139: Thrombocytopenia and Platelet Dysfunction

I. DEFINITION

Thrombocytopenia is defined as a platelet count <150,000/μL and is classified as mild (100–149,000/μL), moderate (50–99,000/μL), or severe (<50,000/μL). One percent of normal neonates may have mild thrombocytopenia.

II. INCIDENCE

Thrombocytopenia is the most common hematologic abnormality among sick newborn infants (when admitted to the neonatal intensive care unit [NICU], incidence is as high as 35%). Its incidence reaches 70% in newborn infants with birthweight <1000 g.

III. PATHOPHYSIOLOGY

1. Normal platelets. Similar to older children and adults, the platelet life span in neonates is 7–10 days, and the mean platelet count is >200,000/μL.

2. Etiology of thrombocytopenia. See Figure 139–1.

   1. Maternal disorders causing thrombocytopenia in infant

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

      2. Preeclampsia (in particular with HELLP syndrome [hemolysis, elevated liver enzymes, low platelet count]). Thrombocytopenia is present at birth, is usually associated with neutropenia, and should recover by the second week of life.

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

      4. Infections (eg, TORCH [toxoplasmosis, other infections, rubella, cytomegalovirus, and herpes simplex virus] infections, bacterial or viral infections).Disseminated intravascular coagulation (DIC).

      5. Antiplatelet antibodies

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

            • (a) Idiopathic thrombocytopenic purpura (ITP)

            • (b) Drug-induced thrombocytopenia

            • (c) Systemic lupus erythematosus

         2. Antibodies against fetal platelets (isoimmune thrombocytopenia)

            • (a) Neonatal alloimmune thrombocytopenia is the most common cause of severe thrombocytopenia, seen mostly in term infants <72 hours of age. It is due to an incompatibility in human platelet antigen (HPA) between the newborn infant and its HPA-negative mother. HPA-1a is the most common incompatibility in Caucasians, while HPA-4b incompatibility is mostly seen in Asians. Only 10% of HPA-1a–negative women become sensitized after being exposed to HPA-1a because this immunological response occurs in the presence of specific human leukocyte antigens (HLAs) such as HLA-B8, HLA-DR3, and HLA-DR52a. HLA antibodies, though common, do not cause significant thrombocytopenia.

            • (b) Immune thrombocytopenia can be found in some cases of hemolytic disease of the newborn.

   2. Placental disorders causing thrombocytopenia in infant (rare)

      1. Chorioangioma

      2. Vascular thrombi

      3. Placental abruption

   3. Neonatal disorders causing thrombocytopenia

      1. Decreased platelet production

         1. Isolated.

         2. Thrombocytopenia and absent radius syndrome (TAR syndrome) is characterized by normal neutrophil and red blood cell counts; absent radii, usually bilateral; and the presence of a normal thumb.

         3. Fanconi anemia is characterized by pancytopenia and the presence of abnormal (hypoplastic or aplastic) thumb.

         4. Rubella syndrome.

         5. Congenital leukemia.

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

         7. Inherited metabolic disorders include methylmalonic, propionic, and isovaleric acidemia; ketotic glycinemia.

         8. Congenital amegakaryocytic thrombocytopenia.

      2. Increased platelet destruction

         1. Many “sick” newborns develop thrombocytopenia that is not associated with any specific pathologic state. About 20% of newborns admitted to the NICU have thrombocytopenia, and 20% of those counts are <50,000/μL. This form of thrombocytopenia generally improves after the primary sickness (respiratory distress syndrome [RDS], persistent pulmonary hypertension of the newborn [PPHN], etc.) resolves.

         2. Pathologic states associated with thrombocytopenia

            • (a) Sepsis. Bacterial and Candida sp.

            • (b) Congenital infections. TORCH infections, especially cytomegalovirus (CMV). Neonates with human immunodeficiency virus (HIV) and Enterovirus frequently have thrombocytopenia.

            • (c) Thrombosis (renal vein, intracardiac, vascular).

            • (d) DIC.

            • (e) Intrauterine growth restriction.

            • (f) Birth asphyxia.

            • (g) Necrotizing enterocolitis (NEC) or bowel ischemia.

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

3. Platelet dysfunction

   1. Drug-induced platelet dysfunction

      1. Maternal use of aspirin

      2. Indomethacin

   2. Metabolic disorders

      1. Phototherapy-induced metabolic abnormalities

      2. Acidosis

      3. Fatty acid deficiency

      4. Maternal diabetes

   3. Inherited thrombasthenia (Glanzmann disease)