What are Common Causes of Anaphylaxis?

Patient Presentation
A 4-year-old female came to clinic for her health maintenance appointment. She was known to have multiple food allergies and asthma and was managed by allergy specialists. Overall she was growing and developing well. The past medical history was positive for several episodes of rashes, facial edema with lip swelling, and wheezing that were provoked by various foods. She also had dust-mite allergy. She usually was treated with diphenhydramine and/or albuterol but once she started to have stridor and epinephrine was given and she was taken to the emergency room and hospitalized over night. The family history was positive for asthma and allergies.

The pertinent physical exam showed a fair-skinned smiling female with normal vital signs and growth parameters in the 10-25%. She had sensitive skin but otherwise had a normal examination.

The diagnosis of a healthy female with multiple allergies and one episode of anaphylaxis was made. The parents were very well versed in how to use her Epi-pen® and how to activate the emergency medical system. “We have several Epi-pens® but I think a couple of them are about to expire so we need some refills. This summer we are thinking about sending her to a daycare camp that will be at a farm. The allergist said it was okay as long as the daycare staff knows what to do if she seems to be having a reaction. We already checked and the ambulances are called using 911 since they are close to the city and the hospital is on that side of town too,” they stated. “It seems like a reasonable plan. I’d just make sure that her Epi-pen® is with them all the time like in a backpack and that the providers could really give her the epi if she needed it. You never know where they will be on the farm. You want her to be a normal kid but planning is important. Maybe if she doesn’t go this year, then another year when she is also even older and could possibly let people know if she seems to be having a problem. When you talk with them I’d ask them about the food the other kids will bring for lunch and snacks. You’ll need to do the same thing when she goes to kindergarten as well,” the pediatrician offered.

Discussion
Anaphylaxis is a potentially life-threatening hypersensitivity reaction of the body. Usually anaphylaxis is IgE mediated but complement-mediated immune complex reactions or IgG mediated reactions can cause anaphylaxis. Usually mucous membranes or skin are involved, but it is a systemic disease process with at least 2 systems involved (respiratory is second most common followed by gastrointestinal system). The epidemiology is difficult to discern but the estimated incidence is about 50-112 episodes per 100,000 person-years and estimated prevalence is 0.3-5.1%. There is data supporting an increased incidence. Overall fatality is stable at about 0.63-0.75 per million adults in the US/year.

While it would seem to be easy to diagnose, anaphylaxis can be difficult for the patient and healthcare providers to recognize. Common signs and symptoms of anaphylaxis include:

  • Skin rash with or without pruritus, flushing, angioedema, conjunctival or perioral edema, urticaria
  • Respiratory – rhinitis or nasal congestion, dyspnea, wheezing, stridor, sensation of throat closing, choking, hypoxia
  • Gastrointestinal – nausea, emesis, abdominal pain, diarrhea
  • Cardiovascular – chest pain, diaphoresis, tachycardia or bradycardia, presyncope/syncope, hypotension, end-organ dysfunction
  • Central nervous system – confusion, headache, hypotonia, unconsciousness, seizure

Treatment with epinephrine right away and then transportation to a medical facility that can care for patients and appropriately monitor them is critical. Patients and families should be instructed that if epinephrine is given that the emergency medical system should be activated as the next step. Epinephrine may help but its duration of action is very short. Often it is needed to be given again. Health care providers can help patients by reviewing signs of anaphylaxis, and to make sure the family has enough epinephrine available (and it is not expired) as the patient may need multiple prescriptions to have on hand in multiple locations (ie home, school, relative or friends home, backpack, etc.). They should also be reminded how to use the epinephrine and to activate the medical system if they do.

Learning Point
The most common causes of anaphylaxis include:

  • Food – Overall, egg and milk are the most common food allergies. In children, egg, milk, soy, wheat and peanut allergies predominate. In adults, crustaceans, tree nuts, peanuts and fish predominate.
  • Drugs – beta-lactam antibiotics, nonsteroidal anti-inflammatory drugs
  • Exercise-induced anaphylaxis
  • Hymenoptera stings – honeybee, hornet, wasp, yellow jacket, fire ant
  • Latex – non-latex products are being used more often but still an important cause
  • Idiopathic

A recent review article by Dr. Katherine Anagnostou finishes by clearly stating, “Anaphylaxis is a severe life-threatening systemic reaction, which constitutes a clinical emergency. Prompt assessment and management are crucially important. Anaphylaxis is primarily a clinical diagnosis and health professionals should be appropriately trained in order to recognize and treat patients in a timely manner. Studies suggest that anaphylaxis is on the rise and that it is an under-recognized and under-reported medical diagnosis. Despite the increase in hospitalizations, fatalities from anaphylaxis are fortunately, rare. The commonest trigger in childhood is food. Severe, unstable asthma has been highlighted as a risk factor for severe anaphylaxis, therefore optimal control is key in order to manage risk. In addition, caregivers and patients are often reluctant to administer epinephrine due to uncertainty on whether this is required. Regular education of patients and families on how to identify anaphylactic episodes and respond appropriately is very important and should form part of the routine management.”

Questions for Further Discussion
1. Which proteins cause cow’s milk protein allergy? A review can be found here

2. What are risk factors for latex allergy? A review can be found here
3. What are common food allergy cross-reactivities? A review can be found here
Related Cases

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

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Anaphylaxis and Allergy.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Anagnostou K. Anaphylaxis in Children: Epidemiology, Risk Factors and Management. Curr Pediatr Rev. 2018;14(3):180-186. doi:10.2174/1573396314666180507115115

Guo C, Greenberger PA. Idiopathic anaphylaxis. Allergy Asthma Proc. 2019;40(6):457-461. doi:10.2500/aap.2019.40.4271

Poowuttikul P, Seth D. Anaphylaxis in Children and Adolescents. Pediatr Clin North Am. 2019;66(5):995-1005. doi:10.1016/j.pcl.2019.06.005

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

What Are Risk Factors for Bronchopulmonary Dysplasia?

Patient Presentation
A 10 week-old male came to clinic for his first well-child visit after being discharged from the neonatal intensive care setting.

The past medical history showed an infant born prematurely at 28 weeks gestation and 965 grams (10%) to a G2P2 female who presented to a local emergency room in active labor. He was transported to a regional children’s hospital and his hospitalization had been complicated by mechanical ventilation for 3 weeks, medical closure of his patent ductus arteriosus, poor initial weight gain and presumed sepsis that occurred early in his treatment. For the past 3 weeks he had been on 1.5 liters of oxygen by nasal cannula without apnea and bradycardia, was slow but consistently eating 24 kcal formula with consistent weight gain. From a health maintenance standpoint, he did not have retinopathy of prematurity, he had received his first vaccines and first dose of palivizumab to prevent respiratory syncytial virus infections. The family was living in a local charity’s long-term accommodation facility for the first 2 weeks after discharge, so this visit was for temporary outpatient care until they returned to their own home. Once home, a visiting nurse was scheduled for the first month to monitor him and support his family, along with establishing care with his own doctor.

The pertinent physical exam showed a small infant with a weight of 2410 gram (5%) which was up 15 grams/day for 2 days with a nasal cannula in place. His saturation was 91-94% in clinic. He was proportional in his other growth parameters. His physical examination was non-contributory.

The diagnosis of a premature infant was made. The family was to continue his routine care and was to followup in 1 week and when he returned he was gaining 11 grams/day with a stable physical examination. He was to followup with neonatology the next week before returning home. He also already had another neonatology appointment 2 months later to follow his weight, his bronchopulmonary dysplasia and weaning off of oxygen and developmental status.

Discussion
Bronchopulmonary dysplasia (BPD) was first described in 1967 by Northway et.al. At that time it was described as “relatively mature preterm infants with severe respiratory failure to survive their initial respiratory distress syndrome after receiving aggressive respiratory support with high oxygen and positive pressure ventilation. Their clinical course was characterized by severe chronic respiratory failure with a radiographic picture showing areas of hyperinflation alternating with adjacent increased densities.” This is often referred to as “Old BPD.”

Over time more has been learned and improvements in care of preterm and term infants has occurred. “New BPD” occurs in younger preterm infants but they are treated with antenatal steroids, surfactant and gentler methods of mechanical ventilation. Pathologically the lung has less emphysema, fibrosis, smooth muscle hypertrophy and epithelial metaplasia. There are various specific definitions especially for BPD severity, but basically it is defined as the need for chronic supplemental oxygen. Usually this is for more than 28 days and the need for oxygen at 36 weeks corrected gestation. In extremely low birth weight premature infants (<28 weeks gestation) about 40% develop BPD.

The lung embryologically undergoes changes that are characterized as increased branching of the airway tubules, differentiation of the airway cells, and thinning of the cellular walls of the lung. Many preterm infants are born at the canalicular stage at 16-26 weeks gestation that has acinar tubules, and at 26-36 weeks gestation in the saccular stage with terminal saccules. The alveolar stage occurs from then on. Simplistically, the lung at the canalicular and saccular stages has relatively few branches, there is “thick” tissue where air exchange/diffusion occurs, and the lung doesn’t make as much surfactant to help keep the tubular structures patent. So simplistically the lung has less surface area for air exchange, it is harder for the air exchange/diffusion to occur, and the tubular structures can easily close down and not allow air to flow through the lung. These problems along with others make it difficult for the preterm infant to have successful respiration and ventilation such as immature bones and muscles of the chest wall and diaphragm which are needed to exert the pressures required to move a relatively stiff lung. Premature infants also have an immature central nervous system trying to regulate respiration.

Trying to treat a premature infant is a real balancing act. Neonatologists are trying to balance the ongoing needs of the premature infant which constantly are physiologically changing even moment to moment, in an infant who is still rapidly developing all organ systems but which are all immature, using equipment and methods in tiny body spaces, and with incomplete medical knowledge regarding physiology where optimal levels of many treatments still are not conclusively known. The neonatologist must try to balance the specific immediate needs with the potential for increasing other problems in the future.

The most efficacious treatment has not been determined with strategies for BPD prevention centering on use of antenatal steroids to accelerate lung development of the fetus and use of exogenous surfactant to aid lung tubule patency and improve mechanics. Additionally, minimizing the respiratory support needed by using noninvasive respiratory support measures such high flow nasal cannula or intermittent positive pressure ventilation is very important for BPD prevention. Using these measures for the least amount of time necessary and the least pressures decreases BPD. However, stiff lungs make it difficult to ventilate a premature infant to allow for adequate air exchange and oxygenation to occur.

Oxygen therapy really highlights the delicate balancing act of managing competing priorities. Oxygen therapy needs to keep the oxygen levels up to minimize hypoxia and potential brain damage, but it is also directly toxic to the lungs. Therefore using the minimal supplemental oxygen needed is important but also the “best” oxygen levels aren’t totally elucidated. Different oxygen levels are also associated with other problems such as mortality, necrotizing enterocolitis, and retinopathy of prematurity and have to be balanced.

Optimizing premature infant nutrition also helps prevent BPD. However it can be difficult to provide adequate calorie and nutrient needs because the gastrointestinal system itself is immature and parenteral nutrition has risks of infection, extravasation and the pragmatic problems of obtaining and maintaining parenteral access.

Other treatments that may have some beneficial effects are caffeine and Vitamin A. Diuretics are also commonly used to treat fluid retention and pulmonary edema that may be associated with BPD.

Learning Point

Risk factors for BPD include:

  • Gestational age which is inversely proportional to the risk of BPD
  • Birth weight, which is also inversely proportional to the risk of BPD
  • Oxygen therapy – higher concentrations have higher risks
  • Mechanical ventilation trauma – more invasive measures, for longer periods with higher pressures have higher risks of BPD
  • Antenatal factors – maternal smoking, hypertension, lower socioeconomics factors
  • Genetics
  • Male gender
  • White race
  • Inflammation – trauma, infection (systemic or pulmonary)
  • Colonization or microbiome – possibly
  • Patent ductus arteriosus – possibly
  • Transfusion – possibly

Note that not all of these risk factors have clearly indicated causality in studies. They may only be associated with BPD.

Questions for Further Discussion
1. What are the relationships to BPD of respiratory distress syndrome and hyaline membrane disease?
2. What makes oxygen so potentially toxic to living tissue?
3. What are the long term potential problems with BPD?

Related Cases

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

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Bronchial Disorders and Premature Babies.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Hwang JS, Rehan VK. Recent Advances in Bronchopulmonary Dysplasia: Pathophysiology, Prevention, and Treatment. Lung. 2018;196(2):129-138. doi:10.1007/s00408-018-0084-z

Bancalari E, Jain D. Bronchopulmonary Dysplasia: 50 Years after the Original Description. Neonatology. 2019;115(4):384-391. doi:10.1159/000497422

Tracy MK, Berkelhamer SK. Bronchopulmonary Dysplasia and Pulmonary Outcomes of Prematurity. Pediatr Ann. 2019;48(4):e148-e153. doi:10.3928/19382359-20190325-03

Thebaud B, Goss KN, Laughon M, et al. Bronchopulmonary dysplasia. Nat Rev Dis Primers. 2019;5(1):78. doi:10.1038/s41572-019-0127-7

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

What Are Some Etiologies for Intellectual Disability?

Patient Presentation
A 4-year-old male came to clinic with his mother to establish care after they moved to the area. He was a former 26 week premature infant, who was known to have problems related to retinopathy of prematurity, global developmental delay after bilateral grade IV intraventricular hemorrhages and lung problems due to bronchopulmonary dysplasia. They were in the process of re-establishing his specialty medical and service care. They had already contacted the local school district and had appointments with the occupational, physical and speech therapists. The mother needed additional referrals to Developmental Disabilities, Ophthalmology, Orthopaedics and Pulmonary to continue his followup. “The neonatologists had already transitioned him to the Developmental Disabilities people to continue to monitor him, so I need to get that arranged too,” his mother noted. “He needed a feeding tube before but he has been eating fine and gaining weight, so I don’t think we need GI at this time, and I already have appointments with Neurology and Neurosurgery to followup on his seizures and VP shunts,” she stated. “He’s well controlled on his medications and so far has only needed one shunt revision,” she explained.

The pertinent physical exam showed a smiling thin male who was polite but spoke little during the visit. His weight was in the 10% and height was 25% and was tracking from his previous records. He wore glasses and had some caps on his teeth. Bilateral ventriculoperitoneal shunts were in place. His abdomen showed previous surgerical scars. His neurological examination had increased tone throughout and increased DTR +2/+2 but his strength was normal. His ankle-foot orthoses appeared to fit well without skin breakdown.

The diagnosis of a child with global developmental delay secondary to prematurity and its complications was made. “I will order those consultations. He also will need a dentist and I can refer you to one in the area who works with lots of children who need special care. There’s also recreational services for families with a family member with special needs and I can tell you more about those too,” the pediatrician offered.

Discussion
“Intellectual disability (ID) is a neurodevelopmental disorder that is characterized by deficits in both intellectual functioning and adaptive function whose onset is in the development period.” Global developmental delay (GDD) is used to describe children from 0-5 years old with significant delays in 2 or more developmental areas. These delays may be transient but up to 2/3 of children with GDD will have ID. Overall 1-3% of the general population has ID which makes it very common.

Most children with GDD/ID are identified because of delays in meeting milestones or general academic achievement. ID patients who have more severe problems are usually identified earlier. Each person with ID is individual and their strengths and weaknesses will be different. There are different ID severity levels which are grouped as:

  • Mild
    • 85% of ID population
    • Associated IQ score: 55-70
    • Described as having: academic problems, communication/thinking more concrete, more immature socially, may live and work independently and provide own personal care but may also need intermittent support often with complex daily activities
    • Projected academic achievement: up to 6th grade
  • Moderate
    • 10% of ID population
    • Associated IQ score: 40-55
    • Described as having: academic problems, more problems with providing own personal care, can live and work in a supervised environment
    • Projected academic achievement: up to 2nd grade
  • Severe
    • 3-4% of ID population
    • Described as having: severe academic problems, limited communication, needs extensive oversight and supervision for all activities of daily living
    • Projected academic achievement: up to Preschool level
  • Profound
    • 1-2% of ID population
    • Associated IQ score: < 25
    • Described as having: severe problems understanding language but may understand basic instructions, is dependent for personal care and needs constant supervision
    • Projected academic achievement: very limited

When trying to identify a potential cause of ID, during physical examination the skin should be examined for possible neurocutenaous disorders. Head size, especially microcephaly but also macrocephaly, is commonly associated with ID. Evidence of dysmorphic features are also helpful but are not necessarily specific. It is important to remember that it is usually a constellation of findings that may help to distinguish an etiology.

A review of the causes of microcephaly can be found here.
A review of the causes of macrocephaly can be found here.

Evaluations can be helpful for the patient and family as then they can understand the natural history, obtain condition-specific medical surveillance and treatment, and obtain genetic counseling for future pregnancies and family members.
Recommended testing will depend on the history and physical examination.
Review of prior testing such as the neonatal screening testing may be helpful. Additionally testing for TORCH or Zika infections, neuroimaging, hearing and vision testing may be helpful. Other testing such as creatinin kinase, thyroid function, and baseline biochemistry and hematology labs, and urine metabolic screening can be helpful. Genetic testing currently often includes a chromosomal microarray analysis and may also include karyotyping and Fragile X testing. Specific genetic testing for certain syndromes or because of family history are also considered.

Individualized services for education and life functioning are important along with education and support for family members. Early intervention services for young children and school based services with appropriate goals for vocation and education along with individual preferences, strengths and weakness should be considered. For teenagers, transition planning for after school is important to start early.

Learning Point
Potential etiologies for ID include:

  • Unknown – a very common reason
  • Environment
    • Fetal alcohol syndrome
    • Hypoxic-ischemic encephalopathy
    • Infections – TORCH, Zika, meningitis
    • Toxin – lead
    • Traumatic brain injury
  • Genetic – a very common reason
    • Chromosomal – Down syndrome, Neurofibromatosis
    • Continuous gene deletions – 22q11 deletion, Angleman syndrome, Cri-du-chat, Prader-Willi, Smith-Magenis syndrome, Williams syndrome
    • Single gene deletion – Fragile X syndrome, Rett syndrome, Rubenstin-Taybi syndrome, Tuberous sclerosis
  • Inborn errors of metabolism – congenital hypothyroidism, phenylketonuria
  • Neurologic disorders – Brain malformations, central nervous system disorders
  • Nutritional deficiency – iron deficiency, severe malnutrition

The differential diagnosis for ID includes:

  • Autism spectrum disorder
  • Language disorder
  • Psychiatric problems
  • Specific learning disorders
  • Sensory deficits – vision, hearing
  • Trauma – adverse childhood experiences, post-traumatic stress disorder, abuse/neglect

It should be noted that many of these conditions could be co-morbid or overlap. For example, autism spectrum disorder often does not have ID but can. About 30% of people with ID have co-morbid conditions.

Questions for Further Discussion
1. What are some of the clinical features of Fragile X syndrome? A review can be found here
2. What is the classification of intraventricular hemorrhage? A review can be found here
3. What information should be in a health care plan for special needs children? A review can be found here
4. What is the role of the primary care provider for families with a special needs child?

Related Cases

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

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Developmental Disabilities

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Purugganan, Oscar. Intellectual Disabilities. Pediatrics in Review. June;39(6):299-309.

Amor DJ. Investigating the child with intellectual disability. J Paediatr Child Health. 2018;54(10):1154-1158. doi:10.1111/jpc.14202

Bass N, Skuse D. Genetic testing in children and adolescents with intellectual disability. Curr Opin Psychiatry. 2018;31(6):490-495. doi:10.1097/YCO.0000000000000456

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

Are There Developmental Changes in Platelet Function for Children?

Patient Presentation
The new clinical medical student was rounding with the general pediatric inpatient team. She presented a 3-day-old, 37 0/7 week male who had been admitted for hyperbilirubinemia. She noted that the brother had had hyperbilirubinemia as well, and also had thrombocytopenia. “Apparently it was worked up but the parents said nothing was found. We did a CBC too and the platelet count was 149,000. It’s just below normal. I haven’t had a chance to ask if we need to worry about this. I think babies can have some different laboratory values but I don’t really know,” she said.

Discussion
While most people realize that each stage of a child’s life is different, there are some areas that people do not realize are different. For example, there are many laboratory values which are different based on the age because there are developmental changes. Within the hematopoietic system there are many developmental changes that are common such as hemoglobin and hematocrit. Others are less well known such as children have quantitatively less fibrinogen, but the activity is the same as adult fibrinogen.

Platelets are an important part of both the primary and secondary hemostasis processes. They develop from megakaryocytes in the bone marrow, and circulate in the blood with a lifespan of 7-10 days. “Following a vascular injury, platelets are activated by collagen exposed from the endothelium and engagement with von Willebrand factor (vWF), and this initiates subsequent formation of the hemostatic plug.” More platelets arrive at the vascular injury and they are cross-linked by fibrin to stabilize the plug.

There are many tests that can be done to evaluate platelet function including platelet function analysis-100/200 which is one of the standards for assessment ofprimary hemostasis in children, thromboelastrometry, flow cytometry, platelet ELISA assay and others.

Learning Point
Developmental changes for platelets in children includes:

    Platelet count

    Around 22 weeks gestation, the fetal platelet count reaches adult levels.
    Preterm infants have platelet counts between 150-450 x 1000/mm2 with the adult normal value 150 – 350 x 1000/mm2.
    Preterm infants (up to 70%) often have thrombocytopenia (platelet count below 150 x 1000/mm2) though. It is believed to be caused by a transient decrease in survivability in at least 20% of premature infants.
    Thrombopoietin is the major platelet hemostasis regulator of platelet production. It is detectable at all gestational ages and some studies have found premature infants having higher levels than term infants.

    A differential diagnosis of thrombocytopenia can be found here.
    A differential diagnosis of thrombocytosis can be found here.

    Platelet function

    Preterm infants have a higher risk of bleeding problems particularly intraventricular hemorrhage. There are many reasons for this including blood vessel fragility, but decreased platelet functioning is part of the problem. Major studies of platelet function in preterm infants have not been conducted relative to full-term infants because of the difficulties of obtaining blood from preterm infants and the large volumes needed to perform the testing. Phlebotomy is also a cause of anemia in preterm infants.
    Both platelet aggregation and platelet hyporeactivity have been reported in neonates. There is also decreased platelet adhesion and some differences in how platelets interact with vWF have been noted. Neonates also have increased high molecular weight vWF which increases platelet adhesions and may help compensate for platelet activity.

    Full-term infants also have decreased platelet activation and aggregation relative to adults. Timing of when platelet function reaches adult levels depends on the study and ranges from a few weeks to up to 15 years. But most healthy children > 1 year of age have platelet aggregation similar to adults.

    A review of congenital platelet function abnormalities can be found here.
    A review of thrombophilias can be found here.

Questions for Further Discussion
1. What are causes of hyperbilirubinemia in infants? A review can be found here.
2. What causes anemia? A review can be found here.

Related Cases

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

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Platelet Disorders

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Matthews DC. Inherited disorders of platelet function. Pediatr Clin North Am. 2013;60(6):1475-1488. doi:10.1016/j.pcl.2013.08.004

Del Vecchio A, Motta M, Romagnoli C. Neonatal Platelet Function. Clin Perinatol. 2015;42(3):625-638. doi:10.1016/j.clp.2015.04.015

Hvas A-M, Favaloro EJ. Platelet function testing in pediatric patients. Expert Rev Hematol. 2017;10(4):281-288. doi:10.1080/17474086.2017.1293518

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa