Tag Archives: blood tests

March 2019 PDF published

Part 2 of Medically Unexplained Symptoms this month.  Also antibiotics in cystitis, too many investigations in community acquired pneumonia, carotenaemia and heart murmurs in unwell children.  Do leave comments below:

June 2018 PDF published

June 2018 features include the rotavirus immunisation, febrile myoclonus, investigating normochromic anaemia, complications of sinusitis and the first in our adolescence series.  Please do leave comments below:

April 2018 newsletter uploaded

NICE on Lyme disease this month – just in time for the weather to pick up and the tics to start biting.  Also a reminder on the risk factors for SIDS, what to do in a terrorist attack, how to manage a child with a non-blanching rash and a discussion on the use of the antistreptolysin O titre.  Do leave comments below:

Decoding the FBC (3): MCV

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

Liver disease

Marrow aplasia

Myelofibrosis

Reticulocytosis

Hypothyroidism

Iron Deficiency AnemiaThalassemiaHemoglobinopathy

Anemia of Chronic Disease

Sideroblastic Anemia

Chronic Renal Failure

Lead Poisoning

Source: http://www.fpnotebook.com/HemeOnc/Lab/MnCrpsclrVlm.htm

 

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
Ferritin decreased Normal increased Normal/increased
Iron Decreased Normal Increased Decreased
TIBC increased Increased Normal decreased
transferrin decreased normal Normal Decreased
Hb electropheresis normal Β thalassaemia- raised A2

α trait- normal

normal normal

 

 

Decoding the full blood count (haematocrit)

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

DOI: 10.1002/14651858.CD004074.pub3

US: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004074.pub3/abstract

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.

Potted background, assessment and management of vitamin D deficiency

Vitamin D deficiency in children with thanks to Dr Jini Haldar, paediatric registrar at Whipps Cross University Hospital.

Introduction

Vitamin D is an essential nutrient needed for healthy bones, and to control the amount of calcium in our blood. There is recent evidence that it may prevent many other diseases.  There are many different recommendations for the prevention, detection and treatment of Vitamin D deficiency in the UK.  The one outlined below is what we tend to do at Whipps Cross Hospital.

 Prevention

The Department of Health and the Chief Medical Officers recommend a dose of 7-8.5 micrograms (approx. 300 units) for all children from six months to five years of age. This is the dose that the NHS ‘Healthy Start’ vitamin drops provide. The British Paediatric and Adolescent Bone Group’s recommendation is that exclusively breastfed infants receive Vitamin D supplements from soon after birth. Adverse effects of Vitamin D overdose are rare but care should be taken with multivitamin preparations as Vitamin A toxicity is a concern. Multivitamin preparations often contain a surprisingly low dose of Vitamin D.

Indications for measurement of vitamin D

 1. Symptoms and signs of rickets/osteomalacia

  • Progressive bowing deformity of legs
  • Waddling gait
  • Abnormal knock knee deformity (intermalleolar distance > 5 cm)
  • Swelling of wrists and costochondral junctions (rachitic rosary)
  • Prolonged bone pain (>3 months duration)

2. Symptoms and signs of muscle weakness

  • Cardiomyopathy in an infant
  • Delayed walking
  • Difficulty climbing stairs

3. Abnormal bone profile or x-rays

  • Low plasma calcium or phosphate
  • Raised alkaline phosphatase
  • Osteopenia or changes of rickets on x-ray
  • Pathological fractures

4. Disorders impacting on vitamin D metabolism

  • Chronic renal failure
  • Chronic liver disease
  • Malabsorption syndromes, for example, cystic fibrosis, Crohn’s disease, coeliac disease
  • Older anticonvulsants, for example, phenobarbitone, phenytoin, carbamazepine

5. Children with bone disease in whom correcting vitamin D deficiency prior to specific treatment would be indicated:

 

Symptoms and signs in children of vitamin D deficiency

1. Infants: Seizures, tetany and cardiomyopathy

2. Children: Aches and pains: myopathy causing delayed walking; rickets with bowed legs, knock knees, poor growth and muscle weakness

3. Adolescents: Aches and pains, muscle weakness, bone changes of rickets or osteomalacia

 

Risk factors for reduced vitamin D levels include:

  • Dark/pigmented skin colour e.g. black, Asian populations
  • Routine use of sun protection factor 15 and above as this blocks 99% of vitamin D synthesis
  • Reduced skin exposure e.g. for cultural reasons (clothing)
  • Latitude (In the UK, there is no radiation of appropriate wavelength between October and March)
  • Chronic ill health with prolonged hospital admissions e.g. oncology patients
  • Children and adolescents with disabilities which limit the time they spend outside
  • Institutionalised individuals
  • Photosensitive skin conditions
  • Reduced vitamin D intake
  • Maternal vitamin D deficiency
  • Infants that are exclusively breast fed
  • Dietary habits – low intake of foods containing vitamin D
  • Abnormal vitamin D metabolism, abnormal gut function, malabsorption or short bowel syndrome
  • Chronic liver or renal disease

 

Management depends on the patient’s characteristics:

 A. No risk factors

No investigations, lifestyle advice* and consider prevention of risk factors

 

B. Risk Factors Only

1. Children under the age of 5 years: Lifestyle advice* and vitamin D supplementation.

Purchase OTC or via Healthy Start

Under 1 year: 200 units vitamin D once daily

1 – 4 years: 400 units vitamin D once daily

 

2. Children 5 years and over – offer lifestyle advice*

 

 

C. Risk Factors AND Symptoms, Signs

Lifestyle advice*

Investigations:

  • Renal function, Calcium, Phosphate, Magnesium (infants), alkaline phosphatase,
  • 25-OH Vitamin D levels, Urea and electrolytes, parathyroid hormone

 

Children can be managed in Primary Care as long as:

  • No significant renal impairment
  • Normal calcium (If <2.1 mmol/l in infants, refer as there is a risk of seizures)

If further assessment is required consider referral to specialist. **

Patient’s family is likely to have similar risk of Vitamin D deficiency – consider investigation ant treatment if necessary.

 

 

*Life style advice

 

1. Sunlight

Exposure of face, arms and legs for 5-10 mins (15-25 mins if dark pigmented skin) would provide good source of Vitamin D. In the UK April to September between 11am and 3pm will provide the best source of UVB. Application of sunscreen will reduce the Vitamin D synthesis by >95%. Advise to avoid sunscreen for the first 20-30 minutes of sunlight exposure. Persons wearing traditional black clothing can be advised to have sunlight exposure of face, arms and legs in the privacy of their garden.

2. Diet

Vitamin D can be obtained from dietary sources (salmon, mackerel, tuna, egg yolk), fortified foods (cow, soy or rice milk) and supplements. There are no plant sources that provide a significant amount of Vitamin D naturally.

 

  **Criteria for referral
  • Criteria for management in primary care not met
  • Deficiency established with absence of known risk factors
  • Atypical biochemistry (persistent hypophosphatemia, elevated creatinine)
  • Failure to reduce alkaline phosphatase levels within 3 months
  • Family history (parent, siblings) with severe rickets
  • Infants under one month with calcium <2.1mmmol/l at diagnosis as risk of seizure.  (Check vitamin D level of mothers in this group immediately and treat, particularly if breast feeding.)
  • If compliance issues are anticipated or encountered during treatment.
  • Satisfactory levels of vitamin D not achieved after initial treatment.

 

  Vitamin D levels, effects on health and management of deficiency

level effects

management

< 25 nmol/l (10micrograms/l) Deficient.  Associated with rickets, osteomalacia Treat with high dose vitamin D

Lifestyle advice AND vitamin D (ideally cholecalciferol)

• 0 – 6 months: 3,000 units daily

• 6 months – 12 yrs: 6,000 units daily

• 12 – 18 yrs: 10,000 units daily

vitamin D 25 – 50 nmol/l (10 – 20micrograms/l Insufficient and associated with disease risk Over the counter (OTC) Vitamin D supplementation (and maintenance therapy following treatment for deficiency) should be sufficient.

 

• Lifestyle advice and  vitamin D supplementation

< 6 months: 200 – 400 units daily (200 units may be inadequate for breastfed babies)

Over 6 months – 18 years: 400 – 800 units daily

50 – 75 nmol/l (20 – 30micrograms/l) Adequate Healthy Lifestyle advice
> 75 nmol/l (30 micrograms/l) Optimal Healthy None

 

Course length is 8 – 12 weeks followed by maintenance therapy.

 

 Checking of levels again

As Vitamin D has a relatively long half-life levels will take approximately 6 months to reach a steady state after a loading dose or on maintenance therapy. Check serum calcium levels at 3 months and 6 months, and 25 – OHD repeat at 6 months. Review the need for maintenance treatment.  NB:  the Barts Health management protocol uses lower treatment doses for a minimum of 3 months and then there is no need for repeat blood tests in the majority of cases of children satisfying the criteria for management in primary care.

 Serum 25 OHD after 3 months treatment Action

level action review
>80nmol/ml Recommend OTC prophylaxis and lifestyle advice as required
50 – 80 nmol/mL Continue with current treatment dose reassess in 3 months
< 50 nmol/mL Increase dose or, in case of non-adherence/concern refer to secondary care.  

It is essential to check the child has a sufficient dietary calcium intake and that a maintenance vitamin D dose follows the treatment dose and is continued long term.

Follow-up:

Some recommend a clinical review a month after treatment starts, asking to see all vitamin and drug bottles. A blood test can be repeated then, if it is not clear that sufficient vitamin has been taken.

Current advice for children who have had symptomatic Vitamin D deficiency is that they continue a maintenance prevention dose at least until they stop growing. Dosing regimens vary and clinical evidence is weak in this area. The RCPCH has called for research to be conducted.  The RCPCH advice on vitamin D is at http://www.rcpch.ac.uk/system/files/protected/page/vitdguidancedraftspreads%20FINAL%20for%20website.pdf

JINI HALDAR

 

Obesity – assessment in secondary care and associated dysmorphisms

Article by Dr Hajera Sheikh, paediatric registrar

Assessment in Secondary Care

History:
• Lifestyle Assessment
• Menstrual History
• Obstructive Sleep Apnoea:  Snoring, difficulty breathing during sleep, morning headaches or fatigue
• Symptoms of co-morbidity including psychological
• Drug use (particularly glucocorticoids and atypical antipsychotics)
• Family history, particularly diabetes <40 yrs, early heart disease <60 yrs
Examination:
• Height, weight, BMI
• Obesity pattern: generalised, central (greater risk of adverse cardiovascular outcomes), buffalo hump and neck (may be suggestive of Cushing syndrome)
• Blood pressure
• Pubertal assessment
• Acanthosis nigricans (indicative of insulin resistance, first seen round neck and axillae)
• Signs of endocrinopathy
• Dysmorphisms: (Look out for early onset obesity, learning difficulties, deafness, epilepsy, retinitis, dysmorphic features, hypogonadism)

Investigations (directed)
• Urinalysis
• Thyroid function
• Fasting lipids (total and HDL cholesterol), triglycerides
• Liver function, including ALT
• Fasting glucose and insulin not usually done first line

Refer to Paediatric Obesity/Endocrinology or other specialist service if further investigation is required

Aetiology
• Genetic studies
• Thyroid studies: T3, thyroid antibodies, calcium, phosphate
• Cushing syndrome investigations

For co-morbidities
• Oral glucose test
• PCOS studies (LH, FSH, adrenal androgens, Sex Hormone Binding Globulin, prolactin, pelvic ultrasound)
• Sleep Study

Dysmorphic and monogenic syndromes associated with obesity:

Main clinical obesity associated syndromes:
• Chromosomal
Prader-Willi syndrome
Trisomy 21
• Autosomal dominant
Biemond syndrome (some cases)
• Autosomal recessive
Aistrom syndrome
Bardet-Biedl syndrome
Biemond Syndrome(some cases)
Carpenter syndrome
Cohen syndrome
• X-linked inheritance
Borjeson-Forssman-Lehmann syndrome
• Single gene lesions affecting leptin metaboilsm
Congenital leptin deficiency
Leptin receptor mutation
Prohormone convertase 1 mutation
Melanocortin 4 mutation

Clinical features suggesting obesity may be secondary to another condition or syndrome
• Severe unremitting obesity
• Disorders of the eyes
Colobomata
Retinal problems, especially retinitis pigmentosa
Narrow palpebral fissures
Abnormally positioned palpebral fissures
Severe squint (eg Prader-Willi)
• Skeletal abnormalities
Polydactyly
Syndactyly
Kyphoscoliosis
• Sensorineural deafness (eg Alstrom syndrome: sensorineural deafness, diabetes mellitus, retinal dystrophy, obesity)
• Microcephaly and/or abnormally shaped skull
• Mental retardation
• Hypotonia
• Hypogonadism
Crptorchidism
Micropenis
Delayed puberty
• Renal abnormalities
• Cardiac abnormalities

July 2013 PDF

Neglect and emotional abuse is the safeguarding topic this month.  ED advice on the management of minor head injuries, a report from BPSU in hypocalcaemic fits secondary to vitamin D deficiency, the new UK immunisation poster and a bit on crying babies.  Hope you find it all helpful.  Comments welcome below