Diagnosis, Management and Prevention of Acute Hemolytic Anemia in Infants, Children and Adolescents

Anemia, defined as decreased red blood cell (RBC) mass and or decrease in hemoglobin

level, is a common disease that affects nearly one quarter of the population worldwide. [7,

8] Overall, anemia can be categorized as acute or chronic. [9, 10] The most pressing concerns for the emergency physician are the acute anemias that can cause immediate, life-threatening complications. [10].

        The most common causes of acute hemolytic anemia where early interventional treatment can reduce the risk or extent of end-organ failure are Glucose-6-phosphate-dehydrogenase (G6PD) deficiency, autoimmune hemolytic anemia and hemolytic uremic syndrome. [11, 12, 13, 14]

       Glucose-6-phosphate-dehydrogenase (G6PD) deficiency; the most common red cell

enzyme deficiency in the world, with over 400 million affected. African, Asian,

Mediterranean, and Middle- Eastern descents are most commonly affected by this disorder.

The prevalence of G6PD deficiency among Egyptian neonates is 8.9%. The deficiency is

caused by mutations in G6PD gene, located on the long arm of the X chromosome. A

deficiency of the enzyme causes reduced glutathione, which makes RBCs more

susceptible to oxidant stress and can result in episodic hemolytic anemia. [15,16]

       Autoimmune hemolytic anemia; the clinical condition where autoantibodies are

produced and directed against self RBCs. [16, 17] where IgG or IgM antibodies bind to

antigens on the surface of the RBC, leading to decreased survival of the RBC. [17, 18, 19]

Autoimmune hemolytic anemia (AIHA) can be primary (idiopathic) or secondary to a

systemic disease or drugs. A large range of medications can induce AIHA, including methyldopa, penicillin, cephalosporin’s, several nonsteroidal anti-inflammatory

medications, quinidine, and isoniazid [18]. Furthermore, depending on the type and the

thermal sensitivity of the antibody, AIHA can be the warm antibody type, cold antibody

type, or mixed type. [17, 18]. Warm antibody AIHA is caused by IgG antibodies, which bind strongly at room temperature. These antibodies are pan agglutinins – that is, they react with all the red cell antigens. Patients with warm AIHAs can present with severe, life threatening symptoms [17, 18, 20].

The initial treatment of AIHA depends on the severity of hemolysis [12]. As with any

unstable patient, abnormal vital signs should be first addressed. RBC transfusion should be

limited to cases of life-threatening anemia [14, 15, 18]. This is because transfusions can

induce further autoantibody production, and it might be difficult to find an accurate

crosshatch [18]. Corticosteroids slow the rate of hemolysis and considered as a first-line

therapy that should be started as soon as possible [17, 18, 21].

         Hemolytic Uremic Syndrome (HUS); a clinical syndrome characterized by progressive

renal failure that is associated with microangiopathic (nonimmune, Coombs-negative)

hemolytic anemia and thrombocytopenia. It is one of the common causes of acute kidney

injury in children and is increasingly recognized in adults. [22]

Typical HUS should be suspected in any child who presents with a history of bloody

diarrhea and new-onset anemia, thrombocytopenia, and acute renal injury. Atypical HUS

should be suspected in patients with similar symptoms but no history of acute diarrheal

illness. [23] The treatment of typical HUS is supportive as well as possible dialysis. [24]

         To aid the clinician in AHA management, we present these guidelines that represent and highlight distinct clinical presentations with separate diagnostic and therapeutic pathways

that can be used in clinical practice setting. We also review the parameters present in

diagnostic testing that allow for prognostic insight and present algorithms for both

diagnosis and treatment of the AIHA patient in diverse situations. This is done in the hope

that this work may offer guidance regarding personalized therapy recommendations.

➡️Purpose and Scope

These guidelines have been developed to standardize the delivery of services and to implement the guidance on the prevention, diagnosis and management of acute hemolytic anemia.

It provides guidance to primary health care providers, pediatricians and specially trained nurses.

The guidelines aimed to s to assist health care practitioners to apply the best available evidence to clinical decisions about the diagnosis, management, and prevention of acute hemolytic anemia with the following objective in mind: putting a differential diagnosis and approach to the diagnosis and proper management of acute hemolytic anemia in infants, children, and adolescents; identification of infants, children, and adolescents at high risk of developing acute hemolysis; prevention of recurrence of hemolysis in the targeted

population.

This version of the guideline includes recommendations and good practice statements for diagnosis, management, and prevention of Glucose-6-phosphate-dehydrogenase (G6PD) deficiency, autoimmune hemolytic anemia and hemolytic uremic syndrome.