Neonatal thrombocytosis following G-CSF treatment

Abstract

Thrombocytosis is defined as an elevetion of the platelet count to more than 500,000/mm³ (). Primary thrombocytosis rarely occurs in the pediatric age group and is usually caused by a clonal bone marrow disorder (). The more common phenomenon is secondary thrombocytosis which is a reactive process. lists the main causes of secondary thrombocytosis (). Complications of severe thrombocytosis include bleeding and thromboses. Unless additional risk factors are present, secondary thrombocytosis is not associated with a significant risk of thromboembolic events, regardless of the degree of elevation of the platelet count (). The aim of this case report is to add a new possible cause of neonatal thrombocytosis.

Keywords: :

• Thrombocytosis
• G-CSF
• Neonate

Case report

A full-term male infant was found to have leukopenia (white blood cell count 7000/mm³) and neutropenia (absolute neutrophil count 1200/mm³) on the first day of life. The medical history revealed that the infant was delivered vaginally after 38 weeks' gestation with birth weight 2536 g, length 47 cm, and head circumference 34.7 cm. The 35-year-old mother had chronic neutropenia and hypothyroidism treated with levothyroxine. The 30-year-old father was healthy with no chronic diseases. There was no parental consanguinity.

Table 1. Clinical conditions associated with thrombocytosis in the newborn infant

1. Hematologic:

Acute blood loss

Asplenia

Neuroblastoma

Leukemia like syndromes

2. Inflammation:

Infection – viral, bacterial or protozoal

3. Nutritional:

Iron deficiency

Vitamin E deficiency

Total parenteral nutrition

4. Endocrine:

Hyperadrenalism

5. Immune Process:

Graft versus host reaction

Nephrotic syndrome

6. Traumatic:

Surgery

Splenectomy

Fractures

7. Others:

Low birth weight

Caffey's disease

8. Medications:

Maternal – drug abuse

methadone

Infant – steroids

vinca alkaloids

all trans retinoic acid

zidovudine

meropenem

Findings on triple test, amniocentesis and targeted fetal ultrasound were within normal range. The physical examination of the newborn was normal. A sepsis work-up was performed. Full chemistry profile and thyroid function tests revealed no abnormalities. Blood and cerebrospinal fluid cultures were negative. A complete blood count showed a platelet count of 413,000/mm³ and neutropenia with a nadir of 100/mm³ on the sixth day of life. Bone marrow aspirate demonstrated cellular bone marrow with normal erythroid precursors, an arrest in the white cell population in the myelocyte stage, sparse bands, and normal megakaryocytes.

Treatment with granulocyte-colony-stimulating factor (G-CSF) was initiated on the fourth day of life at a dose of 10 mcg/kg produced no effect on the white blood cell count. The dose was increased to 20 mcg/kg after three days of treatment, which led to a gradual improvement in the white cell and absolute neutrophil counts. The newborn was treated with G-CSF for five days.

During G-CSF treatment, increasing thrombocytosis was noted, with a maximal platelet count of 921,000/mm³ six days after starting G-CSF treatment. There were no complications of bleeding or thrombosis. At discharge at age 16 days, the platelet count was 842,000/mm³. No treatment was administered. The thrombocytosis gradually resolved during follow-up: 630,000/mm³ at one month, 65,000/mm³ at two months, 578,000/mm³ at three months, 538,000/mm³ at five months, 512,000/mm³ at six months, and 512,000/mm³ at nine months of age. At 1 year of age, the child presented for a routine blood count because of rota-positive gastroenteritis; platelet count was 381,000/mm³. Follow-up revealed normal growth and development, with weight and length at the 65^th percentile.

Discussion

Although recombinant erythropoietin treatment is a recognized cause of pediatric thrombocytosis (7,8), there are almost no reports to date for the same side effect for G-CSF (1,2). Kawachi et al. described a 44-year-old man with non-Hodgkin's lymphoma receiving G-CSF who developed an acute arterial thrombosis with thrombocytosis and rapid rise in platelet number (13). Karpova et al., in mice experiments, demonstrated thrombocytosis in peripheral blood after repeated G-CSF treatment (14).

In our infant, thrombocytosis occurred after administration of G-CSF for leukopenia and neutropenia. The infant's mother was known to have chronic immune neutropenia so the infant's neutropenia was most likely the result of anti-neutrophil antibodies of maternal origin.

In underlying diseases and thrombohemorrhagic events, the reported platelet count was more than 650,000/mm³ (3). In our patient, who had a hematologic disease (leukopenia with neutropenia), the platelet count rose to 921,000/mm³. In our case, the decision concerning the extent of evaluation treatment and follow-up was dictated by the clinical situation.

The aim of the present case report was to draw attention to the possible side effect of G-CSF treatment. This secondary thrombocytosis in the neonate with an underlying hematologic disease could be hazardous. This possible side effect of G-CSF should be brought to the attention of neonatologists and hematologists. Additional reports of thrombocytosis in neonates receiving G-CSF treatment are needed to confirm this finding.