Low-molecular-weight heparins: do we have the GUSTO to identify differences between alternative formulations?
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Chemistry, Pharmaceutical↗
Biomedical subjects
Anaadriana Zakarija
Publications and source records attributed to Anaadriana Zakarija.
Hairy cell leukemia: survival and relapse. Long-term follow-up of purine analog-based therapy and approach for relapsed disease.
Since its initial description approximately 50 years ago, there has been an impressive evolution in therapies for hairy cell leukemia. Long-term follow-up with 2-cholorodeoxyadenosine and 2'-deoxycoformycin demonstrates that both agents result in a high complete remission rate and overall survival. Relapse rates appear to be between 20% and 30%. Therapeutic strategies for patients with relapsed disease include retreatment with a purine analog, rituximab, or the anti-CD22 pseudomonas exotoxin A immunoconjugate, BL-22.
ADP Ribose Transferases↗
Drug-induced thrombotic microangiopathy.
Drug-associated thrombotic thrombocytopenic purpura and hemolytic uremic syndrome (TTP/HUS) has been recognized for several years. The most commonly implicated drugs are mitomycin-C, cyclosporine, quinine, and ticlopidine. As with idiopathic cases of TTP/HUS, basic science discoveries in the late 1990s now suggest that the likely mechanisms by which these agents lead to a thrombotic microangiopathy (TMA) include either an immune-mediated phenomenon involving the ADAMTS13 metalloprotease or direct endothelial toxicity. This article reviews the current understanding of the pathogenesis, the clinical and laboratory features, and the recommended treatments, prognosis, and outcomes of drug-associated TMA.
ADAM Proteins↗
Update on angiogenesis inhibitors.
PURPOSE OF REVIEW: A number of therapeutic agents have been developed which have anti-angiogenic potential. Here we present the most recent data from clinical trials with some of the promising inhibitors of angiogenesis. RECENT FINDINGS: Agents that target the vascular endothelial growth factor signaling pathway are the furthest along in clinical development. The last year has brought US Food and Drug Administration approval of bevacizumab (Avastin), a recombinant humanized anti-vascular endothelial growth factor monoclonal antibody. Bevacizumab has demonstrated a survival advantage in combination with chemotherapy for patients with metastatic colorectal cancer. Other agents with early promising results include PTK787/ZK 222584 (Vatalanib), ZD6474, and BAY 43-9006 (Sorafenib). SUMMARY: Angiogenesis inhibitors show promise, but evaluation for optimal efficacy has been a problem, given that the mechanisms of action of these agents differ from conventional cytotoxic agents and surrogate markers for inhibition of angiogenesis are not available.
Angiogenesis Inhibitors↗
Clopidogrel-associated TTP: an update of pharmacovigilance efforts conducted by independent researchers, pharmaceutical suppliers, and the Food and Drug Administration.
BACKGROUND AND PURPOSE: Since the 1999 identification of clopidogrel-associated thrombotic thrombocytopenic purpura (TTP) through independent active surveillance, subsequent cases have been identified by pharmaceutical suppliers of clopidogrel and the Food and Drug Administration (FDA). For cases of clopidogrel-associated TTP reported between 1998 to 2002, we evaluated the quality and timeliness of data from 3 reporting systems-independent active surveillance (n=13), pharmaceutical suppliers (n=24), and the FDA (n=13)-and identified prognostic factors associated with mortality. METHODS: This study assessed the completeness of information on TTP diagnosis, treatment response, and causality from the 3 reporting systems. In addition, predictors of mortality were identified through classification tree analysis. RESULTS: Completeness, timeliness, and certainty of diagnosis were best for cases obtained by active surveillance, intermediate for cases reported to the pharmaceutical supplier, and poorest for cases reported directly to the FDA. Clopidogrel had been used for </=2 weeks by 65%. The survival rate for patients with clopidogrel-associated TTP was 71.2%. Receipt of therapeutic plasma exchange within 3 days of onset of TTP increased the likelihood of survival (100% versus 27.3%, P<0.001). CONCLUSIONS: Compared with reports submitted by suppliers or the FDA, reports obtained through active surveillance provided timelier and more complete information. Clopidogrel-associated TTP often occurs within 2 weeks of drug initiation, occasionally relapses, and has a high mortality if not treated promptly.
Adult↗
Factor IX replacement in surgery and prophylaxis.
Considerations for treatment of hemophilia B patients in high-risk settings are the focus of this paper, including differences in recoveries of factor IX products and variable patient responses to replacement therapy. Data support the importance of performing individual pharmacokinetic studies in determining treatment programs for hemophilia patients-for both high-risk periods such as surgery and for prophylaxis. Other considerations in choice of plasma-derived or recombinant factor IX concentrate in high-risk and other situations include product safety, cost, and availability.
Adult↗
Splenectomy and treatments of historical interest.
Hairy-cell leukaemia (HCL) was initially described as a distinct clinical entity in 1958. Various types of therapy have been evaluated since this initial description and several are currently important only for historical comparison. Hairy-cell leukaemia serves as an example of rapid progress in the development of effective therapeutic strategies. Splenectomy was the first effective treatment because it resulted in an improvement in cytopenias and relief from symptomatic splenomegaly. However, complete remission of the disease was observed only very rarely. Splenectomy was considered an appropriate initial therapy from the 1950s to the early 1980s, although no randomized controlled studies have ever shown improved survival with this approach. In the early 1980s, more effective treatments were identified, initially interferon-alpha, then the purine analogues 2-deoxycoformycin and 2-chlorodeoxyadenosine (2-CdA). These types of therapy have been so effective that most previous treatments are now obsolete. Although the purine analogues result in sustained remissions in the majority of patients, a relatively small percentage of patients relapse and require other types of therapy. Splenectomy may be necessary in some instances. In this chapter the role of splenectomy is reviewed and other types of therapy of historical interest are presented.
Antineoplastic Agents↗
Bleeding and thrombosis in the cancer patient.
There is an increased risk not only of bleeding but also of thrombosis in the cancer patient. The double jeopardy creates an additional problem in their management and requires special attention. This review provides information on pathophysiology in the regulation of hemostasis, leading to bleeding and thrombotic complications. The process is complex with multiple factors being involved. In addition to the pathogenesis, a number of clinical syndromes, diagnostic methods and the management of hemostatic abnormalities in the cancer patient are presented. Potential effects of cancer treatment on these risks magnify the hazards encountered by the managing team. Wherever management is discussed, emphasis is placed on the scientific basis for the rationale of the therapeutic approach.
Disease Progression↗
Acquired hemophilia: diagnosis and management.
In this review, we describe our current understanding of the mechanisms of autoimmunity, the effect of antibodies on factor VIII, and immunosuppressant agents currently in use. Factor VIII autoantibodies may arise because of dysregulation of the immune system leading to increased autoreactivity or to clonal expansion of reactive B cells. Patients generally have several antibodies directed against a variety of functional epitopes. These antibodies may inhibit binding of factor VIII to the von Willebrand factor or phospholipid, prevent the association of factor VIII with factor IXa, block the binding of factor Xa to factor VIII, or interfere with the formation of the factor VIIIa-factor IXa-phospholipid (tenase) complex. Additionally, antibodies have been described that catalyze the hydrolysis of factor VIII. The production of antibodies has been effectively suppressed by a number of drugs, including steroids, cyclophophamide, cyclosporine, and rituximab. Beginning with a short course of steroids and then adding one or more agents as needed is a currently accepted strategy for restoring normal factor VIII levels.
Autoantibodies↗