Sickle cell disease

Cite this article as:
Rowenne Smith. Sickle cell disease, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.27598

Abigail is a 10 month-old female presenting to the Emergency Department with a history of profound lethargy, pallor and a mildly distended abdomen over the last few hours. She has no past medical history, her immunisations are up to date, and she has no known allergies. Her parents report that she is usually well, however they have noticed recent swelling of her hands and feet over the last month. Her parents are originally from Nigeria. In the Emergency Department she is pale and flat. 

She is tachycardic with a heart rate of 180bpm and afebrile. On examination she has a prolonged capillary refill time of 5 seconds and cool peripheries. She has a soft systolic murmur. Her spleen measures 7cm below the costal margin and she squirms on abdominal palpation. There is no history or evidence of trauma. 

Intravenous (IV) access is obtained and bloods are sent including a venous blood gas, blood culture, FBE, blood group and cross match, LFT and UEC. 

Abigail is given a 10ml/kg fluid bolus of 0.9% sodium chloride and commenced on broad-spectrum antibiotics. After a second 10ml/kg bolus her capillary refill time and heart rate improve but she remains very lethargic. 

You are notified by pathology that Abigail’s formal haemoglobin is 64 g/L and she is thrombocytopaenic with a platelet count of 80 x 109/L. The white cell count is within normal limits. 

You send for an urgent blood transfusion and arrange a PICU review.

The treating team is contacted by the haematologist who has reviewed her blood film and noted the presence of target cells, Howell-Jolly bodies and sickle cells. 

What is the diagnosis? Abigail has presented in hypovolaemic shock secondary to splenic sequestration as a first presentation of sickle cell disease. 

What is sickle cell disease?

Sickle cell disease (SCD) is a genetic disorder of haemoglobin synthesis.

Haemoglobin is a tetramer comprised of four polypeptide globin chains, each containing a haem molecule (which reversibly binds oxygen). Beyond infancy, adult haemoglobin (HbA) replaces foetal haemoglobin (HbF) as the predominant haemoglobin molecule. HbA consists of two alpha and two beta globin chains. 

SCD is caused by a point mutation in the beta globin gene resulting in a structurally abnormal haemoglobin molecule, HbS. 

The primary event in sickle cell pathology is polymerisation of HbS, distorting the red cell shape and leading to the characteristic sickle appearance.  Polymerisation can occur in the setting of deoxygenation, acidosis, pyrexia and dehydration. Recurrent episodes of sickling cause red blood cell (RBC) membrane damage and an irreversibly sickled cell.

Sickled RBCs adhere to the vascular endothelium and circulating RBCs causing occlusion of the microvascular circulation (vaso-occlusion). Sickled RBCs also undergo haemolysis, with an average RBC lifespan of only 17 days.

The physiological changes in RBCs result in a multisystem disease with the following key features:

  • Chronic haemolytic anemia
  • Painful vaso-occlusive episodes
  • Multi-organ damage from micro-infarcts (including cardiac, skeletal, splenic and central nervous system).

Inheritance and incidence

Sickle cell anaemia is inherited in an autosomal recessive pattern.

It is one of the most common, severe monogenic disorders worldwide. The prevalence of the disease is high among individuals of sub-Saharan African, Indian, Saudi Arabian and Mediterranean descent. 

It is estimated that 312 000 neonates are born with sickle cell anaemia globally each year, over 75% of whom are born in sub-Saharan Africa.

Terminology

SCD refers to a group of disorders characterised by the presence of at least one HbS allele in addition to a second beta globin gene mutation. 

In sickle cell anaemia, individuals are homozygous for HbS (HbSS). This is the most frequent and severe form of the disease. Other variants of SCD include sickle β thalassaemia (HbSβ0 or HbSβ+ thalassaemia) and haemoglobin SC disease (HbSC)

Individuals with sickle cell trait are benign carriers for the condition, inheriting HbS and a normal beta globin gene (HbAS). Sickle cell trait confers a survival advantage in malaria endemic areas. 

Diagnosis

Universal newborn screening for SCD has been implemented in the United States and United Kingdom. SCD is not part of the newborn screening program in Australia.

SCD can be diagnosed through the identification of haemoglobin variants using haemoglobin electrophoresis, high-performance liquid chromatography (HPLC) or isoelectric focusing. 


Clinical manifestations 

Symptom onset usually occurs within the first year of life, often at around 5 months. The delay in clinical signs and symptoms is due to the higher levels of HbF in infancy preventing the polymerisation of HbS.

Clinical manifestations include:

Anaemia

  • Patients have a chronic, compensated haemolytic anaemia.
  • Major causes of an acute drop in haemoglobin include splenic sequestration and aplastic crisis. 
  • Aplastic crisis is caused by a transient arrest in erythropoiesis. This is typically caused by infection, commonly human parvovirus B19.

Vaso-occlusive pain episodes

  • This is the cardinal feature of SCD and accounts for the majority of hospital admissions.
  • Acute pain occurs due to ischaemic tissue injury secondary to vaso-occlusion of sickled cells.
  • The majority of episodes have no identifiable cause, however common triggers include infection, fever, acidosis, hypoxia, dehydration and exposure to temperature extremes. 
  • Common sites of pain include the chest, abdomen, back and extremities. Dactylitis is a common presentation in infants and toddlers, with back and abdominal pain more common in older children.
  • Management of vaso-occlusive episodes involves early and aggressive pain relief.

Splenic sequestration 

  • Splenic sequestration occurs when large quantities of sickled RBCs pool within the spleen. This is a potentially life threatening complication of SCD, with a risk of hypovolaemic shock.
  • Splenic sequestration is characterised by the sudden enlargement of the spleen, an acute drop in haemoglobin (>20 g/L), thrombocytopaenia and an increase in reticulocytes.
  • It typically occurs between the ages of 6 months and 2 years.
  • Management includes: 
    • Restoration of circulating blood volume with a blood transfusion. This increases the haemoglobin level directly and promotes the release of trapped RBCs by the spleen. 
      • Always discuss transfusion targets with the on-call haematologist, as autotransfusion will occur if haemoglobin is increased excessively or too quickly thereby increasing the risk of hyperviscosity syndrome. 
    • Active fluid resuscitation for hypovolaemia while awaiting a blood transfusion.

Infection

  • Functional hyposplenism occurs early in life due to splenic infarction.
  • Patients are at an increased risk of invasive bacterial infections, particularly by encapsulated organisms (Streptococcus pneumoniae, Haemophilus influenzae type B and Neisseria meningitidis).
  • Children with SCD presenting with a febrile illness require prompt assessment and empiric IV antibiotics.
  • Prevention strategies include: 
    • Prophylactic penicillin for all young children, ideally by the age of 2-3 months. This has been shown to significantly reduce the morbidity and mortality of pneumococcal infections.
    • Vaccinations as per the functional asplenia/hyposplenia guidelines.

Acute chest syndrome (ACS)

  • This is the leading cause of mortality in patients with SCD.
  • ACS is defined as a new infiltrate on chest x-ray associated with new respiratory symptoms (chest pain, respiratory distress, hypoxia or cough) and/or fever. 
  • The majority of patients do not have a single identifiable cause. Possible aetiologies include infection, atelectasis, vaso-occlusion and fat emboli from infarcted bone marrow.
  • Management includes supplemental oxygen, IV antibiotics, exchange transfusion, analgesia, physiotherapy and early PICU involvement if hypoxia or respiratory distress.

Stroke

  • Prior to routine screening with transcranial doppler ultrasound (TCD), clinically evident strokes occurred in up to 11% of patients with SCD by the age of 20 years.
  • Silent cerebral infarcts (evidence of infarction on neuroimaging in the absence of overt neurological symptoms) occur in up to 20% of children with sickle cell anaemia.
  • Management includes: 
    • Prompt neuroimaging – MRI is the modality of choice, however if unavailable non-contrast CT should be performed (contrast increases the risk of hyperviscosity).
    • Exchange transfusion.
  • Primary prevention strategies include:
    • Regular TCD assessment starting from the age of 2 years. 
    • Prophylactic regular transfusions for children with persistently elevated TCD velocity.

Priapism

  • Priapism is an unwanted, persistent erection in the absence of sexual activity.
  • The majority of episodes occur due to impaired venous outflow from the penis causing increased pressure, preventing normal arterial circulation.
  • Prolonged episodes of priapism (>4 hours) may lead to permanent tissue damage, with a risk of erectile dysfunction.
  • The optimal treatment is unknown. 
  • Management strategies include hydration, analgesia, oxygen therapy, showering, short aerobic exercise and urination (consider catheterisation if unable to empty bladder). Ice should not be used as cold temperatures may exacerbate sickling. 
  • Priapism extending beyond 4 hours is a urological emergency and consultation with the on-call haematologist and general surgical/urology team is required.

Avascular necrosis

  • Avascular necrosis occurs at a higher rate in children with SCD.
  • It commonly affects the femoral and humeral heads.

Sickle cell disease and COVID-19


There is limited data on the relationship between SCD and COVID-19. Children with sickle cell disease, thalassaemia and rare anaemias without other risk factors do not seem to be at increased risk of having severe disease. 

Emergency department management

Examination

  • Vital signs
  • Pallor or jaundice
  • Hydration status
  • Respiratory examination
  • Spleen examination, with comparison to baseline
  • Neurological examination
  • Localising signs of infection

Investigations

  • FBE and reticulocyte count
    • Splenic sequestration: haemoglobin below baseline, thrombocytopaenia, reticulocytosis
    • Aplastic anaemia: haemoglobin below baseline, decreased reticulocyte count (<1%)
  • Blood group and cross match
  • UEC and LFT (if jaundice or dehydrated)
  • Based on assessment
    • If febrile 🡪 blood and urine culture
    • If respiratory symptoms 🡪 consider chest x-ray
    • If neurological findings 🡪 urgent neuroimaging

Acute management

  • Prompt review and early discussion with the on-call haematologist.
  • Aggressive pain management – all patients with SCD presenting with pain should initially be managed as a vaso-occlusive episode, with the exception of chest pain, which should be treated as ACS.
  • Oxygen therapy for hypoxia or respiratory distress, aiming for SaO2 >96% or for comfort.
  • Fluid management:
    • Encourage oral fluids.
    • Consider IV fluids for fluid resuscitation or maintenance fluids if unable to tolerate oral intake.
    • It is important to recognise that excessive fluid administration can increase the risk of ACS.
  • A blood transfusion may be required, however this should always be in consultation with the on-call haematologist to discuss both the type of transfusion and transfusion targets. 
    • There is a risk of hyperviscosity if the haemoglobin is increased significantly over the patient’s baseline.
  • If febrile, commence IV antibiotics with a third generation cephalosporin, in addition to atypical coverage if there is a significant respiratory component. 
  • If respiratory symptoms, suspect ACS.

Chronic management

Blood transfusions are used to treat and prevent the complications of SCD. Types of transfusions include simple, manual partial exchange and automated red cell exchange (erythrocytapheresis).  

Hydroxyurea is a myelosuppressive agent used in the management of individuals with SCD, which has been shown to reduce the vaso-occlusive complications. 

A life-long cure for SCD is only available through haematopoietic stem cell transplantation.

Prognosis

Individuals with SCD have reduced overall life expectancy. In high-income countries, the survival of individuals with SCD is improving steadily through measures such as newborn screening, early initiation of antibiotic prophylaxis, immunisations and screening for children at high risk of stroke.

This is not the case worldwide. The majority of countries where SCD is a major public health concern lack national programs and key public health interventions. As a result, sickle cell anaemia-related childhood mortality in Africa is as high as 50-90%, with less than half of affected children reaching the age of five. The World Health Organization (WHO) estimates that 70% of sickle cell anaemia deaths are preventable with simple, cost-effective interventions. 

Key messages

SCD is a multisystem disease characterised by haemolytic anemia, painful vaso-occlusive episodes and multi-organ damage from micro-infarcts.

Early diagnosis, simple prophylactic measures and parental education improves the morbidity and mortality of SCD.

Always discuss with the on-call hematologist prior to transfusing a sickle cell patient due to the risk of hyperviscosity. 

References

Arlet JB, de Luna G, Khimoud D, et al. Prognosis of patients with sickle cell disease and COVID-19: a French experience [published online ahead of print, 2020 Jun 18]. Lancet Haematol. 2020;S2352-3026(20)30204-0. doi:10.1016/S2352-3026(20)30204-0

Bainbridge R, Higgs DR, Maude GH, Serjeant GR. Clinical presentation of homozygous sickle cell disease. J Pediatr. 1985;106(6):881-885. doi:10.1016/s0022-3476(85)80230-4

Brousse V, Buffet P, Rees D. The spleen and sickle cell disease: the sick(led) spleen. Br J Haematol. 2014;166(2):165-176. doi:10.1111/bjh.12950

Dick M, Rees D. Sickle Cell Disease in Childhood: Standards and Recommendations for Clinical Care (3rd edition, 2019). Available at https://www.sicklecellsociety.org/wp-content/uploads/2019/11/SCD-in-Childhood_Final-version-1.pdf [accessed 24 June 2020]

Grosse SD, Odame I, Atrash HK, Amendah DD, Piel FB, Williams TN. Sickle cell disease in Africa: a neglected cause of early childhood mortality. Am J Prev Med. 2011;41(6 Suppl 4):S398-S405. doi:10.1016/j.amepre.2011.09.013

Meier ER, Miller JL. Sickle cell disease in children. Drugs. 2012;72(7):895-906. doi:10.2165/11632890-000000000-00000

Odunvbun ME, Okolo AA, Rahimy CM. Newborn screening for sickle cell disease in a Nigerian hospital. Public Health. 2008;122(10):1111-1116. doi:10.1016/j.puhe.2008.01.008

Pace BS, Goodman SR. Sickle cell disease severity: an introduction. Exp Biol Med (Maywood). 2016;241(7):677-678. doi:10.1177/1535370216641880

Piel FB, Patil AP, Howes RE, et al. Global epidemiology of sickle haemoglobin in neonates: a contemporary geostatistical model-based map and population estimates. Lancet. 2013;381(9861):142-151. doi:10.1016/S0140-6736(12)61229-X

Therrell BL Jr, Lloyd-Puryear MA, Eckman JR, Mann MY. Newborn screening for sickle cell diseases in the United States: A review of data spanning 2 decades. Semin Perinatol. 2015;39(3):238-251. doi:10.1053/j.semperi.2015.03.008

World Health Organization. Geneva. World Health Organization – 59th World Health Assembly resolutions; 2006. Sickle-cell anaemia. https://apps.who.int/gb/archive/pdf_files/WHA59/A59_9-en.pdf [Accessed on 30th June 2020]

Blood Lactate: Freshly Squeezed

Cite this article as:
Alasdair Munro. Blood Lactate: Freshly Squeezed, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20682

Hermione is a 15-day old baby girl brought in for prolonged jaundice. She is breastfed and has no other risk factors. Her examination is normal other than being a bit on the yellow side. You ask the nurse to perform a blood gas to check her bilirubin, which is below 200. You notice the lactate on the gas is 4, but the nurse reports it was a “squeezed sample” which she suggests could explain the result?

Day 5: Bone marrow transplant

Cite this article as:
Tessa Davis. Day 5: Bone marrow transplant, Don't Forget the Bubbles, 2014. Available at:
https://doi.org/10.31440/DFTB.6203

In cases where leukaemia has not responded to treatment, or when the patient relapses, then a bone marrow transplant is a common course of treatment.

Bone marrow transplants are used with the aim of completely resetting the patients immunity.

View all our Acute Lymphoblastic Leukaemia Week posts

What are the other indications for a bone marrow transplant?

BMTs are usually done for:

  • Malignancies – ALL, CML, neurblastoma, non-Hodgkin’s lymphoma, Wilm’s tumour, rhabdomyosarcoma
  • Bone marrow disease – aplastic anaemia, thalassaemia, sickle cell disease, Wiskott-Aldrich syndrome, chronic granulomatous disease, severe combined immunodeficiency, Diamond-Blackfan syndrome
  • Metabolic disease – mucopolysaccharoidoses, adreneleukodystrophy, glycogen storage disorders

Where do the cells come from?

BMTs can be allogenic or autogenic.

Allogenic transplants can be from a sibling, an unrelated donor, or from cord blood (related or unrelated). Any full sibling has a 1 in 4 chance that they will be a match.

Matching is done via tissue typing and mainly checks the HLA match – aiming for  6 out of 6 alleles matched in a sibling donor, or 5 out of 6 in a cord transplant (as this is a more naive immune system).

Stem cells with be collected from the donor via a bone marrow aspirate, from the cord of a newborn, or via apheresis (peripheral blood stem cell collection).

Autologous transplants are more commonly used in children with brain tumours – these are often given as mini-transplants. As these patients often have intense chemotherapy, the stem cells are collected from the patient prior to starting chemo and then give back to them at the end of each cycle to help build them up before the next cycle.

What are the stages of a bone marrow transplant?

The key stages are:

Pre-transplant evaluation – this will include the decision to proceed to transplant, donor selection and tissue typing, and also an assessment of pre-transplant organ function.

Conditioning therapy – this usually lasts 5-10 days and consists of high dose chemotherapy and radiation. These will be termed minus days i.e. the first day of conditioning might be D -7.

Infusion of the stem cells – this is known as D0. Stem cells are infused over minutes to hours (depending on the volume). Isolation commences from the time of infusion. Note that patients can have toxicity from DMSO (dimethyl sulfoxide) which is used to preserve the stem cells – this can cause nausea/vomiting, haematuria, an unpleasant odour. It is mainly excreted via the lungs over 48 hours.

Engraftment – this is when a neutrophil count of 0.5 is achieved on two consecutive days.

Post-transplant – this is usually split into early (0-3 months) and late (3-12 months)

What are the complications?

Some patients will experience early problems that are not directly related to the stem cells, but rather are side effects from the high dose chemotherapy.

Complications from the actual BMT include:

  • Nausea/vomiting
  • Mucositis
  • Pancytopenia – bleeding and life-threatening infections
  • Veno-occlusive disease
  • Graft versus host disease
  • Opportunistic infections – CMV, PCP

What are the mortality rates?

Treatment-related mortality in matched sibling donors is 5-10%. In unrelated donors it is 20-25%.

There are huge psychosocial implications for families during the transplant. There will be fear that the child will die during treatment, or relapse after the treatment. There will be the distress of watching their child endure complications of the treatment we are giving. Also, being stuck in a room for months can lead to loneliness and isolation. Parents can often second guess their decision to proceed to transplant. Overall is it a highly stressful time, and it’s important to be mindful of this when dealing with these families.

Acute lymphoblastic leukaemia – tumour lysis syndrome

Cite this article as:
Tessa Davis. Acute lymphoblastic leukaemia – tumour lysis syndrome, Don't Forget the Bubbles, 2014. Available at:
https://doi.org/10.31440/DFTB.6185

Treating leukaemia produces its own complications. The most common time to have complications is during induction. For any new presentations of tumours, or for patients at the start of treatment, be aware of tumour lysis and how it can present.

View all our Acute Lymphoblastic Leukaemia Week posts

Tumour lysis syndrome is most commonly seen at the start of treatment as this is when there is the highest tumour load.

What is tumour lysis syndrome (TLS)?

TLS results from cell death and the subsequent release of chemicals from these cells.

It can be triggered by steroids, chemotherapy, fever, or dehydration.

What are the chemical abnormalities in TLS?

When cells die, they release their intracellular potassium and phosphate. Calcium then binds to the phosphate in the tissues. Urate is also deposited in the kidneys. The usual order of detected abnormalities is:

  1. High potassium
  2. High phosphate
  3. Low calcium – this can also be associated with kidney calcification
  4. High urea and creatinine  – this is due to renal failure and if this happens then the renal team need to be involved and the patient will likely require dialysis.

How do we treat TLS?

Treatment is through three main ways:

  • Hydration
  • Allopurinol – aiming to reduce the urate
  • Rasburicase – a medication that converts uric acid to allantoin which is water soluble and excreted in the urine.

Also, beware that if the patient has a high potassium, they are at risk of cardiac arrest so may also need standard hyperkalaemia management.

What are the other potential complications of ALL?

Anaemia – often the presenting complaint and result of treatment. Most patients require platelet & red cell transfusions.

Febrile neutropenia – most patients will have an episode of febrile neutropenia during induction. This can be due to life-threatening sepsis. Find your hospital guideline and if you suspect febrile neutropenia, talk to your consultant early.

Hyperviscosity syndrome – can be a presenting complaint, associated with WCC >100×109/L 

Acute lymphoblastic leukaemia – risk factors and prognosis

Cite this article as:
Henry Goldstein. Acute lymphoblastic leukaemia – risk factors and prognosis, Don't Forget the Bubbles, 2014. Available at:
https://doi.org/10.31440/DFTB.6182

 We suspect that Hamish has ALL – how do we confirm this, and more importantly, what is his prognosis?

View all our Acute Lymphoblastic Leukaemia Week posts

What are the initial investigations?

  • Repeat FBC & send group & hold; coagulation profile; blood cultures if febrile; electrolytes, including PO4-, Mg+, Ca++ as high WCC at risk of tumor lysis syndrome; liver function tests; Hep B, C, HIV, EBV, CMV, herpes simplex, HHV6, syphilis & toxoplasma serology
  • Blood film must be reviewed & reported by a consultant haematologist
  • ECG – sinus tachycardia, normal axis
  • Chest radiograph – to check for mediastinal mass
  • Urinalysis
  • Official height & weight – for chemotherapy & body surface area calculations (standard scales/measure, sighted by two staff)
  • Pregnancy test in females of childbearing age

Once clinically stabilised (including meeting minimum platelet counts), they will have a GA lumbar puncture (usually with intrathecal chemotherapy) a bone marrow aspirate, and if there is no contraindications, insertion of a tunnelled central line.

What are the risk factors for ALL?

  • Family history
  • Immunosuppression
  • Alkylating agents (more commonly linked to AML rather than ALL)
  • Trisomy 21
  • Neurofibromatosis
  • Ataxia telangiectasia
  • Bloom syndrome

What are good prognostic factors for ALL?

1. Age  >1yo and <10yo at diagnosis

2. White cell count <50×109/L at presentation

3. No testicular involvement at presentation

4. Not a child with Down Syndrome

5. No prior steroid exposure – this is important, as steroids are themselves chemotherapeutic and can put a child into remission as a single agent. If there has been a history of URTI or wheeze, they may have been prescribed (or been given a sibling’s) steroids. There are reports of spontaneous tumour lysis syndrome in undiagnosed patients as a result of steroids. Steroid exposure will move the child to a high-risk protocol.

6. No CNS disease – established with first CSF examination

In recent years, cytogenetics & minimal residual disease (MRD) has added a further layer to prognosis and treatment. This analysis requires CSF & bone marrow samples.

What do remission, relapse, and cure mean?

For diagnosis – a patient has to have over 25% blasts in the peripheral blood film

For remission – a patient has to have <5% blasts in the peripheral blood film

For cure – a patient has to have no evidence of leukaemia over 5 years from diagnosis

Bone marrow is the most common site for relapses and 10% of relapses are central nervous system only. In boys, testes are a known site of relapse and present as a hard testicular lump – so make sure you examine the tests during follow-up appointments.

Using the most up to date study outcomes, the 5 year survival is 85%

Once the child gets further through the initial treatment and is given a standard risk, then the 5 year survival is 97%

Acute lymphoblastic leukaemia – presentation

Cite this article as:
Henry Goldstein. Acute lymphoblastic leukaemia – presentation, Don't Forget the Bubbles, 2014. Available at:
https://doi.org/10.31440/DFTB.1248

Hamish, 5, has been tired and miserable for the last week of the school holidays. On the second day back at school, his Mum is asked to collect him after a bleeding nose that lasts about fifteen minutes. The teacher comments to Mum that Hamish is looking a bit “thin & pale”, and they’ve noticed a lot of bruising on his shins.

The GP agrees and orders a full blood count, which shows: Hb 50 g/L (100 – 150); Plt 2 x109/L (150 – 450); WCC 45.8 x109/L (80% lymphocytes, 30% blasts); “Blasts seen on film”.

View all our Acute Lymphoblastic Leukaemia Week posts

Bottom Line

ALL is the most common childhood haematological malignancy

Paediatric oncology is strongly consultant-driven

First presentation to the tertiary oncology centre is extremely stressful and a medically intense time

Aim is to achieve remission in induction

ALL may present in a broad variety of signs & symptoms<

The GP phones you, the Paeds Oncology registrar, with these results, and Hamish soon arrives into Emergency. You phone the consultant, who attends to meet family, take the history and examine Hamish.

Hamish looks pale but bright eyed. Vitals are 36.9oC, HR 130, RR 25, SaO2 97%, BP is normotensive with brisk capillary refill.

Further History

Has been grizzly and “not himself” for the last ten days: picking at food; complaining of sore legs for 2/7.  Not recently unwell/coryzal symptoms/diarrhoea. No wheeze. No steroid exposure. No blurry vision. Developmentally meeting milestones. No FHx of childhood malignancy.

(When taking the history, specifically ask about B symptoms: fever, night sweats, and weight loss).

Further examination

Pale boy with signs of weight loss. Bruising of the elbows, knees and legs. HS 2+ flow murmur. Lungs – no wheeze, good equal air entry. Abdomen soft, bowel sounds, liver 5cm below the costal margin, spleen 8cm below costal margin, not tender. Enlarged inguinal nodes bilaterally. Testicular examination – normal size for age. Aside from the bruising, you identify no areas of broken skin, boils, erythema or rashes. ENT examination is unremarkable. Fundoscopy unremarkable.

(Also, note any dysmorphism, Tanner stage, Lansky performance score).

What is ALL?

Acute lymphoblastic leukaemia is the most common childhood cancer. It is bimodal in incidence in childhood with peaks at around 2 years, and then at around 16 years of age.

ALL accounts for around 80% of childhood leukaemias, the remainder being acute myeloid leukaemia and rarer types. Approximately 85% of children with acute lymphoblastic leukaemia have B-cell ALL, with ~15% having T-Cell ALL. 2-3% will have Burkitt lymphoma, a mature B-cell leukaemia, treated differently from most leukaemias.

How does ALL usually present?

The most common presentations are with bone pain. Many children experience bone aches due to ‘growing pains’, so it’s important to know how to differentiate bone pain related to oncology issues, and growing pains.

  • bone pain tends to wake you up in the middle of the night, whereas growing pains are usually felt more when the child is falling asleep
  • children with growing pains should not have difficulty walking
  • growing pains tends to present as a pattern i.e. same type of pain at the same of day
  • children with growing pains will have completely normal blood counts
  • there should be no fever or weight loss associated with growing pains

As with this case, ALL can also present with bleeding. Other presentations include splenomegaly (10-20%), mediastinal mass, renal failure (due to hyperuricaemia), or leukostatic symptoms (respiratory distress, altered mental status) in patients with a high WCC .

Rarely patients who initially are thought to have ITP actually turn out to have ALL.

ALL can also include extramedullary sites e.g. CNS, testes, liver/spleen, kidneys, skin (rare). With this in mind, the list of presenting features include…

  • Typically weight loss (or failure to thrive), anaemia, fatigue will be present
  • Bone or joint pain
  • Bruising
  • Epistaxis or bleeding gums
  • Recurrent fever (low grade)
  • Persistent cough
  • Dizziness
  • Lymphadenopathy (including tonsillar hypertrophy)
  • Priapism
  • Wheeze (from a mediastinal mass) or
  • Blurry vision/diplopia
  • Testicular enlargement
  • Headaches (with papilloedema & retinal haemorrhages)
  • Respiratory distress (hyperviscosity)
  • Cranial nerve palsies

Practical points at diagnosis

For some paeds oncology departments, there is a policy that the most senior ED doctor should place the cannula for a patient’s first presentation. In a stressful time for the child and family, this is a drip that needs to go in first time with as little fuss as possible. It is important for the medical staff to build trust with child and family early.

Although most specialties would have the registrar or senior resident “do the admission”, oncologists will often meet the family as soon as they are referred. The family will be seeing a lot of their oncologist, and establishing trust and rapport very early in the piece is important.

In this kind of presentation – from the community in a stable child during daylight hours – the oncologist will often have spoken to the haematologist about the film prior to meeting the patient. This enables them to give the most likely diagnosis (based on the film and history/examination) & answer a few questions.

References

National Cancer Institute – Childhood Acute Lymphoblastic Leukaemia Treatment (PDQ) – Risk-based Treatment Assignment

Peppercorn J et al. Comparison of outcomes in cancer patients treated within and outside clinical trials: conceptual framework and structured review. Lancet 2004; 363: 263–70

QPHON Guide to the Care of Children with Cancer in Queensland Document No. 2.1 15062012 © 2012 State of Queensland Queensland Health. via Q-Health intranet.

ABO incompatible blood transfusion

Cite this article as:
Marc Anders. ABO incompatible blood transfusion, Don't Forget the Bubbles, 2013. Available at:
https://doi.org/10.31440/DFTB.3786

UNOS Policy: ABO incompatible HTX for children up to 2 years (with acceptable isohaemoglutinin titres – less than 1:4)

Recipient Donor compatible Donor incompatible Antibodies to avoid Plasma / Platelets RBC
0 0 0
0 AB Anti AAnti B AB 0
0 A Anti A AB or A 0
0 B Anti B AB or B 0
A A
A 0
A AB Anti AAnti B AB A or 0
A B Anti AAnti B AB A or 0
B B
B 0
B AB Anti AAnti B AB B or 0
B A Anti AAnti B AB B or 0
AB AB AB
AB A AB
AB B AB
AB 0 AB

 


Preoperative preparation:

Isohaemagglutinin titres. Avoid transfusion. Consider transfusion in regards to guide.


Perioperative management:

If elevated iso-titre: plasma exchange once on CPB, iso-haemagglutinin quick test before AoCx release, repeat plasma exchange as required.


Postoperative management:

Isohaemaggluttinin titres daily of ABOi HTX. Repeat plasma exchange if required.


Outcome:

Similar long term outcome. Reduced rate of infection and rejection compared to ABO compatible blood transfusions.


References:

[1] Paediatric Heart Transplant Society: www.uab.edu/phts/

[2] Heart Lung Transplant. 2012 Feb;31(2):173-9: Henderson et al: ABO-incompatible heart transplantation: analysis of the Pediatric Heart Transplant Study (PHTS) database.


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ITP – Idiopathic Thrombocytopenic Purpura

Cite this article as:
Tessa Davis. ITP – Idiopathic Thrombocytopenic Purpura, Don't Forget the Bubbles, 2013. Available at:
https://doi.org/10.31440/DFTB.2865

A 4-year-old girl presents with bruising over her legs, trunk and face.  Mum has noticed them appear over the last week.  She has been completely well with no other symptoms.  There is no history of trauma.  After an anxious 1 hour wait, the bloods are back-Hb 113, WCC 7.3, Plt 8 x 109/L.

 

Bottom Line

  • Uncomplicated idiopathic thrombocytopenic purpura (ITP) is new-onset bruising and bleeding with a platelet count <100 x 109/L in the absence of other symptoms
  • It generally resolves itself in 80% by six months
  • 5% will have a recurrence
  • Only treat if there is active bleeding, not just because of a low platelet count
  • Advise parents to avoid NSAIDS and lookout for signs of bleeding
  • Follow up regularly for the first six weeks or until platelet count stabilises

 

What is it and how did she get it?

Idiopathic thrombocytopenic purpura (ITP) is a reduction in platelet count in the absence of any other cause (<100 × 109/L).  Whilst normal platelets last eight to ten days, in ITP there are autoantibodies that destroy them in the first few hours. It has a peak incidence of two to five years of age (chronic ITP peaks in adolescence).  There is often a recent history (one to six weeks) of a viral illness or immunisation.

What are the commons symptoms and signs?

The most common sign is petechiae (1-5 mm red or purple non-blanching spots) on the skin or mucosa – these indicate capillary haemorrhages.  Some mucocutaneous bleeding is often seen, but it is rare for this to be severe (<5%).

Other symptoms of autoimmune disorders should NOT be present in ITP – e.g. no weight loss, rashes, alopecia, joint swelling. The examination should be normal with no hepatosplenomegaly or lymphadenopathy.

How is it diagnosed?

It is diagnosed by having a low platelet count with a normal haemoglobin (unlike in leukaemia, TTP, HUS and DIC). If there is a history of previous bleeding then consider other diagnoses. Bone marrow aspirate is only recommended if there is persistent bleeding in spite of a platelet count >20 × 109/L.

 

What treatment should we use?

The answer is simple: treat the patient not the platelet count.  Assess if the patient has haematuria, melaena, menorrhagia, epistaxis, mucosal bleeding or tonsillar purpura/petechiae.

Although there is variation between specialists, they will all be more concerned with the signs of wet purpura or haematuria rather than just the petechiae on the skin.

Steroids

Prednisolone 1-2mg/kg OD for at least three weeks then taper

OR

Methylprednisolone 30mg/kg/day for three days, then 20mg/kg /day for four days

 

IVIG (intravenous immunoglobulin)

Consider where there is significant bleeding (0.8-1g/kg) – can rapidly raise the platelet count Effects takes place in one to five days and lasts for two to four weeks

 

Platelets

Only give platelets if there is an intracranial hameorrhage (ICG) or significant bleeding.  Can be effective after IVIG administration and this can prolong platelet survival (otherwise transfused platelets are quickly destroyed)

 

When to admit?

Admit if there is significant bleeding: epistaxis>1 hour; haematemesis; haemoptysis, intracranial haemorrhage, melaena.  Or if there is an unclear diagnosis or problematic social circumstances.

When will it go away?

Most ITP self resolves.  80% will have resolved by six months (with or without treatment).  5% of ITP patients will have a recurrence. Although it seems counterintuitive, the lower the platelet count at the beginning, the better.  Uncomplicated ITP normally has a platelet count of <20 × 109/L. Chronic ITP does not resolve within six months and accounts for 10% of ITP.

Could it be anything else?

Confirmation is based on excluding other differentials such as acute leukaemia, aplastic anaemia, HUS.  A full blood count and film us usually adequate to make the diagnosis.

What do you need to inform the parents to look out for?

While the platelets are low, the patient is at risk of bleeding.  ICH is a serious but rare (1%) side effect.  Parents should watch out for any signs of ICH, urinary bleeding, GI bleeding, excessive mucosal bleeding and menorrhagia (in older patients).

They should avoid NSAIDs while the platelet count is low.

Older children should avoid contact sports.  This is completely impractical for young children so is not helpful advice – will only stress out the parents!

When to follow up?

Patients should be reviewed within two weeks of initial presentation and have a repeat FBC. Aim for weekly GP follow up initially and then PRN until resolution.

Paediatric outpatient review at six weeks three months and six months. Refer to haematology if unclear diagnosis, unresolved after six months or a haematological malignancy is suggested by the blood count.

 

Selected references

Pediatric EM Morsels – Wet purpura and ITP

UMEM Educational Pearls – ITP

Royal Children’s Hospital, Melbourne – Guidelines for ITP

Princess Margaret Hospital for Children – ITP Guideline

BMJ BestPractice – ITP

Grainger JD, Rees, JL, Reeves M, Bolton-Maggs PHB.  Changing trends in the UK management of childhood ITP. Arch. Dis. Child. 2012;97:8-11.[/toggle]