Title: Patient with Severe Anemia Presenting with Right Leg Pain: A Case of Cold Agglutinin Auto-Immune Hemolytic Anemia

Author(s): Farah Naz Taufiq, MD; Saveda Ali, MD; Patrick Brine, MD

Email: FTaufiq@mercy.com

Introduction: Cold agglutinin auto-immune hemolytic anemia is a form of autoimmune hemolytic anemia in which IgM autoantibodies against RBC antigens can cause red blood cell agglutination in cooler parts of body and cause hemolytic anemia. Patients usually present with symptoms of hemolytic anemia and cold induced symptoms. Here we present a case of cold agglutinin autoimmune hemolytic anemia which presented atypically with right leg pain and numbness.

Case Report(s): Patient is a 63-year-old female who presented with right leg pain and numbness. Pain was burning in nature, intermittent, extending from right hip to foot. Patient denied intermittent claudication, chest pain, palpitation, shortness of breath. No history of weight loss and blood in stool. Patient endorsed having chronic fatigue unchanged during presentation. On physical exam, patient was pale. Examination of right leg showed coldness to touch, absent dorsalis pedis pulse, loss of crude and fine touch, loss of vibration sense. Left leg examination normal except diminished peripheral pulse. Muscle strength was normal bilaterally. Homan’s sign negative bilaterally. Labs showed very low Hemoglobin (4.6 g/dL), Elevated MCV, Low haptoglobin, High reticulocyte percentage, elevated LDH, Elevated total bilirubin. FOBT was negative. Patient got blood transfusion. Direct agglutinin test was done which showed Positive polyspecific and C3 and negative IgG. Cold agglutinin titer was 1:32. Patient was diagnosed with cold agglutinin Auto-immune hemolytic anemia. CTA abdominal aorta with bilateral runoff with contrast showed severe stenosis/occlusion throughout the right common iliac artery with reconstitution at the level of the right hip and abdominal aortic aneurysm. Vascular surgery was consulted and according to vascular surgery the stenosis was likely chronic which became symptomatic as the patient became severely anemic. Patient was discharged and was being followed up outpatient with heme-onc for possible bone marrow biopsy.

Discussion: Primary cold agglutinin disease is extremely rare, incidence being about 1- 1.8 per million per year.[1] Incidence is higher in colder climates. [2] Females between 60 to 70 years are most likely affected. Cold agglutinin disease is less common than warm auto-immune hemolytic anemia. Common diseases associated with cold agglutin disease are mycoplasma pneumonia, Epstein Barr virus and lymphoproliferative disorders like lymphoma, chronic lymphocytic leukemia.[2] Apart from symptoms of anemia, patients usually have cold induced symptoms like acrocyanosis, livedo reticularis, Raynaud phenomenon. Cutaneous ulceration or necrosis can occur too.[3] Direct agglutination test should be positive for C3 and polyspesific IgM and negative for IgG. Cold agglutinin titer is usually greater than 64 at 4 C. Management includes cold avoidance, treatment of anemia if symptomatic and management of underlying disorders.