Treatment of refractory thrombotic thrombocytopenic purpura using multimodality therapy including splenectomy and cyclosporine.

ADAMTS13 mediated thrombotic thrombocytopenic purpura (TTP) is an immunological disease that is very difficult to treat. Plasma exchange, with plasma replacement and steroids have been the first line of treatment for this condition. Ten to 20% of the patients either have no response or a partial response to the treatment. Refractory TTP has been treated in few case reports with anti-CD20 agents, intravenous gamma globulin, vincristine and splenectomy. We report two cases of refractory TTP that responded to multimodality immunosuppressive therapy that included splenectomy, intravenous gamma globulin, and cyclosporine after numerous plasma exchange treatments, steroids, rituximab and vincristine had failed to induce remission. Combining drugs that target T and B lymphocytes is a standard in organ transplantation and deserves more consideration in the treatment of severe and refractory autoimmune diseases such as TTP.

Long-term safety and efficacy of low-density lipoprotein apheresis in childhood for homozygous familial hypercholesterolemia.

Untreated pediatric patients with homozygous familial hypercholesterolemia usually have myocardial infarctions, heart failure, or death by the teenage years. Low-density lipoprotein (LDL) apheresis effectively lowers LDL cholesterol in the short term, but there is little published information on the long-term safety and efficacy of this treatment in children. An analysis was performed of a registry of all 29 patients who began LDL apheresis before 18 years of age at 15 sites during the 11 years since approval by the United States Food and Drug Administration. A chart review of 9 patients treated at The Rogosin Institute was also performed to obtain additional details about lipid lowering, adverse events, and cardiovascular status. Of the 29 patients, 20 are currently treated, with a mean age at the start of treatment of 9 +/- 4 years (range 3 to 15) and a mean treatment duration of 6 +/- 4 years (range 2 to 21). The baseline LDL cholesterol (521 +/- 126 mg/dl) is acutely lowered by 75% and chronically lowered by 48% with biweekly sessions. Systemic adverse events have been uncommon. Atherosclerotic disease of the coronary arteries and/or aorta or aortic valve was evident by angiography and/or echocardiography in 12 patients (60%) at baseline and progressed to more severe, symptomatic disease in 6 (30%). In conclusion, LDL apheresis is well tolerated for decades by even very young pediatric patients with homozygous familial hypercholesterolemia. It effectively lowers LDL cholesterol, but target LDL levels are not achieved, and some patients will show progression of cardiovascular disease.