THROMBOCYTOPENIA

Definition

§  Platelet count <150,000 in a neonate

Background

§  Fetuses begin making platelets 5 days post conception and reach adult levels by 22w gestation

o   For this reason, the definition of thrombocytopenia has the same parameters as adults

o   Platelet counts increase with increasing postnatal age

o   Recent studies questioning the validity of using adult parameters for neonates, but no change in definition yet

§  Normal term neonates have incidence of thrombocytopenia <1% while the incidence for NICU admits is 18-35%

§  Most cases are mild and resolve within 7-14 days, but a small subset of cases (2.5-5%) are severe and take months to resolve

§  Severe, persistent, and symptomatic patients must be evaluated

Etiology

§  Increased Platelet Destruction

o   Alloimmune thrombocytopenia: maternal ab against fetal platelets

§  Neonatal Alloimmune Thrombocytopenic Purpura (NATP): fetal platelets contain an antigen inherited from the father that the mother lacks. Mother makes IgG against the paternal antigen which crosses the placenta and causes thrombocytopenia

·       Infants are at risk for intracranial hemorrhage. 25-50% occur in utero

o   Autoimmune thrombocytopenia: maternal ab against maternal and fetal platelets

§  SLE, ITP: maternal ab against maternal and fetal platelets

§  Drug-related: maternal or fetal ab

·       antiepileptics, quinidine, PCN, heparin, hydralazine, thiazides

o   Peripheral Consumption

§  Hypersplenism

§  Kasabach-Merritt Syndrome: DIC with capillary hemangiomas

§  DIC

§  Infection: bacterial, viral, or fungal.

§  Necrotizing enterocolitis

§  Thrombosis

§  Hemorrhage (most IVH, pulm, or GI)

·       premature IVH: normal platelet counts at time of bleed, so causal relationship difficult to determine

·       term IVH: thrombocytopenia common at time of bleed

§  Decreased Platelet Production

o   Genetic Disorders           

§  Thrombocytopenia-absent radius syndrome: AR, bilateral absent radii, thumbs present

§  Fanconi’s Anemia

§  Congenital amagakaryocytic thrombocytopenia

§  Chromosome abnormalities: trisomies (21, 18, 13), Turner syndrome

§  Congenital platelet disorders: Wiskott-Aldrich, May-Hegglin, Bernard-Soulier, Alport

o   Infiltrative Disorders: neoplasms. Rare in the neonatal period.

o   Toxic injury to megakaryocytes by infections/drugs

§  Miscellaneous Causes

o   Neonatal Cold injury: mechanism unclear

o   Asphyxia: mechanism unclear, but possibly related to hypoxic injury

o   Von Willebrand Disease: platelet aggregation

o   Preeclampsia: nadir at 2-4 days with resolution typically by 7-10 days

o   Dilution

Management

§  Initial evaluation

o   Thorough history and physical exam of mother and neonate, including birth history

§  Healthy appearing infant more likely to have congenital/immunologic mediated cause

§  Ill appearing infant more likely to have infection, DIC, NEC, asphyxia as cause

o   Labs:

§  Neonate: CBC (repeated to confirm thrombocytopenia), platelet ag typing, peripheral smear, coags, sepsis work up if ill appearing, eval for congenital infection, genetic testing

§  Maternal: CBC (repeated to confirm thrombocytopenia if present), platelet ag typing

o   Cranial US to evaluate for IVH. If present, low threshold for transfusion. Repeat prior to discharge

§  Treatment

o   If underlying cause known (mom with SLE, ITP, known infection, etc), treat.

o   Platelet counts should be more aggressively maintained for first 72-96 hours of life as risk for IVH highest in this time period. If no IVH, then clinical situation used to guide need for transfusion

§  High dose IVIG for 3-4 days is used as adjunct

§  Methylprednisolone used only in emergency situations as evidence lacking

o   When to transfuse?

§  No clear guidelines

§  Term infant, healthy, no other risks for hemorrhage: typically if <30,000

§  Preterm, ill, or with other risk factors: typically if <50,000

§  Benefit of platelet transfusion not clearly established; some recent suggestion that transfusion may be harmful

o   Other therapies

§  IVIG, steroids, exchange transfusion typically used for immune mediated causes

§  Current research into using thrombopoeitic mimetics as an alternative to transfusion

 

References

Murphy S. Consultation with the Specialist. Thrombocytopenia. Pediatrics in Review. Feb 1999; 20(2): 64-68.

Albert TS. Throbopoietin in the Thrombocytopenic Term and Preterm Newborn. Pediatrics. June 2000; 105(6):

     1286-1291.

Silver RM. Neonatal Alloimmune Thrombocytopenia: Antenatal Management. American Journal of Obstetrics and

     Gynecology. May 2000; 182(5): 1233-1238.

Behrman: Nelson Textbook of Pediatrics, 16th ed (2002). Philadelphia: W.B. Saunders Company.

Gomella: Neonatology: Management, Procedures, On-Call Problems, Diseases and Drugs, 4th ed (1999). McGraw
      -Hill/Appleton and Lange.

Ferrar-Marin F, et al. Neonatal Thrombocytopenia and Magakaryocytopoeisis. Seminar in Hematology. July                 
      2010; 47 (3) 281-288
UpToDate. Neonatal Thrombocytopenia.