Category Archives: Haem/Oncology

Neuroblastoma

General paediatrics, Haem/Oncology

Neural crest tumours – cells that migrate to form sympathetic chain, including adrenal glands. 

Usually young children, usually already metastases at presentation – that’s because mostly vague symptoms until an abdominal mass or lymphadenopathy obvious.

Several eye related symptoms possible –

  • Dancing eyes (opsoclonus-myoclonus) a famous association – only seen in 1% of neuroblastoma but 1/3 of opsoclonus-myclonus syndrome (includes ataxia too!) have it.
  • Horner’s syndrome associated, as sympathetics (dilated pupil) run with oculomotor nerve.
  • “Panda eyes” are a rare clinical finding – proptosis, bruising – from orbital mets. 

Catecholamines are a marker but only rarely do you get symptoms eg hypertension, sweating, diarrhoea. 

Bone pain and fever are not uncommon. Otherwise depends were the mass effects are eg obstructive jaundice, dysphagia.

Investigations

GD-2 marker. Catecholamines as above.

MRI full body else MIBG scintigraphy. 

“Metastatic special” risk category – under 18 months, only skin, liver, marrow. Resolve spontaneously even when extensive!

Screening programmes in Germany and US doubled pick up rate but no change in mortality… Probably because detected more of these Metastatic special cases.

Transfusions

Emergency medicine, General paediatrics, Haem/Oncology

January 2022 – safety alert from MHRA/CMO regarding deaths where there was a delay in providing emergency transfusion.

Should be agreed criteria for rapid concessionary release of blood products.

One issue is Autoimmune haemolytic anaemia, where the presence of red cell antibodies will complicate cross matching (11% mortality!).

Another issue highlighted is failure to give Prothrombin complex concentrate to reverse warfarin (and some other anticoagulants) where severe or limb/sight threatening bleeding.

Cyclical neutropenia

General paediatrics, Haem/Oncology, Immunology

=elastase defect.

Regular pattern of fever (periodic), approximately three-weekly, perhaps associated with malaise, periodontitis, aphthous ulceration, impetigo, sore throat and enlarged lymph glands.

But by the time the child presents, the neutrophil count may have returned to normal (although unlikely to be high).

Check FBC twice weekly for 4-6 weeks to demonstrate the fluctuation of the neutrophil (and monocyte) count.

Important not to miss, as children can develop severe bacterial sepsis while neutropaenic (mortality rate of up to 10%).

Management

Need antimicrobial prophylaxis, and possibly GCSF.

Differential is PFAPA (periodic fever, aphthous stomatitis, pharyngitis, adenitis)



Hemihypertrophy

General paediatrics, Genetics, Haem/Oncology, Orthopaedic

=Asymmetric overgrowth of one limb, or one side of the body, or just one side of the face.

Can be associated asymmetric overgrowth of internal organs.

Can be an isolated finding (of unknown cause) or associated with syndromes such as Beckwith-Wiedmann, Klippel-Trenaunay-Weber, or McCune-Albright syndromes.

Essentially a cosmetic problem. But increased risk of tumours, including Wilm’s tumour, adrenal cell carcinoma, hepatoblastoma and small bowel sarcoma.

Risk of tumour development in isolated hemihyperplasia is about 1 in 20 or approximately 5%. Given that oldest reported case was 6yrs and shortest interval between tumour presentation and ultrasound was 5 months, suggested hat till age of 6 years these children should have abdominal ultrasound scans at three monthly intervals.

Coagulation

General paediatrics, Haem/Oncology

Extrinsic pathway triggered by tissue factor on cells outside blood vessels.

Intrinsic pathway triggered by subendothelial surfaces activating factor XII, then XI, then IX.  IX and VIII combination with calcium and platelet membrane phospholipids activates X.

Common pathway then continues, with X combining with V, platelet membrane phospholipids and calcium to convert prothrombin to thrombin.

Thrombin converts fibrinogen to fibrin, to form thrombus.  Factor XIII stabilises clot.

Issues:

  • Vitamin K deficiency: 1:1200 breast fed (low levels), 1: 8500 formula fed. Preventable with single IM dose of Vitamin K. Can present up to 6 months later though typically 3 months.
  • Vitamin K may be affected in babies by maternal medicines eg anti-epileptics, or by liver disease.
  • Disseminated intravascular coagulation especially sepsis. Platelets fall too.
  • Haemophilia
  • Haemophagocytic syndrome (anaemia and other cell lines affected)
  • Thrombophilia

Fanconi anaemia

Genetics, Haem/Oncology

Autosomal recessive condition characterized by severe hypoplasia or aplasia of the bone marrow (so anaemia, low white cells and thrombocytopenia). Clue is congenital hand defect, but lower limb, head/eye/ear/genital abnormalities also common.

Majority also have cafe au lait spots.

It is possible to diagnose Fanconi anemia before bone marrow failure occurs, with potential to find bone marrow match.

Diagnosis is by Chromosomal breakage studies.

Sickle cell disease

General paediatrics, Genetics, Haem/Oncology

Autosomal recessive genetic disorder caused by a single nucleotide mutation of the haemoglobin ß-unit, from glutamic acid to valine. The resulting mutant haemoglobin S (HbS) is prone to distortion in cooler or hypoxic conditions, turning into a sickle shape. This damages the erythrocyte causing haemolysis.

The gene is more common among Africans and is occasionally seen in races from the Middle East and South Asia. Its existence is due to protection from malaria seen in sickle cell trait (the heterozygote form), due to shortened red cell lifespan.

You can of course get combinations of sickle cell with other genetic haemoglobin disorders.

Triggers for sickling include cold environment, acidosis, hypoxia and hyperviscosity eg dehydration. Blood flow in capillaries is impaired by the damaged red cells, which leads to a vicious cycle of increased tissue acidosis and hypoxia. Infarction may occur.

Diagnosis

Can be diagnosed even in newborns by hemoglobin electrophoresis.

Screening programmes exist in some countries, so that prophylactic oral penicillin can get started early, preventing sepsis.

Clinical

Presents in infancy or early childhood. The neonate with its high proportion of Haemoglobin F does not get symptoms until there is enough abnormal haemoglobin A produced for red cells to start to sickle.

Acute Crisis

  • Pain
  • Chest syndrome
  • Aplastic crisis
  • Gut crisis
  • Stroke
  • Priapism
  • Sepsis (may precipitate crisis or complicate it)

Pain

Pain can be widespread, but particularly involves bones, the spine, the chest.

Acute Chest syndrome

Can mimic pneumonia, with unilateral or bilateral signs of consolidation, pleuritic pain, and hypoxia. Pain is in chest wall, thoracic spine and upper abdomen. Leads to hypoventilation, causing vicious cycle of atelectasis and subsequently worse sickling. High mortality, so low threshold of suspicion.

  • Hypoxia should be managed aggressively, with respiratory support if necessary.
  • Antibiotics in infection contributing.
  • Avoid diuretics – signs may suggest pulmonary oedema, but likely to exacerbate hyperviscosity.

Aplastic Crisis

Usually secondary to Erythrovirus B19 (formerly known as parvovirus B19) infection, which can trigger transient bone marrow arrest. So sudden drop in haemoglobin with an absence of reticulocytes. Classic “slapped cheek” appearance may never become apparent. Can affect multiple members of a family simultaneously. Differential is spleen sequestration.

Abdominal crisis

Manifest as anorexia, abdominal pain, distension. Usually not diarrhoea or vomiting. Usually not rebound. Bowel sounds usually quiet.

  • Girdle or Mesenteric syndrome – ileus with vomiting. Associated with liver enlargement and bilateral basal consolidation.
  • Differential includes appendicitis, biliary colic or cholecystitis, ischaemic colitis.

Stroke

Typically affects middle cerebral artery territory but may affect any region of the brain; may be transient or permanent. Seizures may occur. Predictive factors are:

  • Previous TIA/stroke
  • Chest syndrome
  • Hypertension
  • Family history of SCD related stroke
  • Low HbF and/or low total haemoglobin
  • Doppler velocities >200cm/sec in children

Differential is meningitis, subarachnoid haemorrhage (associated with multiple intracranial aneurysms).

Sequestration syndromes

  • Splenic sequestration – Seen in infants and young children. Precipitated by fever or dehydration. Symptoms are:
    • Abdominal pain/distension
    • Rapidly expanding spleen (may or may not be painful)
    • Shock, pallor due to drop in haemoglobin (but high reticulocytes cf aplastic crisis)
  • Management is by fluid resuscitation with blood (type specific/O negative if necessary).
  • Hepatic sequestration: similar to splenic, although less shock, and possibly jaundice along with enlarging liver.
  • Priapism: =sustained painful erection. Potentially leads to peripheral gangrene, else cavernosal fibrosis and hence impotence. A urological emergency. Management:
    1. Warm bath, hydration, analgesia
    2. Catheterize if unable to urinate
    3. Sedation eg diazepam
    4. Aspiration + irrigation – ideally within 4-6hrs of onset. Else shunt.
    5. Top-up transfusion may be considered if unstable with other sickle related problems (aiming for Hb 10-12g/dl).
  • Sepsis. Children are relatively immunocompromised due to functional hyposplenism from recurrent spleen infarction. This increases susceptibility to capsulated organisms eg pneumococcus, salmonella, haemophilus.
    • Yersinia is a particular risk in children on desferrioxamine. Causes diarrhoea.

Management

  • Analgesia, aiming to get rapid symptom control with IV bolus doses of opiates eg morphine, diamorphine ideally within 30 minutes of admission, followed by infusion or regular oral doses. Paracetamol and non-steroidal anti-inflammatories may be synnergistic.
  • Oxygen, esp for acute chest syndrome. Debatable if effective for other problems.
  • Hydration, even hyperhydration eg 150% normal daily requirements, IV if necessary. Impairment of renal concentrating power may contribute to dehydration.
  • Warm environment
  • Identification and treatment of infection. Give treatment doses of penicillin (else erythromycin) even if no specific agent identified.
    • Treat with IV antibiotics if severe symptoms/signs
    • Add macrolide eg clarithromycin if chest symptoms
    • Treat empirically for Yersinia with ciprofloxacin if diarrhoea on desferrioxamine.
  • Folic acid (should be on already)

Transfusion

Although anaemia is common in SCD, repeated transfusions lead to the possible complications of:

  • Allo-immunization
  • Iron overload

Hence top up transfusion is only used for acute symptomatic anaemia eg cardiac failure, severe sequestration or pre-operatively. Do not transfuse above Hb 11g/dl. Regular transfusions have a prophylactic role – see on-going treatment below.

Hyperhaemolysis is a life threatening complication of red cell transfusion in sickle cell disease. Can be acute (within 7 days of transfusion) or delayed. Affects not just transfused but autologous cells so Hb can drop below previous level. Fever, haemogobinuria as usual; negative DAT, reticulocytopenia seen (cf parvo). Cover subsequent transfusion with IVIG and steroids; use erythropoietin to maintain. For elective surgery, prophylactic postop CPAP has been used without transfusion. Risk factors poorly defined.

Exchange transfusion

Undertaken to rapidly reduce the percentage of sickle cells in the circulation where life-threatening eg severe chest syndrome, stroke, multi-organ failure. The aim is to reduce %HbS to <20%. Complications are common eg fluid overload, transfusion reaction.

Other Treatments

  1. Pneumococcal prophylaxis is essential for all children. Polysaccharide vaccine should be offered with repeat doses as per Green book.
  2. Folic acid
  3. Hepatitis B immunization
  4. Splenectomy for recurrent splenic sequestration.

On-going treatment

Consider for:

  • Recurrent or stuttering priapism (etilefrine orally is another option here)
  • Stroke/TIA
  • Chronic organ damage eg renal failure
  • Failure to thrive
  • Intractable crises

Options:

  • Regular transfusions. The aim is to keep %HbS <25%. Compared with exchange transfusion, regular transfusions are just as good at reducing complications, are less challenging in terms of vascular access, involve less donor exposure, but cause more iron accumulation.
  • Hydroxyurea. Reduces frequency of crises and transfusion requirements, improves growth. Trials ongoing. Long term risks need to be clarified (toxicity, mutagenicity, teratogenicity).
  • Bone marrow transplant

Iron overload and chelation therapy

Iron overload can be monitored by means of Ferritin levels. Chelation therapy should commence at ferritin levels of 1000mcg/l, with desferrioxamine (desferal) the chelator of choice. Treatment should include vitamin C. Ophthalmological, audiological and cardiological review is necessary.

Anaemia

General paediatrics, Haem/Oncology, Nutrition

Like many things, low red cell count can be problem of production, loss or destruction.

So causes include:

  • Bone marrow failure or infiltration (leukaemia, Fanconi’s, Blackfan Diamond, erythrovirus/parvovirus)
  • Nose bleeds, gastrointestinal losses eg Meckel’s, gastritis, heavy periods
  • Haemolysis eg G6PD deficiency, hypersplenism, autoimmune
  • Iron, folate or B12 deficiency

In children, one of the most common causes is excessive milk consumption, which appears to lead to a low level colitis. Pica is often the presenting problem.

Investigations

  • Blood film – Howell Jolly bodies if hypersplenism. Leucoerythroblastic reaction (with immature red cells, as well as immature white cells) can be due to malignancy but can also be due to infection and haemolysis. Spherocytes or other abnormal forms may suggest a hereditary haemolytic condition. Sickle cells in sickle cell disease.
  • Low MCV suggests lack of iron, but may also be due to thalassaemia.
  • Reticulocyte count – indicates on going red cell production, may be high if recovering from low production
  • White cell count and platelets – if low too, suggests bone marrow failure but parvovirus can knock off all cell lines too.
  • Coagulation – deranged coagulation with low platelets suggests disseminated intravascular coagulation (DIC), usually due to sepsis, but can also reflect haemophagocytosis syndrome (due to sepsis or rheumatological disease)
  • Renal function – haemolytic uraemic syndrome (usually with diarrhoea and bloody stools, but not always)

Iron is found in red meat, pulses, green leafy vegetables, wholemeal bread, nuts, dried fruit, fortified breakfast cereals.

Polycythaemia

General paediatrics, Haem/Oncology

Polycythemia vera very rare in kids but described from age 7 months! More typically age 5-14yrs. 

Haemoglobin range of 15.5 to over 25, with haematocrits from 41-80%.  Yet high values often seen in asymptomatic teenagers. Partly this is because pre-pubertal range is different, but lab can’t know pubertal status so will cut off at an arbitrary age. Our lab gives normal up to 18 for adult males and 16.5 for adult females.

Symptoms are headaches, pruritus, dizziness/syncope.  Serious complications not uncommon, often part of presentation eg Budd-Chiari syndrome, stroke, haemorrhage.  Leukocytosis appears to be associated with higher risk of complications.   Thrombocytosis often seen. 

Molecular studies available. [Ann Hem 2009 PMID PMID: 19468728]