Sickle Cell

Sickle cell disease is really common where I work and I've seen lots of different presentations. Our management seems a little different, and more rational, than some of the guidelines I've found on the internet - it was an interesting literature search.

Patho-physiology
Once again, the Calgary guide explains this better than I ever could.

The Calgary Guide

Glu --> Val substitution of the sixth amino acid of the beta-globin chain
Get HbS instead

Heterozygous: 45% HbS, 52% HbA, 2% HbA2, 1% HbF
  Sickle trait - increased renal cancer but no "disease"
Homozygous: 90% HbS, 8% HbF, 2%HbA2

HbS is less soluble so might precipitate. This means they become sickle shaped. Can be precipitated by dehydration, hypoxemia or acidosis.

Clinical Signs
Have you looked at the Calgary guide? It is a very under-rated resource.

 

Crisis

A painful crisis is the most common presentation to the ED for sickle cell.  Vaso-occlusion causes many problems - priapism, splenic sequestration, dactylitis, splenic infarction, stroke, renal failure, necrosis of the femoral head, blockage of the lung vessels and painful crises. 

Painful crises are more common in the limbs and backs. The pain is normally throbbing, sharp or gnawing. 

- Splenic infarction means RBC not removed by the spleen leading to Howell-Jolly bodies on blood smear. 

- Aplastic crisis causes anaemia, pallor, tachycardia and a low reticulocyte count. 

- Extravascular haemolysis causes a normocytic anaemia. As the red blood cells breakdown, there can be jaundice, and increase in gallstone formation. There can be increased marrow production to compensate for haemolysis. 

Nocturnal Enuresis

Pulmonary Hypertension

Develops in 15-35% of children with SCD.

Acute Chest Syndrome

This is most common in children, especially at around age three. It presents with fever, chest pain, difficulty in breathing and shadows on CXR. 

Need to treat the pneumonia / infection and have urgent transfusion. Be careful as overhydration may lead to oedema and pulmonary vascular congestion. 

Splenic Sequestration

This is a major cause of mortality, especially in those less than five years old. Major causes a rapid drop of Hb, pallor, LUQ pain, splenomegaly. Minor is more gradual onset. 

Neurological Disease

Strokes are common - up to 25% of patients. They need urgent imaging, and urgent exchange transfusion.

Dactylitis

This is often the presenting feature in children, and normally resolves in a few days. 

Hyphema

If there is any eye trauma, look carefully for a hyphema - it may not be obvious. Refer anyone who has protrusion of the eye, changes in visual acuity or loss of vision. 

Patients with sickle are risk of hyphema triggering acute narrow angle closure glaucoma. 

Investigations

Two group and saves if transfusion likely - patients with sickle cell likely to have abnormal antigens. 

D-dimers are unhelpful as levels are usually elevated. 

CXR, ABG, LFTs (jaundice or abdo pain), reticulocytes, blood and urine cultures (if febrile), USS abdo, parvovirus B19 serology (Hb drop, low reticulocytes Transient red cell aplasia (TRCA) is caused by infection with parvovirus B19, which causes red cell production to halt for 3-7 days), brain imaging, limb x-rays, CRP. 

Consider serology for atypical respiratory organisms and urine for pneumococcal and legionella antigen. 

Look for mycoplasma infection - red cell agglutination on a stained blood film and cold agglutinins in serum.

Look for parvovirus B19 - erythema infectiosum or slapped cheeks, gloves and socks syndrome (painful erythema of hands and feet), arthropathy, aplastic crisis.

Management

Oxygen - only if sats are low. 

Antibiotics - really consider antibiotics if CRP>25 - but not amoxicillin as it is so similar to pen v - consider co-amox or tax. Stop prophylactic antibiotics if starting regular treatment. Prophylactic penicillin should be used in children until five years old, unless they had a splenectomy or invasive pneumococcal infection. 

Transfusion - consider. If Jehovah's witness need transfusion, go ahead as per normal,  then contact legal department who arrange out of court hearing and you can normally transfuse them within an hour! And most parents are happy because they've done their bit. 

Hydroxycarbamide  (also known as hydroxyurea) - stop if febrile or low platelets as can cause cardiomyopathy and neutropenia. 

Hydroxyurea - more than three crisis in twelve years, or sickle cell-associated pain, or any infants older than nine months. 

Folic acid - 5mg OD
Hydrozine - 25mg BD PO for itching
Analgesia
Hydration - oral if tolerated
Thrombo-prophylaxis

NICE Guidelines
- Treat as a medical emergency
- Analgesia within 30min
- Obs
- Offer opioid bolus for severe and moderate pain
- Do NOT give pethidine

- Offer patients PCA, and treat opiate side effects

References
http://learning.bmj.com/learning/module-intro/.html?moduleId=10047809&searchTerm=%E2%80%9Csickle%E2%80%9D&page=1&locale=en_GB
http://calgaryguide.ucalgary.ca/slide.aspx?slide=Sickle%20cell%20disease.jpg
http://calgaryguide.ucalgary.ca/slide.aspx?slide=Sickle%20cell%20disease%20signs.jpg
http://www.epmonthly.com/departments/cme/cme-archive/sickle-cell-10-things-every-ep-should-know-about-scd-/
http://www.nice.org.uk/guidance/cg143/chapter/recommendations 
http://thorax.bmj.com/content/58/8/726.full
http://lifeinthefastlane.com/ccc/sickle-cell-crisis/
http://wikem.org/wiki/Sickle_cell_crisis
http://wikem.org/wiki/Acute_Chest_Syndrome
http://radiopaedia.org/articles/sickle-cell-disease
http://www.nhlbi.nih.gov/health-pro/guidelines/sickle-cell-disease-guidelines
http://www.bcshguidelines.com/documents/sicklecelldisease_bjh_2003.pdf
http://www.rch.org.au/clinicalguide/guideline_index/Sickle_Cell_Disease_Guideline/
http://www.rch.org.au/clinicalguide/guideline_index/Sickle_Cell_Disease_Guideline/#fever
http://emedicine.medscape.com/article/205926-treatment
https://www.rcog.org.uk/globalassets/documents/guidelines/gtg_61.pdf
http://www.spah.scot.nhs.uk/Documents/Adult%20Guidelines.pdf
http://www.transfusionguidelines.org.uk/transfusion-handbook/8-effective-transfusion-in-medical-patients/8-6-haemoglobinopathies
http://www.ststn.co.uk/wp-content/uploads/2012/02/e.-hydroxyurea-2010.pdf

http://www.nice.org.uk/guidance/cg143