Microangiopathic Hemolytic Anemia with Stomach Cancer

Abstract

Microangiopathic Hemolytic Anemia [MAHA] is a rare hematological condition due to red blood cell breakdown. Various etiologies has been noted, however its occurrence in oncological condition is sparse. Carcinoma stomach associated with MAHA is generally having fulminant course. Detection of MAHA at diagnosis of malignancy has been noted earlier as well. We encountered a case of carcinoma stomach that developed MAHA during early treatment phase and had short survival.

Keywords: Microangiopathic hemolytic anemia; Carcinoma stomach; Signet cell; Cancer-related hemolytic anemia

Introduction

Microangiopathic Hemolytic Anemia (MAHA) has been characterized by hemolysis due to non-immune lysis of RBC. Presence of dysmorphic fragmented red blood cells and schistocytes on peripheral smear are indicative of this entity. Associated thrombocytopenia is also noted. It has been associated with variable physiological (pregnancy induced) or pathological conditions (thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, malignancy associated, hematological diseases) [1]. Among malignant conditions, association with carcinoma stomach, lung, breast, unknown primary and lymphoma are common [2]. We describe a case report of patient with carcinoma stomach who developed MAHA during the course of treatment and had rapid downhill course.

Case Summary

A 45 year old man was admitted with recurrent vomiting and abdominal discomfort for 4 weeks. Physical examination showed an ECOG performance status of III. Systemic examination revealed mild abdominal distension with a vague lump in upper half of abdomen. There was no palpable peripheral lymphadenopathy or hepato-splenomegaly. He was evaluated with endoscopy and found to have ulcerative growth in distal stomach. Biopsy was suggestive of carcinoma stomach with signet rings. Immunohistochemistry was positive for cytokeratin and negative for CK7, CK20, Napsin A, TTF, Synaptophysin, Hep-par 1, p63, PLAP and AFP confirming the diagnosis of adenocarcinoma stomach. PET CT evaluation showed stage IV disease involving thoracic and abdominal nodes as well as diffuse involvement of bone marrow. Bone marrow biopsy confirmed diffuse disease infiltration. He was started on chemotherapy [capecetabine-oxaloplatin]. He became asymptomatic after first cycle but developed acute onset progressive anemia and jaundice before second due course. Evaluation showed indirect hyperbilirubinemia with anemia and thrombocytopenia. Peripheral smear showed marked aniso-poikilocytosis with schistocytes (Figure 1). Direct coombs test was negative. Serum creatinine was normal and urine analysis showed hemoglobinuria. He was diagnosed to have microangiopathic hemolytic anemia with thrombocytopenia and started on steroid [methylprednisolone 1gm IV x 3 days]. Transfusions of packed red cell and platelets were done but showed no improvement in blood parameters. Intravenous immunoglobulin [IVIG 1gm/kg infusion] was administered along with fresh frozen plasma which showed transient improvement in blood parameters. His chemotherapy was held as Oxaliplatin induced MAHA was considered differential. However hemolysis along with thrombocytopenia continued and patient developed one episode of brief unconsciousness. MRI brain showed nodular lesion in left parietal cortex, possibly disease metastasis. A rapidly progressing disease with cancer related MAHA was considered and he was restarted on chemotherapy with steroid and IVIG dosing. However his hematological parameters remained deranged with persistent hemolytic anemia and thrombocytopenia. He became symptomatic for increased abdominal mass as well. He was transfused with packed red cells and platelet pharesis units under steroid cover but showed no response. He developed fever and decreased cognition. Family opted for supportive terminal care and he succumbed to his ailments in next 3 days.

Discussion

Metastatic signet ring cell carcinoma has been sparsely associated with MAHA. Reports of MAHA as first clinical feature leading to diagnosis of underlying malignancy are noted in literature [3]. Hahn et al reported a very high incidence (25.5%) of underlying carcinoma stomach in MAHA cases; however similar incidences were not noted elsewhere [4]. However a thorough search of malignancy, including bone marrow examination should be done in an unexplained case of MAHA. Index case developed MAHA during early phase of treatment. Absence of MAHA during diagnosis and first chemotherapy was unusual. A chemotherapy induced MAHA was considered as differential however further course with rapid clinical worsening was more suggestive of cancer related MAHA [CR-MAHA].

    

    

    Figure 1: Peripheral smear showing marked aniso-poikilocytosis with schistocytes.