MATISSE study

Background 

Premature neonates are at high risk for cerebral bleeding, especially intraventricular hemorrhage (IVH), due to the fragility of the premature vessel walls. To prevent IVH and other major bleeding, frequent prophylactic platelet transfusions are administered with the aim to keep the platelet count above 20x109/L in stable neonates and above 50x109 in clinically ‘ill’ patients. These thresholds are based on expert opinion, as there is hardly any evidence available on the effect of different platelet triggers on major bleeding and IVH. The only RCT that has addressed this issue compared transfusion triggers of 50x109 and 150x109.

A recent prospective observational study in the UK showed that 81% of platelet transfusions that neonates receive is given prophylactically. Also, it showed that out only 9% of the 194 neonates with platelet counts < 60x109/L developed severe hemorrhage. There was no clear relationship between the severity of thrombocytopenia and the occurrence of hemorrhages.

Study Objectives

1. To compare the effect of a liberal transfusion trigger (50 x109/l )with a more restrictive trigger (25 x109/l ) for transfusion of platelets on the occurrence of major bleeding and death in very preterm thrombocytopenic neonates (gestational age < 34 weeks, birth weight < 1500 gram).
2. To study the association between platelet count, hemorrhages and thrombocyte transfusions in premature thrombocytopenic neonates.

Study design

Randomized controlled Trial comparing:
Arm A:        Liberal prophylactic transfusion trigger:         50 x109/l
Arm B:        Restrictive prophylactic transfusion trigger:   25 x109/l
Primary outcome: Neonatal mortality, IVH (grade 3 and 4), other major bleeding (threatening life/limb/organ)
Longitudinal, observational study.

Study population

For both studies preterm neonates (gestational age < 34 weeks) with a platelet count of < 50x109/L admitted to a Neonatal Intensive Care Unit are eligible. Exclusion criteria: major IVH or other major bleeding (threatening life/limb/organ), known hemorrhagic disorder in neonate, maternal ITP, NAITP, need for surgery. 

Research staff 

• SF Gunnink MD (PhD student, Sanquin Blood Supply) (coordinating investigator)
• K Fijnvandraat MD PhD (Pediatric hematologist, AMC & Sanquin Blood Supply)
• E Lopriore MD PhD (Neonatologist, Leiden University Medical Center)
• JG van der Bom MD PhD (Clinical epidemiologist, LUMC & Center for Clinical Transfusion Research, Sanquin Research, Leiden)  

Collaborators

Dutch National Neonatal Research Network

All Dutch neonatal intensive care units collaborate for research purposes within this organization.

Dr Simon J. Stanworth
Department of Haematology/Transfusion Medicine, John Radcliffe Hospital,
NHS Blood & Transplant/Oxford Radcliffe Hospitals Trust and University of Oxford,
Osler Road, Headington, Oxford, OX3 9BQ, United Kingdom
Email: [email protected]