Sickle Cell Disease

A: phenoxymethyl penicillin (PO) 125mg for children younger than 3years; phenoxymethyl penicillin (PO) 250mg for children 3 years and older twelve hourly until 5years of age in all  children with SCA.  

Immunisation against pneumococcal infection 

A: pneumococcal conjugate vaccine (PCV-13) from two months of age, 3 doses 8 weeks apart (i.e at age 2months, 4 months and 6 months) and a booster dose between 12-15  months. If the child has not previously received this vaccine, then at least one dose should  be given between 6-18 years. PCV-13 and vaccine against H. influenza is incorporated in  Tanzania EPI schedule. 

S: pneumococcal polysaccharide vaccine (PPSV-23) - at 2 years then after every 5 years  for life. 

Encourage  oral  fluids  first;  it  should  be  used  whenever  possible.  Give  IV  fluids,  preferably  normal  saline,  if  the  patient  is  unable  to  drink  well,  has  severe  pain,  or  abdominal  symptoms.

All children older than nine months with proven SCD; and in adolescents and adults with the following;  

• Recurrent  vaso-occlussive  crisis  (3  or  more  severe  episodes  requiring  admission  in  the last 12 months), 
• Severe and/or recurrent acute chest syndrome (ACS) (2 or more episodes in a lifetime), 
• Severe symptomatic chronic anemia that interferes with daily activities or quality of life,  
• Where chronic transfusion therapy is not feasible use it as an alternative to prevent new or recurrent stroke,  
• Silent infarcts, stroke and in patients with abnormal TCD (199cm/sec), 
• Recurrent priapism,  
• Chronic kidney disease on erythropoietin to improve anaemia. 

Principle of Dosage Initiation and Monitoring: 

S: hydroxyurea (PO) 15 mg/kg/day 24hourly; (5–10 mg/kg/day if patient has chronic kidney disease).  

S: hydroxyurea (PO) 20mg/kg/day, starting dosage for infants and children.    

Increase the dose by 2.5–5 mg/kg/day every 3 months,Maximum tolerated dose (MTD) should not  exceed 30mg/kg/day.  

Blood work monitoring 

• Bi-monthly  FBP,  reticulocyte  count  for  1  month,  then  monthly  for  3months,  then  once every 3months if blood counts remain stable. 
• HbF % analysis, liver function test, serum creatinine and urea every 6months. 
• Weigh patient every three months and adjust the dosage accordingly. 

Threshold for dose reduction 

• Neutrophil ANC < 1.5 X10⁹/L 
• Reticulocyte count < 80 X10¹²/L 
• Platelet count < 80 X10⁹/L 
• Hb < 6g/dl 

If haematologic toxicity occurs; 

• Discontinue hydroxyurea until counts recover, usually 1-2 weeks, 
• Reinitiate hydroxyurea at a dose 2.5 mg/kg/day less than the dose given before onset of cytopenias to achieve the maximum tolerable therapeautic dose,  
• Do FBP according to the initiation schedule. 

Note: 

• Clinical response to treatment with hydroxyurea may take 3-6months. A 6month trial on MTD is required before considering discontinuation due to treatment failure. 
• Hydroxyurea should be stopped at least three months prior to conception in both males and females  
• Hydroxyurea should be discontinued in all pregnant women 
• Hydroxyurea should be discontinued in all breastfeeding women 

Simple (Top-Up) Blood Transfusion:   

Indicated in symptomatic anaemia, orhaemoglobin level has dropped by > 2g/dl below the steady- state value.  

Exchange Blood Transfusion:   Aim to reduce HbS to 30%.  

Indications for Exchange Blood Transfusion 

• Cerebrovascular Accidents (CVAs)  
• Acute Chest Syndrome (ACS)  
• Prior to major surgery  
• Multi-organ failure, including Systemic Marrow Fat Embolism (SMFE)  
• Multiple pregnancies  
• Prevention of recurrent stroke.  

Relative Indications for Exchange Blood Transfusion 

• Intractable or very frequent severe crises
• Major priapism unresponsive to other therapy.

Note:

• Because  the  cardiovascular  system  adjusts  to  the  chronic  anaemia,  blood  transfusion  is  not routinely indicated in steady state SCD simply for the reason that haemoglobin level is below 8– 10g/dl.
• Packed red cells transfusion is preferred to minimize the risk of fluid overload

• Stop hydroxyurea 3 months before conception
• Educate the patient about the risks associated with pregnancy in SCD.
• Determine the haemoglobinopathy status of the partner.
• Document pre-pregnancy baseline results if any.
• Refer the patient to a high-risk antenatal clinic for proper follow up
• Prescribe routine prenatal vitamins, see under Obstetric and gynaecology chapter
• Prophylactic blood transfusion is not recommended.
• Vaginal delivery is preferred unless there is indication for caesarian section.
• Prescribe prophylaxis for venous thromboembolism (VTE) for patients with additional risk factors for VTE e.g history of VTE. See details under coagulation disorders section 3.5
• Monitor hydration status, warmth and give analgesia as needed after delivery.
• Assess and manage neonatal opioid dependency and withdrawal all infants with history of in utero opioid exposure.

Pharmacological Treatment. 

A:  acetylsalycylic acid (PO) 75mg 24hourly, starting from the second trimester to reduce  the risk of pre-eclampsia.

Acute chest syndrome 

• Life threatening – admit the patient in a high dependency unit or ICU,
• Diagnostic criteria – respiratory distress (fast breathing, SPO₂<95% on air) and/or pleuritic pain, cough, fever, tachycardia, infiltrates on CXR,
• Investigations – arterial blood gases, creatinine, electrolytes, ALT, FBP, malaria test, blood and urine culture and sensitivity, CRP, CXR, HPLC,
• Management  –  Give  supplemental  oxygen  to  maintain  SPO₂>95%,  analgesia  for  pain relief, fluids per hydration protocol, broad spectrum antibiotics while awaiting culture and sensitivity results, top up blood transfusion or exchange transfusion if expertise available.

Acute anaemia 

• Haemoglobin < 5g/dl or recent acute drop in Hb >2g/dl below steady state.
• Causes – infection, splenic sequestration, haemolytic crisis and aplastic crisis.
• Investigations – do FBP, reticulocyte count, creatinine, bilirubin, ALT, LDH, malaria test, urine and blood culture and sensitivity, blood grouping and cross-matching,
• Management  –  immediately  transfuse  packed  red  cells  10mls/kg  over  4hours,  repeat transfusion as needed as per transfusion protocol, treat the underlying cause, document size of liver and spleen.

Stroke

• See management details under central nervous system chapter,
• Exchange transfusion or top up transfusion to prevent recurrent stroke.