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An important approach to the successful treatment of thrombocytopenia is the understanding of the underlying pathophysiological processes in the development of the disease. Thrombocytopenia can either be primary or secondary, in that it can accompany a broad spectrum of syndromes and diseases and may be caused by various mechanisms. Prompt investigation and identification may be crucial and sometimes life-saving as in TTP, heparin-induced thrombocytopenia, acute leukemia or even severe ITP. Taking a detailed history and a thorough physical investigation can provide clues regarding possible underlying diseases and medical treatments. Careful examination of the peripheral blood smear is mandatory. When differential diagnosis is problematic, sometimes a short trial of treatment can help to clarify the cause. For example, it may be difficult to distinguish inherited thrombocytopenia (without a family history) from ITP; in this example, intravenous immunoglobulin infusion will likely have no effect in inherited thrombocytopenia, but will usually be helpful in ITP. Notable progress has been made in recent years in developing new treatment options for thrombocytopenia patients, especially in ITP. In addition to rituximab and the thrombopoietin agents, combinations of different diagnostic and therapeutic modalities and various therapeutic approaches are the main strategies for difficult cases. A number of issues complicate the differential diagnosis and treatment of thrombocytopenia. There is no specific diagnostic test for many of the thrombocytopenias, such as ITP. Alternatively if the definitive test of a suspected condition is molecular, it may require months before the results become available. Also, the natural history and prognosis are often unpredictable and the response to treatment is unknown. Another factor is that it may be difficult to choose an effective treatment for a specific patient. For example, in ITP there is no universally accepted specific test currently available to predict response to splenectomy or rituximab. More targeted therapies and preventative strategies are crucial for the treatment of thrombocytopenia, ideally defining and eliminating etiologic factors. Clinical trials are needed to determine the efficacy and safety of new approaches and to compare different therapeutic modalities. Long-term maintenance treatment options for chronic patients should be investigated, not only in regard to efficacy but also toxicity, and with a special view to potential curative effects.
Immunomodulatory Effects of Drugs for Treatment of Immune-Related Diseases
The last 10 years have witnessed robust development of several drugs as a consequence of intense collaboration among academics, clinicians, scientists, and pharmaceutical companies. This has led to approval of these drugs for treatment of autoimmune diseases, cancer and AIDS, among many other diseases. This research topic focuses on the mechanism of action (MOA) of these drugs and reports new findings related to autophagy and adjuvanticity of drugs. In an article by Kim et al., the function of the chemical 2-hydroxypropyl -β-cyclodextrin (HP-β-CD) was examined. This chemical has been previously used to facilitate the delivery of hydrophobic drugs and recently used as an adjuvant. The authors reported that HP-β-CD induced the maturation of dendritic cells (DCs), including upregulating the expression of co-stimulatory molecules and MHC class II molecules (Kim et al.). This maturation promoted these cells to become professional antigen- presenting cells inducing the proliferation of T cells. The adjuvanticity of the chemical was further examined in a mouse footpad immunization model, and it was concluded that HP-β-CD functions as a potent adjuvant inducing DCs maturation, a process mediated through lipid draft formation. The theme of new adjuvants was further discussed in an article by Miccadei et al., who reviewed the potential effects of ω3-polyunsaturated fatty acids (PUFA) as an adjuvant for chemotherapy and/or radiotherapy regiments to treat colorectal cancer. Interest has been recently generated in the effects of diets on cancer, obesity, diabetes, and many more metabolic disorders. Administration of PUFA-enriched diets may have several advantages in controlling inflammatory responses that may benefit patients with inflammatory disorders. Further, PUFA-enriched diets might also be considered for preventing colorectal cancer, provided that the MOA of this adjuvant is clearly understood. Musters et al. advocated the use of off-label drugs to treat immune-mediated diseases that failed all other possible treatments. The authors described a case of multicentric Castleman’s disease (MCD) with disseminated polyclonal B cell proliferation throughout multiple lymph nodes. This patient was treated in the authors’ center with tocilizumab, a humanized monoclonal antibody against human IL-6 receptor, which was approved for treatment of rheumatoid arthritis (RA) and juvenile RA patients, but not for Castleman’s disease patients. The patient showed a remarkable response to the drug including lower C-reactive protein level, improved sedimentation rate, and normalization of hemoglobin level. The authors concluded that off-label prescription drugs can be used after carefully evaluating the efficacy and safety of these biologic drugs. The effects of latency-reversing agents (LRAs) on natural killer (NK) cells during clearance of HIV infection was explored in this issue (Garrido et al.). NK cells are the predominant innate immune cells that are important to fight against HIV infection (1), as well as many other viral infections.