Journal of Blood & Lymph

An Audit on Management of G6PD Deficiency Acute Hemolytic Crisis

Abstract

Alaa Mohammed Abd El-Aty, Safiea Abd El-Fattah El-Deeb and Mostafa Mohamed Embaby

Introduction: Hemolytic anemia is a common cause of anemia in our country. It may results from a cellular defect that changes the shape of RBCs from biconcave to spherical as in spherocytosis or elliptical as in elliptocytosis. It may results from RBCs enzyme deficiency as in cases with pyruvate kinase deficiency or glucose-6-phosphate dehydrogenase enzyme deficiency (G6PD deficiency). Other causes of hemolytic anemia include hemoglobinopathy‚ autoimmune antibodies against RBCs‚ hypersplenism and others.
G6PD deficiency is the most important disease of the hexose monophosphate pathway and is responsible for two clinical syndromes‚ an episodic hemolytic anemia induced by infections‚ certain drugs or fava beans and a spontaneous chronic non spherocytic hemolytic anemia.
G6PD deficiency is an inherited disorder caused by a genetic defect in the RBCs enzyme G6PD‚which generates NADPH and protects RBCs from oxidative injury. G6PD deficiency is the most common enzymatic disorder of RBCs. Although G6PD is a critical enzyme in the redox metabolism of all aerobic cells‚ yet its role in the RBCs is more critical because it is the only source of NADPH which directly and via GSH defends these cells against oxidative stress. G6PD deficiency is an example of hemolytic anemia due to interaction between an intra-corpuscular cause and an extra corpuscular cause‚ because in the majority of cases hemolysis is triggered by an exogenous agent. The severity of hemolytic anemia varies among individuals with G6PD deficiency. Education of patients and their parents regarding safe and unsafe medications and foods is crucial to prevent future episodes of hemolysis. In many cases all members of the patient’s family should avoid such precipitating foods. G6PD deficiency is a sex-linked disorder. As result males who inherit a G6PD mutation are hemizygous for the defect all their RBCs are affected. Females who inherit a heterozygous G6PD mutation usually do not have severe hemolytic anemia‚ since half of their RBCs express the abnormal allele. The majority of females who inherit an abnormality in G6PD are unaffected carriers. However, the cells that express the abnormal allele are vulnerable to hemolysis as the enzyme deficient RBCs in males. The presence of anemia will vary depending on the severity of the deficiency in the affected cells and whether there is skewed x-inactivation (lyonization) that results in a greater expression in a large percentage of RBCs. G6PD deficiency is a common genetic disorder‚ affecting nearly 400 million individuals worldwide. Whilst it is known that a number of drugs‚ foods and chemicals can trigger hemolysis in G6PD deficient individuals‚ the association between herbal and dietary supplements and hemolysis is less clear. Amongest nutrients blamed as triggers for hemolysis in G6PD deficient individuals are fava beans and related ligaments. Oxidant drugs and infections also predispose to hemolytic attacks. Provided that the blood of a G6P deficient person is normal‚ acute hemolysis results from the action of an exogenous factor on the RBCs deficient in glucose-6-phosphate dedydrogenase (G6PD). The function of G6PD in RBCs is to provide the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) necessary for the conversion of oxidized glutathione to the reduced state (GSH) as protection against the oxidation of RBCs. So that reduced glutathione (GSH) acts as an anti-oxidant that inactivates oxidant compounds such as hydrogen peroxide‚ that are normally generated within the RBCs. If GSH or any enzyme needed for maintaining glutathione in the reduced form (GSH) is deficient‚ the SH group in the RBCs membrane is oxidized and the hemoglobin of the RBCs is denatured and may precipitate in the RBC inclusions called Heinz bodies. An acute hemolytic process (crisis) results from damage to the RBC membrane by precipitated hemoglobin induced by the exogenous oxidant agent. The damaged RBCs are rapidly removed from the circulation causing acute drop in Hb level and the acute hemolytic crisis. This episodic acute hemolytic anemia may be induced by infections‚ certain drugs and fava beans. Glucose-6-phosphate dedydrogenase (G6PD) deficiency is inherited in an x-linked manner‚ so that the synthesis of RBCs G6PD is determined by a gene on x-chromosome. Thus most females do not usually have evident clinical hemolysis after exposure to oxidant agents‚ unless new gene mutation has occurred. In Egypt ingestion of fava beans produces an acute severe hemolytic crisis known as favism. Fava beans contain divicine‚ isouramil and convicine which ultimately lead to production of hydrogen peroxide and other reactive oxygen species production. Therefore, seasonal increased prevalence of G6PD deficiency crisis occurs in the green beans growth season. This is usually manifested by drop in Hb‚ hemoglobinuria‚ hyperbilirubinemia and reticulocytosis. These patients usually have to be rescued by packed RBCs transfusion. The list of drugs to be avoided in G6PD deficient individuals (whether causing predictable or possible hemolysis) must be given to all cases that present in crisis.
The aim of the study: To find out how much the staff in the Emergency unit are sticking to the agreed upon unit’s protocol as well as to compare the unit’s protocol with European Guidelines.
Subjects: Children from 1 day to 18 years of age with G6PD acute hemolytic crisis attending Assiut University Children Hospital over one year 2015-2016.
Inclusion criteria: All cases of G6PD deficiency acute hemolytic crisis.
Tools of study: The investigations stated in the unit’s protocol included CBCs‚ urine dipsticks‚ blood urea and creatinine‚ serum bilirubin (direct and indirect) as well as blood grouping and cross matching. After treatment of the crisis (as stated in the unit’s protocol) a list of drugs and agents to be avoided was given to the patients. The patients were advised to return to follow up after four weeks for the measurement of G6PD enzyme level in the outpatient department in Assiut university children Hospital.
Patients and methods: This study was performed in the Emergency Unit in Assiut University Children Hospital for one year 2015-2016 (Nov‚ 2015 to Nov‚ 2016). The study included fifty cases of acute G6PD hemolytic crisis admitted to the emergency unit: they were aged nine months to four years. They were 45 males and 5 females. The investigations stated in the unit’s protocol included CBCs‚ urine dipsticks‚ blood urea and creatinine‚ serum bilirubin (direct and indirect) as well as blood grouping and cross matching. After treatment of the crisis (as stated in the unit’s protocol) a list of drugs and agents to be avoided was given to the patients. The patients were advised to return to follow up after four weeks for the measurement of G6PD enzyme level in the outpatient department in Assiut university children Hospital.
Results: The study included fifty cases of acute G6PD hemolytic crisis admitted to the emergency unit: they were aged nine months to four years. They were 45 males and 5 females.