Thromboembolism prophylaxis in orthopaedics: an update

Venous thromboembolism (VTE) is a serious complication during and after hospitalization, yet is a preventable cause of in-hospital death. Without VTE prophylaxis, the overall VTE incidence in medical and general surgery hospitalized patients is in the range of 10% to 40%, while it ranges up to 40% to 60% in major orthopaedic surgery. With routine VTE prophylaxis, fatal pulmonary embolism is uncommon in orthopaedic patients and the rates of symptomatic VTE within three months are in the range of 1.3% to 10%. VTE prophylaxis methods are divided into mechanical and pharmacological. The former include mobilization, graduated compression stockings, intermittent pneumatic compression device and venous foot pumps; the latter include aspirin, unfractionated heparin, low molecular weight heparin (LMWH), adjusted dose vitamin K antagonists, synthetic pentasaccharid factor Xa inhibitor (fondaparinux) and newer oral anticoagulants. LMWH seems to be more efficient overall compared with the other available agents. We remain sceptical about the use of aspirin as a sole method of prophylaxis in total hip and knee replacement and hip fracture surgery, while controversy still exists regarding the use of VTE prophylaxis in knee arthroscopy, lower leg injuries and upper extremity surgery.Cite this article: EFORT Open Rev 2018;3:130-142. DOI: 10.1302/2058-5241.3.170018

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Hemopericardium with subsequent cardiac tamponade secondary to rivaroxaban treatment: a case report

European Heart Journal - Case Reports ◽

10.1093/ehjcr/ytaa482 ◽

2020 ◽

Author(s):

Pinang Shastri ◽

Sapan Bhuta ◽

Carson Oostra ◽

Todd Monroe

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Venous Thromboembolism ◽

Cardiac Tamponade ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Factor Xa ◽

Thromboembolism Prophylaxis ◽

Cardiac Device ◽

Large Pericardial Effusion

Abstract Background The use and utility of novel oral anticoagulants has been increasing in clinical practice due to their relatively lower incidence of side effects such as intracranial haemorrhage, particularly in the elderly, when compared with vitamin K antagonists. Rivaroxaban is a factor Xa and prothrombinase inhibitor indicated for stroke and venous thromboembolism prophylaxis in non-valvular atrial fibrillation as well as treatment of venous thromboembolism. Case summary A patient with history of paroxysmal atrial fibrillation on Rivaroxaban presented with generalized malaise, lightheadedness, and dizziness. The patient was found to be in profound cardiogenic shock despite unremarkable cardiac enzymes. Electrocardiogram revealed rate controlled atrial fibrillation and T-wave inversions in the inferolateral leads without associated electrical alternans. Bedside echocardiogram revealed a large pericardial effusion consistent with cardiac tamponade physiology. Following anticoagulation reversal, the patient underwent urgent pericardiocentesis yielding haemorrhagic fluid, with subsequent improvement in haemodynamic status. Despite the presence of retroperitoneal lymphadenopathy on previous computed tomography of the abdomen and concern for underlying malignant effusion secondary to lymphoma, cytology of the fluid revealed no evidence of malignant cells and follow-up flow cytometry and bone marrow biopsy were unremarkable. Discussion While hemopericardium is not listed as a known side effect of Rivaroxaban, previous cases of hemopericardium secondary to Rivaroxaban have been described in the literature secondary to pre-disposing risk factors including CYP450 drug interactions or cardiac device implantations. In this case, the patient experienced a spontaneous hemopericardium on Rivaroxaban without any previously elucidated risk factors or evidence of malignancy.

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Mechanical prophylaxis of venous thromboembolism in ill hospitalized medical patients: evidence and guidelines

Reviews in Health Care ◽

10.7175/rhc.20233193-207 ◽

2012 ◽

Vol 3 (3) ◽

pp. 193

Author(s):

Luca Masotti ◽

Roberto Cappelli ◽

Grazia Panigada ◽

Giancarlo Landini ◽

Mario Di Napoli

Keyword(s):

Venous Thromboembolism ◽

Randomized Clinical Trials ◽

Oral Anticoagulants ◽

Intermittent Pneumatic Compression ◽

Medical Patients ◽

Compression Stockings ◽

Mechanical Prophylaxis ◽

Mortality And Morbidity ◽

Vte Prophylaxis ◽

Unfractioned Heparin

Venous thromboembolism (VTE) represents one of the leading causes of mortality and morbidity in ill medical patients. Avoiding VTE is therefore of utmost importance in clinical practice. VTE prophylaxis can be assured by pharmacological strategies, such as heparinoids, unfractioned heparin, low molecular weight heparins, fondaparinux or oral anticoagulants and, when these are contraindicated, by mechanical measures, such as graduated compression stockings (GCS) and/ or intermittent pneumatic compression (ICP). However, due to the lack of solid literature evidence, VTE mechanical prophylaxis is not standardized in hospitalized ill medical patients. Much recently, findings from randomized clinical trials on VTE prophylaxis in ill medical patients, such as CLOTS I in patients with stroke and LIFENOX in patients with other kind of medical diseases, seem to increase doubts and reduce certainness in this context and recommendations from guidelines don’t help in reducing confusion. Therefore the aim of this review is to focus on mechanical prophylaxis of VTE in hospitalized ill medical patients.http://dx.doi.org/10.7175/rhc.v3i3.202

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Mechanical prophylaxis of venous thromboembolism in ill hospitalized medical patients: evidence and guidelines

Reviews in Health Care ◽

10.7175/rhc.v3i3.202 ◽

2012 ◽

Vol 3 (3) ◽

pp. 193-207

Author(s):

Luca Masotti ◽

Roberto Cappelli ◽

Grazia Panigada ◽

Giancarlo Landini ◽

Mario Di Napoli

Keyword(s):

Venous Thromboembolism ◽

Randomized Clinical Trials ◽

Oral Anticoagulants ◽

Intermittent Pneumatic Compression ◽

Medical Patients ◽

Compression Stockings ◽

Mechanical Prophylaxis ◽

Mortality And Morbidity ◽

Vte Prophylaxis ◽

Unfractioned Heparin

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Spectrophotometric Assays of Prothrombin in Plasma of Patients Using Oral Anticoagulants

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657025 ◽

1979 ◽

Vol 42 (04) ◽

pp. 1296-1305 ◽

Cited By ~ 29

Author(s):

R M Bertina ◽

W van der Marel-van Nieuwkoop ◽

E A Loeliger

Keyword(s):

Prothrombin Time ◽

Vitamin K ◽

Oral Anticoagulation ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Factor Xa ◽

Factor V ◽

Anticoagulant Treatment ◽

Factor Ii ◽

K Deficiency

SummaryTwo spectrophotometric assays for prothrombin have been developed and compared with a one stage coagulant and an immunological assay. One of these assays (called the XAPC assay) uses a combination of factor Xa, phospholipid, Ca2+ and factor V as activator of prothrombin, and measures only normal prothrombin. The second (the ECAR assay) uses Echis carinatus venom as activator. This assay measures both normal prothrombin and PIVKA II (protein induced by vitamin K antagonists/absence). Combination of the results obtained by the XAPC and ECAR assays provides rapid and reliable information on the degree of “subcarboxylation” of prothrombin (oral anticoagulation, vitamin K deficiency).For patients on long term anticoagulant treatment the prothrombin time (Thrombotest) shows better correlation with the ratio prothrombin/prothrombin plus PIVKA II (XAPC/ ECAR) than with the factor II concentration. For patients starting the anticoagulant treatment there is no correlation between the Thrombotest time and the XAPC/ECAR ratio.It seems doubtful that (a) spectrophotometric factor II assay(s) will be as useful as the prothrombin time in the control of oral anticoagulation.

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Reversal Strategies for Intracranial Hemorrhage Related to Direct Oral Anticoagulant Medications

Critical Care Research and Practice ◽

10.1155/2018/4907164 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 7

Author(s):

Alok Dabi ◽

Aristides P. Koutrouvelis

Keyword(s):

Side Effects ◽

Intracranial Hemorrhage ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Factor Xa ◽

Coagulation Cascade ◽

Reversal Agents ◽

United States Food ◽

Life Threatening

Direct oral anticoagulants (DOACs) are a new class of anticoagulants that directly inhibit either thrombin or factor Xa in the coagulation cascade. They are being increasingly used instead of warfarin or other vitamin K antagonists (VKAs). Adverse side effects of DOACs may result in hemorrhagic complications, including life-threatening intracranial hemorrhage (ICH), though to a much lesser degree than VKAs. Currently there are relatively limited indications for DOACS but their usage is certain to expand with the availability of their respective specific reversal agents. Currently, only idarucizumab (antidote for dabigatran) has been United States Food and Drug Administration- (FDA-) approved, but others (andexanet-α and ciraparantag) may be approved in near future, and the development and availability of such reversal agents have the potential to dramatically change the current anticoagulant use by providing reversal of multiple oral anticoagulants. Until all the DOACs have FDA-approved reversal agents, the treatment of the dreaded side effects of bleeding is challenging. This article is an attempt to provide an overview of the management of hemorrhage, especially ICH, related to DOAC use.

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The Severity of Intracranial Hemorrhages Measured by Free Hemoglobin in the Brain Depends on the Anticoagulant Class: Experimental Data

Stroke Research and Treatment ◽

10.1155/2017/6516401 ◽

2017 ◽

Vol 2017 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

Kyle M. Ware ◽

Douglas L. Feinstein ◽

Israel Rubinstein ◽

Prudhvi Battula ◽

Jose Otero ◽

...

Keyword(s):

Vitamin K ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Factor Xa ◽

Hemoglobin Concentration ◽

Thrombin Inhibitor ◽

Free Hemoglobin ◽

Intracranial Hemorrhages ◽

The Brain

Background and Purpose. Anticoagulant therapy is broadly used to prevent thromboembolic events. Intracranial hemorrhages are serious complications of anticoagulation, especially with warfarin. Direct oral anticoagulants reduce but do not eliminate the risk of intracranial hemorrhages. The aim of this study is to determine the degree of intracranial hemorrhage after application of anticoagulants without additional triggers. Methods. Rats were treated with different anticoagulant classes (vitamin K antagonists, heparin, direct thrombin inhibitor, and factor Xa inhibitor). Brain hemorrhages were assessed by the free hemoglobin concentration in the brain parenchyma. Results. Vitamin K antagonists (warfarin and brodifacoum) significantly increased free hemoglobin in the brain. Among direct oral anticoagulants, thrombin inhibitor dabigatran also significantly increased free hemoglobin in the brain, whereas treatment with factor Xa inhibitor rivaroxaban did not have significant effect on the free hemoglobin concentration. Conclusions. Our data indicates that the severity of brain hemorrhages depends on the anticoagulant class and it is more pronounced with vitamin K antagonists.

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Update on Edoxaban for the Prevention and Treatment of Thromboembolism: Clinical Applications Based on Current Evidence

Advances in Hematology ◽

10.1155/2015/920361 ◽

2015 ◽

Vol 2015 ◽

pp. 1-19 ◽

Cited By ~ 5

Author(s):

Ali Zalpour ◽

Thein Hlaing Oo

Keyword(s):

Vitamin K Antagonists ◽

Dabigatran Etexilate ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Factor Xa ◽

Coagulation Factors ◽

Current Evidence ◽

Thrombin Inhibitor ◽

Prevention And Treatment ◽

Financial Impacts

Vitamin K antagonists (VKA) and heparins have been utilized for the prevention and treatment of thromboembolism (arterial and venous) for decades. Targeting and inhibiting specific coagulation factors have led to new discoveries in the pharmacotherapy of thromboembolism management. These targeted anticoagulants are known as direct oral anticoagulants (DOACs). Two pharmacologically distinct classes of targeted agents are dabigatran etexilate (Direct Thrombin Inhibitor (DTI)) and rivaroxaban, apixaban, and edoxaban (direct oral factor Xa inhibitors (OFXaIs)). Emerging evidence from the clinical trials has shown that DOACs are noninferior to VKA or low-molecular-weight heparins in the prevention and treatment of thromboembolism. This review examines the role of edoxaban, a recently approved OFXaI, in the prevention and treatment of thromboembolism based on the available published literature. The management of edoxaban in the perioperative setting, reversibility in bleeding cases, its role in cancer patients, the relevance of drug-drug interactions, patient satisfaction, financial impacts, and patient education will be discussed.

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The NOACs: clinical pharmacology

ESC CardioMed ◽

10.1093/med/9780198784906.003.0056 ◽

2018 ◽

pp. 268-272

Author(s):

Jeffrey Weitz

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Active Site ◽

Randomized Clinical Trials ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Factor Xa ◽

Vitamin K Antagonist ◽

Phase Iii ◽

High Affinity

The limitations of vitamin K antagonists prompted the development of new oral anticoagulants that could be administered in fixed doses without routine coagulation monitoring. Focusing on thrombin and factor Xa because of their prominent roles in coagulation, structure-based design led to the development of small molecules that bind to the active site pockets of these enzymes with high affinity and specificity. Four non-vitamin K antagonist oral anticoagulants are now licensed: dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. In phase III randomized clinical trials that included over 100,000 patients these agents have proven to be at least as effective as vitamin K antagonists for prevention of stroke in patients with non-valvular atrial fibrillation and for treatment of venous thromboembolism, and to produce less bleeding, particularly less intracranial bleeding.

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Old and new anticoagulants

Hämostaseologie ◽

10.5482/ha-1149 ◽

2011 ◽

Vol 31 (01) ◽

pp. 21-27 ◽

Cited By ~ 26

Author(s):

U. Harbrecht

Keyword(s):

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Factor Xa ◽

New Oral Anticoagulants ◽

Thrombin Inhibitors ◽

Clotting Factor ◽

Direct Thrombin Inhibitors ◽

Self Monitoring ◽

New Anticoagulants ◽

Gastrointestinal Side Effects

SummaryVitamin-K-antagonists (VKA) and heparins have been complementary anticoagulants for prevention and treatment of thrombosis for almost 70 years. In contrast to heparins, VKA have not been modified pharmacologically, however treatment surveillance has improved by introducing INR and self-monitoring/management. Disclosure of the molecular basis of interaction with VKORC1, the target enzyme of VKA, has helped to better understand coumarin sensitivity and resistance. New oral anticoagulants have now been approved and stimulated expectations in patients and physicians to get rid of the burdening frequent controls of VKA without loss of efficacy and safety.This review will summarize the development and profile of the new substances. Main difference compared to VKA is their direct mode of action against one clotting factor which is factor IIa in dabigatran and factor Xa in rivaroxaban and other “xabanes” currently under intensive investigation. Half lifes of the new anticoagulants are much shorter than that of the mainly used coumarins (phenprocoumon, warfarin), making “anticoagulation bridging” unnecessary before surgery. Therapeutic width of direct thrombin inhibitors and factor Xa inhibitors is broader and they are given at fixed doses. Clinical studies in thromboprophylaxis, thromboembolism and atrial fibrillation indicate at least non-inferiority or even superior efficacy compared with enoxaparin and VKA at comparable safety outcomes. Limitations of the new substances may arise from gastrointestinal side effects, mode of metabolism and route of elimination. Specific antidots are not available for none of them.Undoubtedly, the new oral anticoagulants are very promising. But, although thousands of study patients already have been treated, there are questions to be answered such as treatment adherence in absence of monitoring, safety and efficacy in risk patients, dosage adjustment and interactions with other drugs, before conclusions can be drawn towards their potential to replace VKA.

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Complex clinical scenarios with the use of direct oral anticoagulants in patients with atrial fibrillation: a multidisciplinary expert advisory board

Netherlands Heart Journal ◽

10.1007/s12471-020-01424-y ◽

2020 ◽

Vol 28 (10) ◽

pp. 504-513 ◽

Cited By ~ 1

Author(s):

B. A. Mulder ◽

J. ten Berg ◽

H. ten Cate ◽

N. van Es ◽

M. E. W. Hemels ◽

...

Keyword(s):

Atrial Fibrillation ◽

Treatment Guidelines ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Factor Xa ◽

Daily Practice ◽

Advisory Board ◽

Vascular Surgeon ◽

Clinical Scenarios

Abstract The risk of developing atrial fibrillation (AF) and the risk of stroke both increase with advancing age. As such, many individuals have, or will develop, an indication for oral anticoagulation to reduce the risk of stroke. Currently, a large number of anticoagulants are available, including vitamin K antagonists, direct thrombin or factor Xa inhibitors (the last two also referred to as direct oral anticoagulants or DOACs), and different dosages are available. Of the DOACs, rivaroxaban can be obtained in the most different doses: 2.5 mg, 5 mg, 15 mg and 20 mg. Many patients develop co-morbidities and/or undergo procedures that may require the temporary combination of anticoagulation with antiplatelet therapy. In daily practice, clinicians encounter complex scenarios that are not always described in the treatment guidelines, and clear recommendations are lacking. Here, we report the outcomes of a multidisciplinary advisory board meeting, held in Utrecht (The Netherlands) on 3 June 2019, on decision making in complex clinical situations regarding the use of DOACs. The advisory board consisted of Dutch cardiovascular specialists: (interventional) cardiologist, internist, neurologist, vascular surgeon and general practitioners invited according to personal title and specific field of expertise.

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