Adalimumab-induced platelet antibodies resulting in severe thrombocytopenia

Anti-tumour necrosis factor-α (TNFα) agents are effective in diseases including Crohn's disease but may cause cytopenias. The mechanisms involved in anti-TNFα agent-induced thrombocytopenia are scarce. We report a 73-year-old male with Crohn's disease for which he currently used adalimumab, an anti-TNFα agent. He had received mesalazine and infliximab before the treatment of adalimumab. No comorbidities were present. Routine laboratory tests revealed a deep thrombocytopenia (thrombocytes 24 × 109/L), after which adalimumab was discontinued. Bleeding symptoms included cutaneous haematomas and mild epistaxis. Direct monoclonal antibody-specific immobilization of platelet antigens revealed autoantibodies specific to glycoprotein IIb/IIIa and glycoprotein V platelet receptors. There was no bone marrow suppression. Other causes of the thrombocytopenia were ruled out. The platelet count normalized after adalimumab discontinuation. No further interventions were required. Monitoring thrombocyte levels after initiating anti-TNFα agents is recommended, which could lead to prevention of this potentially fatal phenomenon</p

CD34+ cells home, proliferate, and participate in capillary formation, and in combination with

Objective - Emerging evidence suggests that human blood contains bone marrow (BM)-derived endothelial progenitor cells that contribute to postnatal neovascularization. Clinical trials demonstrated that administration of BM-cells can enhance neovascularization. Most studies, however, used crude cell populations. Identifying the role of different cell populations is important for developing improved cellular therapies. Methods and Results - Effects of the hematopoietic stem cell-containing CD34+ cell population on migration, proliferation, differentiation, stimulation of, and participation in capillary-like tubule formation were assessed in an in vitro 3-dimensional matrix model using human microvascular endothelial cells. During movement over the endothelial monolayer, CD34+ cells remained stuck at sites of capillary tube formation and time- and dose-dependently formed cell clusters. Immunohistochemistry confirmed homing and proliferation of CD34+ cells in and around capillary sprouts. CD34+ cells were transduced with the LNGFR marker gene to allow tracing. LNGFR gene-transduced CD34 + cells integrated in the tubular structures and stained positive for CD31 and UEA-1. CD34+ cells alone stimulated neovascularization by 17%. Coculture with CD34- cells led to 68% enhancement of neovascularization, whereas CD34- cells displayed a variable response by themselves. Cell-cell contact between CD34+ and CD34- cells facilitated endothelial differentiation of CD34+ cells. Conclusions - Our data suggest that administration of CD34+-enriched cell populations may significantly improve neovascularization and point at an important supportive role for (endogenous or exogenous) CD34- cells. © 2005 American Heart Association, Inc. Chemicals / CAS: nitric oxide, 10102-43-9; Antigens, CD34; Biological Marker

Prognostic impact of low muscle mass and low muscle density in patients with diffuse large B-cell lymphoma

Low muscle mass (LMM) and low muscle density (LMD) are increasingly recognized as prognostic factors for survival in different malignancies. This study determined the association of LMM and LMD with survival in DLBCL (diffuse large B-cell lymphoma) patients. CT-based measurement of muscle was performed in 164 DLBCL patients prior to chemo-immunotherapy. Z-scores adjusted for gender, age, and body mass index were derived from a healthy reference population. LMM or LMD were defined as a Z-score below −1 and were related to OS and PFS. The co-existence of both LMM and LMD was observed in 13% of the DLBCL patients and was significantly associated with shorter OS and PFS. Also, these patients more often did not complete the planned treatment. The combination of LMM and LMD is an independent prognosti

Prognosis of IGLV3-21R110 chronic lymphocytic leukemia after chemotherapy-based treatment in a real-world analysis

Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

Heavy menstrual bleeding on direct factor Xa inhibitors: Rationale and design of the MEDEA study

Background: In premenopausal women, treatment with direct oral factor Xa inhibitors is associated with an increased risk of heavy menstrual bleeding (HMB) compared with vitamin K antagonists (VKA). Treatment with the direct oral thrombin inhibitor dabigatran appears to be associated with a reduced risk of HMB compared with VKA. These findings come from small observational studies or post hoc analyses of trials in which HMB was not a primary outcome. Use of tranexamic acid during the menstrual period may be effective in patients with HMB, but prospective data regarding efficacy and safety in patients on anticoagulant treatment are lacking. Rationale and Design: A direct comparison of a factor Xa inhibitor and a thrombin inhibitor with HMB as primary outcome, as well as an evaluation of the effects of adding tranexamic acid in women with anticoagulant-associated HMB is highly relevant for clinical practice. The MEDEA study is a randomized, open-label, pragmatic clinical trial to evaluate management strategies in premenopausal women with HMB associated with factor Xa inhibitor therapy. Outcomes: Women using factor Xa inhibitors with proven HMB, as assessed by a pictorial blood loss assessment chart (PBAC) score of >150, will be randomized to one of three study arms: (i) switch to dabigatran; (ii) continue factor Xa inhibitor with addition of tranexamic acid during the menstrual period; or (iii) continue factor Xa inhibitor without intervention. The primary outcome is the difference in PBAC score before and after randomization. Here, we present the rationale and highlight several unique features in the design of the study

Vascular progenitor cells in renal and cardiovascular disease

Maintenance of endothelial integrity plays a central role in the protection against the development and progression of renal and atherosclerotic cardiovascular disease (CVD). Damaged or lost endothelial cells may be replaced through proliferation of local endothelium and by circulating bone marrow derived endothelial progenitor cells (EPC). There are also smooth muscle progenitor cells (SPC) in the blood, which may contribute to both physiological and pathological remodeling of the vascular wall. In this thesis we show that a ‘pro-atherosclerotic milieu’ in the presence of cardiovascular risk factors affects the number, function and differentiation of circulating progenitor cells. In patients with end-stage renal disease, EPC differentiation is impaired and the capacity of EPC to stimulate angiogenesis is reduced, while SPC differentiation was unaffected. Dialysis sessions induce EPC apoptosis, resulting in a temporary aggravated reduction of circulating EPC. Women with quiescent systemic lupus erythematosus (SLE) have reduced EPC levels, which may contribute to the high incidence of CVD observed in these patients. Increased apoptosis of HSC may be the underlying mechanism for the decrease in HSC-derived EPC in SLE. In diabetes, EPC levels are reduced, while SPC outgrowth is increased. The increased SPC-outgrowth is associated with increased TGF-? with decreased BMP-6 expression and aggravated neointima formation. We observed that diabetes not only negatively affects circulating angiogenic cells, but also angiogenic cells residing in the vessel wall. In obese men with the metabolic syndrome but without diabetes or manifest CVD, lower levels of circulating EPC were observed. In this thesis we propose that ‘vascular niche dysfunction’ in the bone marrow may underlie impaired endothelial progenitor cell mobilization and availability in the circulation. We show that impaired mobilization of endothelial and hematopoietic progenitor cells in diabetes is associated with dysfunction of the bone marrow stromal environment. eNOS levels in diabetic stroma were reduced and NO-inhibition impaired endothelial support of progenitor cells, suggesting a potential role for attenuated endothelial NO-release in diabetic stroma in dysfunctional progenitor cell mobilization. Impaired endothelial NO-availability occurs in various pro-atherosclerotic conditions and may be a common mechanism for reduced EPC levels. We explored pharmacological strategies to modulate EPC levels. We evaluated if treatment with PPAR-gamma agonist rosiglitazone could stimulate EPC-homing to the injured glomerulus, but although renal recovery from anti-Thy1 glomerulonephritis was improved, we did not observe a detectable increase in the number of incorporated EPC. EPC-homing involves the RANTES-chemokine, which is also an anti-atherosclerotic target because of its pro-inflammatory characteristics. We show that treatment with RANTES-inhibitor impairs ischemia-induced angiogenesis. In obese men with the metabolic syndrome, we found that intensive lipid-lowering therapy using simvastatin and ezetimibe could normalize reduced EPC-levels. Taken together, progenitor cells from the bone marrow circulate in the blood and contribute to physiological and pathophysiological vascular and renal remodeling. CVD risk factors influence the mobilization, differentiation and function of these progenitor cells. This occurs through various mechanisms, which include common pathways relevant for various CVD risk factors, and risk-factor specific mechanisms. Vascular progenitor cell levels represent a novel therapeutic target in cardiovascular and renal disease

The potential health gain and cost savings of improving adherence in chronic myeloid leukemia

Contains fulltext : 204847.pdf (publisher's version ) (Open Access)Healthcare costs are rising due to an increase in chronic diseases, including chronic myeloid leukemia (CML) due to improved survival. In CML care, patient adherence and physician adherence are key elements. We assessed the potential health gain and cost savings when both are improved, using a decision analytic model that integrated various sources of evidence. The current situation was compared to a theoretical situation in which either patient or physician adherence is improved, in terms of costs and quality-adjusted life years (QALYs). Current patient adherence rate is 74%, improvement to 100% resulted in 0.1031 QALYs gained and a saving of euro17,509 per patient over a 25-year period. Improving physician adherence from 72% to 100%, resulted in 0.0380 QALYs and euro7606. Enhancement of either adherence results in substantial health gain and cost savings. Regarding the rising healthcare costs, new strategies should focus on improving adherence to keep healthcare affordable in the future