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Neonatal thrombocytopenia: Clinical manifestations, evaluation, and management

Neonatal thrombocytopenia: Clinical manifestations, evaluation, and management
Literature review current through: Jan 2024.
This topic last updated: May 22, 2023.

INTRODUCTION — Although thrombocytopenia is relatively rare in the general newborn population, it occurs frequently in patients admitted to neonatal intensive care units (NICUs). Severe neonatal thrombocytopenia (platelet count <50,000/microL) can be associated with bleeding and, potentially, significant morbidity. As a result, it is important to identify at-risk neonates and, if needed, initiate therapy to prevent associated complications.

The clinical manifestations, diagnostic evaluation, and management of neonatal thrombocytopenia are reviewed here. The causes of neonatal thrombocytopenia are discussed separately. (See "Neonatal thrombocytopenia: Etiology".)

DEFINITIONS — Thrombocytopenia is defined as a platelet count <150,000/microL. Severity of thrombocytopenia is defined by the following:

Mild – Platelet count 100,000 to 149,000/microL.

Moderate – Platelet count 50,000 to 99,000/microL.

Severe – Platelet count <50,000/microL.

Neonatal thrombocytopenia can also be classified based on the timing of presentation, which is used in the diagnostic evaluation:

Early thrombocytopenia occurs within the first 72 hours of life.

Late thrombocytopenia occurs ≥72 hours after delivery.

CLINICAL PRESENTATION — Neonates with thrombocytopenia may present as follows:

Incidental presentation ‒ Neonates diagnosed incidentally by a low platelet count when a complete blood count (CBC) is obtained for other reasons (eg, sepsis work-up). These patients may be asymptomatic or ill-appearing due to the underlying disorder.

Screening for at-risk neonates ‒ At-risk infants for thrombocytopenia are detected by a screening CBC. Risk factors include a maternal history of thrombocytopenia due to autoimmune disease (eg, immune thrombocytopenia or systemic lupus erythematous [SLE]), previous affected sibling (eg, neonatal alloimmune thrombocytopenia [NAIT]), or specific disorders associated with thrombocytopenia that may be identified by characteristic physical findings. These include genetic and chromosomal disorders (eg, trisomies 21, 18, and 13) and congenital infections such as cytomegalovirus (CMV) and rubella (table 1). (See "Neonatal thrombocytopenia: Etiology", section on 'Genetic disorders' and "Neonatal thrombocytopenia: Etiology", section on 'Infection'.)

Symptomatic infants ‒ Symptomatic patients present with evidence of bleeding, including the presence of petechiae, large ecchymoses, cephalohematoma, or oozing from the umbilical cord or puncture sites.

DIAGNOSTIC EVALUATION TO IDENTIFY UNDERLYING CAUSE

Overview and general principles — Because bleeding from thrombocytopenia is a potentially life-threatening condition, initial management, including platelet transfusion of symptomatic patients with severe bleeding, takes precedence over any diagnostic evaluation. (See 'Management' below.)

The evaluation is focused on determining and, if possible, directing specific therapy to the underlying cause of neonatal thrombocytopenia. However, establishing a diagnosis can be challenging because of the overlap of the clinical presentation among different conditions, and because frequently there may be multiple potential causes. (See "Neonatal thrombocytopenia: Etiology".)

The first step of the evaluation is verification of a low platelet count by repeat complete blood count (CBC). The diagnostic approach is centered on the onset of thrombocytopenia, the severity of thrombocytopenia, the infant's clinical condition, and the maternal and neonatal history, including labor and delivery. Based on this initial evaluation, the etiology of the thrombocytopenia is usually identified (algorithm 1 and table 2).

The following factors based on the clinical setting and history guide the diagnostic evaluation (algorithm 1) [1,2]:

Age of onset – Neonatal thrombocytopenia that presents within the first 72 hours of life (early onset) is more likely to be caused by conditions due to complications of pregnancy (placental insufficiency) or delivery (perinatal asphyxia), or from maternal antibody-mediated platelet destruction (eg, neonatal alloimmune thrombocytopenia [NAIT]). In contrast, neonatal thrombocytopenia that presents after 72 hours of life (late onset) is usually due to postnatally-acquired conditions such as bacterial sepsis or necrotizing enterocolitis (NEC), particularly in preterm infants.

Severity of thrombocytopenia – In patients with an incidental finding of mild thrombocytopenia (platelet count between 100,000 and 150,000/microL) in whom the platelet count stabilizes and improves without intervention, further evaluation is typically not warranted. Similarly, infants with moderate thrombocytopenia (platelet count between 50,000 and 100,000/microL) born following a history of or clinical evidence of placental insufficiency usually only need monitoring of the platelet count to ensure it is transient. However, in patients with moderate thrombocytopenia without an etiology or severe thrombocytopenia, further evaluation is warranted.

Clinical status – Neonates with immune-mediated thrombocytopenia typically are well-appearing except for the clinical manifestations related to thrombocytopenia (eg, petechiae and mucosal bleeding). In contrast, infants who are ill-appearing are more likely to have thrombocytopenia associated with systemic disease such as sepsis, NEC, and severe asphyxia. However, NAIT should also be considered in ill-appearing infants, particularly if the severity of the thrombocytopenia is disproportionate to the degree of clinical illness. (See "Neonatal immune-mediated thrombocytopenia", section on 'Neonatal alloimmune thrombocytopenia' and "Neonatal immune-mediated thrombocytopenia", section on 'Neonatal autoimmune thrombocytopenia'.)

Gestational age – The relative frequency of specific causes of thrombocytopenia differ between preterm and term infants:

Preterm infants are more likely to have thrombocytopenia due to placental insufficiency, perinatal asphyxia, congenital infections (eg, cytomegalovirus [CMV]), or disseminated intravascular coagulation (DIC) associated with systemic diseases (eg, sepsis or NEC).

In term infants, the most common causes of early-onset thrombocytopenia are immune-mediated platelet destruction (ie, NAIT or maternal autoimmune disease [immune thrombocytopenia]) and perinatal asphyxia.

Several genetic disorders and syndromes associated with thrombocytopenia have specific physical findings, including thrombocytopenia-absent radius syndrome; trisomies 21, 18, and 13; Noonan syndrome; Jacobsen syndrome; and congenital Fanconi anemia (table 1). Importantly, in Fanconi anemia, the thrombocytopenia is almost never present in the neonatal period.

History — Historical clues include the following:

Maternal history:

The mother may have thrombocytopenia caused by a known condition, such as ITP or systemic lupus erythematosus (SLE). A history of a previous splenectomy may also be a clue to an underlying maternal autoimmune disorder. Occasionally, the first manifestation of maternal SLE is fetal heart block.

Other maternal conditions associated with neonatal thrombocytopenia include infection (eg, CMV) and maternal drug exposure, which may be due to drug-induced immunoglobulin G (IgG) antibodies. (See "Neonatal thrombocytopenia: Etiology", section on 'Infection' and "Neonatal immune-mediated thrombocytopenia", section on 'Drug-induced immune thrombocytopenia'.)

Family history – There may be a family history of bleeding disorders, or a previously affected infant (eg, NAIT).

Pregnancy, labor, and delivery:

History of a fetal brady-arrhythmia should prompt investigation for maternal SLE. (See "Fetal arrhythmias", section on 'Bradyarrhythmias'.)

Histopathologic examination of the placenta should be performed as it may provide clues to the diagnosis. The placenta may show evidence of congenital infection (eg, CMV, syphilis), vasculopathy (eg, preeclampsia or other maternal vasculopathy), hemorrhage, infarcts, thrombi, and rarely, vascular malformations or malignancy. (See "The placental pathology report".)

Abnormal fetal monitoring or neonatal resuscitation in the delivery room may be indicative of perinatal asphyxia. (See "Overview of antepartum fetal assessment" and "Perinatal asphyxia in term and late preterm infants".)

Examination — The infant should be examined for evidence and extent of bleeding. Bleeding into the skin is one of the most common findings in patients and may include petechiae, non-palpable purpura, and ecchymoses. In addition, neonatal bleeding may be manifested by more serious bleeding, including cephalohematoma, oozing from the umbilical cord or puncture sites, hematemesis, melena, and blood-tinged secretions. The presence of these findings is an indication that platelet transfusion should be considered. (See 'Platelet transfusion' below.)

As noted above, the infant's clinical condition should be assessed for the following:

Overall clinical status – Is the patient healthy or ill? Healthy infants are more likely to have immune or genetic causes of thrombocytopenia. In contrast, ill-appearing infants (eg, poor perfusion, lethargy, respiratory distress, and/or apnea) are more apt to have systemic illness with thrombocytopenia associated with infection, asphyxia, NEC, or DIC.

Evidence of liver disease – The presence of jaundice or hepatosplenomegaly suggests congenital infection, as well as other more rare disorders such as hemophagocytic lymphohistiocytosis (HLH) or liver failure due to hemochromatosis.

Dysmorphic features – Dysmorphic features including limb abnormalities (eg, absent radii, limb hypertrophy) may suggest an underlying genetic or syndromic cause. (See "Causes of thrombocytopenia in children", section on 'Inherited platelet disorders' and "Neonatal thrombocytopenia: Etiology", section on 'Genetic disorders'.)

Fetal (intrauterine growth) restriction – Infants with intrauterine growth or fetal restriction (also referred to as small for gestational age [SGA]) are more likely to have thrombocytopenia, albeit seldom severe enough to need treatment [3]. Neutropenia is often a concomitant finding. (See "Infants with fetal (intrauterine) growth restriction".)

Laboratory studies

Complete blood count

Involvement of other cell lines ‒ The CBC, which demonstrates a low platelet count, should also be evaluated for anemia and/or neutropenia. If present, this suggests the underlying pathogenesis is decreased production due to bone marrow suppression, or (more rarely) disorders characterized by two or more cytopenias (ie, HLH, or congenital thrombotic thrombocytopenic purpura, which presents with microangiopathic hemolytic anemia and thrombocytopenia).

Immature platelet fraction ‒ Another method to differentiate between decreased production and increased destruction of platelets in neonates with thrombocytopenia (table 3) is determination of the immature platelet fraction (IPF), a laboratory measurement analogous to the reticulocyte count. While not widely used, the IPF (expressed as a percentage of platelets that are immature or as an absolute number per microL blood) is increased in consumptive thrombocytopenias (eg, immune-mediated thrombocytopenia, infection, disseminated intravascular coagulation, and necrotizing enterocolitis) and some inherited thrombocytopenia syndromes (eg, Wiskott-Aldrich syndrome), and decreased with reduced platelet production (eg, some syndromic causes of thrombocytopenia, and neonates with intrauterine growth restriction and birth asphyxia) [4]. (See "Neonatal thrombocytopenia: Etiology", section on 'Classification of etiology' and "Approach to the child with unexplained thrombocytopenia", section on 'Reticulated platelets/immature platelet fraction'.)

Peripheral smear ‒ Examination of the peripheral smear determines the platelet size and morphology, which can help distinguish between a destructive or consumptive process (large platelet size) and a decrease in platelet production (normal or small platelet size). In addition, platelet size and morphology can also be helpful in detecting congenital platelet disorders, which may have varying platelet sizes (table 1). (See "Neonatal thrombocytopenia: Etiology", section on 'Decreased production' and "Neonatal thrombocytopenia: Etiology", section on 'Genetic disorders' and "Inherited platelet function disorders (IPFDs)", section on 'Specific disorders'.)

Ongoing monitoring of the platelet count should be performed to see if the platelet count improves. In general, no further diagnostic testing is needed for a patient with mild thrombocytopenia (platelet counts between 100,000 and 149,000/microL) or for those with moderate thrombocytopenia (platelet counts between 50,000 and 99,000) due to placental insufficiency whose platelet counts rise.

Other tests — Other laboratory tests are obtained based on the clinical setting and include the following (algorithm 1) [1,2]:

Any infant with early-onset (before 72 hours of life) severe thrombocytopenia (platelet count <50,000/microL) – These infants are at risk for serious underlying disease. As a result, a full evaluation is performed. This includes:

Coagulation studies to determine whether DIC is the underlying cause of severe neonatal thrombocytopenia (platelet count <50,000/microL), as this has implications regarding intervention. Studies include prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration, and fibrin split products (d-dimer).

Blood cultures should be obtained. Prophylactic antibiotics should be administered while awaiting culture results. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Complete blood count' and "Management and outcome of sepsis in term and late preterm neonates", section on 'Initial empiric therapy'.)

If there is no evidence of DIC or sepsis, further evaluation is directed by maternal and neonatal history and neonatal physical findings.

Evaluation for NAIT ‒ If the mother has a normal platelet count and a previous history of NAIT for herself or her sister, an evaluation for NAIT should be performed. An evaluation should also be performed in a well appearing term infant with severe thrombocytopenia and a mother with a normal platelet count. The assessment entails platelet antigen typing of the mother, father, and sometimes newborn and testing the mother's serum for antiplatelet alloantibody. (See "Fetal and neonatal alloimmune thrombocytopenia: Parental evaluation and pregnancy management", section on 'Screening'.)

Karyotype ‒ If there are obvious dysmorphic features or physical findings suggestive of an underlying genetic condition, karyotype testing is performed. (See "Neonatal thrombocytopenia: Etiology", section on 'Chromosome abnormalities' and "Tools for genetics and genomics: Cytogenetics and molecular genetics", section on 'Detecting cytogenetic abnormalities'.)

Ill-appearing infants with early onset of thrombocytopenia and platelet counts between 50,000/microL and 149,000/microL – These patients are at risk for serious underlying disease. Patients who are ill-appearing are more likely to have DIC or sepsis. For these patients, the following studies are obtained:

Coagulation studies to determine whether DIC is the cause of thrombocytopenia, as this has implications regarding intervention. Studies include prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration, and fibrin split products (d-dimer).

Blood cultures should be obtained. Prophylactic antibiotics should be administered while awaiting culture results. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Complete blood count' and "Management and outcome of sepsis in term and late preterm neonates", section on 'Initial empiric therapy'.)

Well-appearing infants with early onset of thrombocytopenia and platelet counts between 50,000/microL and 150,000/microL – No evaluation is necessary if the infant has evidence of intrauterine hypoxia/placental insufficiency, but the platelet count should be monitored. Evaluation is needed if the thrombocytopenia becomes severe or has not resolved by 10 days. Consider evaluating for NAIT in well-appearing full-term infants with no obvious cause.

Infants with late-onset (72 hours after delivery) thrombocytopenia are most likely to have acquired thrombocytopenia due to sepsis, DIC, or necrotizing enterocolitis. Coagulation studies and blood cultures are obtained based on the clinical status of the infant and the suspicion for a specific underlying condition. These infants are unlikely to have alloimmune thrombocytopenia, autoimmune thrombocytopenia, or an underlying genetic defect.

MANAGEMENT

Overview — In the majority of cases, thrombocytopenia resolves within a week with no intervention, and without subsequent major sequelae. However, because bleeding from thrombocytopenia is a potentially life-threatening condition, initial management, including platelet transfusion of symptomatic patients with active bleeding, takes precedence over any diagnostic evaluation.

Monitoring — Ongoing monitoring of the platelet count should be performed to see if the platelet count improves. The frequency of such testing will depend on the gestational age (GA) of the patient, the postnatal age, the presumed etiology of the thrombocytopenia, the severity of the thrombocytopenia, whether platelet administration is provided, and the response to any platelet transfusions.

In our practice, we usually monitor neonates frequently on the first day of diagnosis, especially in patients who are clinically unstable, to determine the ongoing trend. As a result, a complete blood count (CBC) may be obtained as often as every six hours. As the patient's clinical status stabilizes and/or there is a clearer understanding of the course of the platelet count with evidence of improvement, the timing between tests is adjusted.

Neuroimaging — Neuroimaging is provided for the following:

Infants with suspected neonatal alloimmune thrombocytopenia (NAIT) ‒ Infants with NAIT are at risk for intracranial hemorrhage, which may have occurred in utero [5]. As a result, a cranial ultrasound should be performed in infants with suspected NAIT to detect hemorrhage as quickly as possible after delivery. If an intracranial hemorrhage is present, we typically use a higher threshold for platelet transfusion (platelet count <50,000/microL) (see 'Indications' below). Clinical suspicion for NAIT is discussed elsewhere. (See "Neonatal immune-mediated thrombocytopenia", section on 'When to suspect NAIT'.)

Preterm infants – Cranial ultrasounds are performed routinely for very preterm infants (GA <32 weeks) as they are at-risk for germinal matrix and intraventricular hemorrhage (IVH) (see "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Risk factors, clinical features, screening, and diagnosis", section on 'Preterm infants'). Ultrasounds are also obtained in more mature infants based on individual assessments of their risk for intracranial hemorrhage, including the severity of thrombocytopenia.

Interventions — Interventions include:

Targeted measures focused on the underlying etiology (eg, antibiotic therapy for sepsis). Intravenous immunoglobulin (IVIG) is also used for infants with immune-mediated thrombocytopenia (eg, alloimmune, autoimmune, and drug immune-mediated thrombocytopenia). (See "Neonatal immune-mediated thrombocytopenia".)

Platelet transfusion is the primary general intervention administered to infants who are actively bleeding or at-risk for significant bleeding (algorithm 2) (see 'Indications' below).

Platelet transfusion — Platelet transfusions are provided to neonates with thrombocytopenia with evidence of active bleeding. In addition, prophylactic platelet transfusions are given to infants with the highest risk of serious bleeding (eg, intracranial hemorrhage), such as those with NAIT and preterm infants.

Indications — Although most platelet transfusions in neonates are given prophylactically to patients without evidence of bleeding, there is no one optimal threshold, as the risk of significant bleeding varies based on the clinical setting [6,7]. Although there are variations in clinical practice based on limited available evidence, most experts in the field set thresholds based on clinical setting and favor lower transfusion threshold based on results from a multicenter trial [7,8].

In our center, the threshold for platelet transfusion is dictated by the clinical setting as follows [9]:

Platelet transfusion is given to any neonate with major bleeding diagnosed within the previous 72 hours and a platelet count <100,000/microL. At our center, we define major bleeding as intracranial hemorrhage, pulmonary hemorrhage, frank rectal bleeding, and life-threatening bleeding requiring emergent fluid resuscitation or red blood cell transfusion.

Platelet transfusion is given prior to major surgery for any neonate if the platelet count is <100,000/microL.

For any neonate without active bleeding, a platelet transfusion is performed if the platelet count is <20,000/microL.

For any ill-appearing or clinically unstable neonates (eg, poor perfusion, lethargy, respiratory distress, and/or apnea, or increasing need for cardiorespiratory support), a platelet transfusion is performed if the platelet count is <50,000/microL.

For extremely preterm infants (GA <28 weeks or birth weight <1000 g) without evidence of active bleeding, we use a platelet count of <50,000/microL as a threshold for platelet transfusion during the first week of life. Determining an optimal threshold has been an area of ongoing debate as the indication for platelet transfusions has been more liberal for these infants with the highest risk of serious bleeding. Other centers use a more conservative threshold of <30,000 or 25,000/microL for transfusions in this setting [10].

A multicenter trial of preterm infants with GA <34 weeks (mean GA 26.6 weeks) compared a high-threshold group (platelet count threshold of 50,000/microL) with a low-threshold group (platelet count threshold of 25,000/microL) using a primary composite outcome of death or major bleeding (defined as intracranial hemorrhage, pulmonary hemorrhage, frank rectal bleeding, and life-threatening bleeding [eg, shock or requiring emergency fluid or red blood cell transfusion]) within 28 days after randomization. Results of the study showed a higher incidence of death or major bleeding in the high-threshold compared with the low-threshold group (26 versus 19 percent, respectively; odds ratio 1.57, 95% CI 1.06-2.32) [7]. The incidences of new major bleeding episodes were similar for the high- versus low-threshold groups (14 versus 11 percent). There was no difference between the groups in the rates of serious adverse events (eg, multiorgan failure, renal failure, necrotizing enterocolitis, respiratory failure, sepsis, and stage 2 or greater retinopathy of prematurity). The risk of bronchopulmonary dysplasia was slightly higher in the survivors of the high-threshold group (63 versus 54 percent). A subsequent analysis reported the benefit associated with a low-threshold platelet count <25,000 regardless of the baseline risk of bleeding and mortality [11]. However, there are limitations of this study as only one-third of the infants were randomized on or before five days of life and 39 percent of patients had already received one or more transfusion prior to randomization [12]. This raises the concern that prior transfusions were administered during the period of highest risk, which may confound the findings of the trial.

As a result, for infants with birth weight (BW) <1000 g or <28 weeks gestation, we maintain the platelet count >50,000/microL by transfusion for at least the first 72 to 96 hours after birth.

For infants who are being treated by extracorporeal membrane oxygenation (ECMO), the threshold for platelet transfusion is <100,000/microL.

Other factors may modify these "trigger" guidelines. Higher platelet count triggers (ie, <50,000/microL) may be considered in newborns who are receiving drugs that cause platelet dysfunction (eg, indomethacin, inhaled nitric oxide) or who are being treated with anticoagulants. Newborns with conditions such as disseminated intravascular coagulation (DIC), in which platelets are consumed rapidly, should also be transfused at similarly higher levels in anticipation of briskly falling platelet levels.

Preparation — Platelets are obtained from a fresh unit of whole blood or by apheresis and prepared in a standard suspension. (See "Platelet transfusion: Indications, ordering, and associated risks".)

Additional measures include:

Irradiation – Platelet irradiation is used to prevent graft-versus-host disease, in which contaminating white blood cells attack host tissue. Irradiation damages the nuclei of donor lymphocytes in the transfusion, so that they cannot proliferate and mount an immune response against the recipient. Platelets are anucleate, so their functions are unaffected by irradiation (see "Platelet transfusion: Indications, ordering, and associated risks", section on 'Irradiation'). Irradiated platelets are used in the following circumstances:

Very preterm (defined as a BW <1500 g or GA <32 weeks)

Infants receiving donated platelets from a relative (eg, maternal donor for an infant with NAIT)

Infant with a known immunodeficiency to avoid transfusion-associated graft-versus-host disease

Human leukocyte antigen (HLA)- or cross-matched

Leukoreduction – Leukocytes are removed during the apheresis process, thereby providing a cytomegalovirus (CMV)-safe product. Pre-storage leukoreduction can be performed on whole blood-derived platelets. (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Leukoreduction'.)

CMV-seronegative donor – These interventions significantly reduce the risk of transfusion-transmitted CMV (TT-CMV). In one study, the use of leukoreduced CMV-seronegative units completely prevented TT-CMV in a cohort of preterm neonates [13]. (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'CMV'.)

Donor selection – In most cases, platelets from a random donor can be used [14]. In infants with NAIT, an antigen-compatible donor is preferable. If NAIT is anticipated, the mother's platelets can be collected prior to delivery and used for transfusion. Maternal platelets need to be concentrated, however, in order to reduce the amount of antibody-containing serum given to the neonate. Otherwise, donor platelets that are typed and matched for the patient can be used. (See "Neonatal immune-mediated thrombocytopenia", section on 'Neonatal alloimmune thrombocytopenia'.)

Volume reduction should not be done unless there is a need for strict volume restriction, recurrent severe allergic reaction, or reduction on antibody-containing serum as in the case of NAIT. Volume reduction may be necessary when fluid restriction is critical, such as in patients with heart failure, oliguria or anuria due to renal injury, or generalized edema (eg, pleural effusion and ascites). Volume reduction may cause platelet activation due to centrifugation, resulting in a lower recovery of platelets. However, one retrospective study reported that volume-reduced platelet transfusions appear to have similar efficacy to nonreduced preparations [15].

Dosing — In general, administration of 10 to 15 mL/kg of platelet suspension will increase the platelet count from 50,000 to 100,000/microL. In our practice, we use a dose of 10 mL/kg (see "Platelet transfusion: Indications, ordering, and associated risks", section on 'Ordering platelets'). Of note, these doses are significantly higher than doses used in adults (3 to 5 mL/kg), and there is concern that the amount of fluid during the transfusion (particularly given rapidly) could increase the bleeding risk in neonates.

Administration — There are no established published guidelines for the administration of platelets in neonates. In our practice, based on clinical experience, we routinely transfuse platelets through a peripheral intravenous catheter. The infusion is given as rapidly as the infant will tolerate the volume of infusion, which is usually over one hour and no longer than two hours to minimize any risk due to a large fluid bolus [16]. Platelets should not be administered either through an arterial line or into the liver (ie, low-lying umbilical venous line) because of a high risk of thrombosis.

OUTCOME — There are limited data on the outcome of severe neonatal thrombocytopenia (platelet count <50,000/microL) and the effect of platelet transfusions. Large observational studies have shown that most neonates with severe thrombocytopenia receive platelet transfusions according to previously recommended neonatal intensive care unit (NICU) thresholds [17-19]. However, it remains unclear whether platelet transfusions were beneficial in the majority of infants with no or minor bleeding symptoms as no study to date has shown that platelet transfusion decreases bleeding in neonates.

In the first study of 3652 neonates admitted to NICUs, 5 percent developed severe neonatal thrombocytopenia defined as a platelet count less than 60,000 microL, with 34, 39, and 28 percent of infants having platelet count nadirs of <20,000, 20,000 to 39,000, and >40,000 microL, respectively [17]. The following findings were noted:

Among study infants, minor hemorrhage was noted in 73 percent, no bleeding in 18 percent, and major hemorrhage in 9 percent. There was no difference in the median platelet count among the three groups.

Of the 15 major bleeding episodes, 9 were due to intraventricular hemorrhage (IVH) including 1 case of concomitant hematuria, 3 to pulmonary hemorrhage, and 1 case each to isolated hematuria, rectal bleeding, and intra-abdominal bleeding. No relationship between platelet count and bleeding was demonstrated; however, gestational age (GA) <28 weeks and postnatal age less than 14 days were associated with major hemorrhage.

Thirty-one neonates had grade 3 IVH or periventricular hemorrhage (previously referred to as grade 4 IVH) before study enrollment. Five of these infants developed extension or progression of IVH during the study.

Platelet transfusions (n = 415) were administered to 116 infants (69 percent), primarily based upon a low platelet count. Platelet transfusions increased the median platelet counts from 27,000 to 79,000 microL. Mortality rates were highest for infants receiving five or more transfusions.

In the second study of 11,281 infants admitted to the NICU, severe thrombocytopenia (platelet count <50,000/microL) was identified in 2.5 percent of neonates with 326 episodes [18].

Cutaneous bleeding was most common in patients with platelet counts less than 20,000/microL. In contrast, there was no significant correlation between platelet count and pulmonary, gastrointestinal, or intraventricular bleeding.

Platelet transfusions were administered to 86 percent of patients.

Mortality rate did not correlate with the lowest platelet count, but increased with the number of platelet transfusions.

SUMMARY AND RECOMMENDATIONS

Definition – Neonatal thrombocytopenia is defined as a platelet count <150,000/microL. Although severe neonatal thrombocytopenia (defined as a platelet count <50,000/microL) is uncommon in the general healthy newborn population, the risk increases for infants admitted to the neonatal intensive care unit (NICU) especially for the extremely preterm infants (birth weight [BW] <1000 g or gestational age [GA] <28 weeks). (See "Neonatal thrombocytopenia: Etiology", section on 'Definitions' and "Neonatal thrombocytopenia: Etiology", section on 'Severe thrombocytopenia'.)

Presentation – The clinical presentation of neonatal thrombocytopenia includes patients detected incidentally by a low platelet count from a complete blood count (CBC) obtained for other reasons, at-risk patients identified by a screening CBC, and symptomatic infants with evidence of bleeding (eg, petechiae, large ecchymoses, cephalohematoma, or oozing from the umbilical cord or puncture sites). (See 'Clinical presentation' above.)

Initial management for active bleeding – Because bleeding from thrombocytopenia is a potentially life-threatening condition, initial management, including platelet transfusion of symptomatic patients with active bleeding, takes precedence over any diagnostic evaluation. (See 'Management' above.)

Diagnostic evaluation – The diagnostic evaluation is focused on determining and, if possible, directing specific therapy to the underlying cause of neonatal thrombocytopenia. However, establishing a diagnosis can be challenging because of the overlap of the clinical presentation among different conditions, and because frequently there may be multiple potential causes. The diagnostic approach to neonatal thrombocytopenia is centered on the timing of presentation (early within the first 72 hours of life or later), the severity of thrombocytopenia, the infant's clinical condition, and the maternal and neonatal history, including labor and delivery. Based on this initial evaluation of history, physical findings, and CBC, the etiology of the thrombocytopenia usually can be identified (table 2 and algorithm 1). (See 'Diagnostic evaluation to identify underlying cause' above.)

The need for further laboratory testing is determined by the clinical setting and includes coagulation studies, blood culture, review of the mother's platelet count, and in some cases, platelet antigen typing of the mother, father, and newborn. (See 'Other tests' above.)

Management approach

In the majority of cases, neonatal thrombocytopenia resolves without intervention. Specific therapy, if available, should be given to patients in whom an etiology has been identified (eg, sepsis). (See 'Overview' above.)

Monitoring of the platelet count is performed to determine the ongoing trend and whether a prespecified threshold is met for platelet transfusion. In our practice, we monitor neonates frequently on the first day of diagnosis to note any further decline in the platelet count, especially in patients who are clinically unstable. As a result, a CBC may be obtained as often as every six hours and as the patient's clinical status stabilizes and/or there is a clearer understanding of the course of the platelet count with evidence of improvement, the timing between tests is increased. (See 'Monitoring' above and 'Indications' above.)

Neonates with thrombocytopenia who have clinical bleeding require platelet transfusion.

Platelet transfusion: Indications – Most platelet transfusions in neonates are given prophylactically to patients without evidence of bleeding. However, there is no specified threshold as bleeding risk varies based on the clinical setting, and there are variations in clinical practice based on limited available evidence and expert clinical experience. (See 'Indications' above.)

In our practice, prophylactic platelet transfusion is administered to infants at-risk for bleeding for the following conditions and platelet count thresholds:

For infants without active bleeding, when the platelet count is <20,000/microL.

For ill-appearing infants (eg, poor perfusion, lethargy, respiratory distress, and/or apnea), a platelet transfusion is performed if the platelet count is <50,000/microL.

In extremely preterm infants (BW <1000 g or GA <28 weeks) in the first week of life, when the platelet count is <50,000/microL.

Prior to major surgery, if the platelet count is <100,000/microL.

Higher target levels (eg, platelet count <50,000/microL) may be indicated in neonates who receive drugs that cause platelet dysfunction, such as indomethacin or ibuprofen, or who have disseminated intravascular coagulation (DIC).

Platelet preparation and administration – Platelets are obtained from either a fresh unit of whole blood or by apheresis. Platelets undergo irradiation, leukoreduction, and are from a cytomegalovirus-seronegative donor. (See 'Preparation' above.)

In general, administration of 10 to 15 mL/kg of platelet suspension will increase the platelet count from 50,000 to 100,000/microL. In our practice, we use a dose of 10 mL/kg, which is typically administered through a peripheral intravenous catheter over 30 minutes. (See 'Dosing' above and 'Administration' above.)

Neuroimaging – Neuroimaging is performed for infants with neonatal alloimmune thrombocytopenia (NAIT) and preterm infants with a GA <32 weeks to identify those with intracranial hemorrhage. (See 'Neuroimaging' above.)

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Topic 97752 Version 27.0

References

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