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CASE REPORT
Year : 2017  |  Volume : 44  |  Issue : 1  |  Page : 55-57

Aplastic anemia in a patient with chronic liver disease


Department of Medicine, Sri Ramachandra Medical College, Chennai, Tamil Nadu, India

Date of Web Publication20-Mar-2017

Correspondence Address:
Deepak Rajkumar Vangipuram
Department of Medicine, Sri Ramachandra Medical College, No. 1 Ramachandra Nagar, Porur, Chennai, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jss.JSS_31_15

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  Abstract 

The association of aplastic anemia with chronic liver disease is rare. We report the case of a 47-year-old male patient who presented with bleeding gums and melena. He was found to have pancytopenia and on evaluation, had an aplastic bone marrow. He also had cirrhosis with portal hypertension (cryptogenic cirrhosis) for which no cause could be ascertained. This case illustrates that in a patient with cirrhosis and pancytopenia, we must look for causes other than hypersplenism.

Keywords: Aplastic anemia, cryptogenic cirrhosis, pancytopenia


How to cite this article:
Vangipuram DR, Singh S, Varadan S, Jayachandran D. Aplastic anemia in a patient with chronic liver disease. J Sci Soc 2017;44:55-7

How to cite this URL:
Vangipuram DR, Singh S, Varadan S, Jayachandran D. Aplastic anemia in a patient with chronic liver disease. J Sci Soc [serial online] 2017 [cited 2017 Mar 26];44:55-7. Available from: http://www.jscisociety.com/text.asp?2017/44/1/55/202545


  Introduction Top


Aplastic anemia is a disorder characterized by pancytopenia and bone marrow hypocellularity. It can be both congenital and acquired. Acquired aplastic anemia most commonly occurs due to immune-mediated destruction of progenitor cells in the bone marrow that are replaced by fat cells and marrow stroma. Aplastic anemia in liver disease has been reported following hepatitis, usually viral, whereas chronic liver disease and cirrhosis are commonly associated with anemia due to gastrointestinal (GI) blood loss.[1] This is the case report of a patient with cirrhosis and portal hypertension of unknown etiology who presented with pancytopenia, epistaxis, and melena. His symptoms were initially thought to be due to portal hypertension and hypersplenism; but after evaluation, he was found to have aplastic anemia. Aplastic anemia is rare in a patient with chronic liver disease and cirrhosis.


  Case Report Top


A 47-year-old male patient had bleeding gums and passed dark-colored stools for 3 days. He also complained of progressive tiredness for 2 months prior to the episode. There were no other symptoms. He was admitted to another hospital where he was found to have low platelet count (less than 15,000/mm 3). Despite transfusions, the platelet counts did not improve. He was referred to Sri Ramachandra Hospital for further treatment.

The patient did not have any fever, abdominal pain, jaundice, or rash. There was no history of abdominal distension, weight loss, or prior bleed. Also, the patient had never smoked or consumed alcohol. He did not have any other chronic illness. He was a grocery store owner and did not have a history of exposure to any chemicals.

On examination, his body temperature was 98°F, pulse rate was 84/min, and blood pressure was 110/50 mmHg. The patient had pallor and mild pedal edema. There was no icterus, cyanosis, clubbing, or significant lymph node enlargement. There was no rash or bone tenderness. Examination of his abdomen showed normal findings. Examination of his chest and cardiovascular systemwas essentially normal.

His initial lab values were as follows: hemoglobin 5.9 g/dl, total leukocyte count 3100/mm 3, and platelet count 15,000/mm 3. Peripheral smear showed mostly normocytic and normochromic RBCs with occasional macrocytes. There was leukocytopenia with thrombocytopenia. His reticulocyte count was 1.7 % and mean corpuscular volume (MCV) was 99.4 fl. The other findings were: bleeding time 14 min, prothrombin time 16.4 s (control 14.1 s) with International Normalized Ratio (INR) 1.21, and partial thromboplastin time 32.2 s (control 29.5 s). Direct Coombs test was negative.

The patient was transfused packed cells and platelets. Hemoglobin improved to 9.2 g/dl and platelets improved to 35,000/mm 3.

Biochemistry revealed the following: total bilirubin 1.90 mg/dl, direct bilirubin 0.63 mg/dl, aspartate aminotransferase (AST) 57 IU/l, alanine aminotransferase (ALT) 54 IU/l, alkaline phosphatase 71 IU/l, lactate dehydrogenase 349 IU/l, serum albumin 2.8 g/dl, globulins 2.7 g/dl, blood urea nitrogen (BUN) 14 mg/dl, and serum creatinine 0.9 mg/dl. Enzyme-linked immunosorbent assay (ELISA) for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) was negative. The test for hepatitis B virus (HBV) DNA was negative. Antinuclear antibodies were negative. Serum iron level was 35 µg/dl, and serum ferritin level was 73.60 ng/ml. Thyroid profile of the patient was normal.

The patient also underwent ophthalmology evaluation for Kayser–Fleischer ring that was negative. Serum ceruloplasmin level of the patient was within normal limits.

Ultrasonogram of abdomen showed cirrhosis of liver with mild splenomegaly (14 cm). The diameter of portal vein was 14 mm. On Doppler test, there was decreased flow suggestive of portal hypertension. The upper GI endoscopy showed severe portal gastropathy with grade 3 esophageal varices and red signs. Variceal ligation was done.

The patient improved symptomatically and did not have any further episodes of epistaxis or GI bleed. In addition to transfusion, he also received parenteral hematinics in view of low iron stores. The reticulocyte count did not improve even 3 weeks after he received hematinics.

Though he was initially assumed to have hypersplenism, he only had a mild splenomegaly. Also, he had a persistently low reticulocyte count. So, a bone marrow aspiration and biopsy were done. Bone marrow aspiration had a dry yield. The bone marrow biopsy showed features of aplastic anemia [Figure 1]a and [Figure 1]b.
Figure 1: (a and b) Aplastic bone marrow

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The patient could not undergo a liver biopsy because of the low platelet count.

He was diagnosed to have cryptogenic cirrhosis with aplastic anemia. The cirrhosis and portal hypertension were managed with diuretics, beta blockers, and other supportive medications. He was offered immunosuppressive therapy for the aplastic anemia, but he refused treatment and wanted discharge for personal reasons. He was discharged against medical advice and was lost to follow-up.


  Discussion Top


This patient has chronic liver disease that progressed to cirrhosis and portal hypertension. He did not have any ascertainable cause for chronic liver disease and was therefore labeled as a case of cryptogenic cirrhosis. Although the GI bleed could be explained by portal hypertension and gastropathy, the epistaxis was likely due to a bleeding diathesis secondary to thrombocytopenia. Also, the thrombocytopenia could have precipitated the GI bleed in this person who was already prone for it due to the portal hypertension.

Initially, it was assumed that severe anemia occurred due to GI bleed and the pancytopenia occurred due to hypersplenism. But the patient's splenomegaly was very mild (14 cm) and insufficient to cause symptoms of hypersplenism. Even though low iron stores could have contributed to the anemia, there was no improvement in reticulocyte counts even after iron replacement. This is the reason we had to look for other causes of anemia in this patient. Only after a bone marrow biopsy, we could ascertain the cause of anemia in this patient to be aplastic anemia.

Aplastic anemia is the result of immune-mediated destruction of hematopoietic stem cells causing pancytopenia and an empty bone marrow.[2] Viruses and/or antigens, through the mediation of interferon-γ or the cytokine cascade, induce lymphocyte activation and ultimately apoptotic death of hematopoietic cells in the bone marrow.[3] It can be successfully treated with either immunosuppressive therapy or hematopoietic stem cell transplantation.

Aplastic anemia that occurs after liver disease is usually associated with hepatitis. Hepatitis-associated aplastic anemia has been defined as a variant of aplastic anemia, which occurs concurrently with or within 6 months of an increase in the serum level of ALT to at least five times the upper limit of the reference range.[1] Severe marrow aplasia may be induced by hepatitis viruses, such as the HBV and HCV, and also by other viruses, such as HIV, Epstein–Barr virus, transfusion-transmitted virus, and echovirus.[4],[5] It is also seen in patients with toxin-induced and autoimmune hepatitis.[6]

Treatment of aplastic anemia in liver disease is with immunosuppressive therapy with anti-thymocyte globulin (ATG) and hematopoietic stem cell transplant, which have shown response rates of 75–80% and 75–88%, respectively.[1],[2]

This patient was negative for HIV, HBV, and HCV infections. He had no history of exposure to toxic materials. Also, he had cirrhosis without biochemical evidence of hepatitis activity. Therefore, the cause of aplastic anemia in this patient cannot be explained by these mechanisms and must be assumed to be due to idiopathic immunological mechanisms.

Cases of aplastic anemia with cryptogenic cirrhosis have not been reported. These cases illustrate that we must look for other causes of pancytopenia in a patient with chronic liver disease and mild splenomegaly and should not assume it to be an outcome of hypersplenism. Also, it is necessary to study the association between aplastic anemia and chronic liver disease in greater detail.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Gonzalez-Casas R, Jones EA, Moreno-Otero R. Spectrum of anemia associated with chronic liver disease. World J Gastroenterol 2009;15:4653-8.  Back to cited text no. 1
    
2.
Young NS, Scheinberg P, Calado RT. Aplastic anemia. Curr Opin Hematol 2008;15:162-8.  Back to cited text no. 2
    
3.
Young NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood 2006;108:2509-19.  Back to cited text no. 3
    
4.
Gonzalez-Casas R, Garcia-Buey L, Jones EA, Gisbert JP, Moreno-Otero R. Systematic review: Hepatitis-associated aplastic anaemia - A syndrome associated with abnormal immunological function. Aliment Pharmacol Ther 2009;30:436-43.  Back to cited text no. 4
    
5.
Qureshi K, Sarwar U, Khallafi H. Severe aplastic anemia following acute hepatitis from toxic liver injury: Literature review and case report of a successful outcome. Case Reports Hepatol 2014;2014:216570.  Back to cited text no. 5
    
6.
Cariani E, Pelizzari AM, Rodella A, Gargiulo F, Imberti L, Manca N, et al. Immune-mediated hepatitis-associated aplastic anemia caused by the emergence of a mutant hepatitis B virus undetectable by standard assays. J Hepatol 2007;46:743-7.  Back to cited text no. 6
    


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