An Unexpected Cause of Thrombocytopenia

Introduction: Thrombocytopenia can be seen in 10-40% of patients with systemic lupus erythematosus (SLE), in most cases, thrombocytopenia is mild to moderate, and is typically not associated with neurological symptoms or microangiopathic hemolytic anemia. Whereas, lupus associated thrombotic thrombocytopenic purpura (TTP) is only seen in 0.5-3%, and is crucial to recognize quickly, since it has a high mortality rate and requires prompt and targeted treatment. Herein we report such a case. Case Description: A 42-year-old woman came to the emergency department with complaints of fatigue, hematuria, joint aches, and episodes of confusion. She had recently been diagnosed with SLE, with positive ANA (1:1280) and anti-dsDNA (1:160). At first, her symptoms were thought to be from a lupus flare. She met EULAR criteria for SLE with thrombocytopenia, autoimmune hemolysis, joint synovitis, proteinuria (urine protein/creatinine ratio 2.1g/g), low complement levels (C3 <40, C4 <8), and positive anti-dsDNA. However, her labs were concerning. She had severe thrombocytopenia (platelets 3,000/µL), anemia (Hb 7.3 g/dL), elevated LDH, indirect hyperbilirubinemia, and a positive Coombs test for IgG. Her peripheral smear showed schistocytes, pointing toward microangiopathic hemolytic anemia (MAHA), and she also had acute kidney injury (BUN 26 mg/dL, Cr 1.8 mg/dL). These findings led us to be concerned about thrombotic thrombocytopenic purpura (TTP). A PLASMIC score of 6 strongly supported our suspicion. We consulted Hematology and Nephrology urgently. She was started on high-dose IV steroids and daily plasma exchange (PLEX), which continued until her platelets rose above 150,000/µL. A renal biopsy later confirmed thrombotic microangiopathy (TMA) with class II lupus nephritis. ADAMTS13 activity 3%. She was started on Mycophenolate for lupus nephritis, discharged on a prednisone taper and weekly Rituximab, and later transitioned to Belimumab. Discussion: This case highlights the importance of maintaining a high index of suspicion for TTP in SLE patients who present with severe thrombocytopenia and hemolysis, especially when accompanied by neurologic or renal manifestations. Prompt initiation of plasmapheresis and immunosuppression can be lifesaving. TTP must be included in the differential diagnosis of lupus patients with thrombocytopenia and anemia to prevent delayed recognition of this critical entity.