Hematologic disorders, including thrombocytopenia, are a common symptom of systemic lupus – Systemic Lupus Erythematosus (SLE). An important diagnostic and therapeutic issue is the severe and recurrent thrombocytopenia resistant to standard treatment. It requires extensive diagnostics and a multi-directional view on its causes beyond the autoimmune process. Currently, there is no single treatment regimen for these disorders. Corticosteroids (CS) are the first-line drugs, but their chronic use is a big problem, they are not always successful and often generate a number of complications, especially in moderate to high doses. In the case of thrombocytopenia associated with the activity of SLE, immunosuppressive therapy is the gold standard and may result in long-term remission of symptoms and clinical stabilization. The major problem is thrombocytopenia resulting from other causes, such as infection or medications. This study discusses severe recurrent thrombocytopenia on the basis of three clinical cases, analyzing both the various causes of disorders, and providing ways of management and treatment. Special attention is paid to the correlation of thrombocytopenia with the clinical and immunological activity of SLE. It seems that severe and refractory thrombocytopenia may be a critical point and largely determine the management and treatment possibilities of SLE.