolescence in particular in children with HbSC disease. Thus these children require annual ophthalmological assessment from puberty onwards. Also, children on regular transfusion regimens receiving desferrioxamine require annual ophthalmological assessment.
Management
Laser therapy is the treatment of choice for proliferative sickle retinopathy.
Vitreous haemorrhage and retinal detachment may occur.
Surgical treatment should not be undertaken without prior exchange transfusion.
GALLSTONES:
Pigment gallstones due to ongoing haemolysis are common in sickle cell disease, occurring in at least 30% of children. It is often asymptomatic but can precipitate painful abdominal crises and the girdle syndrome. It can also cause:
Differential diagnosis of abdominal complications:
Investigations
Management
Acute episode of cholecystitis:
Recurrent episodes of cholecystitis is an indication for cholecystectomy (see below):
Common bile duct obstruction:
Endoscopic retrograde chloangiopancreatography (ERCP) or emergency surgery. After one attack, refer for surgical opinion re elective cholecystectomy; generally laparoscopic, which does not require prior transfusion, however it may be best to exchange in case full laparotomy becomes necessary.
INTRAHEPATIC CHOLESTASIS:
Some patients experience episodes of severe hyperbilirubinaemia (conjugated + unconjugated) with moderately raised alkaline phosphatase, associated with fever and hepatic pain in the absence of demonstrable stones. These episodes are thought to be due to severe intrahepatic sickling.
Management
This complication may start in adolescence and often gives rise to chronic pain and limitation of movement due to joint damage, rather than ongoing vaso-occlusion.
PRESENTATION:
DIFFERENTIAL DIAGNOSIS:
These are suggested by swinging pyrexia, severe systemic disorder, positive blood cultures and toxic granulation in neutrophils.
Investigations
Management
DELAYED PUBERTY:
Management
FERTILITY:
Girls are normally fertile, whereas many boys with HbSS and S/Beta thalassaemia have reduced sperm counts and reduced sperm motility - some may have erectile impotence because of past priapism.
Anaemia alone in an otherwise well child is not an indication for transfusion unless the haemoglobin falls to less than 5g/dl, in which case discuss with Senior Trainee/Consultant. To prevent red cell alloimmunisation Rh and kell compatible blood should be used whenever possible. All patients should have red cell phenotyping done at diagnosis.
Options for transfusion include simple additive transfusion, exchange transfusion and hypertransfusion regimens. All regularly/heavily transfused patients should be monitored for iron overload.
SIMPLE OR “TOP-UP” TRANSFUSION:
EXCHANGE TRANSFUSION:
Exchange transfusion is undertaken to rapidly reduce the percentage of sickle cells in the circulation when a patient develops a life-threatening complication of the disease. It is not to be undertaken lightly, as the possible complications are considerable. However, patients with the following problems justify the risks:
Exchange transfusions should only be undertaken after discussion with the Haematology consultant on call:
Aim
Critically ill patients may require exchanges to be more frequent than daily. Where possible, leave a 4 - 8 hour break between exchanges. In the very sick patient, the procedure is a continuous process. In these patients, particular attention should be paid to PaO2, CVP, acid-base balance, Ca++, citrate load, core temperature and clotting.
Preliminary Investigations
Automated Exchange Transfusion
A national SNBTS SOP for automated red cell exchange exists and is available through SNBTS
Information required:
Adequate venous access is required. If it is anticipated that adequate access may not be obtained via peripheral access then insertion of a large bore double lumen catheter should be arranged.
Manual Exchange Transfusion
Volumes required
The initial aim is to exchange 1.5 - 2 times the child's blood volume, divided over 2-3 procedures. 28ml/kg is the approximate red cell mass from infancy to teenage years.
Volume (ml) of SAG-M blood for each exchange should be:
28 x weight (in kg) = volume in mls
Venous Access
Two ports of venous access are required; one for venesection, the other for administering blood and crystalloid; in certain circumstances, an arterial line may be used.
Procedure
The aim is that this should be an isovolaemic procedure with frequent, monitoring of blood pressure, heart rate and oxygen saturations every 15 minutes, and 1 hourly temperature monitoring. Exchanges are done in ‘aliquots’ of approximately 1/10 of the total to be exchanged.
At the end of the procedure check FBC, HbS %, urea and electrolytes including calcium. If HbS not <20%, then consider continuing with further exchanges, to give a final Hb of 110g/l and Hb S ideally between 10% and 20%.
Ensure the child is well hydrated between successive exchanges, as the haematocrit of transfused packed cells is higher than that of the venesected blood. Keep PVC <0.4. In larger volume exchanges consider giving a break between 2nd or 3rd unit and giving dextrose/saline to rehydrate.
Possible Immediate Complications
SICKLE CELL - CHRONIC TRANSFUSION
Aims
Investigations
Record results and transfusion volume (see Appendix 2: Transfusion Record)
Consult Trust Transfusions Policy [Staffnet link]
It is important to educate the patient and family about the potential complications of iron overload and the need for chelation therapy and monitoring. Patients and other family members should be encouraged to be involved in the self-administration of medications at home.
When to start:
For those on regular top-up transfusions with a rising ferritin chelation should commence when the ferritin reaches 1000mcg/l, usually after 10-20 transfusions. Ferritin is an acute phase reactant and should be elevated on 2 occasions when the patient is well.
What to start:
Age | 1st line | 2nd line |
<2 years | Desferrioxamine | Deferasirox |
2-6 years | Desferrioxamine OR Deferasirox | |
>6 years | Desferrioxamine OR Deferasirox | Deferiprone |
Chelators, dose, toxicities and drug safety monitoring - for full list of side effects and dosing consult BNF and SPC.
Desferrioxamine |
|
Dose range |
Starting dose 30-40mg/kg/d for 8-12 hours 5 d/wk, increasing to 40-50mg/kg/d 5-7 d/wk |
Side effects |
Ototoxicity Lens opacities Yersinia infection - abdominal pain and fever Growth impairment |
Safety monitoring |
Annual audiometry Annual ophthalmology Stop drug and admit for investigation and treatment if patient develops diarrhea (consider Yersinia) Sitting and standing height |
Deferiprone |
|
Dose range |
75mg/kg/d in 3 divided doses, may increase to 100mg/kg/d |
Side effects |
Neutropenia and agranulocytosis (2%) GI upset, transaminitis Joint pains |
Safety monitoring |
Weekly FBC Patient advice re fever Monthly LFTs |
Deferasirox |
|
Dose range |
20-40 mg/kg/d in 1-2 divided doses |
Side effects |
GI upset Transaminitis Reversible increase in creatinine, protinuria Rash |
Safety monitoring |
Creatinine monthly (weekly 1st 4 weeks) Urine protein creatinine ratio (monthly) LFTs monthly (weekly 1st 4 weeks) |
Drug and Dose adjustment:
Dose increase:
When to change chelator:
Dose reduction:
Iron overload toxicity monitoring
Hydroxycarbamide has been shown, in a randomised controlled trial in young children, to be safe and to reduce the frequency of painful crisis, dactylitis and acute chest syndrome. In long-term studies in adults, it has been shown to similarly reduce episodes of pain and acute chest syndrome and to reduce mortality with no evidence of reduced fertility or increased incidence of malignancy, including leukaemia.
The exact mechanism of action is under investigation but is likely to include the induction of Haemoglobin F production, inhibiting sickle haemoglobin polymerisation within the cell; reduction in adhesion molecule expression, thereby reducing red cell – endothelial interaction; reduction of white cell and platelet counts.
PATIENT ELIGIBILITY:
Patients with sickle cell disease (HbSS or S beta zero-thalassaemia or HbSC) who have:
PATIENT EXCLUSION CRITERIA:
Inability to attend clinic regularly for follow up and FBC monitoring:
BASELINE INFORMATION
Patients and their parents/carers should be given an information leaflet and the use of hydroxycarbamide should be discussed with them on at least 2 separate occasions. Current information about known side effects including myelosuppression and the possible risks of subfertility and malignancy risk should be discussed and documented in the notes. Male patients should be assessed for and offered sperm storage if appropriate.
CONSENT
Written consent should be obtained using the generic chemotherapy consent form (RHC-HAEM-ONC-TEMP-002) and filed in patient record. Toxicity monitoring is carried out as detailed below and documented in the case record.
SIDE EFFECTS:
BASELINE INVESTIGATIONS
DOSE AND MONITORING:
Over 100 stem cell transplants for sickle cell disease have been performed to date.
In the UK and other developed countries, childhood mortality has been considerably reduced through neonatal screening programmes, parent education, the introduction of penicillin prophylaxis and comprehensive health care provision by haemoglobinopathy counsellors, health visitors, social workers and haematologists.
Nonetheless, SCD remains a heterogeneous condition in its manifestations and impact on patients and their families. A subset of children experience major life-threatening disease-related complications in childhood and even with optimal medical care the majority of patients with SCD will have sustained some major organ or tissue damage by the age of 30. This has led several centres to offer HSCT to selected children with SCD who are at risk of major morbidity or premature death, either as a consequence of serious complications sustained early in childhood or because they live in parts of the world where access to good quality medical care is limited.
Current results from Europe and the US give a survival of 90-95% and cure of SCD of around 85%. HSCT is also associated with improved growth, stable CNS imaging and improved pulmonary function in the majority of patients.
CRITERIA FOR SELECTION OF SICKLE CELL PATIENTS FOR SCT:
Paediatric Haematology Forum, UK |
INCLUSIONS |
1. Informed family, including patient, consent |
2. <16 years and HLA matched sibling |
3. One or more of the following conditions: i) SCD related neurological deficit, CVA or subarachnoid haemorrhage ii) > 2 episodes of acute sickle chest syndrome * or |
4. Problems respecting future medical care |
EXCLUSIONS |
1. Absence of informed consent |
2. Patient >16 years |
3. No HLA identical family donor |
4. Donor with ‘major’ haemoglobinopathy |
* There is increasing evidence of the efficacy of hydroxyurea in children with SCD in the prevention of recurrent chest syndrome and recurrent painful crises, and the reduction in blood transfusion requirement, thus it should be considered as an alternative to SCT in the first instance.
General anaesthesia in patients with sickle cell disease is associated with a significant risk for post-operative complications, especially acute chest syndrome. Surgery should be undertaken with close liaison and good communication between the surgeon, anaesthetist and medical and nursing staff.
Preoperative Management
Patients should be scheduled early on the operating list to ensure that they avoid prolonged fasting time and are unlikely to be cancelled. Consider IV hydration whilst fasting.
Transfusion
Most patients with sickle cell anaemia (HbSS, Sβthal) are relatively asymptomatic with an Hb around 65g/l. This chronic steady state anaemia itself is not an indication for transfusion. The decision to transfuse a patient preoperatively depends on the type of operation and the patient’s past sickle related complications. Patients with a history of recurrent chest crises or central nervous system disease or patients undergoing major surgery are at greater risk of developing sickle related problems peri-operatively. A three-tiered approach can be taken:
Note that exchange transfusion needs to be planned well in advance of the expected date of surgery. Early liaison with the Haematology team is essential.
Children requiring emergency surgery should be treated similarly if time allows. If this is not possible surgery should proceed and suitable blood should be cross-matched to allow exchange transfusion post-operatively if the patient experiences sickle related complications.
The need for pre-operative transfusion in children with HbSC should be considered on a case-by-case basis dependent on past history of complications and surgical risk.
Intraoperative Management
Post-operative Management
THE AIMS OF THE CINIC ARE TO:
NEW PATIENTS:
PROPHYLAXIS AGAINST PNEUMOCOCCAL INFECTION:
There is now very good evidence that penicillin prophylaxis protects against pneumococcal septicaemia / meningitis PROVIDED IT IS TAKEN REGULARLY. It is essential that all children with sickle cell disease take penicillin twice daily continuously, starting at the age of three months. Make sure that the parents are prepared to give it continuously and keep this under review. Try and get the children taking tablets as early as possible (crushed and mixed with fruit juice if needed). Pharmacies may be prepared to dispense the dry suspension or receive a batch of prescriptions from the surgery to avoid collecting a weekly script for the suspension.
Penicillin V
From |
To |
Dose |
birth |
1 years |
62.5mg twice daily |
1 year |
6 years |
125mg twice daily |
6 years |
onwards |
250mg twice daily |
If truly Penicillin allergic Erythromycin can be used instead:
From |
To |
Dose |
birth |
2 years |
125mg twice daily |
2 years |
8 years |
250mg twice daily |
8 years |
Onwards |
500mg twice daily |
Folic Acid
From |
To |
Dose |
birth |
1 month |
0.5mg daily |
1 month |
12 years |
2.5mg – 5mgs daily |
12 years |
18 years |
5mg - 10mgs daily |
Management of Nutritional Vitamin D deficiency in children & adolescents
Working Definition of Rickets
Raised Alkaline Phosphatase (ALP) and classic X-ray changes
Classic biochemical picture - Ca (↔/↓), P(↔/↓), ALP(↑), PTH (↔/↑), 25HCC (↓)
Vitamin D serum levels: |
Deficiency <30 nmol/l Insufficiency 30-50 nmol/l Sufficiency >50 nmol/l |
Baseline Investigations
Summary of Suggested Treatment
Age |
Vit D (12 weeks)* |
Calcium 4 weeks** |
Single dose |
Maintenance dose |
<3 months |
2000u od |
none |
Not applicable |
400u |
3-12 months |
2000u -2400u od |
500mg |
50 000u |
400u |
1-12years |
3000- 6400u od |
500mg – 1000mg |
150 000u |
600u |
>12yrs |
6000u – 6400u od |
1000mg – 1500mg |
300 000u |
600u - 800u |
* range of doses given to allow for use of liquid and solid dose forms
**if hypocalcaemic
Full guideline can be found at:
Appointments
Children with Sickle cell disease are seen at least 4 monthly until 2 years of age and four to six-monthly thereafter, unless there are medical, educational or psychosocial concerns in which case they should be seen more frequently.
Vaccination Schedule
In addition to routine childhood vaccinations children with sickle cell disease require:
Pneumococcal polysaccharide (23 valent) vaccine should be given from the age of 2 years at a dose of 0.5ml IM at least 2 months after PCV13. This should be repeated at 5 yearly intervals thereafter. Pneumococcal antibody titres can be checked if the immunisation status is unknown.
Children presenting late for vaccination should receive 2 doses (separated by at least 1 month) of the 13 valent Pneumococcal polysaccharide conjugate vaccine (Prevenar) before 12 months and a 3rd dose at 13 months (See "Green Book" for further information on dosing in those presenting after 12 months of age).
Hepatitis B Vaccine (recommended for all children with HbSS and HbSBthal, mandatory for children receiving blood transfusions).
Injection |
Dose |
Injection |
Dose |
Injection |
Dose |
1st |
0.5 ml IM |
2nd, |
0.5 ml IM |
3rd, |
0.5 ml IM |
All children requiring blood transfusions, whether as an elective or emergency procedure should receive Hepatitis B vaccination. Hepatitis B antibody levels should be checked 2-4 months after 3rd dose to ensure an adequate response (>100 iu/ml).
BCG vaccination should be given according to national guidelines and will be indicated at birth in many children from this patient population.
Influenza vaccine is also recommended to be given each Autumn.
Meningococcal Vaccination: Meningitis B vaccination is now given as part of the Routine Childhood vaccination programme as is Meningitis ACWY. Where vaccination status in unclear or absent, a catch up programme should be given in accordance with the "Green Book" - Immunisation against Infections.
Malaria Prophylaxis is recommended
Click here to open a pdf of the Adolescent Risk Assessment for VTE form.
Last reviewed: 09 May 2018
Next review: 01 December 2019
Author(s): Dr E Chalmers
Version: 6
Approved By: Schiehallion Clinical Governance Group
Document Id: RHC-HAEM-ONC-007