Basics
Description
- Pallor is defined as paleness of the skin and may be a reflection of anemia or poor peripheral perfusion.
- The normal range for hemoglobin is age dependent.
- Anemia can be defined functionally as the inability of hemoglobin to meet cellular oxygen demand.
- Parents often fail to notice pallor of gradual onset.
- Grandparents or others who see the child less often may be the first to suspect pallor.
Risk Factors
- Ages between 6 months and 3 years or adolescent females
- Peak age ranges for iron deficiency
- Gender
- Some red cell " enzyme X-linked defects such as glucose-6-phosphate dehydrogenase (G6PD) and phosphoglycerate kinase deficiencies are sex linked.
- Race
- African: hemoglobins S and C,α- and ²-thalassemia trait, G6PD deficiency
- Southeast Asian: hemoglobin E andα-thalassemia
- Mediterranean descent: ²-thalassemia and G6PD deficiency
Genetics
Familial history: Some of the congenital hemolytic anemias are autosomal dominant.
Diagnosis
- Determine first that the child appears pale, not simply fair skinned. Second, decide if there is a medical emergency associated with circulatory failure. If not, the goal is to investigate the etiology and intervene appropriately.
- Phase 1: Assess for signs of shock.
- If present, initiate emergency procedures as required to stabilize the patient, such as airway, breathing, and circulation.
- Phase 2: If patient is stable, perform history, physical examination, and CBC with reticulocyte count to establish time of onset of pallor, associated symptoms, and level of anemia.
- Phase 3: Follow specific diagnostic workup based on findings in phase 2.
Signs and Symptoms
- Pallor
- Other signs and symptoms dependent on etiology
History
- Acute versus chronic onset
- Helps with differential diagnosis
- Associated symptoms: weight loss, fever, night sweats, cough, and/or bone pain
- Suggest an underlying systemic illness, such as leukemia, infection, or rheumatologic disorder
- Jaundice, scleral icterus, dark urine
- Age <6 months
- May represent a congenital anemia or isoimmunization
- Premature infant
- Increased risk of both iron and vitamin E deficiency
- Exaggerated hyperbilirubinemia can be the presenting symptom of isoimmune hemolytic or other congenital hemolytic anemia.
- Pica
- Often associated with plumbism and iron deficiency
- Medications
- Can cause bone marrow suppression and/or hemolysis
- Milk intake
- Introduction of cow 's milk at <12 months of age is associated with iron deficiency.
- Drinking a lot of cow 's milk (>24 oz/day) puts a toddler at risk for iron deficiency.
- Recent trauma and/or surgery
- Blood loss can result in iron deficiency.
- Recent infection
- Can be associated with hemolysis or bone marrow suppression
- Most common form of mild anemia in childhood
- Family history
- Familial history of splenectomy and/or early cholecystectomy can be a clue for a previously undiagnosed hemolytic anemia.
Physical Exam
- Rapid respiratory rate, decreased BP, weak pulses, slow capillary refill
- Indications of uncompensated anemia and/or shock
- Frontal bossing and prominence of the malar and maxillary bones
- Extramedullary erythropoiesis
- Enlarged spleen
- Hemolytic anemias, malignancy, infection
- Glossitis
- Vitamin B12 deficiency
- Iron deficiency
- Scleral icterus or jaundice
- Systolic flow murmur
- Bruits
- May indicate vascular malformations
- Petechiae and bruising
- May indicate an associated thrombocytopenia, coagulopathy, or vasculitis
- Dysmorphic features
- Diamond-Blackfan and Fanconi anemia are associated with other congenital defects, including thumb abnormalities, short stature, and congenital heart disease.
Diagnostic Tests & Interpretation
Lab
- CBC with red cell indices
- Establishes the diagnosis of anemia, distinguishes by size: normocytic, macrocytic, microcytic
- Reticulocyte count
- Distinguishes between decreased production and increased destruction of red cells
- Coombs test and antibody screen
- Identifies immune-mediated red cell destruction
- Can have false positives and negatives
- Peripheral blood smear
- Specific morphologic findings can be diagnostic.
- Iron studies: iron-binding capacity, serum iron, ferritin, transferrin
- Iron deficiency anemia or anemia of chronic disease
- Hemoglobin electrophoresis with quantification
- Lead studies: serum lead, free erythrocyte protoporphyrin
- Stool guaiac
- Osmotic fragility
- Red cell membrane defects (spherocytosis)
- Any spherocytic anemia may be positive.
- Quantitative red cell " enzyme assays
- Inherited RBC enzyme deficiencies
- Serum folate, RBC folate, and serum vitamin B12 levels
Diagnostic Procedures/Other
Bone marrow aspiration and biopsy: if malignancy or bone marrow failure syndrome suspected
Differential Diagnosis
- Congenital
- Hemoglobinopathies: sickle cell syndromes, thalassemia syndromes, other unstable hemoglobins
- Erythrocyte membrane defects: hereditary spherocytosis, elliptocytosis, stomatocytosis, pyropoikilocytosis, infantile pyknocytosis
- Erythrocyte enzyme defects: G6PD deficiency, pyruvate kinase deficiency
- Diamond-Blackfan anemia: congenital pure red cell aplasia (rare)
- Fanconi anemia: constellation of varied cytopenias, multiple congenital anomalies, abnormal bone marrow chromosomal fragility
- Infectious
- Septic shock
- Can get mild anemia after mild infections in childhood (anemia of inflammation)
- Infection-related bone marrow suppression: parvovirus B19 infection
- Infection-related hemolytic anemias: Epstein-Barr virus, influenza, coxsackievirus, varicella, cytomegalovirus, Escherichia coli, Pneumococcus species, Streptococcus species, Salmonella typhi, Mycoplasma species
- Nutritional/toxic/drugs
- Iron deficiency anemia: common cause of anemia in children, especially those <3 years of age and in female adolescents
- Plumbism: anemia usually due to coexisting iron deficiency; very high lead levels associated with altered heme synthesis
- Vitamin B12 and/or folate deficiency: results in a megaloblastic anemia
- Medication-induced bone marrow suppression: chemotherapy; antibiotics, especially trimethoprim-sulfamethoxazole
- Drug-related hemolytic anemia: antibiotics, antiepileptics, azathioprine, isoniazid, nonsteroidal anti-inflammatory drugs
- Trauma
- Tumor
- Leukemia with bone marrow infiltration
- Metastatic tumors with bone marrow infiltration
- Genetic/metabolic
- Metabolic derangements: severe electrolyte disturbance, pH disturbance, inborn errors
- Shwachman-Diamond syndrome: marrow hypoplasia with associated pancreatic insufficiency and associated failure to thrive
- Other:
- Transient erythroblastopenia of childhood: acquired pure RBC aplasia
- Aplastic anemia: bone marrow failure syndrome with at least 2 of the 3 blood cell lines eventually affected
- Systemic diseases: anemia of chronic disease, chronic renal disease, uremia
- Hypothyroidism
- Sideroblastic anemia: defective iron use within the developing erythrocytes
- Autoimmune and isoimmune hemolytic anemias
- Microangiopathic hemolytic anemias: thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), disseminated intravascular coagulation (DIC)
- Mechanical destruction: vascular malformation, abnormal or prosthetic cardiac valves
Treatment
Initial Stabilization
- Severe anemia of unclear etiology with hemodynamic instability
- Transfuse with packed RBCs cautiously.
- In an autoimmune hemolytic process, the child is at risk for a transfusion reaction, and there may be delay in obtaining cross-matched blood.
- Obtain blood for diagnostic studies before transfusion if possible.
- Circulatory failure without anemia
- Requires intensive monitoring and access to critical care in an emergency department or intensive care unit
- Fluid resuscitation and/or inotropic pressor support as needed
- Acute blood loss
- Treat circulatory failure as described.
- Transfuse with packed RBCs, platelets, and fresh frozen plasma as needed.
- Malignancies
- Emergency care should be directed toward treatment of circulatory failure and possible associated infection and then to rapid diagnosis and treatment of the malignancy.
- Consultation with an oncologist should be sought as soon as possible.
General Measures
- Treat underlying cause.
- Consider packed RBC transfusion if in extremis or severe anemia and low likelihood of recovery in near future.
- Consider emergent plasmapheresis if with microangiopathic hemolytic anemia.
- Consider immunosuppressive medications (corticosteroids, intravenous immunoglobulin (IVIG) if with autoimmune hemolytic anemia.
- Iron deficiency anemia
Medication
Elemental iron for patients with iron deficiency
- 4 " 6 mg/kg/24 h PO divided b.i.d. " t.i.d.
- Absorbed best with acidic drinks, including orange juice; dairy products decrease absorption.
- Reticulocyte should improve 72 hours after starting iron therapy; the hemoglobin may take a week to rise.
- Iron should be continued for at least 3 months to replenish iron stores.
Ongoing Care
Issues for Referral
- Severe or unexplained anemia
- Anemias other than dietary iron deficiency or thalassemia trait
- Recurrent iron deficiency
- May suggest ongoing bleeding or iron malabsorption
- All bone marrow failure or infiltrative processes
Additional Reading
- Baker RD, Greer FR, Committee on Nutrition, American Academy of Pediatrics. Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0-3 years of age). Pediatrics. 2010;126(5):1040 " 1050. [View Abstract]
- Glader BE. Hemolytic anemia in children. Clin Lab Med. 1999;19(1):87 " 111. [View Abstract]
- Graham EA. The changing face of anemia in infancy. Pediatr Rev. 1994;15(5):175 " 183. [View Abstract]
- Monzon CM, Beaver D, Dillon TD. Evaluation of erythrocyte disorders with mean corpuscular volume (MCV) and red cell distribution width (RDW). Clin Pediatr. 1987;26(12):632 " 638. [View Abstract]
- Segal G, Hirsh M, Feig S. Managing anemia in pediatric office practice: part 2. Pediatr Rev. 2002;23(4):111 " 122. [View Abstract]
- Sills RH. Indications for bone marrow examination. Pediatr Rev. 1995;16(6):226 " 228. [View Abstract]
Codes
ICD09
ICD10
SNOMED
- 162738007 On examination - color pale (finding)