Approach to the newborn with thrombocytopenia Dr. Lourdes Asiain Nov 2004

Objectives Define mild, moderate and severe thrombocytopenia List most common causes for the condition List dysmorphic features assoc with Thrombocytopenia Description and management of neonatal alloimmune thrombocytopenia

Thrombocytopenia: Definition Mild100,000 to 150,000 Moderate50,000 to 99,000 SevereLess than 50,000

Thrombocytopenia: Epidemiology Up to 25 % of infants admitted to NICU have the condition. Mild asymptomatic thrombocytopenia occurs in 1% healthy term infants Severe thrombocytopenia in term infants rare

Thrombocytopenia Increased platelet consumption Impaired Megakaryopoiesis

Thrombocytopenia: assesment Term or preterm? Other medical conditions Are there features suggestive of congenital infection? Congenital anomalies/dysmorphism

Differential Diagnosis Sick Neonates, Preterm infants, other medical complications. Hypoxia and acidosis after birth Chronic hypoxia from placental insufficiency Hypothermia Pre-eclampsia Sepsis Congenital viral infections (CMV, rubella) DIC NEC Thrombosis Exchange transfusions

Differential diagnosis Neonates with physical abnormalities/dysmorphism Thrombocytopenia with absent radius Synd Fanconi anemia Chromosomal disorders (13,18,21, Turner) Kasabach-Merritt Syndrome

Differential diagnosis Healthy-appearing infant Occult infection Maternal autoimmune thrombocytopenia Neonatal alloimmun thrombocytopeni Amegakaryocytic thrombocytopenia Hereditary macrothrombocytopenia Wiskott-Aldrich Sydrome

Common causes Pre-eclampsia Magnitude usually correlates with severity of HTN Often have associated neutropenia Nadir at 3-4 days of life, recovering to normal levels by day 7-10 Rarely severe thrombocytopenia Possible etiology is disruption of hematopoietic progenitor cell commitment to megakaryopoiesis Assoc conditions from prematurity may exacerbate condition

Common causes Bacterial Sepsis Several mechanisms that include endothelial damage, immune mediated destruction, platelet aggregation and decreased platelet production.

Common causes Viral infections Viral neuraminidase causes sialic acid loss from platelet membranes Intravascular platelet aggregation Congenital infections + Splenomegaly

Assoc with Physical abnormalities or dysmorphism TAR Syndrome Autosomic recessive Severe thrombocytopenia and skeletal abnormalities Can be associated with congenital heart disease Platelet nadir during first week generally improve by 1-3 years of age.

TAR Syndrome

Anomalies/Dysmorphism Fanconi anemia Aplastic anemia Thumb anomalies Anomalies of GU system

Abnormalities/Dysmorphism Kasabach-Merrit Syndrome Hemangioma Coagulation is activated locally and platelets are sequestered in the vascular malformation May not be apparent

Maternal autoimmune Thrombocytopenia ITP, autoimmune diseases Maternal antibodies vs. platelet antigens Glycoprotein IIb/IIIa and Ib/IX Antibodies cross placenta and bind to these antigens on fetal platelets. Determine the mother’s platelet count

Neonatal alloimmune thrombocytopenia A mother lacks a platelet antogen that her fetus inherited from father. Maternal IgG vs “foreign” antigen on fetal platelets cross the placenta and destroy them. Most common platelet antigen HPA-1a

Management of immune mediated Thrombocytopenia IVIG In cases of severe thrombocytopenia or clinical bleeding 1gram/Kg In cases of NAIT Head US and platelet transfusion with platelets that are free on HPA1 antigen.

Less common etiologies Congenital amegakarocitic thrombocytopenia (AR) Heredetary macrothrmbocytopenias (AD) Wiskott Aldrich Syndrome (WAS protein X) Immunedefiency Eczema Thrombocytopenia

Conclusions Thrombocytopenia is often encountered in newborns, specially sick preterm infants Initial assessment should consider gestational age, co-morbid conditions, congenital-physical anomalies and dysmorphism.

Thank You References NeoReviews.org: Approach to the Newborn who has thrombocytopenia. Vol Curr opinion Obst Gynecol: Platelet disorders in pregnancy. 2001;13: Avery’s Diseases of the Newborn. Taesch et Ballard.