Dr. Deepak Govil

Senior Consultant, Dept. of Gastrointestinal Surgery

Indraprastha Apollo Hospital, New Delhi

A 55-year-old male presented with 4-5 loose stools/day since 5 weeks with crampy abdominal pain. There was associated malaise, anorexia and low-grade fever. He also complained of yellowish discoloration of eyes since 2 weeks. The patient was a nonsmoker and nonalcoholic. There was no history of any drug intake. The patient gave a history of recurrent diarrhea 2 years back. On examination, blood pressure (BP), pulse and respiration were stable. General physical examination revealed pallor and jaundice. Hepatomegaly was present with a palpable spleen. There was no ascites, lymphadenopathy or edema. Systemic examination did not reveal any abnormal findings. The lab results showed hemoglobin (Hb) 6.5 g/dL,total leukocyte count (TLC) 6,000/mm3, reticulocyte count 10%, erythrocyte sedimentation rate (ESR) 20 mm/hour, C-reactive protein (CRP) 10 mg/L, serum albumin 3 g/dL, serum sodium 135 mEq/L, serum potassium 3.2 mEq/L, increased serum lactate dehydrogenase (LDH) and reduced serum haptoglobin. Liver function tests (LFTs) showed mildly elevated liver enzymes and unconjugated hyperbilirubinemia. Serological tests for hepatitis viruses were negative. The direct and indirect Coombs’ tests were positive. Routine stool examination was negative for ova and parasites. Three sequential stool cultures were negative for any infective pathology.

A colonoscopy was done, which showed continuous inflammation of the rectum with edematous mucosa and multiple superficial ulcers. Biopsy confirmed nongranulomatous colitis suggestive of ulcerative colitis (UC).

The patient was hospitalized and put on oral sulfasalazine along with intravenous methylprednisolone for 3 days followed by oral prednisone. He was also transfused 2 units of fresh blood. The patient responded to this line of management and showed improvement in Hb and serum bilirubin levels.

Diagnosis

Ulcerative colitis with associated autoimmune hemolytic anemia.

Discussion

Autoimmune hemolytic anemia (AIHA) is characterized by an increased breakdown of red blood cells (RBCs) due to autoantibodies with or without complement activation. The diagnostic features of AIHA include the combination of clinical and laboratory signs of RBC hemolysis together with the detection of autoantibodies and/or complement deposition on RBC as mostly evidenced by a positive direct antiglobulin test (DAT) also known as direct Coombs test.1

AIHA can range in severity from mildly symptomatic illness to a rapidly fatal syndrome. AIHA is mediated by antibodies, and in the majority of cases immunoglobulin (Ig)G is the mediating antibody. This type of AIHA is referred to as warm AIHA because IgG antibodies bind best at body temperature. Cold AIHA is mediated by IgM antibodies, which bind maximally at temperatures below 37°C.2

In more than 50% of the patients, the development of AIHA is associated with an underlying disease (secondary AIHA), but it can occur without any evidence of an underlying disorder (idiopathic or primary AIHA).1 Primary or idiopathic AIHA is less frequent than secondary AIHA. Secondary cases are often challenging because not only AIHA but also the underlying disease(s) must be diagnosed and treated.3 The most common underlying diseases in which AIHA can occur are lymphoproliferative disorders and immune diseases. The exclusion of a drug-induced hemolytic anemia is particularly important, because stopping the drug is the most effective therapeutic measure in this situation.3 Autoimmune hemolysis can antedate, follow after a few months, or occur simultaneously with the disease process.4

Patients with UC commonly present with a wide range of systemic and local problems that can add to the complexity of treatment. Anemia is a common hematologic complication in these patients. The anemia in patients with UC may be a result of acute or chronic gastrointestinal blood loss, chronic disease, folate deficiency from sulfasalazine therapy or autoimmune hemolysis.5 Furthermore, the association of anemia with jaundice in UC may suggest AIHA, which is uncommon but not an unknown disorder.4 In UC, increased levels of factor V, factor VIII and fibrinogen and decreased levels of antithrombin III have been demonstrated. Coombs positive hemolytic anemia has occasionally been reported in patients with UC.6 The coexistence of UC with Coombs positive hemolytic anemia should be considered in every UC patient with persisting or severe anemia. But, other causes of hemolysis should be excluded such as hemolysis due to frequent transfusions, hereditary spherocytosis, hereditary elliptocytosis, glucose-6-phosphate dehydrogenase deficiency (G6PD), pyruvate-6-kinase deficiency, infections, microvasculitic hemolytic anemia.6

References

1. Zeerleder S. Autoimmune haemolytic anaemia - a practical guide to cope with a diagnostic and therapeutic challenge. Neth J Med 2011;69(4):177-84.
2. DeLoughery TG. Autoimmune hemolytic anemia. Hospital Physician 2013;8(Pt 1):2-11.
3. Lechner K, Jager U. How I treat autoimmune hemolytic anemias in adults. Blood 2010;116(11):1831-8.
4. Sharma SC, Tonk RS, Gadpayale AK, et al. Autoimmune haemolytic anaemia associated with ulcerative colitis. JIACM 2002;3(2):198-201.
5. Osterman ST, Lichtenstein GR. Chapter 112. Ulcerative colitis. In: Feldman: Sleisenger and Fordtrans Gastrointestinal and Liver Disease. 9th edition, Elsevier: Saunders 2011:p.1975-2012.
6. Katsanos KH, Christodoulou DK, Kitsanou M, et al. Thrombophlebitis migrans including Mondors syndrome and autoimmune hemolytic anemia in ulcerative colitis; case report and review of the literature. Ann Gastroenterol 2002;15(2):190-4.