What Are Some Potential Adverse Effects of Blood Donation?

Patient Presentation
A 17-year-old female came to clinic for her health maintenance examination. She was doing well and was participating in cross-country and track. She had no concerns. The pertinent physical exam revealed a healthy female with normal vital signs. Her height and weight were 50%. The diagnosis of a healthy female was made.

“I noticed that you said you had fainted on your sports physical questionnaire. What happened?” inquired the pediatrician. “Well I gave blood in the spring for the first time and passed out when I first stood up. It was really embarrassing. I was okay after that though,” she replied. “It’s never happened before or after?,” he asked. “No, never before or since. I was okay. I just sort of slumped over and fell back on the bed but never really lost consciousness. I just sat there for a bit longer and had some juice. It was really embargassing,” she stated. “And you’ve never had any other problems like your heart racing or beating funny or any other problems when exercising?” he asked. “No, no other problems. They also told me that I can give blood again which I’m going to do. I’m just going to drink more and make sure I stand up more slowly next time,” she commented.

Discussion
Just under 40% of people are eligible to be a blood donor. Up to 6.5% of a population are actual donors. “Blood donors are healthy volunteers who give either whole blood or blood components by apheresis including platelets, plasma, red blood cells, peripheral blood stem cells and leucocytes or a combination of blood components. They represent a large, healthy population exposing themselves voluntarily for altruistic, sometimes financial motives to potential complications and risks.” Blood banking systems world-wide are responsible for caring for individual donors health as well as maintaining a robust blood supply for the general population. The safest blood donors are voluntary, non-remunerated blood donors from low-risk populations,” per the World Health Organization. Young donors < 18 year old make up more than 10% of the donations in the U.S, and therefore are a very important resource for blood.

The common blood types are O+ (39%), A+ (30%), O- and B+ (9%), A- (6%), AB+ (4%) and AB- (2%). “In an emergency, anyone can receive type O red blood cells. Therefore, people with type O blood are known as “universal donors.” In addition, individuals of all types can receive type AB plasma because it does not contain anti-A or anti-B.”

Eligibility criteria for blood donation by the American Red Cross can be found here. Topics related to blood safety by the World Health Organization can be found here.

Learning Point
Adverse events directly related to blood donation is ~1%. Adverse events are more likely in first time donors, younger donors and women. Young age group is at higher risk for adverse events, up to 12% and there is a higher rate in 16-17 year olds compared to 18-19 year olds.


Common and uncommon adverse effects include:

  • Vasovagal reactions – 1.4 – 7% for moderate reaction, 0.1 – 0.5% for severe reaction,
    • Vasovagal effects include apprehension, diaphoresis, dizziness, weakness, pallor, hypotension and bradycardia
    • Hospitalizations are rare and usually due to fall-related injuries
    • Vasovagal events are more likely to occur in first time donors, younger donors, low weight, non-black race, pre-donation rapid pulse or lower blood pressure
  • Venipuncture problems
    • Hematoma – 9 – 23%
    • Nerve injury – 0.016 – 0.9%
    • Arterial puncture – 0.003% – 0.011%
  • Iron deficiency anemia
    • Common in regular frequency donors – 48 – 66%
    • Restless legs syndrome (RLS) due to iron deficiency – 14 – 25%
  • Other
    • Allergic reaction to tape, disinfecting agent, nickle, etc.
    • False positive screening tests – a list of screening tests can be found here
    • Fatalities – a few case reports with underlying problems such as myocardial infarction

Adverse event prevention includes pre-donation education about what to expect, increasing fluid intake before phlebotomy, exercising large muscle groups during phlebotomy and afterwards to increase circulation, support during phlebotomy (e.g. verbal distraction or engagement), and calm environment to provide and maintain psychological support for the donor. For iron deficiency anemia, iron supplementation and/or restriction of donation frequency is usually used.

Questions for Further Discussion
1. How is blood volume estimated for a healthy person?
2. What blood products are made from whole blood?
3. What are the problems with blood that cannot make it easily synthesized?
4. What are indications for bone marrow donation, and what are the eligibility criteria?

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: Blood Transfusion and Donation

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.

Amrein K, Valentin A, Lanzer G, Drexler C. Adverse events and safety issues in blood donation–a comprehensive review. Blood Rev. 2012;26(1):33-42. doi:10.1016/j.blre.2011.09.003

Eder AF. Improving safety for young blood donors. Transfus Med Rev. 2012;26(1):14-26. doi:10.1016/j.tmrv.2011.07.008

Wiersum-Osselton J, Romeijn B, van den Brekel E, et al. Can we prevent vasovagal reactions in young inexperienced whole blood donors? A placebo controlled study comparing effects of a 330 vs 500 mL water drink prior to donation. Transfusion (Paris). 2019;59(2):555-565. doi:10.1111/trf.15065

World Health Organzation. Voluntary non-remunerated blood donation. WHO. http://www.who.int/bloodsafety/voluntary_donation/en/. Accessed October 3, 2019.

Blood FAQ. AABB.org. http://www.aabb.org/tm/Pages/bloodfaq.aspx. Accessed October 4, 2019.

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

How Does Gaucher Disease Present?

Patient Presentation
A child with a rare disease presented in clinic for well child care and the mother reminded the pediatrician of another family she had taken care of while a resident. This family had come from another state to attend a professional conference and see their extended family. Their infant son came to the emergency room of the children’s hospital because of breathing difficulties and was noted to have hepatosplenomegaly and developmental delay. He was admitted to the intensive care unit because of poor respiratory effort and new onset seizures. He was eventually diagnosed with Gaucher Disease but at that time there was no treatment available. The pediatrician remembers the conversation when the family was told and the grief yet calmness on the mother’s face. She was a strong and practical woman, who took her time asking questions, but eventually keyed in on how she could get her baby home to die. The pediatrician had been tasked with arranging the medical transport and remembered the mother putting a special blanket over the child as they left the unit to travel to the airport.

Discussion
Gaucher disease (GD) was first described by Philippe Gaucher in 1882. It was the first lysosomal storage disease (LSD) described and is the comparison prototype for many variations and their treatment. There are about 50 LSD and more well-known ones include Fabry, Niemann-Pick and Pompe diseases. LSDs currently have more than 300 different enzymes or membrane proteins affected which cause central nervous system and visceral disease. Overall the frequency of LSDs in aggregate is 1:3000 – 7000 live births. GD has an estimated prevalence of 1:57,000 – 111,000. It is higher within the Ashkenazi Jewish population (~1:850).

GD is an autosomal recessive disease whose main enzyme defect is acid β-glucosidase which causes accumulation of glucosylceramide, an indigestible lipid. This occurs in macrophage-lineage organs. Activated macrophages also affect a number of inflammatory pathways. Therefore organ systems are affected by lipid accumulation but also inflammation. Primary systems affected are the liver, spleen, bone marrow, lungs and central nervous system but other systems are also affected depending on the phenotype.

Learning Point
GD diagnosis may not occur until later ages when clinical manifestations occur. Splenomegaly is the presenting symptom for 95-99% of patients depending on the age. Diagnosis is by showing deficient enzyme activity in an appropriate tissue such as peripheral blood leukocytes. Genotyping can be helpful to help determine natural history and for genetic counseling. Genetic screening of high risk populations such as Ashkenazi Jews is performed as is newborn screening in certain US states. There are 3 types of GD.

  • GD type 1
    • 95% of cases
    • Sometimes described as adult disease but usually diagnosed by age 20 because of some symptoms in childhood especially hepatomegaly, splenomegaly, and bone disease
    • Clinical manifestations include hepatomegaly, splenomegaly, avascular bone disease or bone marrow fibrosis, delayed puberty, delayed growth, and pancytopenia
  • GD type 2
    • Acute neuronopathic GD
    • Newborns and infant
    • Severely affected with oculomotor, brainstem problems, hypotonia, spasticity and seizures. Lung involvement with respiratory distress is common.
    • Usually die within 2 years
  • GD type 3
    • Chronic neuronopathic disease with 3 of its own subtypes
    • Clinical manifestations include hepatosplenomegaly, poor growth, delayed puberty, ocular (especially saccadic movement) and cerebral involvement. May also affect other organs such as the heart

GD was the first lysosomal disease treated by enzyme replacement therapy (ERT) used mainly for Type 1. It’s availability came not long after the patient encounter above. ERT uses a mannose receptor which then allows delivery of the enzyme to the lysosomes. Unfortunately enzymes are large molecules and are not capable of crossing the blood-brain barrier and therefore are not effective against neurological manifestations of GD. Response to ERT is measured by changes in spleen and liver sizes which are sensitive indicators. Gene therapy is being tried for Type II as well.

Questions for Further Discussion
1. What is in the differential diagnosis of splenomegaly? A review can be found here
2. What is in the differential diagnosis of hepatomegaly? A review can be found here
3. What is in the differential diagnosis of anemia? A review can be found here
4. What is in the differential diagnosis of thrombocytopenia? A review can be found here
5. What is in the differential diagnosis of lymphopenia? 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: Gaucher Disease and Lipid Metabolism 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.

Di Rocco M, Andria G, Deodato F, Giona F, Micalizzi C, Pession A. Early diagnosis of Gaucher disease in pediatric patients: proposal for a diagnostic algorithm. Pediatr Blood Cancer. 2014;61(11):1905-1909. doi:10.1002/pbc.25165

Gupta P, Pastores G. Pharmacological treatment of pediatric Gaucher disease. Expert Rev Clin Pharmacol. 2018;11(12):1183-1194. doi:10.1080/17512433.2018.1549486

Grabowski GA. Gaucher disease and other storage disorders. Hematol Am Soc Hematol Educ Program. 2012;2012:13-18. doi:10.1182/asheducation-2012.1.13

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

What Causes Respiratory Failure?

Patient Presentation
A 4-year-old male came to the emergency room by ambulance with a history of increasing respiratory distress that was worsening over the past 6 hours. He had started having a runny nose in the morning and was having tachypnea by the afternoon. His mother had given him his inhaler but had not started steroid medication. He continued to worsen so she called the ambulance. He was well known to the emergency room and pulmonary staff because he had uncontrolled asthma. He had been hospitalized 3 previous times in the past year for asthma exacerbations for at least 2 days each time but had not been admitted to the intensive care unit. He was supposed to be taking a daily inhaled steroid and montelukast but his mother said she ran out of medication about 3 weeks ago.

The family and social histories revealed asthma and eczema in multiple family members, an older sibling who had been admitted to the intensive care unit for asthma and a difficult social situation. There was smoking in the household.

The pertinent physical exam showed a thin male in moderate respiratory distress on 6 liters of oxygen by facemask. His oxygen saturation was 93% but would quickly drop into the mid-85% if the mask was taken off. His heart rate was 136, respiratory rate of 48, and normal blood pressure and temperature. His weight was at the 5th percentile. HEENT revealed copious clear rhinorrhea, tympanic membranes that were dull and a slightly erythematous posterior pharynx. His respiratory examination had wheezing throughout his lung field with prolonged expiration but no obvious rales. He had tracheal tugging, intercostal retractions, nasal flaring and abdominal breathing. His skin had xerosis throughout with areas of licenification, and bright red erythema in his anticubital and popliteal fossas and adjacent areas. His overall hygiene was poor.

The diagnosis of an acute asthma exacerbation was made. The patient’s clinical course revealed he was started on continuous albuterol and given steroids in the emergency room. An initial venous blood gas showed a pH = 7.31, pCO2 = 53, pO2 = 28, and bicarbonate = 30. The radiologic evaluation of a chest radiograph showed non-specific diffuse pulmonary markings with airway trapping but no focal findings consistent with a viral process. His lung examination sounded slightly better with increased aeration after 30 minutes of continuous nebulization, but he was more sleepy and continued to have tachypnea and tachycardia and increased work of breathing. He was transferred to the intensive care unit for increased monitoring and respiratory support. He needed high flow oxygen for 36 hours and then was slowly weaned. He left the hospital 6 days after admission with the cause being respiratory syncytial virus. Additional social supports including home nursing were put into place to try to assist the family.

Discussion
The respiratory system is a complex system. The upper airways must remain patient. The lower airways must interface with the vascular system. The musculoskeletal system must provide mechanical function and the central nervous system must provide overall control. Respiratory failure occurs when the overall system cannot support the body’s necessarily ventilation, oxygenation or both. Children are at higher risk of respiratory failure. They have few intrinsic lung parenchyma problems, but have very small airways that increase the airflow resistance by themselves but then have to contend with problems such as airway edema, secretions, or bronchoconstriction which dramatically increase resistance. Remember that airflow resistance is inversely proportional to the size of the airway to the 4th power. Therefore small changes in airway size create large resistance forces. The chest wall is also more compliant which makes exerting necessary pressures for ventilation more difficult. The diaphragm also has fewer muscle fibers to exert the necessary pressure when contracting and the central nervous system is also more immature resulting in more bradypnea or apnea.

The signs and symptoms of respiratory failure include tachypnea, retractions, head bobbing, grunting, nasal flaring, tracheal tugging, belly breathing, and altered mental status (agitation is common for hypoxic patients, and somnolence with hypercarbia but either can occur). Other physical examination signs include stridor (e.g. upper airway obstruction), wheezing (e.g. lower airway disease), rales (e.g. pulmonary edema), and absent breath sounds (e.g. pulmonary consolidation, pneumothorax, pleural effusion). Laboratory testing including pulse oximetry can show hypoxia, while a blood gas testing assesses oxygen, carbon dioxide and pH values. Chest radiograph can often identify the underlying cause. Respiratory secretions are important to obtain if an infectious cause is suspected but can be helpful in other disease processes as well.

Normal ventilation provides a negative pressure gradient which causes net movement of air into the lungs. With mechanical ventilation the opposite is true as a positive gradient pushes the air into the lung. Treatment is respiratory support while the underlying cause is determined, managed or necessitates waiting until it resolves by itself. This includes potentially noninvasive methods such as continuous positive airway pressure (CPAP), bi-level positive airway pressure (BiPAP), or high flow nasal cannula oxygen (HFNCO<sub<2). Endotracheal intubation is indicated for patients who have failure of ventiliation or oxygenation despite non-invasive support methods, inability to protect their airway or a cause that necessitates endotrachael intubation (e.g. pulmonary toilet). Inhaled nitric oxide is also a treatment used for pulmonary hypertension as it selectively dilates pulmonary arterioles. Extracorporeal membrane oxygenation is used for patients who still cannot be appropriately ventilated or oxygenated with mechanical ventilation.

Learning Point
Causes of respiratory failure include:

  • Airway disorders
    • Croup
    • Congenital anomalies
    • Foreign body
    • Malacia of the airway
    • Subglottic stenosis
    • Vascular ring
    • Pulmonary edema
    • Enlarging mass
  • Lung parenchyma
    • Acute respiratory distress syndrome
    • Asthma
    • Aspiration
    • Bronchiolitis
    • Pneumonia
    • Pulmonary edema
    • Pulmonary fibrosis
    • Vascular abnormalities, e.g. pulmonary embolism
  • Neuromuscular dysfunction
    • Central nervous system disorders
    • Diaphragmatic paralysis
    • Myopathy
    • Neuropathy
    • Neuromuscular junction disorders
  • Other
    • Trauma

    Questions for Further Discussion
    1. What are some of the risks of endotracheal intubation?
    2. What are initial steps for diagnosis and management of suspected respiratory failure in your practice location?
    3. What is the definition of acute respiratory distress syndrome?
    4. What are the differences between arterial and venous blood gas measurements

    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: Respiratory Failure and Asthma.

    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.

    Smith KA, Flori HR. Critical Care in the Pediatric Emergency Department. Pediatr Clin North Am. 2018;65(6):1119-1134. doi:10.1016/j.pcl.2018.07.004

    Friedman ML, Nitu ME. Acute Respiratory Failure in Children. Pediatr Ann. 2018;47(7):e268-e273. doi:10.3928/19382359-20180625-01

    Viscusi CD, Pacheco GS. Pediatric Emergency Noninvasive Ventilation. Emerg Med Clin North Am. 2018;36(2):387-400. doi:10.1016/j.emc.2017.12.007

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

  • How Is Hidradenitis Suppurativa Treated?

    Patient Presentation
    A 15-year-old female came to clinic because of a recurrent “boil” in her right axilla. She had been seen 3 weeks previously and was diagnosed with hidradenitis suppurativa as this had occurred about 3 months before in the same axilla but a different location. She had spontaneous drainage at that time and was prescribed antibiotics and a topical disinfectant. Because of problems with insurance she had not picked up the medications. She also had been referred to a dermatologist, but did not know if she had an appointment. It had gotten better but was not resolved when 1 day ago, the area became very red, swollen and painful in the same location plus an additional location close to the first. There was no drainage. She had not used any compresses but did use some antipyretic medication which did not help. She had problems sleeping because of the pain but denied any fevers or chills. She also denied any new soaps, lotions, detergents, insect bites or trauma. She had last shaved her axilla 5 days ago. The past medical history was positive for atopic dermatitis, and mild comedomal acne. She also had had some ingrown hairs in her axilla and groin in the past that she treated herself by removing the entrapped hair.

    The pertinent physical exam showed a healthy female in some distress with movement of her right arm. Her vital signs were normal and her growth parameters showed her body mass index at 115% of normal for age. Her right axilla had two areas that were warm, swollen and reddened with a lead point on the swelling. The recurrent one was about 3 cm in size and the other was about 1.5 cm. The area around the larger one looked like it had some mild scarring. She some general xerosis and mild comedomal acne along her hair line. The rest of her examination was normal.

    The diagnosis of hidradenitis suppurativa and obesity was made. The patient’s clinical course showed the pediatrician lancing the abscesses, starting her on antibiotics and appropriate wound management. The pediatrician worked with her pharmacy to ensure that she could get her medications, and she already had a dermatology appointment in 10 days. The laboratory evaluation of a wound culture eventually grew Staphlococcus aureus that was susceptible to all antibiotics. At her dermatology appointment they confirmed the diagnosis and began tetracycline for an initial 3-month course.

    Discussion
    Hidradenitis suppurativa (HS) is a recurrent, chronic inflammatory disease of the hair follicles particularly in the apocrine gland-bearing areas of the axilla, inguinal, perianal, mammary and inframammary areas. Onset is usually after puberty, in the early 20s. It is more common in females than males. Prevalence is estimated to be 0.05- 4.1%. It can be associated with premature adrenarche, metabolic syndrome and obesity.

    The lesions are often pruritic, painful, and with malodorous purulent drainage. It often begins with comedomes and tender nodules, and can easily progress to painful abscesses with purulent fluid. HS can also lead to sinus tracts, hypertropic scarring and potentially contractures.

    Complications include infection, scarring/contractures, lymphedema, and fistula to adjacent structures such as the rectum, bladder or other genitourinary structures. The pain can limit school, work, or activities of daily living including exercise which can also contribute to obesity. HS in the genital area can also cause hygiene and sexual health problems. The differential diagnosis includes follicular pyoderma/furuncles/carbuncles, acne, pilonidal cyst in gluteal area, cat scratch disease, cutaneous tuberculosis, metastasis, and cutaneous Crohn’s disease.

    Learning Point
    There is no cure for HS but treatment is guided by the extent of the problem. Consultation with a dermatologist is usually needed as this is a life-long problem. Primary care physicians can assist patients with their care through counseling about the disorder, recommending wearing loose clothing to prevent friction, good skin hygiene, weight loss and exercise, and providing psychological support.

    Patients with mild disease (nonscarring inflammatory lesions) are often treated with topical antibiotics (e.g. clindamycin or resorcinol) and topical disinfectants. Patients with more extensive disease (having multiple, recurrent lesions with sinus tracts and/or scarring) or failing mild disease treatment may have oral antibiotics (e.g. tetracycline, doxycycline, minocycline, clindamycin and rifampin in various regimens or combinations) prescribed but also have immunomodulators and or steroids added. Patients may also need local surgical treatment for abscesses and sinus tracts. With extensive disease (tunnel formation, extensive scarring, contractures etc.) patients have similar treatment options but may require more extensive surgery or need short course systemic immunosuppression.

    Questions for Further Discussion
    1. What is the difference between a furuncle, carbuncle and abscess?
    2. What are indications for referral to a dermatologist?
    3. How are acne and HS similar and different?

    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: Hidradenitis Suppurativa

    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.

    Liy-Wong C, Pope E, Lara-Corrales I. Hidradenitis suppurativa in the pediatric population. J Am Acad Dermatol. 2015;73(5 Suppl 1):S36-41. doi:10.1016/j.jaad.2015.07.051

    Saunte DML, Jemec GBE. Hidradenitis Suppurativa: Advances in Diagnosis and Treatment. JAMA. 2017;318(20):2019-2032. doi:10.1001/jama.2017.16691

    Pink A, Anzengruber F, Navarini AA. Acne and hidradenitis suppurativa. Br J Dermatol. 2018;178(3):619-631. doi:10.1111/bjd.16231

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