Drug and Alcohol Rehabilitation: Genome-Wide Association Analysis of Anti-TNF Drug Response in Patients With Rheumatoid Arthritis.

Genome-wide association analysis of anti-TNF drug response in patients with rheumatoid arthritis.

Filed under: Drug and Alcohol Rehabilitation

Ann Rheum Dis. 2012 Dec 11;
Umicevic Mirkov M, Cui J, Vermeulen SH, Stahl EA, Toonen EJ, Makkinje RR, Lee AT, Huizinga TW, Allaart R, Barton A, Mariette X, Miceli CR, Criswell LA, Tak PP, de Vries N, Saevarsdottir S, Padyukov L, Bridges SL, van Schaardenburg DJ, Jansen TL, Dutmer EA, van de Laar MA, Barrera P, Radstake TR, van Riel PL, Scheffer H, Franke B, Brunner HG, Plenge RM, Gregersen PK, Guchelaar HJ, Coenen MJ

BACKGROUND: Treatment strategies blocking tumour necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA). However, a significant subset of patients does not respond for unknown reasons. Currently, there are no means of identifying these patients before treatment. This study was aimed at identifying genetic factors predicting anti-TNF treatment outcome in patients with RA using a genome-wide association approach. METHODS: We conducted a multistage, genome-wide association study with a primary analysis of 2 557 253 single-nucleotide polymorphisms (SNPs) in 882 patients with RA receiving anti-TNF therapy included through the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry and the database of Apotheekzorg. Linear regression analysis of changes in the Disease Activity Score in 28 joints after 14 weeks of treatment was performed using an additive model. Markers with p<10(-3) were selected for replication in 1821 patients from three independent cohorts. Pathway analysis including all SNPs with p<10(-3) was performed using Ingenuity. RESULTS: 772 markers showed evidence of association with treatment outcome in the initial stage. Eight genetic loci showed improved p value in the overall meta-analysis compared with the first stage, three of which (rs1568885, rs1813443 and rs4411591) showed directional consistency over all four cohorts studied. We were unable to replicate markers previously reported to be associated with anti-TNF outcome. Network analysis indicated strong involvement of biological processes underlying inflammatory response and cell morphology. CONCLUSIONS: Using a multistage strategy, we have identified eight genetic loci associated with response to anti-TNF treatment. Further studies are required to validate these findings in additional patient collections. HubMed – drug


Perioperative management of patients on chronic antithrombotic therapy.

Filed under: Drug and Alcohol Rehabilitation

Hematology Am Soc Hematol Educ Program. 2012; 2012: 529-35
Ortel TL

Perioperative management of antithrombotic therapy is a situation that occurs frequently and requires consideration of the patient, the procedure, and an expanding array of anticoagulant and antiplatelet agents. Preoperative assessment must address each patient’s risk for thromboembolic events balanced against the risk for perioperative bleeding. Procedures can be separated into those with a low bleeding risk, which generally do not require complete reversal of the antithrombotic therapy, and those associated with an intermediate or high bleeding risk. For patients who are receiving warfarin who need interruption of the anticoagulant, consideration must be given to whether simply withholding the anticoagulant is the optimal approach or whether a perioperative “bridge” with an alternative agent, typically a low-molecular-weight heparin, should be used. The new oral anticoagulants dabigatran and rivaroxaban have shorter effective half-lives, but they introduce other concerns for perioperative management, including prolonged drug effect in patients with renal insufficiency, limited experience with clinical laboratory testing to confirm lack of residual anticoagulant effect, and lack of a reversal agent. Antiplatelet agents must also be considered in the perioperative setting, with particular consideration given to the potential risk for thrombotic complications in patients with coronary artery stents who have antiplatelet therapy withheld.
HubMed – drug


Pharmacologic tools to reduce bleeding in surgery.

Filed under: Drug and Alcohol Rehabilitation

Hematology Am Soc Hematol Educ Program. 2012; 2012: 517-21
Schulman S

Strategies to reduce blood loss and the need for transfusions in surgery include enhancement of coagulation, inhibition of fibrinolysis, and an improved decision algorithm for transfusion based on bedside monitoring of global hemostasis. The synthetic antifibrinolytic drug tranexamic acid has emerged as an effective alternative in this respect for orthopedic and cardiac surgery. Although it seems less effective than aprotinin, it has not been associated with the increased risk of mortality of the latter. Thromboelastography to monitor the global hemostatic capacity and to guide the appropriate use of blood components in cardiac surgery is also effective in reducing the need for transfusion. Patients on antithrombotic drug therapy may need reversal before surgery to avoid excessive blood loss, or intraoperatively in cases of unexpected bleeding. Available options are protamine for unfractionated or low-molecular-weight heparin, recombinant activated factor VII for fondaparinux, prothrombin complex concentrate for vitamin K antagonists and possibly for oral factor Xa inhibitors, dialysis and possibly activated prothrombin complex concentrate for oral thrombin inhibitors, desmopressin for aspirin and possibly for thienopyridines, and platelet transfusions for the latter.
HubMed – drug


Coagulation assays and anticoagulant monitoring.

Filed under: Drug and Alcohol Rehabilitation

Hematology Am Soc Hematol Educ Program. 2012; 2012: 460-5
Funk DM

Anticoagulant therapy, including conventional agents and a variety of new oral, fast-acting drugs, is prescribed for millions of patients annually. Each anticoagulant varies in its effect on routine and specialty coagulation assays and each drug may require distinct laboratory assay(s) to measure drug concentration or activity. This review provides an overview of the assorted assays that can measure anticoagulant drug concentration or activity and includes key assay interferences. The effect of these conventional and new anticoagulant agents on specialty coagulation assays used to evaluate for bleeding or clotting disorders, and whether this impact is physiological or factitious, is included. Also provided is a short review of superwarfarin poisoning and features distinguishing this from warfarin overdose. Knowledge of clinically significant pearls and pitfalls pertinent to coagulation assays in relation to anticoagulant therapy are important to optimize patient care.
HubMed – drug


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