Non-thrombotic hematologic manifestations in APS

Non-thrombotic hematologic manifestations of antiphospholipid syndrome (APS) comprise immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and immune neutropenia, at present not included in APS diagnostic criteria. These cytopenias have been largely reported in APS and share the same underlying pathogenic mechanism mediated by antibodies against blood cells. Thrombocytopenia (platelets 9/L), the most frequent manifestation (20–40 %), is usually mild, although cases with severe bleeding are reported for platelets 9/L. According to published guidelines of primary ITP, treatment is recommended for platelets 9/L, provided that no other bleeding factors are present. First-line treatment includes steroids and intravenous immunoglobulins (IVIG), and second-line treatments of primary ITP splenectomy, rituximab, immunosuppressors, and thrombopoietin (TPO) agonists. However, in APS-associated ITP, immunosuppressors, such as azathioprine, are often the first choice, IVIG are used as second-line treatment, splenectomy is controversial, and TPO agonists are not used. AIHA occurs in about 10 % of APS patients and is clinically heterogeneous, from mild to fulminant life-threatening forms. Conventional therapy of warm AIHA includes corticosteroids as first-line therapy, while immunosuppressive drugs, rituximab, and IVIG are used as second line; steroids are poorly effective in cold forms, whereas rituximab is now recommended as first-line therapy. Last option treatments for refractory cases include plasmapheresis, alemtuzumab, bortezomib, and eculizumab. Both primary ITP and AIHA are associated with thromboembolic events, which should be carefully considered, particularly in the context of APS. The association between leukopenia and antiphospholipid (aPL) antibodies is reported only in few studies, and neutropenia is more frequent in APS secondary to systemic lupus erythematosus.