Neonatal Thrombocytopenia

 

Reviewed by Clinical Practice Committee
September 2016
Clinical Guidelines Back Newborn Services Home Page
Background Incidence Aetiology Risks of Thrombocytopenia
Platelet Transfusion Guidelines References

Please see also Neonatal Alloimmune Thrombocytopenia

Background

Incidence

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
    • e.g.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 3-5days. 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:

Platelet Transfusion Guideline

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]

Platelet Count (x109) Indications for transfusion
<20
  • All neonates
<30
  • Neonates <1000g and <7 days
  • Clinically unstable (e.g. fluctuating BP)
  • Previous major bleeding (e.g. Grade 3-4 IVH, pulmonary haemorrhage)
  • Current minor bleeding
  • Concurrent coagulopathy
  • Requiring surgery or exchange transfusion
  • NAIT
<50
  • Major Haemorrhage

Practice Points

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



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., Bührer, 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).
8 Clinical Guide to Transfusion Canadian Blood Services (On-line edition at http://www.transfusionmedicine.ca ) Chapter 13 (Updated Jan 2014).
9 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.
10 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.