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Chapter 150 Disorders of Coagulation in the Neonate 2193

TABLE Classification of Fetal and Neonatal Thrombocytopenia
150.3
Fetal Early-Onset Neonatal(<72 h) Late-Onset Neonatal(>72 h)
Conditions • Alloimmune • Chronic fetal hypoxia (e.g., PIH, IUGR, diabetes) • Late-onset sepsis
• Congenital infection (e.g., CMV, • Perinatal asphyxia • NEC
toxoplasma, rubella, HIV) • Perinatal infection (e.g., Escherichia coli, GBS, Haemophilus • Congenital infection (e.g.,
• Aneuploidy (e.g., trisomies 18, influenzae) CMV, toxoplasma, rubella,
13, 21) • DIC HIV)
• Autoimmune (e.g., ITP, SLE) • Alloimmune • Autoimmune
• Severe rhesus hemolytic • Autoimmune (e.g., ITP, SLE) • Kasabach-Merritt syndrome
disease • Congenital infection (e.g., CMV, toxoplasma, rubella, HIV) • Metabolic disease (e.g.,
• Inherited (e.g., Wiskott-Aldrich • Thrombosis (e.g., aortic, renal vein) propionic and methylmalonic
syndrome) • Bone marrow replacement (e.g., congenital leukemia) acidemia)
• Kasabach-Merritt syndrome • Inherited (e.g., TAR, CAMT)
• Metabolic disease (e.g., propionic and methylmalonic acidemia)
• Inherited (e.g., TAR, CAMT)
CAMT, Congenital amegakaryocytic thrombocytopenia; CMV, cytomegalovirus; DIC, disseminated intravascular coagulation; GBS, group B Streptococcus; HIV, human
immunodeficiency virus; ITP, idiopathic thrombocytopenic purpura; IUGR, intrauterine growth restriction; NEC, necrotizing enterocolitis; PIH, pregnancy-induced
hypertension; SLE, systemic lupus erythematosus, TAR, thrombocytopenia with absent radii. The most frequently occurring conditions are in bold.
Modified from Roberts I, Stanworth S, Murray NA: Thrombocytopenia in the neonate. Blood Rev 22:173, 2008.

injury, perhaps because fetal megakaryocytes are particularly sensitive TABLE Syndromic, Genetic Conditions and Acquired Marrow
to hypoxia. Transient mild to moderate thrombocytopenia is common 150.4 Disorders as Causes of Neonatal Thrombocytopenia
in newborns from pregnancies that were complicated by intrauterine
growth restriction or pregnancy-induced hypertension. Other rare Inborn Errors of Metabolism
causes of decreased platelet production in neonates include primary Isovaleric acidemia
congenital platelet or marrow disorders and infiltrative disorders. Methylmalonic acidemia (with acute acidosis) and cobalamin metabolic
These are summarized in Table 150.4. defects
Holocarboxylase deficiency
Mitochondrial disorders
Neonatal Alloimmune Thrombocytopenia Pearson syndrome
Kearns-Sayre syndrome
Neonatal alloimmune thrombocytopenia is the platelet equivalent of Genetic Marrow Failure Syndromes
hemolytic disease of the newborn. It affects approximately 1 in 2000 Amegakaryocytic thrombocytopenia
pregnancies. When fetal platelets express paternal human platelet Fanconi anemia
antigens (HPAs) that the mother lacks, transplacental passage of Other Syndromic Thrombocytopenias
maternal immunoglobulin G directed against fetal platelets can occur Thrombocytopenia with absent radii syndrome
and usually results in severe neonatal thrombocytopenia (platelet Paris-Trousseau syndrome
9
count <30 × 10 /L). This may result in major bleeding, particularly X-linked thrombocytopenias
intracranial hemorrhage (ICH), which can occur in 10% to 20% of Wiskott-Aldrich syndrome
12
untreated pregnancies. Incompatibilities for HPA-1a account for GATA1 mutations
the majority of cases of neonatal alloimmune thrombocytopenia in Aneuploidy
white populations. About half of the cases of neonatal alloimmune
thrombocytopenia occur in the first pregnancy because fetal platelets Trisomy 21, 13, or 18
pass into the maternal circulation early in the pregnancy. Treatment Genetic Macrothrombocytopenias
options include transfusion of antigen-negative platelets if available May-Hegglin, Sebastian, and Fechtner syndromes
(HPA-1a ± 5b). Although large randomized studies are lacking, the Bernard-Soulier syndrome
9
threshold count for platelet transfusion in most studies is 30 × 10 /L. Acquired Marrow Disorders
High-dose intravenous immunoglobulin and/or a trial of random Oncologic
donor platelets can be given if compatible platelets are unavailable. Neonatal leukemia
The recommended total dose of intravenous immunoglobulin is 1 to Neuroblastoma
2 g/kg administered either at a dose of 0.4 g/kg daily for 3 to 5 days Histiocytic lymphohistiocytosis
or at a dose of 1 g/kg daily for 1 or 2 days. 13

Inherited Thrombocytopenia
amegakaryocytic thrombocytopenia, X-linked macrothrombocytope-
Most cases of inherited thrombocytopenia are the result of decreased nia caused by GATA1 mutation, giant platelet syndromes, and meta-
platelet production because of abnormal hematopoietic stem or bolic disorders.
progenitor cell development. Such disorders are often associated with
congenital anomalies, which can inform the course of investigation
12
and aid in the diagnosis. Disorders that present with neonatal Platelet Function Disorders
thrombocytopenia include Bernard-Soulier syndrome, type 2B von
Willebrand disease (vWD), Wiskott-Aldrich syndrome, Fanconi Qualitative platelet disorders are rarely associated with overt neonatal
anemia, thrombocytopenia with absent radii syndrome, amegakaryo- bleeding. Patients presenting with bleeding who have normal coagu-
cytic thrombocytopenia with radioulnar synostosis, congenital lation test results and platelet counts require further investigation.