Case 92 – summary

Thanks for your help with the cases.

This week we have looked at three different scenarios regarding bleeding or bruising presenting in the paediatric population.

The cases although different have some common themes:

Coagulation testing in paediatrics is challenging for several reasons:

  1. lack of local reference ranges for tests due to ethical concerns.
  2. physiological differences in coagulation factor and other coagulation protein levels (Factor II, VII, X, IX, XII don’t reach adult range until 6 months with other differences such as elevated factor VIII and VWF levels, reduced platelet function and low protein C and S levels at birth). Children’s reference ranges should be used until age 16.
  3. Sampling much more challenging particularly in babies. Platelet function and nucleotide testing not recommended before 1 year due to challenges of obtaining samples and interpreting results. Stress of venipuncture in children can also affect VWF results. Difficulties in obtaining samples can lead to pre activated samples.

With the above in mind when faced with a child with bleeding or bruising given limitations of the tests the focus should be on good history and examination.

Testing should focus on excluding major bleeding disorders rather than investigating for milder conditions that are unlikely to be cause of presentation. Repeat testing can be helpful if results unclear particularly with VWF tests that are affected by acute trauma and stress. Platelet nucleotide and function should not be performed in young babies as not possible to interpret results with certainty.

History points to consider:

  • Is the bruising or bleeding consistent with history given? – NAI clearly may have inconsistent story but equally bleeding disorders may also cause bruising with apparently minimal trauma.

Pattern of Bruising or bleeding:

  • Bruises consistent with a pattern like a hand would be consistent with NAI.
  • Bruising over shins much less concerning than sites that are not exposed such as the abdomen .

Bleeding history and challenges to haemostasis:

  • Birth: stump bleeds ( suggestive XIII deficiency), cephalohaematomas.
  • Vaccines: significant bleed or bruise post IM injections
  • Mucosal bleeding: VWD
  • Surgery: circumcision, tooth extraction

General Health:

  • Liver disease?
  • Sepsis- DIC picture
  • Recent Infection – Henoch scholein purpura, ITP

Family History:

  • Bleeding issues
  • Hypermobility

Ethnicity:

  • Consanguineous relationships – recessive bleeding traits.
  • Ashkenazy Jewish population – factor XI deficiency

Drug History:

  • Anticoagulants
  • Steroids
  • Maternal drug Hx – Vit K def more common if taking some antiepileptic medications

Diet:

  • Breast fed – risk for Vit k deficiency
  • Poor diet – Vit C deficiency

Hypermobility – Ehlers Danlos

Examination points to consider:

  • Sites of bruising and age – abuse and bleeding disorders varied ages of bruises
  • Petechia? – ITP or HSP?
  • Joint bleeds? – Haemophillia
  • Hypermobility? Scars?- Ehlers Danlos

Investigations:

These are dependent on history and examination and are not needed in all cases. For example if a child has a clear belt buckle shaped bruise that is consistent with NAI further tests won’t be needed. A baby who had clearly prolonged PT and history of breastfeeding may only require Vit K and repeat Coag not the full range of factors.

Basic screen:

  • PT/APTT
  • Thrombin time
  • Fibrinogen
  • 50:50 mix of prolonged Coag times
  • Factor VIII,IX,XI
  • VWD screen
  • Other tests such as factor XIII and platelet function depends on history and presentation.

 

Notes on Specific cases this week:

  1. Vitamin K deficiency resulting in intracranial haemorrhage:

Levels of Vitamin K dependent coagulation factors (II,VII,IX, and X ) are low at birth and these factors are functionally inactive without vitamin K. Vitamin K deficiency classically prolongs PT in isolation but in severe cases may prolong APTT.

It should always be considered as a cause of neonatal bleeding and vitamin K should be given even prior to coagulation results being available in cases of severe bleeding.

Vitamin K deficiency bleeding (VKDB) risk factors are exclusive Breastfeeding (Breast milk does not contain VitK), missing treatment at birth, mother on drugs such as phenytoin that interfere with Vit K metabolism or babies with Liver disease who don’t use vit K the body stores or bowel problems who don’t absorb the vitamin K.

There are 3 types of vitamin K deficiency:

  • Early: first 24 hours after birth commonly due to maternal medications
  • Classical: 1-7 days post delivery
  • Late: 2-12 weeks of age but can be seen up to 6 months. These babies are otherwise well and sadly up to 60% present with significant intracranial bleeds as first event.

Management of vitamin K prophylaxis is varied and there are several approaches.

If a mother is on antiepileptic such as phenytoin she should be counselled about risks and given choice to change medication. She should receive 20mg vit K per day in last 4 weeks of pregnancy and IM 1mg Vit K given at birth.

IM vit K 1mg was traditionally given at birth but there was a single study that linked this to possible childhood cancer ( though no further studies have shown no link). Oral regimens give 2mg at birth and then daily for the next 3 months instead.

Any infant presenting with possible bleeding related to vitamin K deficiency should receive IV or S/C vit K (avoid IM route). This should occur before confirmation.

Octoplas 15ml/kg should be used to correct coagulation anomalies. Care should be taken to avoid volume overload and changes in BP due to rapid volume expansion.

2. Ehlers Danlos

This is a group of 13 different inherited conditions that affect the connective tissues, usually collagen.

The commonest type is classical Ehlers Danlos. This condition causes a defect in type V collagen leading to fragility of collagen fibrils. In classical ED under an electron microscope collagen flowers can be seen due to defects in collagen fibres.

Given the classical clinical presentation of Hypermobile joints, skin elasticity and easy bruising with atrophic scaring the diagnosis is often given on clinical grounds. Skin biopsy and microscopy was the previous diagnostic test however Genetic tests can be performed looking for mutations in COL5a or COL5A2 genes if needed (The condition is autosomal dominant).

A patient will often have fragile skin and inspection will show scars with wide defects or over shins, elbows and knees. They will demonstrate Hypermobile joints and a useful clinical tool is the Beighton score which if >5 suggests hyper mobility. They may also have easy bruising and stretchy skin. There is often a family history of hyper mobility and hernias or prolapses due to weak collagen.

Management of Ehlers Danlos is supportive. Advice includes avoiding skin trauma and contact sport should be avoided due to dislocation risk. Cardiac echo should be considered to ensure cardiac valves not affected. If pregnant then additional care should be taken as high risk for perineal tear and prolapse.

In our case the patient had easy bruising and advice should be to avoid trauma as much as possible. She should have an echo and be advised to inform obstetric team if ever pregnant due to increased perineal tearing rate. Family can be referred to local genetic service if they are concerned.

3. Factor XII deficiency and probable NAI:

Factor XII deficiency s autosomal recessive and affects 1 in a million of the population. Occasionally patients with this condition have poor wound healing but this does not cause bleeding problems.

In this case the factor XII deficiency does not explain bruising and given the bruises suspicious location on the abdomen it is likely NAI is the cause for the presentation.

If NAI is considered you may need to perform testing for rarer bleeding conditions even if initial screen is negative for legal reasons. It is important if NAI is thought to be an issue that advice is sought from experts at an early stage and any testing done in major centre so results can be as accurate as possible.

References:

AE Thomas The bleeding child; is it NAI?. Arch Dis Child 2004, 89, 1163-1167.

CDC website vitamin K deficiency bleeding

The investigation and management or neonatal haemostasis and thrombosis. BJHaem 2002, 119, 295-309.

Ehlers Danlos association website

Factor XII deficiency – Haemophillia.org website

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