Monitoring Outcome in Neonatal Thrombocytopenia

2. INTRODUCTION AND RATIONALE

2.1 The relationship between thrombocytopenia and bleeding A complex relation exists between thrombocytopenia in preterm neonates and bleeding. This is illustrated by a recent observational study that demonstrated that only 9% of neonates with a very low platelet count developed major bleeding.(1) Moreover, patients with normal platelet counts bleed quite frequently, as evidenced by another study in which 25-38% of the patients with an IVH did not have thrombocytopenia.(2,3) Several recent reviews have highlighted that the fact that neonatal bleeding and neonatal thrombocytopenia often occur in the same timeframe, does not necessarily imply a causal relationship.(4,5) It is difficult to identify the role of thrombocytopenia in bleeding, because bleeding is a multifactorial process, and because there are a lot of interactions between bleeding, thrombocytopenia and clinical variables. Moreover, neonatal platelets appear to be different from adult platelets in many ways, which complicates our understanding of the effect of low platelet counts on bleeding risk, or the effect of transfusion of (adult) platelets in the neonatal system.(6)

2.2 potential prognostic variables The most important known risk factor for bleeding is low gestational age.(1) In the specific case of IVH, it is thought that the prematurity of the brain - which has a highly vascularized germinal matrix that can easily be damaged - is an important causal factor. However, several other factors have been associated with an increased risk of bleeding, for example low Apgar scores, acidosis, vaginal birth, need for mechanical ventilation, disordered coagulation,NEC, DIC, indomethacin or surfactant treatment, low oxygen saturation levels, a low Score for Neonatal Acute Physiology (SNAP), and many more. But many of these studies have severe limitations such as lack of multivariate analysis, unclear selection of controls, small numbers and different study populations. Most are also limited to a baseline risk assessment, without a possibility to correct the risk assessment as the clinical status of the child changes. Therefore there is no clarity as to which factors are really relevant in clinical practice when assessing neonatal bleeding in neonates with thrombocytopenia.

2.3 Current prediction models A few prediction models for neonatal bleeding have been published, but to our understanding, none of these is used regularly in clinical practice.(7-9) The main disadvantage of these models is that they only allow assessment of bleeding risk at baseline, and do not correct for changes in clinical status during the admission period. We believe that adding this feature to our prediction model will significantly improve our ability to predict bleeding.

2.4 The MONET study The MONET study is a retrospective, multicenter, observational cohort study that assesses risk factors for neonatal bleeding in thrombocytopenic preterm neonates. This population is chosen because these are the neonates that are currently being treated with prophylactic thrombocyte transfusions. The results of this study will allow us to identify neonates within this population that are at high risk of bleeding. These neonates may potentially benefit from different treatment strategies. Also, modifiable risk factors can be further explored as potential targets for preventing neonatal bleeding.