Year: 2005

What is the Approach to a Child with Thrombocytopenia?

Patient Presentation
A 4-year-old female comes to clinic because of a rash for 2 days. The rash began on her feet and appeared to go up her body. It is mainly on the trunk currently. Her parents describe small, red, flat dots that haven’t changed in appearance. There is no itching.
The past medical history and family history are negative.
Her review of systems reveals no new soaps, detergents, pets, travel, medications, fever, illnesses or sick contacts, blood in stools or urine, oral lesions, or easy bruising or bleeding.
The pertinent physical exam shows pinpoint, red, non-blanching petechiae over her entire body including the palms and soles, but they are concentrated on the trunk. There are some small bruises on the shins. There are no oral lesions. She has shoddy anterior cervical and inguinal nodes. She has no hepatospleenomegaly.
Her laboratory evaluation revealed a hemoglobin of 12.1 mg/dl, hematocrit of 37%, white blood cell count of 10,500/mm2 with normal differential, and a platelet count of 7,000/mm2. The blood smear was normal as was a coagulation profile and liver function tests.
The diagnosis of idiopathic (immune) thrombocytopenic purpura was made. The patient was admitted for treatment with intravenous immunoglobulin because her platelet count was <10,000/mm2, she had evidence of bleeding with the petechiae and she was a very active child. Her platelet count rose to 36,000/mm2 at discharge and at one week follow-up had increased to 266,000/mm2.

Discussion
Thrombocytopenia is usually defined as platelet counts <150,000/mm2. It can be found because of easy bruising, bleeding or can be an incidental finding on a complete blood count done for other reasons.
The differential diagnosis of thrombocytopenia includes:

  • Increased Platelet Destruction
    • Autoimmune hemolytic anemia – Evan’s syndrome
    • Congenital cyanotic heart disease
    • Disseminated intravascular coagulation
    • Drug – quinine, penicillin, digoxin, anti-epileptics, indomethacin, heparin
    • Idiopathic (immune) thrombocytopenic purpura
    • Neonatal illumine thrombocytopenia
    • Infection
    • Hemolytic-uremic syndrome
    • Hyperplenism
    • Kasabach-Merit syndrome
    • Thrombotic thrombocytopenia purpura
  • Decreased Platelet Production
    • Bone marrow infiltration – e.g. leukemia, storage diseases, myelofibrosis, etc.
    • Bone marrow injury – infection or drugs – usually transient
    • Congenital megakaryocytic thrombocytopenia
    • Congenital bone marrow aphasia – i.e. Fanconi’s anemia
    • Chromosome abnormalities – e.g. Trisomy 13, 18, 21, Turner Syndrome
    • Congenital platelet disorders – Weskit-Aldrich syndrome, May-Hegglin anomaly, Bernard-Soulier syndrome, Alport syndrome
    • Hereditary amegakaryocytopoiesis – usually associated with TAR syndrome (thrombocytopenia-absent radius syndrome)
  • Other
    • Pseudothrombocytopenia – caused by clumped platelets

Idiopathic (immune) thrombocyopenia purpura (ITP) usually occurs in children 2-10 years with a peak between ages 2-5 years. Children usually present with sudden onset of petechiae, ecchymosis, purpura, epistaxis, hematuria or gastrointestinal hemorrhage. They often are otherwise well and have a preceding minor viral illness. Physical examination usually shows only the presenting signs, but evidence of infection or malignancy must be carefully looked for.
Most children (~90%) resolve within 6 months usually without sequelae. If it lasts longer than 6 months it is called chronic ITP. Chronic ITP may resolve but this is less likely. Chronic ITP is more common in children <1 year and >10 years. Mortality from acute ITP fortunately occurs rarely and is usually due to central nervous system hemorrhage.

Laboratory testing usually shows isolated thrombocytopenia. The blood smear shows normal to increased platelet size and normal white and red cell morphology. Bone marrow examinations are often not done in typical cases but would have increased numbers of megakaryocytes.

Treatment may include careful observation, intravenous immunoglobulin, steroids and spleenectomy, and avoidance of precipitating medications. Children with atypical presentations, chronic thrombocytopenia, or children who will be treated with steroids, should have a bone marrow biopsy to rule out underlying malignancy or other causes of thrombocytopenia.

Learning Point
The approach to thrombocytopenia includes three major categories – history, physical examination and laboratory evaluation.

  • History should include questions about:
    • Type of bleeding
      • Deep bleeding such as joints or bone is usually due to a clotting factor deficiency such as hemophilia A or B
      • Epistaxis, oral, or excessive menstrual bleeding is usually due to a platelet disorder or fibrinogen abnormality
    • Drug history e.g. aspirin or non-steroidal anti-inflammatory medications
    • Recent infections or immunizations
    • Family history of bleeding

  • Physical examination should be carefully performed looking for:
    • Spleenomegaly with or without hepatomegaly
    • Lymphadenopathy
    • Skeletal abnormalities – these may be subtle and need radiographs to detect
    • Skin – e.g.hemangiomas, purpura

  • Laboratory evaluation generally includes:
    • Complete blood count with white blood cell differential and platelet count
    • Peripheral blood smear for morphology
    • Coagulation profile
    • May also include Coombs test, liver function tests, and bone marrow examination

Questions for Further Discussion
1. When should a hematologist/oncologist be consulted?
2. What are the advantages/disadvantages and indications for using immunoglobulin or steroid treatment?

Related Cases

To Learn More

To view pediatric review articles on this topic from the past year check PubMed.

Information prescriptions for patients can be found at Pediatric Common Questions, Quick Answers for this topic: Bruises.

Rudolph CD, et.al. Rudolph’s Pediatrics. 21st edit. McGraw-Hill, New York, NY. 2003:1555–1559.

Woodhead JC. Pediatric Clerkship Guide. Mosby. St. Louis MO, 2003:170-179.

Author
Donna M. D’Alessandro, MD
Associate Professor of Pediatrics, Children’s Hospital of Iowa

Date
Janaury 18, 2005

What Are the Facial Characteristics of Fetal Alcohol Syndrome?

Patient Presentation
A 15-year-old female comes to the developmental pediatric clinic for a second opinion about fetal alcohol syndrome, attention deficit disorder and school problems. Her academic difficulties began in the Head Start program and continue today with global academic problems. She also suffers from severe inattention in multiple settings.
Previously she received special education help in a separate classroom with similar children. This academic year, she receives extra help in a regular classroom. She was recently suspended for refusing to do any work at school and is more non-compliant at home also.
Her past medical history reveals that her mother drank alcohol before and during pregnancy, and is a recovering alcoholic currently. She has been treated with short-acting methylphenidate (RitalinTM) for her inattention with some symptom relief.
The family history is positive for alcoholism, attention deficit disorder and learning disabilities.
During the physical exam she is fidgety, impulsive and easily distracted. Her growth parameters are at the 25%. Her face has an thin upper lip, flat philtrum and is somewhat ‘fish-mouthed.” Her ears are flat with a enlarged helix. She has abnormal palmar creases and short fifth metacarpals. She is slightly hypotonic.
Her neurodevelopmental evaluation shows her with impulsivity and distractability. She had weaknesses in fine motor function, receptive and expressive language, temporal sequential organization and visual processing. Her strength is in gross motor skills.
Her educational evaluation reveals global learning problems including attention, language, visual spatial orientation and temporal sequential organization. She is behind 1-2 grade levels academically in all subjects.
Her psychologic screening shows no depression and she readily acknowledges her problems. She is frustrated by the lack of help at school.

The diagnosis of fetal alcohol syndrome, attention deficit disorder, and global learning disabilities was confirmed. Recommendations for improved medical management of attention deficit disorder, academic intervention and psychosocial supports were given and were being put into place at follow-up.

Discussion
Fetal alcohol syndrome (FAS) is a group of behavioral, neurological and physical birth defects associated with maternal alcohol abuse during pregnancy. In general, the amount of alcohol and the timing during gestation are associated with the severity of the syndrome.

Neurological abnormalities vary from severe to minimal and include microcephaly, developmental delays, neurobehavioral disorder, memory loss, hyperactivity, and diminished cognition.
Other problems include sleep disorders, information processing problems, and sensory integration problems. These problems can be life-long.

The differential diagnosis includes Cornelia de Lange syndrome, Noonan Syndrome, maternal phenylketonuria, and fetal hydantoin syndrome.

There is no specific test for FAS. Treatment includes neuropsychological and educational assessments to imnprove educational, behavioral, and social skills.

Attention Deficit Disorder with and without Hyperactivity (ADHD) is a common behavioral problem in childhood. It is a group of behaviors that appear early in life and typically persist. The general categories include hyperactivity, inattentiveness and impulsivity. The Diagnostic and Statistical Manual of Mental Disorders 4th Edition has specific criteria for its diagnosis, but each child has a different symptom constellation.
The cause of ADHD is not known but genetic, central nervous system, and environmental factors may all play a part. Often other problems are associated with ADHD including developmental disorders (e.g. speech and language problems or academic problems), mental retardation, oppositional defiant disorder, conduct disorder, and anxiety disorder.
Treatment is a multimodal approach specifically tailored to the individual and may include behavioral and psychosocial supports, appropriate educational placement and medications such as stimulants.

People with learning disorders (LD) have normal cognitive abilities but specific problems with types of learning or information processing. LD can occur alone but often are found as co-morbid conditions. They affect ~5% of children enrolled in United States schools. Each child’s problem constellation is unique.

LD include:

  • Dyslexia – language processing
  • Dyscalculia – math skills
  • Dysgraphia – written expression
  • Dyspraxia – fine motor skills
  • Spelling problems
  • Auditory processing disorder – interpreting auditory information
  • Visual processing disorder – interpreting visual information
  • Verbal processing disorder – interpreting and using verbal information
  • ADHD (some people include this as an LD or categorize it as a related problem)

Learning Point
Characteristic facial features of FAS includes microophthalmia, short palpebral fissures, flat philtrum, thin upper lip, scooped nose, wide nasal bridge, and wide set ears. Some of these features are very subtle and maybe only apparent with age (2-3 years) but may be decreased by adolescence.

Figure 7 – 01-10-05 – Diagram showing the craniofacial features associated with fetal alcohol syndrome from the National Institute on Alcohol Abuse and Alcoholism.

All growth parameters are decreased with weight more affected than height in childhood. Expected adult height is often not obtained. Other physical stigmata include: abnormal position or function of joints, altered palmar creases, small fifth fingers and nails, cardiac anomalies especially ventricular septal defects, ptosis, cleft lip and/or palate, micrognathia, large ears, short or webbed neck, vertebral and rib anomalies, meningomyelocoele, hydrocephalus, and hypoplastic labia majora.

Questions for Further Discussion
1. What educational interventions can be implemented in the classroom for children with ADHD?
2. What is Public Law 504 and how does it relate to children with disabilities?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Information prescriptions for patients can be found at Pediatric Common Questions, Quick Answers for this topic: Fetal Alcohol Syndrome.

Jones KL. Smith’s Recognizable Patterns of Human Malformation. 4th Edit. W.B. Saunders. 1988:491-494.

Morse BA, Weiner L. Fetal Alcohol Syndrome in Behavioral and Developmental Pediatrics: A Handbook for Primary Care. Parker S, Zuckerman B. eds. Little, Brown and Company, Boston, MA. 1995:149-152.

LD At a Glance. National Center for Learning Disorders.
Available from the Internet at <a href="http://www.merck.com/mrkshared/mmanual/section19/chapter262/262c.jsphttp://www.merck.com/mrkshared/mmanual/section19/chapter262/262c.jsp (cited 12/16/04).

Learning Disorders. Merck Manual
Available from the Internet at <a href="http://www.ld.org/LDInfoZone/InfoZone_FactSheetIndex.cfmhttp://www.ld.org/LDInfoZone/InfoZone_FactSheetIndex.cfm (cited 12/16/04).

DSM-IV-TR: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. BehaveNet.
Available from the Internet at <a href="http://www.behavenet.com/capsules/disorders/dsm4tr.htmhttp://www.behavenet.com/capsules/disorders/dsm4tr.htm (cited 12/16/04).

Author
Donna M. D’Alessandro, MD
Associate Professor of Pediatrics, Children’s Hospital of Iowa

Date
January 10, 2005

Does this Child have Hypertension?

Patient Presentation
An 8-year-old female comes to clinic for a health maintenance visit. The visit is unremarkable except that a blood pressure of 109/67 mm Hg which was noted.
The past medical history is negative.
Her family history is negative for cardiovascular, renal or endocrine disease.
The pertinent physical exam shows her to have growth that is 25% for height and weight. The auscultated repeat blood pressure is 111/64. Four point blood pressures show no difference between arms and are not significantly different in the upper or lower extremities.
The chart review shows normal blood pressures in the past, and previous laboratory evaluation shows a normal BUN, creatinine and urinalysis.
The diagnosis of possible borderline hypertension is made. The child was sent home to have bi-weekly blood pressure measurements by the school nurse and follow-up in 3-4 weeks.

Discussion
Hypertension is a serious disease causing morbidity and mortality. Hypertension is defined as a blood pressure persistently greater than the 95th percentile for age, height and gender in children. In adults, hypertension is defined as blood pressures >140/90 mm Hg.
Children with blood pressures within the upper percentiles of the normal range (>90th percentile or >120/80 for adolescents) are also at risk of becoming hypertensive in the future. The is called prehypertensive. Consequently as part of overall health maintenance, blood pressures should be recorded at least yearly after age 3 and at younger ages if indicated.

Essential hypertension is the most common cause of hypertension in children. Obesity is the primary cause of essential hypertension in the U.S. currently. Common secondary causes of hypertension in children include the following:

  • Cardiac (10%)
    • Coarctation of the aorta
    • Aortoenteritis
  • Renal (80%)
    • Congenital renal anomalies
    • Renal vascular problems – renal artery stenosis, renal artery or vein thrombosis, neurofibromatosis
    • Renal parenchymal disease – renal failure, glomerulonephritis, reflux nephropathy, structural abnormalities
  • Endocrine (2%)
    • Congenital adrenal hyperplasia
    • Conn’s syndrome
    • Cushing’s disease
    • Hypo- or hyperthyroidism
  • Oncologic
    • Central nervous system tumors
    • Neuroblastoma
    • Pheochromocytoma
    • Wilm’s tumor
    • Other malignancies
  • Other
    • Acute intermittent porphyria
    • Bronchopulmonary dysplasia
    • Genetic syndromes such as Bardet-Biedl, von Hippel-Landau, Williams, Turners, Neurofibromatosis
    • Guillian-Barre syndrome
    • Over-the-counter cough and cold medications
    • Recent vigorous exercise
    • Recent smoking, alcohol or other medication use (including illicit drugs)

When evaluating hypertension, one must first determine that there is truly hypertension. In the office setting, the blood pressure can easily be rechecked ensuring the correct size cuff is used (i.e. covers 2/3 of the distance between the elbow and shoulder or knee to hip) and the proper number recorded. Repeated measurements (at least 3) are needed and often can be done at school or other location. This is more convenient for families often and children are less likely to have white-coat syndrome where their blood pressure is only elevated in the doctor’s office but not in other settings.
If the blood pressure is still high, then a work-up to find a potentially correctable cause of hypertension should be done. This should include: blood pressure measurement in all four extremities, BUN, creatinine, urinalysis, and CBC. Cardiac echocardiogram looking for ventricular hypertrophy can also be helpful. Additionally, some people also obtain plasma renin level, cholesterol and triglycerides and a renal ultrasound with Doppler.
Other specific testing should be guided by the history, physical examination and laboratory evaluation results.

Treatment for hypertension includes diet, exercise and possibly medication.

Learning Point
Often, a rough estimate of blood pressure above which a health care provider should be concerned is all that is needed by the provider. One rough estimate of age-adjusted blood pressures uses the following formula:

     90/50 + (3/1.5)(Age in Years) 

     Where systolic blood pressure begins with 90 and (3 x age in years) is added
     And diastolic blood pressure begins with 50 and (1.5 x age in years) is added

For this patient who is 8 years old:

     Systolic blood pressure = 90 + (3x8) = 90 + 24 = 114
     Diastolic blood pressure = 50 + (1.5x8) = 50 + 12 = 62

Or the rough estimate of a age-adjusted borderline blood pressure is 114/62.

It should be emphasized that this is AN ESTIMATE ONLY.
If the patient’s blood pressure is close to the estimate or if the healthcare provider is unsure or concerned, then the standards based on gender, age and height standards must be checked. These standards can be found in the To Learn More section below.
For this patient, the standard would be 110/71.

Questions for Further Discussion
1. What medications are commonly used to treat hypertension?

Related Cases

To Learn More

To view pediatric review articles on this topic from the past year check PubMed.

Information prescriptions for patients can be found at Pediatric Common Questions, Quick Answers for this topic: High Blood Pressure.

Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents: a working group report from the National High Blood Pressure Education Program. National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents
Pediatrics, 1996;98:649-658.

Gunn VL, Nechyba C. The Harriet Lane Handbook. 16th. Edit. Mosby Publications: St. Louis. 2002:126-129.

Woodhead JC. Pediatric Clerkship Guide. Mosby., St. Louis MO, 2003:277-284.

Spitzer, A. Hypertension. eMedicine.
Available from the Internet at http://www.emedicine.com/ped/topic1097.htm (rev. 6/29/04, cited 12/13/04).

Author
Donna M. D’Alessandro, MD
Associate Professor of Pediatrics, Children’s Hospital of Iowa

Date
January 5, 2005