Search

This article provides guidelines for the diagnosis and management of heparin-induced thrombocytopenia (HIT), a condition characterized by low platelet count caused by an immune response to heparin. It discusses different types of HIT, the incidence of the condition, and the presentation and assessment of HIT. The article also provides recommendations for platelet monitoring and laboratory diagnosis of HIT, as well as management strategies including the use of alternative anticoagulants and therapies such as intravenous immunoglobulin and plasma exchange. The recommendations are evidence-based and aim to assist healthcare professionals in managing HIT. [Extracted from the article]

In a meta-analysis of 47 studies comprising a total of 447 APS patients who received DOACs, 73 patients (16%) developed a recurrent thrombosis after a mean period of 12-5 months (Dufrost I et al i ., [6]). Patients treated for arterial thrombosis with rivaroxaban or apixaban had a higher risk of recurrent thrombosis compared to those with venous thrombosis (32% vs. 14%; OR = 2-8 [95% CI; 1-4-5.7], I P i = 0-006) (Dufrost I et al i ., [6]). RECOMMENDATIONS Patients with arterial thrombosis B For anticoagulation for treatment and secondary prophylaxis of arterial thrombosis in patients with APS, we recommend vitamin K antagonists (VKAs) and do not recommend DOACs (Grade 1B). b Patients with triple positive APS and venous thrombosis B We recommend against the initiation of DOACs for treatment or secondary prophylaxis in patients with venous thrombosis and known triple positive APS (Grade 1B). b B For patients with triple positive APS who are currently on a DOAC, we recommend switching from the DOAC to a VKA after discussion with patients regarding the available evidence. [Extracted from the article]

With an ageing hemophilia population and decreasing mortality from transfusion-transmitted viruses, it is likely that percutaneous coronary interventions and surgery for coronary artery disease and valvular heart disease will become more commonplace. Eighteen reports of cardiac surgery and coronary interventions in patients with hemophilia B are published, and although limited in number and heterogeneous in nature, they represent the available published experience of this complex and evolving field. Cardiac surgery appears to be feasible and safe in individuals with all severities of hemophilia B, but the optimal factor replacement schedule remains uncertain, and there is a lack of consensus on the minimal target factor IX (FIX) level to attain peri- and postoperatively, in addition to the duration of replacement therapy, the use of antifibrinolytic agents, and the use of antithrombotic therapies following surgery. Close cooperation and good communication between all members of a multidisciplinary team are necessary for successful outcome, and an individualized written protocol is highly recommended. For individuals with hemophilia B undergoing coronary intervention, the bleeding risk for patients with different severities of hemophilia B requiring dual antiplatelet therapies after angioplasty and stent insertion is unclear, and the use of antithrombotic therapies pre-, peri- and postprocedure remains unknown. The aim of this overview is to detail key aspects of the management of patients with hemophilia B undergoing cardiac surgery and percutaneous coronary interventions to enable informed decision-making for individual patients in the future and to assist in the development of future management recommendations. [ABSTRACT FROM AUTHOR]

With an ageing hemophilia population and decreasing mortality from transfusion-transmitted viruses, it is likely that percutaneous coronary interventions and surgery for coronary artery disease and valvular heart disease will become more commonplace. Eighteen reports of cardiac surgery and coronary interventions in patients with hemophilia B are published, and although limited in number and heterogeneous in nature, they represent the available published experience of this complex and evolving field. Cardiac surgery appears to be feasible and safe in individuals with all severities of hemophilia B, but the optimal factor replacement schedule remains uncertain, and there is a lack of consensus on the minimal target factor IX (FIX) level to attain peri- and postoperatively, in addition to the duration of replacement therapy, the use of antifibrinolytic agents, and the use of antithrombotic therapies following surgery. Close cooperation and good communication between all members of a multidisciplinary team are necessary for successful outcome, and an individualized written protocol is highly recommended. For individuals with hemophilia B undergoing coronary intervention, the bleeding risk for patients with different severities of hemophilia B requiring dual antiplatelet therapies after angioplasty and stent insertion is unclear, and the use of antithrombotic therapies pre-, peri- and post-procedure remains unknown. The aim of this overview is to detail key aspects of the management of patients with hemophilia B undergoing cardiac surgery and percutaneous coronary interventions to enable informed decision-making for individual patients in the future and to assist in the development of future management recommendations. [ABSTRACT FROM AUTHOR]

ABSTRACTDeficiency in a coagulation factor VIII (FVIII) causes a genetic disorder hemophilia A, which is treated by repeated infusions of expensive FVIII products. Recombinant FVIII (rFVIII), the culmination of years of extensive international research, is an important alternative to plasma-derived FVIII (pdFVIII) and is considered to have a higher margin of safety. Advances in biotechnology allowed production of rFVIII at industrial scale, which significantly improved treatment of hemophilia A patients. We review the contemporary methods used for FVIII expression in mammalian cell culture systems and discuss the factors responsible for insufficient recoveries of rFVIII, such as inefficient accumulation of FVIII mRNA in the cell, complexity of the mechanisms of FVIII secretion, and instability of secreted FVIII. The approaches to improve the yield of rFVIII in cell culture systems include genetic engineering of B-domain-deleted FVIII, introduction of introns into FVIII cDNA constructs for more efficient processing and accumulation of FVIII mRNA, and introduction of mutations into chaperone-binding sites of FVIII to improve its secretion. Design of FVIII with prolonged half-life in vivo is considered as another promising direction in improving rFVIII protein and efficiency of hemophilia A therapy. As an alternative to expression of rFVIII in cell culture systems, we discuss production of rFVIII in transgenic animals, where high levels of rFVIII have been successfully secreted into milk. We also pay attention to the major limitations of this approach, such as safety issues associated with potential transmission of animal pathogens. Finally, we present a brief characterization of commercial recombinant FVIII products currently available on the market for hemophilia A treatment. [Copyright &y& Elsevier]

Hypercoagulable states can be inherited or acquired. Inherited hypercoagulable states can be caused by a loss of function of natural anticoagulant pathways or a gain of function in procoagulant pathways. Acquired hypercoagulable risk factors include a prior history of thrombosis, obesity, pregnancy, cancer and its treatment, antiphospholipid antibody syndrome, heparin-induced thrombocytopenia, and myeloproliferative disorders. Inherited hypercoagulable states combine with acquired risk factors to establish the intrinsic risk of venous thromboembolism for each individual. Venous thromboembolism occurs when the risk exceeds a critical threshold. Often a triggering factor, such as surgery, pregnancy, or estrogen therapy, is required to increase the risk above this critical threshold.

Hypercoagulable states can be inherited or acquired. Inherited hypercoagulable states can be caused by a loss of function of natural anticoagulant pathways or a gain of function in procoagulant pathways. Acquired hypercoagulable risk factors include a prior history of thrombosis, obesity, pregnancy, cancer and its treatment, antiphospholipid antibody syndrome, heparin-induced thrombocytopenia, and myeloproliferative disorders. Inherited hypercoagulable states combine with acquired risk factors to establish the intrinsic risk of venous thromboembolism for each individual. Venous thromboembolism occurs when the risk exceeds a critical threshold. Often a triggering factor, such as surgery, pregnancy, or estrogen therapy, is required to increase the risk above this critical threshold., (Copyright © 2010 Elsevier Inc. All rights reserved.)

A 57-year-old man developed transient global amnesia within an hour of bolus unfractionated heparin administration on day 4 post-mitral valve replacement. Both immunoglobulin G-specific enzyme-linked immunosorbent assay and serotonin release assay were strongly positive for the antibodies that cause heparin-induced thrombocytopenia. The patient's cognitive functions returned to normal following discontinuation of unfractionated heparin and warfarin and commencement of lepirudin infusion.

Low-molecular-weight heparin (LMWH) inhibits the activity of the intrinsic factor X activation complex, a property that persists when LMWH is rendered low affinity (LA) for antithrombin, but is reduced when it is N-desulfated. When LA-LMWH is hypersulfated (sLA-LMWH), its potency against intrinsic tenase is increased and it acquires inhibitory activity against prothrombinase. sLA-LMWH functions by interfering with the association of enzyme and cofactor in both activation complexes. In a rabbit carotid artery thrombosis prevention model, sLA-LMWH is superior to LMWH. Because of its low affinity for antithrombin and multiple sites of action, sLA-LMWH may prove to be safer and more effective than other anticoagulants.