Neonatal Thrombocytopenia

Reviewed by Alan Groves and Carl Kuschel

April
2003

Background	Incidence	Aetiology	Risks of Thrombocytopenia
	Platelet Transfusion Guidelines	References

Please see also Neonatal Alloimmune Thrombocytopenia

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.

Aetiology

Causes of thrombocytopenia are best separated by time of presentation into fetal, early <3 days) and late.

Timing	Most Common Aetiology	Less Common Aetiology
Fetal	Alloimmune 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 Autoimmune	Congenital infection (e.g. CMV, toxoplasma, rubella) Thrombosis (e.g. aortic, renal vein) Bone marrow replacement (e.g. congenital leukaemia) Kasabach-Merritt syndrome Metabolic disease (e.g. propionic and methylmalonic acidaemia) Congenital/inherited (e.g. 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 impaired placental function 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. Clinically stable preterm infants following this pattern have only a very low risk of bleeding if platelet count remains above 50 x 10⁹/L.

Early-onset neonatal thrombocytopenia without an obvious precipitant is much more of a concern, and may be due to Neonatal Alloimmune Thrombocytopenia, with its high risk of haemorrhage. Neonatal Autoimmune Thrombocytopenia is due to maternal platelet autoantibodies (i.e. mothers are also at risk of thrombocytopenia), principally from ITP and SLE. Infants with this disorder are at only low risk of significant haemorrhage (<1%), but should have platelet count monitored daily. If count falls to <30 x 10⁹/L, consider intravenous immunoglobulin therapy.

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-cut (see platelet transfusion guidelines)

Risks of Thrombocytopenia

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

Neonates with active bleeding should be transfused to maintain platelet count above 100 x 10⁹/L.
Other thresholds at which to transfuse depend on the perceived risk of haemorrhage.
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 raise neonatal platelet counts significantly in a clinically useful time period.

Platelet Transfusion Guideline

Many centres have developed consensus-based guidelines for platelet transfusion while awaiting strong evidence for timing of intervention.¹

Platelet Count (x10⁹) Action

<30

Transfuse if bleeding

Consider transfusion in all other cases

30-49

Transfuse if bleeding

Consider transfusion if:

<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

50-99

Transfuse only if bleeding

>99

Do not transfuse

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References

1	Roberts, I.A. and N.A. Murray, Thrombocytopenia in the newborn. Curr Opin Pediatr, 2003. 15(1): p. 17-23.
2	Murray, N.A., Evaluation and treatment of thrombocytopenia in the neonatal intensive care unit. Acta Paediatr Suppl, 2002. 91(438): p. 74-81.
3	Sola, M.C., A. Del Vecchio, and L.M. Rimsza, Evaluation and treatment of thrombocytopenia in the neonatal intensive care unit. Clin Perinatol, 2000. 27(3): p. 655-79.

Platelet Count (x10⁹)	Action
<30	Transfuse if bleeding Consider transfusion in all other cases
30-49	Transfuse if bleeding Consider transfusion if: <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
50-99	Transfuse only if bleeding
>99	Do not transfuse