Definition

• Antibody made against maternal platelet antigen; antigen is also found on fetal platelets

• Antibody made against paternal platelet antigen; antigen is also found on fetal platelets

Clinical findings

• Mild to moderate thrombocytopenia (20,000–50,000/mm3)
  
• Petechiae and bruising are common
  
• Mother usually has thrombocytopenia or history of ITP
  
• Maternal platelets may be normal because she may have adequate production of platelets to compensate for increased destruction

• May lead to severe thrombocytopenia (<20,000/mm3) and in utero hemorrhagic complications (∼20% of infants with NAIT have intracranial hemorrhages)
  
• Infant appears healthy but may have petechiae and bruising
  
• Maternal platelet count is usually normal
  
• Most common antigen is HPA-1

Pathophysiology

• Maternal autoantibodies cross the placenta and bind to neonatal platelets, causing increased destruction

• Maternal alloantibodies cross the placenta and bind to neonatal platelets, causing increased destruction

Diagnosis

• Identification of autoantibody in maternal serum against antigens on her own platelets

• Identification of alloantibody using paternal platelets and maternal serum

Prenatal management

• Use of steroids to prevent fetal thrombocytopenia is controversial; not shown to be of benefit
  
• Use of immune globulin to prevent fetal thrombocytopenia is controversial; not shown to be of benefit
  
• PUBS (Percutaneous Umbilical cord Blood Sampling) seems to be safe but is invasive, and its use is controversial; not shown to be of benefit
  
• Mode of delivery (cesarean section vs vaginal) does not change maternal or fetal outcomes; cesarean section is not shown to be of benefit

• Use of steroids, immune globulin, PUBS, fetal scalp platelet counts during labor, and elective cesarean delivery can be used on a case-by-case basis

Postnatal management

• May include platelet transfusions (pooled donor), steroids, immune globulin or exchange transfusion
  
• Transfuse platelets for levels <20,000/mm3 or for clinical bleeding

• If diagnosis is made before delivery, maternal platelets are collected 24 h before delivery
  
• If infant requires platelet transfusions postnatally, use collected maternal platelets that have been washed and resuspended in plasma

If emergent transfusion is required and maternal platelets are not available, either maternal whole blood or HPA-1–negative donor platelets may be used

Immune globulin at a dose of 1–2 g/kg total given over 2–3 h for 2–5 d has been reported with some success

Steroids can be considered for persistent thrombocytopenia

Platelet consumption

• DIC

• Treat underlying disorder (remember that DIC is a secondary phenomenon)
  
• Replenish clotting factors and supplement with vitamin K as needed

• Giant hemangioma (Kasabach-Merritt syndrome)

• Transfuse platelets as necessary
  
• Replenish clotting factors as needed
  
• Treatment of hemangioma may involve corticosteroid administration, surgical removal, or embolization of hemangioma

• NEC

• Treatment of underlying disease
  
• Transfuse platelets and replenish clotting factors as needed

• Immune thrombocytopenias

• See table immediately prior
  
• Drug-induced thrombocytopenia is treated with removal of the offending agent

• Hypersplenism

• Associated with viremic illnesses, portal hypertension
  
• Transfuse platelets as needed
  
• Splenectomy in severe cases

• Wiskott-Aldrich syndrome

• Transfuse platelets as needed

• May-Hegglin anomaly

• Bernard-Soulier syndrome

Hypertransfusion

Increased transfer of RBC mass from placenta to infant at the time of delivery

Delayed cord clamping

Cord stripping

Positioning the infant below the placental vascular bed

Maternal–fetal hemorrhage

Intrapartum asphyxia or acidosis

Twin-to-twin transfusion

Forceful uterine contractions

Increased fetal erythropoiesis

Stimulus for increased fetal erythropoiesis from fetal hypoxia

Placental insufficiency related:

• Maternal hypertension
  
• Chronic placental abruption
  
• Postmaturity
  
• Cyanotic heart disease
  
• IUGR
  
• Maternal cigarette smoking

Stimulus for increased fetal erythropoiesis from increased oxygen consumption

Infant of a diabetic (chronic or gestational) mother

Congenital hyperthyroidism

Beckwith-Wiedemann syndrome

Congenital adrenal hyperplasia

Unknown

Trisomies 13, 18 and 21

Decreased relative plasma volume

Concentration of RBC mass in smaller volume of plasma (hemoconcentration)

Dehydration

CNS

Lethargy

Vomiting

Venous thrombosis

Poor feeding

Hypotonia

Cerebral infarction

Hyperirritability

Tremors or jitteriness

Vasomotor instability

Seizures

Cardiorespiratory

Respiratory distress

Tachycardia

CHF

Pulmonary hypertension

GI

Feeding intolerance

NEC (association)

GU

Decreased GFR

Hematuria

Proteinuria

ARF

Renal vein thrombosis

Priapism

Metabolic

Hypoglycemia

Hypocalcemia

Hypomagnesemia

Hematologic

Thrombocytopenia

Hyperbilirubinemia

Other thromboses

Asymptomatic

Expectant management

Increase fluid administration by 20–30 mL/kg/day and repeat HCT within 4–6 h

Partial exchange transfusion

Symptomatic

Partial exchange transfusion

Partial exchange transfusion

Examples

• Protein C deficiency
  
• Protein S deficiency
  
• Antithrombin deficiency

• Activated protein C resistance:
  
• Factor V Leiden mutation G169A
  
• Prothrombin gene mutation G20210A

• Hyperhomocysteinemia
  
• ↑ Lipoprotein (a) levels
  
• Methyltetrahydrofolate reductase polymorphism (C677T)

Incidence

Rare

Common

Common

Relative risk for neonatal thrombotic disease

High

Low

Unknown

General Considerations

• Majority caused by CVLs
  
• <1% of significant venous thromboembolism is idiopathic
  
• Dural sinus thrombosis may cause neonatal cerebral infarction
  
• Short-term consequences of catheter-associated thrombosis include pulmonary embolism and SVC syndrome
  
• Long-term consequences are poorly understood

• Majority caused by vascular access
  
• Short-term consequences are related to impaired blood flow to end organs
  
• Long-term consequences are poorly understood

• Occurs primarily in neonates and young infants
  
• Affected infants are usually term, LGA, with a male predominance
  
• Disease is often bilateral

Signs and Symptoms

• Difficulty infusing through catheter
  
• Signs of venous obstruction
  
• Swelling of affected extremity or head or neck
  
• Superficial vein distention
  
• Thrombocytopenia

• Initial sign is dysfunction of UAC
  
• Hematuria (gross or micro)
  
• Hypertension
  
• Decreased perfusion of lower extremities (poor pulses, pallor)

• Flank mass
  
• Hematuria (gross or micro)
  
• Proteinuria
  
• Thrombocytopenia
  
• Renal dysfunction
  
• Abnormal coagulation studies

Diagnosis

• US with Doppler flow is excellent for major thrombosis but may be inconclusive in smaller infants or low-flow states
  
• Contrast studies (ie, venography)

• US with Doppler flow is usually diagnostic, but the false-negative rate is significant
  
• Contrast studies (ie, arteriography)

• US with Doppler flow
  
• Adjunct studies (urine analysis)

Prevention

• Heparin added to all fluids being infused through catheter (as per individual NICU protocol)
  
• Removal of central venous access as soon as clinically feasible

• Heparin added to all fluids being infused through catheter (as per individual NICU protocol)
  
• Removal of arterial access as soon as clinically feasible
  
• Correct positioning of umbilical arterial catheter (between T6 and T10 on chest or abdominal film)

Management

• For nonfunctional CVLs, remove line; if clinically vital to maintain line, use of thrombolytic agents (tPA) or hydrochloric acid in-line may be considered
  
• Thrombolytic agents can be considered for extensive venous thrombosis with the line in situ for site-directed therapy
  
• Alternatively remove the line and begin heparin therapy

• For nonfunctional arterial catheters, remove line
  
• For large, nonocclusive thrombus (as determined by US or contrast study), remove line and consider heparin therapy
  
• For occlusive clots with significant clinical signs of end-organ compromise, consider aggressive thrombolytic therapy (local vs systemic thrombolytic therapy)
  
• Surgical thrombectomy is not indicated because of significant morbidity and mortality

• Unilateral without renal dysfunction or extension into IVC: Provide supportive care
  
• Unilateral with renal dysfunction or extension into IVC or bilateral disease without renal compromise: Consider heparin therapy
  
• Bilateral with significant renal dysfunction: Consider thrombolytic therapy