Autoimmune hematological disorders can present with variable phenotypes over time, suggesting underlying B-cell dysregulation. We report a unique case of sequential, distinct autoimmune manifestations occurring five years apart in the same patient, highlighting the heterogeneous nature of autoimmune hematological conditions and their potential triggers.

A middle-aged woman with no history of systemic autoimmune disease presented in 2019 with incidentally discovered coagulopathy. Routine laboratory evaluation revealed an INR >3 without bleeding symptoms. Further workup showed prolonged PT with normal aPTT, normal liver function, and normal levels of factors VIII, IX, and XI. Lupus anticoagulant testing was positive, while anticardiolipin and β2-glycoprotein I antibodies were negative. The patient did not meet criteria for systemic lupus erythematosus or antiphospholipid syndrome. Without specific treatment, the coagulation abnormalities spontaneously resolved within three months.

Five years later, in 2024, the patient developed fatigue, jaundice, and anemia two weeks after COVID-19 infection. Laboratory findings revealed: markedly decreased hemoglobin, elevated LDH, suppressed haptoglobin, and elevated indirect bilirubin. Direct antiglobulin test (DAT) was strongly positive for IgG. Interestingly, lupus anticoagulant and other antiphospholipid antibodies were negative at this presentation. Bone marrow aspiration showed normocellular marrow with erythroid hyperplasia, excluding malignancy or dysplasia. The diagnosis of COVID-19-associated autoimmune hemolytic anemia (AIHA) was established.

Treatment with rituximab 375 mg/m² weekly for four doses was initiated. The patient demonstrated dramatic response within two weeks, with rapid normalization of hemoglobin, LDH, and bilirubin levels. The DAT became negative, and the patient remains in remission on regular follow-up.

This case illustrates the dynamic nature of autoimmune hematological disorders. The initial presentation of isolated lupus anticoagulant positivity with spontaneous resolution, followed years later by post-viral AIHA, suggests an underlying predisposition to B-cell mediated autoimmunity with variable clinical expression.

COVID-19 has been increasingly recognized as a trigger for autoimmune phenomena, including AIHA. The temporal relationship between COVID-19 infection and AIHA development in our patient, combined with the excellent response to B-cell depletion therapy, supports this association.

The contrasting immunological profiles between episodes—positive lupus anticoagulant initially versus positive DAT with negative antiphospholipid antibodies later—demonstrates that autoimmune manifestations can evolve independently over time. This heterogeneity poses diagnostic and therapeutic challenges but also provides insights into the complexity of autoimmune regulation.

Sequential development of distinct autoimmune hematological disorders in a single patient underscores the importance of comprehensive evaluation and long-term monitoring. The dramatic response to rituximab in the second episode highlights the central role of B-cell dysregulation in these conditions. This case emphasizes the need for heightened awareness of post-viral autoimmune complications and the potential for evolving autoimmune phenotypes over time.