Approach to neonatal thrombocytopenia: immature platelet fraction has a major role

Abstract

Thrombocytopenia is extremely common in the neonatal intensive care unit (NICU) setting, occurring in upto a quarter of admissions1, 2 but while the disorder is frequently seen it should not be dismissed without consideration of its significance.3 The evaluation and management of thrombocytopenia, which could be a marker of underlying disease as well as an obvious risk factor for haemorrhage is a frequent challenge for neonatologists.3 Neonatal thrombocytopenia is defined as a platelet count < 150 × 109/L regardless of gestational age. However, platelet counts in the 100–150 × 109/L range are somewhat more common among healthy neonates than among healthy adults. Causes of neonatal thrombocytopenia are best separated by time of presentation into foetal (mainly TORCH infections), early (< 3 days) and late.4 Though a large number of varied precipitating conditions have been identified, early-onset thrombocytopenia is most commonly associated with foeto-maternal conditions complicated by placental insufficiency and/or foetal hypoxia, e.g. maternal pre-eclampsia and foetal intrauterine growth restriction (IUGR).1, 2 The thrombocytopenia is usually mild to moderate, resolves spontaneously and requires no specific therapy. Deviation from this pattern suggests the presence of more significant precipitating conditions. The most important of these are the immune thrombocytopenias and every NICU should develop investigation and treatment protocols to manage these cases promptly and avoid unnecessary risk of haemorrhage. In contrast, late-onset thrombocytopenia is almost always associated with sepsis or necrotizing enterocolitis (NEC) and the associated thrombocytopenia is severe, prolonged, often requiring treatment by platelet transfusion. Unfortunately, evidence-based guidelines for platelet transfusion therapy in NICU are currently unavailable leading to difficulty in defining accepted thresholds for transfusion thus leading to variations in transfusion practices.5 The article published in this issue, on the incidence of thrombocytopenia is a good step in identifying the magnitude of the problem in our setting.6 However, as the platelet count was determined as part of complete blood count (CBC) by the coulter cell counter if the authors had taken into account the immature platelet fraction (IPF) which is a component of CBC, it would have helped know the likely cause as well as help predict the likely recovery. Mean platelet volume (MPV) is an indicator of IPF and is similar to the reticulocyte count in the evaluation of anaemia. Mean platelet volume (MPV) is a measure of the average size of circulating platelets and can provide clues to the kinetic mechanism of an infant's thrombocytopenia. MPV is normal (7.5–9.5 fL) when thrombocytopenia is caused by reduced production, and elevated (10–12 fL) when caused by accelerated destruction. Larger platelets are evident when the bone marrow is stimulated to produce more immature platelets in response to increased platelet utilisation. Bone marrow biopsy is the gold standard for diagnosis of thrombocytopenia but is difficult and thus postponed till the infant is out of the neonatal period and in this situation the MPV is the best non-invasive alternative.4 The percentage of reticulated platelets (RPs) is another indicator of the kinetic mechanism. RPs are newly produced platelets having a higher ribonucleic acid content than do older platelets. RP% is low ( 10%) when platelets are being consumed at an accelerated rate. Thrombopoietin (Tpo), a growth factor, is the primary regulator of platelet production in the neonate. Plasma Tpo may be useful in differentiating thrombocytopenia caused by low platelet production and accelerated platelet destruction. Synthesised in the liver, Tpo is removed from the blood by binding to Tpo receptors on megakaryocyte progenitors, megakaryocytes, and platelets. When platelet production is low or fewer megakaryocytes are produced, the plasma Tpo is high. Although still a research tool, measurement of plasma Tpo may provide valuable diagnostic information in infants with thrombocytopenia in the future.1, 7, 8 The nuances have been illustrated with two cases in NICU. Case 1: A 38 weeks' gestation neonate with platelet count < 50 × 109/L since birth. At five days of age: stools are occult blood positive; platelet count is 15 × 109/L; MPV is 7.3 fL. Thus, the underlying cause of low platelets is reduced platelet production. Transfused platelets will have a normal survival. Case 2: A contrasting situation is a 29 weeks' gestation appropriate for gestational age neonate who had normal platelet count at birth. At 25 days of age, recovering from NEC, while on parentral nutrition and antibiotics: platelet count has been 30–40 × 109/L for one week; mean platelet volume 12 fL. The underlying cause in this situation is accelerated platelet usage or destruction. Platelets transfused into this infant are likely to have a short survival.