Gallstones and Choledocolithiasis with Severe Cholestatic Jaundice in-Thalasemia Intermedia Patient

Geographically, -thalassemia can be found in many countries including in Indonesia. Thalassemia intermedia referred to patients as being too haematologically severe to be called minor, but too mild to be called major. Patients with thalassemia intermedia usually present themselves to medical attention in later childhood or even adulthood and are sustainable without the need for regular transfusion therapy. Three main factors are responsible for the clinical sequele of thalassemia intermedia: chronic anemia, ineffective erythropoiesis, and iron overload. There are many complications related to -thalassemia intermedia such as gastroentero-hepatology vascular, endocrine and bone diseases. About 55-63% thalassemia intermedia patients suffer from gallstone with 68–85% of these patients undergo cholecystectomy, and 67-90% patients undergo splenectomy. Therefore, ultrasound examination is required to be performed regularly during illness and before patient underwent surgery or splenectomy to detect the presence of gall stones. In this case report a patient with gallstones and choledocholithiasis was reported. Severe cholestatic jaundice in -thalassemia intermedia was diagnosed six months before hospitalization. The patient underwent open cholecystectomy and exploration common bile duct stones.


Kata kunci:
INTRODUCTION is affected by hemoglobin disorders, and between can be found in the Mediterranean, Middle East, Africa, India, Myanmar, South East Asia including Southern China, Malaysia and Indonesia.hemoglobinopathy in the world, is due to autosomal an absence or low-level synthesis of this protein in globin chain synthesis results in relative increase in the percentages of HbA 2 and HbF compared to HbA.In the presence chain, the excess chain is unstable and precipitates, leading to damage of red blood cell membranes.Thalassemic patients suffer from anemia resulting from shortened erythrocyte survival due to hemolysis, and erythroid precursors premature death in bone marrow. 4,5his case report described clinical performance, intermedia patient with complication of gallstones and choledocolithiasis.

CASE REPORT
chief complaint of yellow eyes and skin, nausea, itching, tea-colored urine, no pale stools and mild epigastric pain for about four days before she was hospitalized.She said that she did not suffer from dyspnea, fever or spontaneous bleeding.Before episode of her disease she did not consume drugs, herbal remedies or alcohol and she said that she was healthy with no past history of diabetes mellitus, chronic hepatitis, hypertension, and gallstone disease.Six months before hospitalization she was diagnosed red cells were transfused.On physical examination severe jaundice (yellow eyes and darken skin), liver and a palpable spleen (schuffner II).On the first day of admission, laboratory examination showed that mm , increased level transaminase such as aspartate aminotransferase albumin, activated partial thromboplastin time (APTT) and prothrombin time (PT), fasting blood sugar and electrolyte were within normal limits.Fasting blood sugar and electrolyte were still normal.
Blood films suggested anemia, which may be laboratory examination confirmed the diagnosis of HbA 2 Accompanied with normal total iron binding capacity (TIBC), ferum and iron binding capacity (IBC) with high level of ferritin.Viral hepatitis sero-markers were negative for anti HCV, HBsAg and Anti HAV.
According to those clinical data and ultrasonography (USG) results, the diagnosis of this patient was gallstones and suspected common bile duct (CBD) stones (Figure 1) with severe cholestatic jaundice in oral ursodeoxycholic acid (Urdafalk 1,500 mg once daily) methylprednisolone 16 mg three times daily.On day 14 th of hospitalization, after the challenge test with methylprednisolone, bilirubin level was decreased Because the lumen of distal common bile ducts was smaller, the surgeon conducted anastomosis of the th day of hospitalization patient went home in a good condition anemia), and iron overload.Clinical consequences of anemia are splenomegaly (resulting from entrapment of abnormal red cells in the spleen) and increased erythropoietin synthesis that stimulates erythroid marrow expansion.Bone marrow expansion also results in characteristic deformities of the skull and face, severe osteopenia, and increased iron absorption.There are several complications in thalassemia intermedia compared to major. 6Iron overload has important clinical consequences in patients with thalassemia intermedia.In thalassemia major iron overload is primarily caused by transfusions, but in thalassemia intermedia iron overload is caused by combination of ineffective erythropoietin and decrease serum levels of hepcidin, which control the concentration of ferroportin on the intestinal epithelium, so that it is increased intestinal iron absorpsion. 7ecause iron accumulation primarily occurs in and cirrhosis, and potentially, hepatocellular carcinoma. 7esides that, iron accumulation cause increased vascular diseases (leg ulcers, thromboembolism, pulmonary hypertension, cerebrovasculare and neural damage), endocrine diseases (diabetes mellitus, growth hormone hypogonagism) and bone diseases. 9,10epatocellular carcinoma (HCC) frequently complicates hepatic cirrhosis secondary to viral infection or iron overload.Twenty-two cases of HCC virus, whereas 19 of 22 patients were diagnosed after frequent with the aging population of the thalassemia patients. 11In this patient, clinically we found high level of ferritin, cholestatic jaundice, gallstones thalassemia intermedia.
Cholestasis is an impairment of bile formation and pruritus and, in its most overt form, jaundice.Besides support diagnostic of cholestatic are 1.5 times of the may be acute or chronic.It is considered chronic if it last more than 6 months.The cause of cholestasis may be intrahepatic or extrahepatic.intrahepatic and extra hepatic, because this tool is and inexpensive.

DISCUSSION
There are minor (asymptomatic or mild Greppi-Micheli, who referred to patients as being "too haematologically severe called to be minor, but too mild to be called major".This criteria differs thalassemia major from intermedia at presentation. 6atients with thalassemia intermedia usually present themselves to medical attention in later childhood or even adulthood.They show mild to moderate anemia dL, which are sustainable without the need for regular transfusion therapy. 7In this case, patient was diagnosed as thalassemia intermedia according to the clinical Hb level, transfusion need) and laboratory results (HbA 2 Three main factors are responsible for the clinical ineffective erythropoiesis (is the main cause of chronic from acute cholestasis because the symptoms appeared 4 days before hospitalization with extrahepatic cause (CBD dilated).Ursodeoxycholic acid (UDCA), time oral corticosteroid were given to reduce the was not only obstructive CBD stones, but might be Gallstones are more commonly found in thalassemia intermedia than in thalassemia major because of ineffective erythropoiesis and peripheral haemolysis. 6allstones typical of hemolitic anemia are so called black pigment stones.The colour of the stone is explained by its content of an insoluble black pigment that probably is a cross-linked network polymer bilirubinate.And 14 About gallstone.Gallstones were more frequently found less blood transfusion requirements.Eleven patients Eight patients received operations on an elective or semi-elective basis.Another patient had incidental cholecystectomy during splenectomy. 15In patients done to detect gallstones and especially before patient undergo splenectomy procedure. 7A cholecystectomy may necessarily be performed, particularly if the patient is experiencing symptomatic gallstones.This should be undertaken to prevent cholecystitis, which can have serious consequences in the splenectomised patients. 7,16hibit concomitant stones in the CBD.The source of common bile duct stone are either migrate from gallbladder (secondary stone) or form primary within the bile ducts, but CBD stones are predominantly secondary stones. 17There are several imaging modalities to detect stones in the common bile duct such as transabdominal USG, endoscopy ultrasonography (EUS), ERCP, intraoperative cholangiography, helical computed tomography cholangiography, magnetic resonance cholangio-pancreatography (MRCP).
Transabdominal USG is recommended as a preliminary and ERCP are generally considered to be the reference standard for diagnosis of CBD stone.However, EUS and MRCP are also recommended as being highly 19 During recent decades endoscopy or laparoscopy has gained wide acceptance as an effective and less invasive alternative.Endoscopic sphincterotomy followed by laparoscopic cholecystectomy is the first choice to manage combined cholecystocholedocholithiasis. 20re removed laparoscopically, laparoscopic CBD exploration is increasingly being performed.It is selected group of laparoscopic surgeons. 17lthough endoscopic and laparoscopic are the open cholecystectomy and exploration of CBD still become a choice for several reasons.First, when there were concomitant problems or past surgeries, making patients undergo an open exploration because of conversion of a laparoscopic procedure, for example, caused by CBD injury.Third, a relative indication for open exploration is large or multiple stones or the need to perfom a transduodenal sphincteroplasty.Finally, open exploration is still considered the gold standard if the surgical team does not have the experience or feels uncomfortable with the laparoscopic approach, 17 Morbidity and mortality of this procedure were low, with the during long term follow up, revisional surgery was patient underwent open exploration because there were combined surgical procedure (splenectomy) and there patients are poor growth and development, increased transfusion demand, hypersplenism and splenomegaly (when accompanied by symptoms such as severe left upper quadrant pain or possible splenic rupture). 21derwent splenectomy. 6Many patients who undergo splenectomy appear to restore hemoglobin levels in demonstrate a marked improvement in growth and development.However, clinical observations have suggested that splenectomy in thalassemia contribute to an increased susceptibility to thrombosis and sepsis. 22n this patient, splenectomy actually was not indicated because there was no severe splenomegaly or clinical symptoms.Splenectomy was conducted while patient underwent open cholecystectomy and common bile duct explorasion, as a preventive action (because There are number of options currently available for managing patients with thalassemia intermedia including splenectomy, transfusion therapy and iron chelating therapy.We still did not know whether our patient has iron overload associated liver injury or not.The principles methods of determining body iron levels are measurement of serum ferritin levels and assessment of liver iron concentration (LIC) from biopsy tissue.In this patient ferritin levels was increased that was caused by increased intestinal absorption and she need chelation therapy or not, because she did not underwent liver biopsy.Chelation therapy should be initiated when liver iron concentration exceeds 7 mg Fe per g dry weight. 22Although the general performance of the patient after hospitalization was good, but in the future, complications related to iron overload and immune compromised, such as liver disease, common bile duct stones relapse, vascular, endocrine and bone disease might possibly happen.So, the patient should be monitored and evaluated regularly to prevent complications.Next, liver biopsy should be done to know whether there was iron overload or not.

Figure 2 .
Figure 2. Endoscopic retrograde cholangio-pancreatography showed dilation and multiple stones in common bile duct