J ournal of Medical Biomedical and Applied Sciences

J Med Biomed App Sci 8 (3), 352–353 (2020) ISSN (O) 2349-0748

Evans Syndrome- An Unresolved Tale

Divya Sharma1, Zubin Pradeep Sharma1, Ravindra Sharma2, Divya Saraswat2

1Department of Medicine, Aditya Hospital, Rajasthan, India 2Department of Gynecology, Vishal Hospital, Yamuna Nagar, Haryana, India

DOI: 10.15520/jmbas.v8i3.214

Accepted 25 march 2020; Received 17 March 2020; Publish Online 28 March 2020

Reviewed By: Dr. ABSTRACT Daniel V. Evans syndrome is a uncommon hematologic characterized by au- toimmune hemolytic anemia and immune thrombo cytopenic with a positive antihuman globulin test. We report a rare case of Evans Syndrome of a 40 years old female who presented with per vaginal since 4 days with anemia and throm- bocytopenia. The purpose of this case report is to increase the level of awareness among clinicians to instigate an appropriate diagnostic workup in patients presenting with anemia in the setting of ITP. Evans syndrome (ES) is a hematologic disorder characterized by the sequential or simultaneous development of DAT positive autoimmune hemolytic anemia (AIHA), immune (ITP) and/or immune in the absence of a known etiology.1 Evan’s syndrome is a rare disorder because it is diagnosed in only 0.8% to 3.7% of all patients with either ITP or AIHA at onset.1 Defined by Robert Evans in 1951 when he studied the relationship between autoimmune hemolytic ane- mia (AIHA) and immune (ITP)2.

1 CASE REPORT Her VDRL, HBV, HIV, HCV, ANA, dSDNA, APLA (an- A 43 years old female presented to gynecology outpatient tiphospholipid antibody) and dengue was found to be neg- department in a private hospital with complaints of bleed- ative. ing per vaginal bleeding since 4 days. Her last menstrual Haptoglobin was found to be 26 mg/dl (30-200mg/dl) period was 15 days prior to the current episode. Her men- and serum lactate dehydrogenase LDH was 433 U/L. strual cycles were regular in duration in past but she com- Haemoglobin electrophoresis and DAT (Direct anti globulin plained of excessive flow and generalized weakness for last test) was positive. Thyroid function test and IgA, IgG was 3 months. She had history of uneventful pregnancy 14 years negative. USG abdomen showed mild hepatosplenomegaly. back. No obvious gynecological cause for bleeding was iden- She underwent four units of blood and six units of tified during examination and investigations. Her routine . Her count was 32000 cells /cumm and blood examination detected anemia, Hb- 4.5 gm/dl and low Hb – 7.2 g/ dl. Her vaginal bleeding complaint was gradu- platelet count (12000 cells/cu mm). Later she was referred ally reduced to normal. Treatment with supportive antibi- to our centre. On examination she was pale, mild hep- otics with prednisolone was initiated. On fifth day patient atosplenomegaly with palpable lymph nodes. Three days developed left sided hemiparesis. Her left plantar was exten- later she developed ecchymotic patches on right forearm sor on examination. Her repeat platelet count dropped to and abdomen. Her haemoglobin was 4.5 g/ dl, white blood 90000 cells/ cumm with haemoglobin of 5.9 g / dl. Repeat cell count 9800 cells / cu mm, reticulocyte count 4% and PT, INR, APTT were normal. Fundal examination showed platelet count was 15000 cells/ cumm. Her peripheral smear retinal haemorrhages. She got detiriorated and she subse- showed microcytic hypochromic anemia with thrombocy- quently died within 2 hours. CT brain showed massive right topenia with no giant cells. Iron studies were 36 micro gm sided intra cerebral hemorrhage with mid line shift. /dl (41 - 141 micro gm / dl), serum ferritin 12 micro gm/dl To sum up the case - Gynecological etiology for the per (10-150 micro gm/ dl) and serum iron binding capacity was vaginal bleeding this patient had thrombocytopenia which slighty high. (251 - 406 micro gm/dl). was immune (Idiopathic) in nature. Her thrombocytopenia Bone marrow examination showed erythroid hyperplasia appeared to be idiopathic in nature as there was no evidence with crowding of megakaryocytes. Her unconjugated biliru- of collagenosis, infection or liver disease. Splenic sequestra- bin was 2.8 mg/dl, profile was in normal range. tion was unlikely as there was only mild splenomegaly on Evans Syndrome- An Unresolved Tale 353

USG. Platelet production was not reduced as bone mar- 3 CONCLUSION row examination evidenced - crowding of mega karyocytes Evan’s Syndrome is a rare, chronic, refractory disease but and absence of neutropenia. Her anemia was haemolytic in sometimes may present acutely. In patients presenting with nature (unconjugated bilirubin and high LDH, high reticu- immune thrombocytopenia and anemia with haemolytic locyte count with reduced haptoglobins) and lastly iron de- factor, DAT is mandatory test. Instead of monotherapy with ficiency anemia was secondary to menorrhagia. With both , combination of steroids with newer modal- the picture of ITP and AIHA the patient was diagnosed to ities like immunosuppressant’s and should be in- with Evans syndrome. [1] stituted as early as possible in order to prevent or delay life threatening complications.

2 DISCUSSION REFERENCES In ES, the AIHA is largely the warm-agglutinin subtype. [1] Benesch M, Urban C, Platzbecker U, Passweg J. Stem cell This subtype represents almost 80% of all cases of AIHA transplantation for patients with Evans syndrome. Expert and is characterized by autoimmune destruction of red Review of Clinical Immunology. 2009;5(3):341–348. Available from: https://dx.doi.org/10.1586/eci.09.9. blood cells (RBCs) [2]. More recent data suggest the spec- [2] Dhingra KK, Jain D, Mandal S, Khurana N, Singh T, Gupta trum of the disease has broadened specially in children and N. Evans syndrome: a study of six cases with review of lit- there is increasing evidence of Evans syndrome reflecting the erature. . 2008;13(6):356–360. Available from: state of profound immune disregulation as opposed to coin- https://dx.doi.org/10.1179/102453308x343518. [3] Savasan S, Warrier I, Ravindranath Y. The spectrum cidental combination of immune cytopenias [3].Evans Syn- of Evans’ syndrome. Archives of Disease in Childhood. drome is classified as primary (Idiopathic) or secondary (As- 1997;77(3):245–248. Available from: https://dx.doi.org/10. sociated with some other disease) and it has been demon- 1136/adc.77.3.245. strated that secondary disease responds better than primary [4] Michel M, Chanet V, Dechartres A, Morin AS, Piette JC, variable [4]. There are case reports of Evan’s Syndrome with Cirasino L, et al. The spectrum of Evans syndrome in adults: new insight into the disease based on the analysis of 68 cases. SLE, incomplete [5],primary antiphospholipid syn- Blood. 2009;114(15):3167–3172. Available from: https://dx. drome, Sjogren’s syndrome common variable immuno de- doi.org/10.1182/blood-2009-04-215368. ficiency, non hodgkin’s malignant lymphomas and chronic [5] Ahn YS, Horstman LL. Idiopathic thrombocytopenic pur- lymphocytic leukaemia [3]. In our case we were not able to pura: Pathophysiology and management. International Jour- detect the cause or association of any disease in our patient. nal of Hematology. 2002;76(S2):123–131. Available from: https://dx.doi.org/10.1007/bf03165102. In a study of Michael etal. sixty eight patients of Evans Syndrome mortality was seen in 23.4 % cases. The possible causes being septic shock, associated cancers, stroke, acute myocardial infarction, refractory anaemia with lymphomas. Importantly one of two patients of stroke was suspected to have intracerebral haemorrhage like in our patient [4]. The management of Evan’s Syndrome is difficult and challeng- ing. Blood and platelets transfusion is the treatment given to improve symptoms and gain time but its use should be minimized. The first line of treatment is prednisolone and intravenous immunoglobulins (IVIG). Second line of treatment consists of immuno suppressants (mycophenolate mofitil, cyclosporine, ) the monoclonal antibody rit- uximab and chemotherapy (vincristine). may also be considered a second-line treatment and even splenec- tomy. More recently small number of patients have been treated by stem cell transplantation. [1, 3, 4] NOTE - We have reported our case to highlight the need for awareness of this particular rare entity. This requires a high index of suspicion among primary care physicians as well as other medical departments like gynecology. Evans syndrome is a rare, chronic and recurrent disease. Acute presentatio n with rapid deterioration as in our patient is uncommon. Significance of Coomb’s test (Direct/Indirect) in patients with thrombocytopenia and anemia needs to be reemphasized.

Journal of Medical Biomedical and Applied Sciences , Vol 8 Iss 3, 352–353 (2020)