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NICU guideline identifier

Neonatal Thrombocytopenia

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Background

Thrombocytopenia is extremely common in the NICU setting, occurring in up to a quarter of admissions, but while the disorder is frequently seen it should not be dismissed without consideration of its significance.

Thrombocytopenia can be a marker of underlying disease as well as an obvious risk factor for haemorrhage.

Incidence

  • The incidence of thrombocytopenia depends on its definition as well as the subgroup of infants examined.
  • Although preterm neonates tend to have slightly lower mean platelet counts than term infants and adults, a lower limit of 'normal' of 150 x 109/L still applies. Around 2% of healthy term infants will fall below this level, with many more sick preterm infants having low counts. Around 20% of neonates <28 weeks gestation develop severe thrombocytopenia (<50 x 109/l).1

Aetiology

Causes of thrombocytopenia are best separated by time of presentation into fetal, early (<72hrs) and late.

Timing Most common aetiology Less common aetiology
Fetal    Alloimmune (NAIT)
Congenital infection (e.g. CMV, toxoplasma, rubella)
Aneuploidy (e.g. trisomies 18, 13, 21, or triploidy)
Autoimmune (e.g. ITP, SLE)
Severe rhesus disease
Congenital/inherited (e.g. Wiskott-Aldrich syndrome)
Early-Onset Neonatal
(<72 hours)
Placental insufficiency (e.g. GPH, IUGR, diabetes)
Perinatal asphyxia
DIC
Alloimmune (NAIT)
Autoimmune 
Congenital infection (e.g. CMV, toxoplasma, rubella)
Thrombosis (e.g. aortic, renal vein)
Bone marrow replacement (e.g. congenital leukaemia)
Metabolic disease (e.g. propionic and methylmalonic acidaemia)
Congenital/inherited, eg
   - Kasabach-Merritt
   - Thrombocytopenia absent radius
   - Congenital TAR
   - Congenital Amegakaryocytic  Thrombocytopenia (CAMT)
Late-Onset Neonatal  Late-onset sepsis
NEC 
Congenital infection (e.g. CMV, toxoplasma, rubella)
Autoimmune
Kasabach-Merritt Phenomenon
Metabolic disease (e.g. propionic and methylmalonic acidaemia)
Congenital/inherited (eg TAR, CAMT)

Fetal Thrombocytopenia

Is most commonly due to Neonatal Alloimmune Thrombocytopenia. Congenital infection and chromosomal abnormalities are the other principal considerations.

Early-Onset Neonatal Thrombocytopenia

This is common in preterm infants following pregnancies complicated by placental insufficiency or fetal hypoxia (which may impair fetal/infant platelet production). These infants show a typical pattern of low/low-normal platelet counts at birth (100-200 x 109/L), with levels falling to a nadir of 50-100 x 109/L at 4-5 days. Counts generally return to normal at 7-10 days. They usually have an associated transient neutropenia, increased number of nucleated RBC and polycythaemia. Clinically stable preterm infants following this pattern have only a very low risk of bleeding if platelet count remains above 50 x 109/L.3

Early-onset neonatal thrombocytopenia without an obvious precipitant is much more of a concern, and may be due to Neonatal Alloimmune Thrombocytopenia (NAIT), with its high risk of haemorrhage. This is the most important cause of thrombocytopenia in term infants who are otherwise well.

Neonatal Autoimmune Thrombocytopenia is due to maternal platelet autoantibodies (i.e. mothers are also at risk of thrombocytopenia), principally from ITP and SLE. Around 10% of infants will be affected. Infants with this disorder are at low risk of significant haemorrhage (<1%), but should have cord FBC and if low, platelet count monitored during the first 3-5 days. If count falls to <30 x 109/L, consider intravenous immunoglobulin therapy.

A small proportion of neonates will have persistent thrombocytopenia and these infants should have further investigations for uncommon conditions.

Late-Onset Neonatal Thrombocytopenia

Thrombocytopenia presenting in a neonate after the first 3 days of life should be presumed to be due to sepsis or NEC until proven otherwise.

In such cases platelet count often drops rapidly, and to levels of 50 x 109/L or below. Once the precipitant is controlled levels rise again over 5-7 days. These infants are at significant risk of haemorrhage, though the benefit of transfusing with platelets isn't clear.

Risks of Thrombocytopenia

Thrombocytopenia increases the risk of bleeding, but this risk is hard to quantify for individual infants. A few factors guide a decision to transfuse:

  • Neonates with active bleeding should be transfused to maintain platelet count above 100 x 109/L (although there is no evidence for this practice).
  • Other thresholds at which to transfuse depend on the perceived risk of haemorrhage. A direct correlation between platelet count and major bleeding has not been shown.4 Strongest predictors for haemorrhage are gestation <28 weeks, early thrombocytopenia, and acute systemic infection or NEC1,5
  • Infants with NAIT should be considered separately as they are at relatively higher risk at the same platelet count when compared to other aetiologies.
  • Prophylactic platelet transfusion has not been shown to reduce morbidity in neonates. Infants receiving transfusions have poorer outcomes (which may be due to only the sickest neonates being transfused). Haemopoietic growth factors such as thrombopoietin and interleukin-11 have not been shown to be of benefit.

Platelet Transfusion

There is only one randomised controlled trial (RCT) evaluating platelet transfusion threshold in VLBW neonates.10 They reported moderate thrombocytopenia (50-150 x 109/l) was not detrimental and suggested transfusions for platelets above 50 x 109/l are not necessary. A prospective observational study suggests 20 x 109/l is a safe threshold in absence of other risk.1 A lower platelet count alone is not a strong predictor of increased bleeding risk. The strongest predictors of risk are gestation <28 weeks, early onset of severe thrombocytopenia and NEC.5

Many centres have developed guidelines based on expert opinion for platelet transfusion while awaiting stronger evidence for the timing of intervention and these are what our guideline is based on.1,2,6,7,8,9 There is a large multicentre RCT currently underway in England. [www.planet-2.com]

See Blood Products - Platelets for further information including indications for transfusion

Practice Points

Consider clinical risk factors in addition to absolute platelet count:

  • Timing of onset (early versus late)
  • Primary origin (maternal, placental or neonatal/fetal)
  • Individual risk for bleeding (gestational age, postnatal age, NEC/sepsis, surgery, signs of bleeding).

In a clinically stable, term neonate without NAIT, signs of infection or pre-existing IVH the threshold for transfusion of <20 x 109/l seems safe.6 Persistent unexplained thrombocytopenia should be investigated for uncommon causes.

References

  1. Stanworth, S.J., Clarke, P., Watts, T., et al. for the Platelets Neonatal Transfusion Study Group. Prospective, Observational study outcomes in Neonates with severe thrombocytopenia. Pediatrics 2009; 124:e826-e834. 
  2. Roberts, I.A. and N.A. Murray, Thrombocytopenia in the newborn. Curr Opin Pediatr, 2003. 15(1): p. 17-23. 
  3. Watts, T.L.R. and Roberts, I.A.G. Haematological abnormalities in the growth-restricted infant. Seminars in Neonatology. 1999;4: 41-54. 
  4. Baer, V.L., Lambert, D.K., Henry, E., and Christensen, R.D. Severe Thrombocytopenia in the NICU. Pediatrics 2009;124:e1095-e1100. 
  5. Muthukumar, P., Venkatesh, V., Curley, A. et al for the Platelets Neonatal Transfusion Study Group. Severe thrombocytopenia and patterns of bleeding in neonates: results from a prospective observational study and implications for use of platelet transfusions. Transfusion Medicine 2012; 22:338-43. 
  6. Cremer, M., Sallmon, H., Kling, P.J., B├╝hrer, C. and Dame, C. Thrombocytopenia and platelet transfusion in the neonate. Seminars Fetal & Neonatal Med. 2016(21);10-18. 
  7. Chakravorty, S. and Roberts, I. How I manage neonatal thrombocytopenia. British Journal of Haematology. 2011;156:155-162.
  8. Clinical Guide to Transfusion Canadian Blood Services (On-line edition at http://www.transfusionmedicine.ca ) Chapter 13 (Updated Jan 2014). 
  9. Clinical Guide to Transfusion Canadian Blood Services (On-line edition at http://www.transfusionmedicine.ca ) Chapter 13 (Updated Jan 2014). 
  10. Gibson, B.E., Todd, A., Roberts, I., Pamphilon, D., Rodeck, C., Bolton-Maggs, P., Burbin, G., et al. Transfusion guidelines for neonates and older children. British Journal of Haematology. 2004;124:433-453. 
  11. Andrew, M., Vegh, P., Caco, C. et al. A Randomized, controlled trial of platelet transfusions in thrombocytopenic premature infants. J Pediatr 1993;123:285-91.

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Document Control

  • Date last published: 28 September 2016
  • Document type: Clinical Guideline
  • Services responsible: Neonatology
  • Owner: Newborn Services Clinical Practice Committee
  • Editor: Sarah Bellhouse
  • Review frequency: 2 years