Seminars in hematology
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Seminars in hematology · Jan 2006
ReviewGlanzmann's thrombasthenia treatment: a prospective observational registry on the use of recombinant human activated factor VII and other hemostatic agents.
Glanzmann's thrombasthenia (GT) is a rare congenital bleeding disorder caused by deficiency or dysfunction of platelet surface glycoprotein (GP) IIb/IIIa receptor. Platelet transfusion is the standard treatment for bleeding that remains non-responsive to conservative measures, and for surgical coverage. Platelet transfusions, however, may result in the development of antibodies to GPIIb/IIIa and/or human leukocyte antigen (HLA), rendering further transfusions ineffective. ⋯ Standardized data will be collected using a customized internet-based (www.glanzmann-reg.org) data collection tool. Data collection will begin in 2005 and continue for up to 6 years. Patients of all ages from any country are eligible for inclusion.
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Coagulopathy following massive transfusion is a consequence of post-traumatic and surgical hemorrhage. Bleeding following massive transfusion can occur due to hypothermia, dilutional coagulopathy, platelet dysfunction, fibrinolysis, or hypofibrinogenemia. ⋯ Excessive fibrinolysis and low fibrinogen are also causes of bleeding in these patients. Currently, however, there are several agents that have been reported to be effective for the prophylaxis of hemorrhage in surgical patients, including aprotinin for cardiac surgery, orthopedic surgery, and hepatic transplantation, and the off-label use of recombinant activated factor VII (NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) as rescue therapy for life-threatening hemorrhage.
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Seminars in hematology · Jan 2006
Case ReportsImpact of choice of treatment for bleeding episodes on inhibitor outcome in patients with mild/moderate hemophilia a and inhibitors.
Patients with mild/moderate hemophilia A (MHA) may develop inhibitors to factor VIII (FVIII). In this condition, FVIII clotting activity (FVIII:C) baseline levels may remain stable for some patients, but may be reduced to less than 0.01 U/mL for others. Several risk factors for the development of inhibitors in MHA have been proposed. ⋯ Several treatment options for the control of bleeding in patients with MHA and inhibitors (MHAI) are currently available, and the choice of therapeutic strategy should be given careful consideration; some treatments may produce an anamnestic response, thus delaying the return to FVIII:C baseline levels and adversely affecting the duration of the severe bleeding phenotype. To increase our knowledge of MHAI, a retrospective collection of data is currently being performed among hemophilia centers in France and Belgium. Based on five examples of patients with MHAI collated from preliminary study data, we illustrate the impact on inhibitor outcome of the therapeutic choices used to treat bleeding episodes in these patients.
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Seminars in hematology · Oct 2005
ReviewManagement of the relapsed/refractory myeloma patient: strategies incorporating lenalidomide.
The immunomodulatory drug (IMiD) lenalidomide is a more potent immunomodulator than thalidomide with respect to its effects on cytokine modulation and increased T-cell proliferation. Of all the IMiDs, clinical trial data are most mature for lenalidomide. In phase I studies, dose-limiting toxicities of lenalidomide were limited to myelosuppression and a response rate of 72% was seen in relapsed/refractory patients. ⋯ Thrombocytopenia was a significant grade 3 or 4 toxicity observed; however, it was manageable with dose reduction. In contrast with high-dose dexamethasone, deep vein thrombosis has emerged as an important toxicity. Lenalidomide is currently being tested in combination with both standard and novel agents, including bortezomib, for patients with relapsed/refractory multiple myeloma.
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Seminars in hematology · Oct 2005
ReviewLenalidomide and thalidomide: mechanisms of action--similarities and differences.
Multiple myeloma is a B-cell malignancy characterized by an excess of monotypic plasma cells in the bone marrow. The molecular mechanisms that are involved in disease progression depend on the interaction between the multiple myeloma cells and the bone microenvironment. Because these mechanisms have been well characterized, it is possible to develop regimens that are more specific to pathways involved in the pathogenesis of multiple myeloma than is typical for conventional chemotherapy in disease management. ⋯ Although thalidomide and IMiDs demonstrate similar biologic activities, IMiDs are more potent than thalidomide and achieve responses at lower doses. Lenalidomide, a thalidomide derivative, has also been shown to have a different toxicity profile. Our understanding of the mechanism of action of these agents has provided a platform for exciting clinical trials evaluating combinations of thalidomide and lenalidomide with both conventional chemotherapy and newer targeted agents.