When to Suspect a Bone Marrow Failure Syndrome in a Child

Akiko Shimamura, MD, PhD


March 13, 2017

Pediatricians face a difficult task in determining when to refer a child for a suspected bone marrow failure syndrome. These different disorders typically have some features in common: low blood counts due to poor blood cell production; congenital anomalies; and cancer predisposition. Only a subset of children with bone marrow failure syndromes will present with the findings described in textbooks, however. These children often appear well and lack classic physical findings. The blood counts may even be normal sometimes or drop only intermittently, but the child remains at risk for malignancy. By the time a child looks sick, the marrow's ability to produce blood cells can be so weakened that it could be too late—or at least much more difficult—to treat the child successfully.

Akiko Shimamura, MD, PhD

These rare disorders range from life-threatening conditions requiring a hematopoietic stem cell transplant to mild cases that are treated either medically or with watchful waiting. Left untreated, some bone marrow failure syndromes can lead to cancers, particularly acute myeloid leukemia (AML). Once AML develops in patients with bone marrow failure syndromes, outcomes are generally poor, so current strategies focus on early diagnosis and surveillance to initiate transplant before the development of AML.

Several findings should lead a primary care physician to refer a patient for evaluation. Children with anemia can present with fatigue and an inability to pursue normal activities. A baby might not have the energy to feed. Children with neutropenia might present with infections, ranging from mouth sores or skin infections to serious, potentially life-threatening infections. Children with thrombocytopenia might bruise easily and have nosebleeds.

In an asymptomatic patient, the clue may come from a routine complete blood count (CBC) ordered for an unrelated reason, such as preparation for surgery or as part of a well-child checkup. Likewise, other combinations of symptoms and characteristics might warrant ordering a CBC to determine whether bone marrow failure might be at work. Other important points in recognizing bone marrow failure:

  • If a viral infection is suspected in a child with leukopenia, the child should be monitored to make sure the white count returns to normal within a few weeks after recovery.

  • Children with bone marrow failure often present with short stature without a clear reason for it. Although short stature is very common, when combined with abnormal blood counts it should raise suspicion for a bone marrow failure syndrome.

  • A child with low counts in more than one type of blood cell should be referred for evaluation.

  • Mild anemia is not an automatic signal for referral, but anemia and macrocytosis, without an apparent cause, should be evaluated further. Macrocytosis can be a sign of bone marrow stress and an early indicator of a bone marrow failure disorder or a malignant or premalignant condition.

  • If a patient reports a family history of cancer—particularly leukemia or solid tumors—at a young age, obtaining a CBC is in order. Leukemias, such as AML, are most common in people older than age 60. If a patient's father had leukemia at age 30 or a cousin/sibling had leukemia at age 7, that's a red flag.

  • Neutropenia is common and not a reason for referral in and of itself. But if a patient has neutropenia together with short stature, poor growth, severe diarrhea, or physical anomalies, an evaluation is indicated.

  • Unexplained, persistently low platelets can be a presenting sign of bone marrow failure. The most common reason for low platelets in childhood is idiopathic thrombocytopenic purpura (ITP), which typically resolves over 3-6 months. If it doesn't, then the child should be evaluated.

  • Patients with physical anomalies and low blood counts without apparent cause may have a bone marrow failure syndrome.

If you suspect a bone marrow failure syndrome, refer the child to a multidisciplinary program with the expertise to evaluate and treat problems in a wide range of organs—including the gastrointestinal system, lungs, heart, and kidneys—that might be affected by marrow failure syndromes. Cutting-edge genomic testing now allows individualized, tailored therapies and surveillance strategies. Patients benefit from referral to a center with expertise in evaluating and treating these complex disorders.

Working together, the primary care pediatrician and specialty clinic can ensure that children with bone marrow failure are caught early enough to enjoy the maximum likelihood of successful treatment.


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