A variety of pharmacologic and mechanical means can be used to prevent thromboembolic disease following total hip or knee arthroplasty. The existing pharmacologic options are parenteral heparin, fondaparinux, oral warfarin, and oral acetylsalicylic acid. An oral form of heparin as well as direct thrombin inhibitors of factors IIa, IXa, and Xa are being developed in the hope of discovering an agent that effectively prevents thrombi formation but carries a low risk of bleeding complications. Mechanical prophylaxis devices include foot pumps, calf pumps, and calf and thigh pumps for standard pneumatic compression, sequential compression, or rapid inflation compression. Although an ideal prophylaxis does not exist, a multimodal approach incorporating pharmacologic and mechanical prophylaxis has been proved safe and effective. The published recommendations of the American College of Chest Physicians (ACCP) for deep venous thrombosis prophylaxis of total joint patients are widely used throughout the world. These ACCP guidelines have a rigorous foundation in evidence-based medicine and meet the requirements of many oversight groups; some recommendations also meet the standards of certain state and federal programs. In the view of many orthopaedic surgeons, however, these ACCP guidelines have some notable disadvantages. The routine use of relatively aggressive pharmacologic prophylaxis has led to complication rates higher than those reported in the studies used by the ACCP. Equivalent results have been achieved in reducing symptomatic deep venous thrombosis, pulmonary embolisms, and deaths with less aggressive, less expensive prophylaxis protocols that still meet the requirements of recently enacted federal programs that monitor deep venous thrombosis.

https://digitalcommons.wustl.edu/cgi/viewcontent.cgi?article=2117&context=open_access_pubs

Venous thromboembolic disease after total hip and knee arthroplasty.

Coagulation factor Xa induces an inflammatory signalling by activation of protease-activated receptors in human atrial tissue.

Rivaroxaban, an anti-clotting medication, acts at a crucial point in the blood-clotting process and stops the formation of blood clots. In this study, RP-HPLC method was developed for the determination of rivaroxaban in tablets (Xarelto® (10 mg)). Phenomenex Luna 5 µm C18 100 A LC Column (250 x 4.6 mm) was used at 40 oC. Isocratic elution was performed with ACN:Water (55:45 v/v) mixture. The flow rate was 1.2 mL min-1 and UV detection was at 249 nm. Internal standard (Caffeine) and rivaroxaban were eluted within 2.21 and 3.37 minutes, respectively. The developed method was validated according to the ICH guidelines and found to be linear within the range 0.005 - 40.0 µg mL-1. The method was accurate, precise, robust and rapid. Thus, it was applied successfully for the quality control assay of rivaroxaban in tablet dosage form.

/pdf/rp-hplc-method-development-and-validation-for-estimation-of-4tr20xbki9.pdf

RP-HPLC method development and validation for estimation of rivaroxaban in pharmaceutical dosage forms

Design of Novel Aminopyrrolidine Factor Xa Inhibitors from a Screening Hit.

Standardization of VTE prophylaxis may offer significant benefit in the care of the critically ill trauma patient. Current randomized, prospective controlled trials on the effectiveness of various VTE prophylaxis remain lacking. The potential problems with currently available trials, associated with the potential ramification of bleeding and HIT in subsets of trauma patients, require caution in adopting an extremely aggressive approach to VTE prevention. However, improved understanding and administration of VTE prophylaxis appears to be a promising and prudent approach to decreasing morbidity and mortality in injured patients. The goal of this standard operating procedure (SOP) was to standardize the management of injured patients enrolled in the Inflammation and Host Response to Injury Large-Scale Collaborative Program across multiple clinical sites. It is based on the available medical evidence and expert opinion when evidence is not available. The steps in this SOP represent one method of attempting to reach the goal of VTE prevention. Additional prospective randomized controlled trials will likely provide additional information that may stimulate further revisions of this SOP as the VTE prevention in critically ill trauma patients is better defined.

/pdf/inflammation-and-the-host-response-to-injury-a-large-scale-51gew4pv24.pdf

Inflammation and the host response to injury a large-scale collaborative project: patient-oriented research core standard operating procedure for clinical care X. Guidelines for venous thromboembolism prophylaxis in the trauma patient.

Rivaroxaban (Xarelto) is a novel, oral, direct Factor Xa (FXa) inhibitor in late-stage development for the prevention and treatment of thromboembolic disorders. Rivaroxaban inhibits clot-associated and free FXa activity, and prothrombinase activity, and reduces thrombin generation. In animal models, rivaroxaban prevented venous and arterial thrombosis, and was effective at treating venous thrombosis. Rivaroxaban has high oral bioavailability, a rapid onset of action and predictable pharmacokinetics. In phase II studies, rivaroxaban was effective and well tolerated for the prevention of venous thromboembolism (VTE) after major orthopaedic surgery, and for the treatment of deep vein thrombosis. In a phase III study, rivaroxaban demonstrated significantly superior efficacy to enoxaparin for thromboprophylaxis after total knee arthroplasty, with similar low bleeding. Rivaroxaban is also being assessed for the treatment and secondary prevention of VTE, prevention of stroke in patients with atrial fibrillation and secondary prevention in patients with acute coronary syndrome. Rivaroxaban is a promising alternative to current pharmacological agents for thromboembolic disorders.

Rivaroxaban - A novel, oral, direct factor Xa inhibitor in clinical development for the prevention and treatment of thromboembolic disorders

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Rivaroxaban - A novel, oral, direct factor Xa inhibitor in clinical development for the prevention and treatment of thromboembolic disorders