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  1. Definition. Thrombocytopenia is defined as a platelet count <150,000/μL, although a few normal neonates may have counts as low as 100,000/μL in the absence of clinical disease. The best measure of platelet function is the standardized (Ivy) bleeding time (1.5–5.5 min). During the first week of life, bleeding times are shorter than those in adults (<3.5 min).

  2. Incidence. Thrombocytopenia is the most common hematologic abnormality among preterm infants. In healthy term infants the incidence is ~1%. In neonatal intensive care unit (NICU) patients, the incidence is as high as 35%; in low birthweight preterm infants, it is 15–20%; and in extremely low birthweight infants, it is 73%. Approximately 25% of the cases are severe (<50,000/μL); 75% are considered mild to severe.

  3. Pathophysiology

      1. Normal platelets. The rate of platelet production and turnover in neonates is similar to that of older children and adults. The platelet life span is 7–10 days, and the mean platelet count is >200,000/μL. Platelet counts are slightly lower in low birthweight infants, in whom platelet counts <100,000/μL have occasionally been observed in the absence of a clinical disorder. Low platelet counts should nonetheless be investigated in low birthweight infants. Platelet counts vary according to the method of determination. Phase microscopy determinations are generally 25,000–50,000/μL lower than those obtained by direct microscopy.

      1. Etiology of thrombocytopenia

          1. Maternal disorders causing thrombocytopenia in infant:

              1. Chronic intrauterine hypoxia. This is the most frequent cause of thrombocytopenia in preterm neonates in the first 72 h of life. This is seen in cases of placenta insufficiency such as diabetes and pregnancy induced hypertension.

              1. Drug use (eg, heparin, quinine, hydralazine, tolbutamide, and thiazide diuretics).

              1. Infections (eg, TORCH [toxoplasmosis, other infections, rubella, cytomegalovirus, and herpes simplex] infections, bacterial or viral infections).

              1. Disseminated intravascular coagulation (DIC).

              1. Pregnancy-induced hypertension (in particular with HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count).

              1. Antiplatelet antibodies

                  1. Antibodies against maternal and fetal platelets (autoimmune thrombocytopenia):

                      1. Idiopathic thrombocytopenic purpura (ITP).

                      1. Drug-induced thrombocytopenia.

                      1. Systemic lupus erythematosus.

                      1. Gestational or incidental thrombocytopenia.

                  1. Antibodies against fetal platelets (isoimmune thrombocytopenia):

                      1. Neonatal alloimmune thrombocytopenia (mostly anti-HPA-1a alloantibodies).

                      1. Isoimmune thrombocytopenia associated with erythroblastosis fetalis.

          1. Placental disorders causing thrombocytopenia in infant (rare):

              1. Chorioangioma.

              1. Vascular thrombi.

              1. Placental abruption.

          1. Neonatal disorders causing thrombocytopenia:

              1. Decreased platelet production or congenital absence of megakaryocytes

                  1. Isolated.

                  1. Thrombocytopenia and absent radius (TAR) syndrome.

                  1. Fanconi anemia.

                  1. Rubella syndrome.

                  1. Congenital leukemia.

                  1. Trisomies 13, 18, 21 or Turner syndrome.

                  1. Inherited metabolic disorders (methylmalonic, propionic, and isovaleric acidemia, ketotic glycinemia).

                  1. Congenital amegakaryocytic thrombocytopenia.

              1. Increased platelet destruction

                  1. Increased platelet consumption occurs in many sick infants not associated with any specific pathologic state. This form of thrombocytopenia is the most common hemostatic abnormality in the newborn admitted to the NICU. About 20% of newborns admitted to the NICU experience thrombocytopenia; for 20% of those, counts are <50,000/μL. This form of thrombocytopenia, generally present by 2 days of life, reaches a nadir by 4 days and usually recovers to normal by 10 days of life.

                  1. Pathologic states associated with increased platelet destruction.

                      1. Bacterial and Candida sepsis.

                      1. Congenital infections. TORCH infections especially CMV. Neonates with HIV and Enterovirus frequently have thrombocytopenia.

                      1. Thrombosis (renal vein, intracardiac, vascular).

                      1. DIC.

                      1. Intrauterine growth retardation.

                      1. Birth asphyxia.

                      1. Necrotizing enterocolitis (NEC).

                      1. Platelet destruction associated with giant hemangioma (Kasabach-Merritt syndrome).

      1. Platelet dysfunction

          1. Drug-induced platelet dysfunction:

              1. Maternal use of aspirin.

              1. Indomethacin.

          1. Metabolic disorders:

              1. Phototherapy-induced metabolic abnormalities.

              1. Acidosis.

              1. Fatty acid deficiency.

              1. Maternal diabetes.

          1. Inherited thrombasthenia (Glanzmann disease).

  4. Risk factors. Low birthweight, lower gestational age, small for gestational age, growth restriction, hypoxia at birth, umbilical line placement, respiratory assistance, hyperbilirubinemia, phototherapy, prematurity, respiratory distress syndrome, low 5-min Apgar score (<7), sepsis especially by Candida infection, meconium aspiration, NEC, mother with ITP, preterm infants of hypertensive mothers. Risk factors for preterm infants includes growth restriction, lower gestational age at delivery, and low 5-min ...

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