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Life-threatening Bleeding (life-threatening + bleeding)
Selected AbstractsPorcine factor VIII in the treatment of high-titre inhibitor patientsHAEMOPHILIA, Issue 2002M.B. Garvey Development of an inhibitor against factor VIII (FVIII) is an important complication of haemophilia. It occurs in approximately 25,30% of patients with haemophilia A [1]. FVIII inhibitors may also occur as autoantibodies. The latter occur in nonhaemophiliacs and, although rare (occurring in approximately one per million of the population), are frequently associated with life-threatening bleeding. Inhibitors are considered low level if they are < 5 Bethesda Units (BU) or high level if they are > 10 BU. The former usually remain low and rarely give anamnestic response, the latter do so frequently. Despite various approaches to their management, the presence of inhibitors remains a major cause of morbidity and mortality. The effectiveness of porcine FVIII (pFVIII) in treating patients with both auto- and alloantibodies to FVIII has been well demonstrated when adequate circulating levels of FVIII are obtained [2,10]. However, pFVIII therapy may give rise to antibodies to the pFVIII and the utility of this treatment in the presence of high levels of porcine antibody is less well recognized and understood. Nonetheless, pFVIII under these circumstances may be useful in a select group of patients where management is difficult. [source] Bleeding risk with AZD6140, a reversible P2Y12 receptor antagonist, vs. clopidogrel in patients undergoing coronary artery bypass grafting in the DISPERSE2 trialINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 4 2009S. Husted Summary AZD6140, the first reversible oral P2Y12 receptor antagonist, exhibits greater and more consistent inhibition of platelet aggregation than the irreversible thienopyridine clopidogrel. As a result of its reversible effect, AZD6140 may pose less risk for bleeding when antiplatelet treatment cannot be stopped at least 5 days before coronary artery bypass graft (CABG) surgery or other invasive procedures. The Dose conflrmation Study assessing anti-Platelet Effects of AZD6140 vs. clopidogRel in NSTEMI (DISPERSE2) trial showed overall comparable bleeding rates with antiplatelet treatment with AZD6140 90 mg twice daily or 180 mg twice daily vs. clopidogrel 75 mg once daily in 984 patients with non-ST-elevation acute coronary syndromes. A post hoc exploratory analysis of bleeding outcomes in the subset of 84 patients undergoing CABG in DISPERSE2 suggests reduced risk for total bleeding (41% and 58% vs. 62%), all major bleeding (38% and 50% vs. 62%), and life-threatening bleeding (22% and 38% vs. 54%) with AZD6140 90 mg (n = 32) and 180 mg (n = 26) vs. clopidogrel (n = 26) respectively. Trends suggested that major bleeding rates were reduced with AZD6140 (combined groups) vs. clopidogrel when treatment was stopped , 5 days prior to surgery (39% vs. 63%, p = 0.15) but not when treatment was stopped > 5 days before surgery (50% vs. 60%). This observation is consistent with the reversible binding of AZD6140 to the P2Y12 receptor. Further prospective studies are planned to assess the relationship between this potential clinical benefit of AZD6140 and the reversibility of its antiplatelet effects. [source] Is There a Role for Statins in Atrial Fibrillation?PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 8 2009DAVID E. DAWE M.D. 3-Hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins) are some of the most commonly prescribed drugs in the world. While lipid modification remains the primary function of statins, there has been increasing interest in its potential pleiotropic effects, particularly as an anti-inflammatory agent in its role as an antiarrhythmic. Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice and carries with it a significant burden in both morbidity and mortality. Treatment for AF currently involves either rate or rhythm control where both have demonstrable associated risks. Rate control necessitates anticoagulation, which can cause life-threatening bleeding, while rhythm control has a poor side-effect profile that may lead to greater mortality and may not completely eliminate the need for anticoagulation. Considering this pressing need for novel therapeutic interventions in AF, this long overdue systematic review explores the potential role of statins in the treatment and prevention of AF. Physicians, especially cardiologists, need to be aware of the host of currently available literature and, more importantly, need to be stimulated to generate discussion and formulate studies that will help debate the issues under the most erudite standards. [source] The inhibition of platelet aggregation and blood coagulation by Micropechis ikaheka venomBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2001I. B. Sundell Uncoagulable blood and life-threatening bleeding can result from the action of some snake venom toxins on haemostatic components of blood and vessel walls. Although envenoming by Micropechis ikaheka primarily affects neurones and muscle cells causing post-synaptic neuromuscular blockade and rhabdomyolysis, disturbances of haemostasis also occur. Therefore, the present study explored the effects of M. ikaheka venom on platelets and endothelium, which are important components of the haemostatic mechanism. The venom inhibited platelet aggregation in response to ADP and collagen, and also delayed clotting dependent on platelet activation or endothelial cell tissue factor expression. Some of these effects were reduced by the incubation of venom with a phospholipase A2 (PLA2) inhibitor and could be reproduced by a 17 kDa venom fraction containing a PLA2. In addition, an 11 kDa fraction containing a long-chain neurotoxin reduced ADP-induced aggregation. The venom was also found to reduce endothelial cell adherence to vitronectin-, fibronectin- and collagen-coated surfaces. These results suggest that, by inhibiting procoagulant activities of platelets and endothelial cells, a 17 kDa PLA2 plays an important role in the anticoagulant action of M. ikaheka venom. [source] The relevance of the bleeding severity in the treatment of acquired haemophilia , an update of a single-centre experience with 67 patientsHAEMOPHILIA, Issue 102 2010H. ZEITLER Summary., Acquired haemophilia (AH), an autoimmune disorder with clinical features ranging from harmless haematomas to life-threatening bleedings, still has a mortality rate of up to 25%. Owing to its low frequency (1,4 × 106), standardized treatment protocols for its variable manifestations are not available. In case of prominent severe bleedings, the treatment should aim at rapid elimination of the antibody to protect patients from bleedings and on reinduction of long-term immune tolerance. Clinical data, short- and long-term treatment results of 67 patients diagnosed by our centre are presented. Patients were treated depending on their bleeding severity either by an immunosuppressive treatment alone, or in case of life-threatening bleedings, by a combined protocol (modified Bonn,Malmö protocol, MBMP) consisting of antibody depletion through immunoadsorption, intravenous immunoglobulin treatment, immunosuppression and high-dose factor VIII (FVIII) substitution. Mild bleedings occurred in two patients who were treated successfully alone by immunosuppression. Complete remission (CR) was achieved in 90% of the patients treated with MBMP (60). Of the six patients (10%) who achieved a partial remission (PR), four suffered from cancer. Mortality under MBMP was not seen. In contrast, five patients, in whom diagnosis of AH was delayed, experienced fatal outcome during surgical interventions before initiation of MBMP treatment. Prognosis in AH depends mainly on its prompt diagnosis. Treatment procedures should be adapted to bleeding severity and inhibitor titres. Under these conditions, AH is a potentially curable autoimmune disorder with an excellent prognosis. [source] | ||||||||||