Acute Abdomen in a Non-Splenectomised Patient with Hereditary Spherocytosis - Case Study Example

Name Institutional Affiliation Course Tutor Date А case of acute abdomen in a non-splenectomised patient with hereditary spherocytosis Abstract Twenty five old Caucasian male presented with jaundice, pallor, fatigue, and abdominal pain. Haematological investigations revealed low haemoglobin, elevated reticulocyte count, and poikilocytosis with several spherocytes. Biochemistry results showed increased erythrocyte osmotic fragility, spectrin, ankyrin-1 and band-3 deficiencies, hyperbilirubinaemia and elevated plasma lipase. Ultrasonography of the abdomen revealed splenogemaly and bilirubinate gallstones. Family history and the medical tests were positive for the diagnosis of hereditary spherocytosis. Splenectomy was performed as an active part of managing the condition. The pathogenesis of hereditary spherocytosis is discussed and recommendation given on how to minimise the risk of critical HS condition. Clinical presentation A 25 year old Caucasian male presented with abdominal pain. The abdominal pain was recurrent in the upper right quadrant. Yellow discoloration of eyes and skin was noted. The patient also had nausea and vomiting, fever, dizziness and appeared fatigued. He reported urine hyperpigmented and diarrhoea stool that had lasted 24 hours. The patient was not on any drugs. He had repeated manifestations of jaundice, pallor and fatigue for the past six months. His two other family members –father and elder sister –had similar symptoms. The father receives regular blood transfusions while the sister has received two blood transfusions. They are splenectomised unlike the patient. The patient has a history of neonatal jaundice but was untreated. Laboratory investigation: An abdominal ultrasonagraphy revealed splenomegaly and hepatomegaly. The spleen and liver was enlarged, palpable, soft tender mass along the coastal margin. Gallstones were present in the gall bladder. Haematology results revealed normal morphology and differential count of white blood cells and platelets. The reticulocyte count was 12%. Normal range is 120-180g/L. (Bianchi et al. 2012). Mean corpuscular haemoglobin concentration (MCHC) was 38.1 g/dL. Normal range is 32-36 g/dL (Sharma et al. 2010). The peripheral blood smear showed polychromasia, anisocytosis and poikilocytosis with several spherocytes present. The biochemistry results showed negative direct antiglobulin test. Liver function test revealed a pronounced bilirubinaemia at 50.3µmol/L. The SDS-PAGE (Sodium dodecyl sulphate polyacryalamide gel electrophoresis) of the red blood cell membrane revealed a deficiency of spectrin 20%, ankyrin-1, 55% and band-3, 25%. Osmotic fragility tests of erythrocytes in hypotonic solutions showed it was increased. Lipase test was ordered because of the abdominal pain and the results showed a markedly elevated plasma lipase level. Based on the presenting patient symptoms, past medical history and current results from laboratory investigations, the diagnosis of severe hereditary spherocytosis (HS) was confirmed. Gallstones in the gall bladder are a common complication in non-splenectomised HS (Weinreb & Rosenbloom 2013). Gallstones caused obstruction of the biliary ducts leading to pancreatitis and the reason for the elevated lipase along with the upper abdomen pain, nausea and vomiting symptoms (Tonsi et al. 2009). Appropriate treatment was started after the patient was counselled. Treatment and disease progression and clinical outcome Survival of erythrocytes in patients with HS is mainly determined by splenic sequestration (Kanellopoulou et al. 2011). Therefore, splenectomy was decided as the most appropriate treatment for the patient. The patient was first immunized against Streptococcus pneumonia, Haemophilia influenza type B, and Neisseria meningitides to guard against sepsis. The patient was also put on 1mg folic acid per day, a treatment for anaemia and preventative to haemolysis because folic acid aids in the production of mature red blood cells (Bolton-Maggs et al. 2012). Four weeks later, the splenectomy was performed concurrently with cholecystectomy. Deformed erythrocytes and spherocytes are excessively produced in severe HS but destroyed in the spleen resulting in haemolytic anaemia, hyperbilirubinaemia and splenomegaly; conditions which are well alleviated by splenectomy (Huq et al. 2010). Reticulocyte count which is elevated during haemolysis is lowered after splenectomy (Bolton-Maggs et al. 2012). Cholecystectomy which entails removal of the gall bladder removed the biliary duct obstruction hence treating the acute pancreatitis and returning the plasma lipase to normal while eliminating abdominal pain (Tonsi, et al. 2009). The patient was put on life-long prophylaxis with oral penicillin to reduce sepsis post-splenectomy (Kanellopoulou et al. 2011). The patient will also be receiving blood transfusions in the course of his life depending on his haemoglobin levels. The goal is to keep the haemoglobin above 60g/l (Hassan et al. 2009). Discussion Hereditary spherocytosis is a familial haemolytic anaemia disorder due to red cell membrane defect (Yaish et al. 2013). It is the most common cause of inherited chronic haemolysis in North America, Europe and Japan where the prevalence is high (Bolton-Maggs et al. 2012). HS has a wide spectrum of severity ranging from asymptomatic HS without anaemia, mild to moderate disease with minimal haemolysis, to severe haemolytic anaemia requiring splenectomy and frequent blood transfusions to sustain life (Hassan et al. 2009). HS is usually transmitted as autosomal dominant trait rather than autosomal recessive trait (Dehdashtian et al. 2013). This means that the chances of a person with HS having members of the family with similar condition are higher than those without family history. As seen in the case, the patient’s father and sibling had HS. The most common molecular defects of HS come from spectrin and ankyrin which are major components of the cytoskeleton of the red blood cell shape (Han et al. 2015). In HS, there are two factors that are mainly implicated in the pathophysiology: an intrinsic red blood cell membrane defect and an intact spleen that selectively retains destructs and eliminates the defective erythrocytes (Huq et al. 2010). The pathways that lead to reduced membrane surface area are protein, spectrin, and ankyrin defects which reduce the density of the membrane skeleton, destabilize the overlying lipid layer, releasing microvesicles containing band 3 (Han et al. 2015). The second pathway involves defects of band 3 which lead to deficiency and loss of the lipid-stabilizing effect and loss of the band 3 free microvesicles from the membrane (Huq et al. 2010). Both pathways lead to reduced membrane surface area of the erythrocyte to volume ratio, and the formation of spherocytes (Huq et al. 2010). The patient in this case is classified as severe HS because of high deficiency in these major RBC proteins- spectrin, ankyrin and band-3, which are not symptomatic in mild disease. The spherical shape of the erythrocytes in HS impairs their smooth passage in the spleen; hence, the deformed erythrocytes are selectively retained and damaged in the spleen (Sharma et al. 2010). In mild disease, the spherocytes are barely present in the peripheral smear. Some spherocytes are present in moderate disease and are several in severe diseases as in this case (Sharma et al. 2010). Splenic destruction of abnormal erythrocytes or spherocytes results is the main reason for haemolysis in patients with HS because of the genetic determination that causes production of the deformed, immature erythrocytes which triggers their splenic destruction Yoshida et al. 2009). Chronic haemolysis which is the continuous destruction of the abnormal erythrocytes by the spleen results in severe anaemia (Yoshida et al. 2009). In this case, the anaemia is evidenced by the polychromasia and low haemoglobin concentration. Haemoglobin concentration is normal in mild disease because the number of spherocytes is almost negligible (Kanellopoulou et al. 2011). Haemoglobin concentration gets lower in moderate and lowest in severe disease because of the increasing number of spherocytes being destructed. The jaundice in this clinical presentation is also because of the increased haemolysis in severe HS (Hassan et al. 2009). The reticulocyte count is elevated in severe disease because of the increased number of immature, deformed RBCs in the circulation. The increased spleen activity in destroying the deformed spherocytes results in enlargement of the spleen (Weinreb & Rosenbloom 2013). Hyperpigmentation of urine presented in this case is because of the high amount of bilirubin excreted following the chronic haemolysis where haemoglobin is broken down to heme and globin (Nigwekar et al. 2010). Heme is converted to biliverdin and then to bilirubin which is taken up by hepatocytes and secreted in bile (Nigwekar et al. 2010). Bile salts usually activate lipase to aid in digestion of lipids. Since the secretion of bile was too high and uncontrolled in this HS case, it led to the markedly elevated plasma lipase levels (Tonsi et al. 2009). Excessive secretion of bilirubin results in hyperbilirubinimia, in which the bilirubin is unconjugated (Dehdashtian et al. 2013). Hyperbilirubinimia leads to formation of gall stones which is a common occurrence in non-splenectomised HS patients (Nigwekar et al. 2010), as the one in this case. The abdominal pain experienced by the patient was due to the haemolytic crisis, a complication in severe HS also associated with other complications including gallbladder, tender splenomegaly, jaundice, anaemia and lethargy (Hassan et al. 2009). Conclusion and recommendations The patient presented with acute abdominal pain, jaundice, pallor, fatigue and hyper-pigmented urine. An ultrasonography revealed splenomegaly and presence of gallstones in the bile duct. The family history revealed two members of his family have had similar symptoms. Haematological and biochemistry investigations revealed, low haemoglobin content, elevated, MCHV, poikilocytosis with several spherocytes in peripheral smear, spectrin, ankyrin and band-3 deficiencies in RBC membrane, increased osmotic fragility, hyperbilirubinaemia, and elevated plasma lipase. HS was confirmed as the diagnosis. It is at its severe stage with complications of haemolytic crisis and gallbladder obstruction, leading to the acute abdominal pain and the other symptoms of haemolysis. Splenectomy was decided as the most appropriate treatment option with possible blood transfusions in the future depending on the patient’s haemoglobin levels. It is recommended that all family members undertake common HS screening tests such as the Eosin-5-malemide (EMA) binding test and Osmotic fragility test when a family member is diagnosed with, or has the symptoms of HS. HS is an autosomal dominant condition and the likelihood of one or more family members inheriting the mutated gene is high. This will minimise the risk of developing the severe form of the condition. Management of HS with folate therapy, frequent blood tests, and observing for infections and their treatment can help prevent severe consequences of HS. References Bianchi, P, Fermo, E, Vercellati, C, Marcello, A, Porretti, A,…2012, ‘Diagnostic power of laboratory tests for hereditary spherocytosis: a comparison study in 150 patients grouped according to molecular and clinical characteristics’, Haematologica, vol. 97, no. 4, pp. 516-523. Bolton-Maggs, P, Langer, J, Lolascon, A, Tittensor, P, & King, M 2012, ‘Guidelines for the diagnosis and management of hereditary spherocytosis’, British Journal of Haematology, vol. 156, no. 1, pp. 37-49. 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