Possible causes of macrocephaly this month. Also the start of a new series on causes of coca-cola coloured urine and updates on safeguarding CPD requirements and the terminology of children “in care”. Do leave comments below:
With thanks to Dr David Gardiner, one of our current paediatric FY2 doctors at Homerton University Hospital, for updating us on HUS.
- Profuse diarrhoea that typically turns bloody after 1-3 days
- Abdominal pain (crampy)
- Fever (sometimes)
- Reduced urine output (abrupt onset) but also polyuria/normal urine output (rarer)
- Neurological complications: seizure, coma, cranial nerve palsies, confusion, hallucinations
- Classic triad – anaemia, uraemia and thrombocytopaenia
- Most common in children under the age of 5
- B/P – hypertension
- Blood film: Fragmentation and signs of haemolysis (Coombs test negative)
- Raised WCC and neutrophils, low platelets, low Hb
- Raised LDH
- Clotting screen typically normal (cf DIC)
- Raised bilirubin, low albumin
- Urea and creatinine raised
- Stool for PCR E.Coli
- Refer to secondary care urgently
- Strict input/output fluid monitoring
- Correction of anaemia
- Correction of electrolyte imbalances
- Antihypertensive therapy if required
- Furosemide to induce diuresis
- Report to PHE – can’t go back to school until 2 negative stool samples
Haematuria this month with links to an algorithmic Australian guideline on how to manage it in children, assessing paediatric hypertension, postural orthostatic tachycardia syndrome and the last for the time being in the “decoding the FBC” series – MCHC.
Please do leave comments below:
MCV- Mean Corpuscular Volume. (with thanks to Dr Xanna Briscoe and Prof Irene Roberts)
A measure of the size of the red blood cells.
Raised MCV- macrocytosis– may occur with or without anaemia. Physiological macrocytosis in the absence of anaemia occurs in neonates, especially those with Down syndrome, and during pregnancy.
Macrocytic anaemia- may be secondary to nutritional deficiencies in B12 and Folate leading to ineffective or abnormal erythropoiesis. This is easily diagnosed using simple blood tests. Where deficiency is excluded bone marrow examination may be required to identify rare causes such as myelodysplasia or Fanconi anaemia.
There are several drugs that may lead to macrocytosis, some of which are commonly used in the paediatric population. These include several chemotherapeutic agents, antibiotics and antiviral medications. It is also seen in congenital heart disease, hypothyroidism and Down Syndrome.
Additional investigations- guided by the history. It is important to check a reticulocyte count if a macrocytic anaemia is discovered. Reticulocytes are immature erythrocytes- which are large, and indicate increased erythropoiesis. Chronic reticulocytosis may falsely elevate the MCV. The absence of a raised reticulocyte count in the presence of severe anaemia suggests an inability of the bone marrow to produce red cells, eg due to inherited or acquired red cell aplasia.
Kaferle, Joyce, and Cheryl E. Strzoda. “Evaluation of macrocytosis.” American family physician 79.3 (2009).
Microcytosis– small red blood cells. Typically seen in iron deficiency anaemia; in the paediatric population at different ages the cause differs. In younger children and toddlers lack of supplementation may lead to deficiency. This is a particular issue in those that drink large volumes of cows milk as a substitute for iron containing foods. The main differential diagnosis is beta- or alpha-thalassaemia trait. Measurement of serum ferritin is the most useful test to identify iron deficiency- this will be low in iron deficiency and normal in beta- or alpha-thalassaemia trait.
In adolescence the pubertal growth spurt, and menorrhagia may be a causative factor. Further investigation will aid in determining the causes of microcytic anaemia (see below).
W Owen Uprichard, James Uprichard. Investigating microcytic anaemia. BMJ 2013;346:f3154
As published in April 2017 Paediatric Pearls newsletter…..
|Increased MCV (macrocytosis)||Decreased MCV (microcytosis)|
|Vitamin B12 DeficiencyFolic Acid DeficiencyAlcohol Abuse
|Iron Deficiency AnemiaThalassemiaHemoglobinopathy
Anemia of Chronic Disease
Chronic Renal Failure
MCV is expressed in femtoliters = 10^-15 liters
MCV cutoffs vary by age and by lab reference
MCV Normal Range:
- Newborn: 95 to 121 fl
- Ages 6 months to 2 years: 70 to 86 fl
- Ages 12 to 18 years
- Boys: 78 – 98
- Girls: 78 – 102
- Age over 18 years: 78 to 98 fl
MCV Cutoffs for Microcytic Anemia:
- Age 1-2 years: <77 fl (CDC)
- Age 3-5 years: <79 fl (CDC)
- Age 6-11 years: <80 fl (CDC)
- Age 12-15 years: <82 fl (CDC)
- Age >15 years: <85 fl (CDC)
- Recommended adult microcytic MCV cutoff varies
Some sources advocate MCV <78 and others <82
So, you’ve got the FBC back and it shows microcytic anaemia. How can you work out which of the above factors is causative?
If you only asked for FBC and the child is more than 6 months old, try this:
|Anaemia of chronic disease||Thal trait (alpha OR beta)||Iron deficiency anaemia||Thal trait + IDA||Haemoglobinopathy|
|Hb||↓||N / ↓||↓ / ↓↓||↓ / ↓↓||↓ or ↑|
|MCV||N / ↓||↓ / ↓↓||↓ / ↓↓||↓ / ↓↓||↓ or ↑|
|MCH||N / ↓||↓ / ↓↓||↓ / ↓↓||↓ / ↓↓||↓ or ↑|
|RBC||↓||N/↑||N / ↓||N / ||↓ or ↑|
|RDW||N||N||↑||↑||↓ or ↑|
Therefore a child of 6 months or older with hypochromic, microcytic anaemia with an increased RDW has presumed iron deficiency. They could have thalassaemia trait as well….
If you asked for other tests or are at liberty to repeat the blood test, here are some suggested extra investigations and their interpretation:
|Investigation||Iron deficiency anaemia||Thalassaemia trait||Sideroblastic anaemia||Chronic disease|
|Hb electropheresis||normal||Β thalassaemia- raised A2
α trait- normal
Part 2 of “Decoding the full blood count” with thanks to Dr Alexandra Briscoe, paediatric registrar at Whipps Cross University Hospital, and Professor Irene Roberts, professor of paediatric haematology at Oxford.
Haematocrit/packed cell volume
Haematocrit/ packed cell volume- the proportion of blood that is made up of cells (not plasma); it is measured as a percentage or fraction.
Low haematocrit is seen in anaemia, though it will not tell you the direct cause for the anaemia.
Raised haematocrit is seen in polycythaemia, in the newborn infant this is termed Neonatal Polycythaemia.
Defined as a venous haematocrit > 65%, occurring in 0.4-5% of healthy newborns. Symptoms are believed to be due to hyperviscosity. On examination children appear plethoric, and may have multi-systemic symptoms. These include- CNS features of irritability, cerebrovascular accidents and seizures. Apnoea and respiratory distress occur as a result of decreased pulmonary blood flow. In addition infants may demonstrate poor feeding, and may in rare cases develop necrotising enterocolitis (NEC.) Renal effects include renal vein thrombosis, oliguria, proteinuria and haematuria. Hypoglycaemia and thrombocytopenia (Vlug, 2013) are also seen commonly.
The development of polycythaemia occurs secondary to increased erythropoiesis as a consequence of chronic fetal hypoxia. IUGR and placental insufficiency- due to post-dates pregnancies, pre-eclampsia and maternal smoking, increase the incidence of polycythaemia. Infants of diabetic mothers, those with Beckwith –Weidemann, and congenital thyrotoxicosis are also at increased risk.
There has been much debate as to whether delayed cord clamping increases the incidence of polycythaemia. Current NICE guidelines recommend cord clamping between 1-5 minutes after delivery, provided there is no concern regarding the infant’s heart rate or need for resuscitation. In a Cochrane review of cord clamping practices and neonatal outcomes in 2013 McDonald et al found that delayed cord clamping was associated with increased risk of jaundice requiring phototherapy, however beneficial outcome in terms of iron stores- with a 50% reduction in iron deficiency at 3-6 months. They reported no difference in incidence of polycythaemia in 5 trials measuring this outcome.
Current management of symptomatic polycythaemia is a partial exchange transfusion.
Vlug RD, Lopriore E, Janssen M, et al. Thrombocytopenia in neonates with polycythemia: incidence, risk factors and clinical outcome. Expert Rev Hematol. 2015 Feb. 8 (1):123-9. [Medline].
ID: CD004074 McDonald, Susan J, Middleton, Philippa, Dowswell, Therese Morris, Peter S
Effect of timing of umbilical cord clamping of term infants on maternal and neonatal outcomes
Cochrane Database of Systematic Reviews 2013
What are normal haematocrit levels?
(taken from http://www.medicinenet.com/hematocrit/page2.htm)
The normal ranges for haematocrit depend on the age and, after adolescence, the sex of the individual. The normal ranges are:
- Newborns: 55% to 68%
- One (1) week of age: 47% to 65%
- One (1) month of age: 37% to 49%
- Three (3) months of age: 30% to 36%
- One (1) year of age: 29% to 41%
- Ten (10) years of age: 36% to 40%
- Adult males: 42% to 54%
- Adult women: 38% to 46%
These values may vary slightly among different laboratories.
The burns triage tool this month plus a bit on urinalysis (pH) and the start of our decoding the FBC series. Also a reminder about the MAP guideline for management of CMPA in primary care, a link to some good courses on this topic and to a document I have put together on milks to use in the UK for CMPA.
With thanks to Dr Alexandra Briscoe and Professor Irene Roberts for their collaborative work.
The red cell count and haemoglobin (see February 2017 newsletter for normal ranges)
The red cell count is the actual number of red cells per mL of blood, and the haemoglobin (Hb) is the concentration of the Hb protein itself- the oxygen carrying protein.
A raised red cell count due to increased production of red cells is seen in children with chronic hypoxia, such as congenital heart disease and, in neonates, manifests as neonatal polycythaemia, usually due to chronic in utero hypoxia.
During the last 2 months of pregnancy erythropoiesis occurs at a rate of 3-5 x that of adults, consequentially the healthy newborn has a relative polycythaemia compared to infants and children- manifest as a raised Hb, red cell count and haematocrit.
The Hb falls over the first 2-3 months of life in response to several factors- with the onset of respiration at birth- oxygenation increases, erythropoieitin production and erythropoiesis is decreased via negative feedback. Neonatal red blood cells have a shorter half-life of 90 days compared to 120 days for red cells in healthy children and adults. In addition over this time period, neonates undergo rapid growth and weight increase with a subsequent increase in circulatory volume- leading to relative haemodilution. This physiological anaemia requires no intervention in otherwise healthy term infants and will rarely fall below 90g/L.
In contrast, infants born extremely prematurely at <28 weeks of completed gestation, will frequently require red cell transfusion. This is due to anaemia of prematurity. The cause is multifactorial, including low erythropoietin, shortened red cell lifespan, nutritional deficiency and iatrogenic blood letting, however the nadir in Hb occurs earlier (4-8 weeks compared to 8-12 weeks in term babies) and is more severe. Premature red blood cells have a life span of 35-50 days, and infants have a circulating blood volume of 90- 105 mls/kg, which could be as little as 45mls in a 24 week 500g infant. In addition, these infants do not receive maternal iron transfer via the placenta. Preterm infants also have a slow erythropoietin response to hypoxia and anaemia- this is because the site of production of erythropoietin is the liver rather than the kidney as per term infants. There is also evidence of increased metabolism of EPO in the preterm infant. (Strauss, 2010). Despite multiple studies into the use of exogenous erythropoietin for preterm infants, current guidelines recommend red cell transfusion for the management of anaemia of prematurity.
Ronald G. Strauss, Anaemia of prematurity: Pathophysiology and treatment, Blood Reviews, Volume 24, Issue 6, November 2010, Pages 221-225, ISSN 0268-960X, http://dx.doi.org/10.1016/j.blre.2010.08.001.