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1.
A Scoping Review of Alternative Anticoagulation Strategies for Hemodialysis Patients with a Mechanical Heart Valve.
Thomson, BKA, Pilkey, NG, Monteith, B, Holden, RM
American journal of nephrology. 2021;(10-11):861-870
Abstract
INTRODUCTION Patients with end-stage renal disease (ESRD) have high rates of cardiac valvulopathy but can develop contraindications for vitamin K antagonist (VKA) therapy. We explored the evidence for alternative anticoagulation strategies in patients with ESRD with a contraindication for VKA therapy. METHODS A scoping review was completed, searching MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Conference abstracts from inception to March 30, 2021. The study population was patients with ESRD who were on VKA therapy and developed a contraindication to VKA therapy use. All data regarding studies, patient characteristics, anticoagulation strategy, and clinical outcomes were summarized. RESULTS Twenty-three articles met inclusion criteria. These articles included 57 patients. Contraindications to VKA therapy included calcific uremic arteriolopathy (CUA) (n = 55) and warfarin-induced skin necrosis (n = 2). All studies were either case reports or case series. There were 10 anticoagulation strategies identified. Continuation of VKA therapy was associated with increased death and decreased rates of CUA resolution (80.0% and 10.0%, respectively), compared to apixaban (24.0% and 70.8%), subcutaneous (SC) low-molecular-weight heparin (LMWH) (14.3%, 85.7%), and SC unfractionated heparin (0.0%, 100.0%). While only 5 patient cases were reported with mechanical heart valves, SC LMWH use has been reported in this context with good outcomes. CONCLUSIONS In patients with ESRD who develop a contraindication to VKA therapy, several alternative anticoagulation strategies have been reported with superior outcomes to VKA continuation. While outcomes appear superior to continuation of VKA therapy, more data are required before definitive recommendations can be made for the patient with ESRD and a mechanical heart valve.
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2.
Rationale for the Role of Heparin and Related GAG Antithrombotics in COVID-19 Infection.
Magnani, HN
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2021;:1076029620977702
Abstract
The SARS-CoV-2 pandemic has focused attention on prevention, restriction and treatment methods that are acceptable worldwide. This means that they should be simple and inexpensive. This review examines the possible role of glycosaminoglycan (GAG) antithrombotics in the treatment of COVID-19. The pathophysiology of this disease reveals a complex interplay between the hemostatic and immune systems that can be readily disrupted by SARS-CoV-2. Some of the GAG antithrombotics also possess immune-modulatory actions and since they are relatively inexpensive they could play an important role in the management of COVID-19 and its complications.
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3.
Venous Thromboembolism in Children: From Diagnosis to Management.
Lassandro, G, Palmieri, VV, Palladino, V, Amoruso, A, Faienza, MF, Giordano, P
International journal of environmental research and public health. 2020;(14)
Abstract
Venous thromboembolism (VTE) in children is a rare occurrence, although in recent decades we have seen an increase due to several factors, such as the rise in survival of subjects with chronic conditions, the use of catheters, and the increased sensitivity of diagnostic tools. Besides inherited thrombophilia, acquired conditions such as cardiovascular diseases, infections, chronic disorders, obesity and malignancy are also common risk factors for paediatric VTE. The treatment of paediatric VTE consists of the use of heparins and/or vitamin K antagonists to prevent dissemination, embolization, and secondary VTE. Randomized clinical trials of direct oral anticoagulants in paediatric VTE are ongoing, with the aim to improve the compliance and the care of patients. We reviewed the physiological and pathological mechanisms underlying paediatric thrombosis and updated the current diagnosis and treatment options.
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4.
Rationale and evidence for the incorporation of heparin into the diclofenac epolamine medicated plaster.
Rainsford, KD, Roberts, MS, Nencioni, A, Jones, C
Current medical research and opinion. 2019;(6):989-1002
Abstract
OBJECTIVE The nonsteroidal anti-inflammatory drug (NSAID) diclofenac epolamine (DHEP) formulated as a topical patch has demonstrated efficacy and safety in the localized treatment of acute pain from minor strains, sprains and contusions, and for epicondylitis and knee osteoarthritis. The glycosaminoglycan heparin enhances the activity of topical NSAIDs formulated as a medicated plaster, even in the absence of any significant release of heparin. Therefore, DHEP plus, a new formulation of the DHEP medicated plaster containing a small amount of heparin sodium as excipient, has been developed. METHODS We reviewed the pivotal and supportive studies of the clinical development program of the new patch and evaluated the role of heparin as an enhancer in the treatment of localized pain/inflammation of musculoskeletal structures, associated with post-traumatic and/or rheumatic conditions. RESULTS The data was consistent with the concept that heparin increased the clinical activity of the DHEP plus medicated plaster versus the reference DHEP medicated plaster through improved bioavailability due to enhanced movement of diclofenac from the plaster. Both DHEP formulations have the same dissolution profile, indicating that heparin does not change the physical and chemical characteristics of the plaster. Permeation testing showed that heparin is not released from the DHEP plus medicated plaster. Efficacy studies showed that the DHEP plus medicated plaster was significantly more effective in reducing pain than the reference marketed DHEP medicated plaster. CONCLUSIONS The benefit/risk assessment of DHEP plus 180 mg medicated plaster is favorable, with a safety profile equal to placebo and improved efficacy over the reference marketed DHEP medicated plaster.
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5.
An update on evidence based diagnostic and confirmatory testing strategies for heparin induced thrombocytopenia using combined immunological and functional assays.
Amiral, J, Seghatchian, J
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2018;(6):804-811
Abstract
This manuscript aims to provide a concise review on current diagnostic/ confirmatory strategies of Heparin Induced Thrombocytopenia (HIT) with the combined use of immunological / functional assays in addition to the clinical probability. Laboratory diagnosis of HIT is of primordial importance as the related complications could become rapidly severe and life-threatening and can provoke limb amputation in some cases. The first action in the presence of HIT suspicion is to withdraw heparin and to initiate an alternative anticoagulant. Whilst vitamin K antagonists are not appropriate, anticoagulant options include Fondaparinux, Sodium Danaparoid, DOACs, Argatroban, and Bivalirudin. However, if HIT is excluded, patients can benefit again from the high therapeutic and antithrombotic efficacy of this drug, which remains superior to all the substitutive anticoagulant treatments. HIT is suspected in the presence of a platelet count drop > 50% on 2 successive counts, or a platelet count < 100 G/L, and of a significant clinical probability (4 Ts score). Testing patients' plasma is required for establishing the diagnosis. Laboratory investigation involves first the immunological measurement of heparin dependent IgG antibodies (mainly targeted to Heparin-Platelet Factor 4 complexes). When positive, a functional assay for platelet activation, performed at a low and high heparin concentration, allows confirming this disease. In any case, if the immuno-assay is negative, HIT can be excluded with a high probability, and heparin can be continued (if clinical examination favors this decision). Conversely, the higher the IgG antibody concentration is (and affinity), the higher is the probability of developing HIT. The functional assay has now become for confirming the platelet activation capacity of antibodies, and therefore confirming the presence of HIT. Up to now, the gold reference method for testing antibody-dependent platelet activation is the C14-Serotonin Release Assay, available only in very few laboratories working with radio-isotopes. A simple, sensitive, and accurate flow cytometry assay becomes now available to all clinical sites, and it can be easily used for testing the capacity of heparin dependent-antibodies to activate platelets, at low heparin concentration. This technique can be performed in any laboratory equipped with a flow cytometer and can make the HIT confirmation diagnosis rapidly available, which introduces a great improvement for management of patients with HIT. We believe that an evidence-based update on this topic is timely and well warranted.
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6.
Management of Perioperative Anticoagulation for Device Implantation.
Stewart, MH, Morin, DP
Cardiac electrophysiology clinics. 2018;(1):99-109
Abstract
Periprocedural management of anticoagulation for cardiac device implantation has evolved over the past 20 years. The traditional paradigm of vitamin K antagonist interruption with heparin bridging has now been shown to be less safe than continuation of vitamin K antagonists at therapeutic levels. Dual antiplatelet therapy during device implantation poses substantial risk but is often necessary. The safest dosing strategy for newer direct oral anticoagulants is still not clear.
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7.
Management of the multiple phases of heparin-induced thrombocytopenia.
Cuker, A
Thrombosis and haemostasis. 2016;(5):835-842
Abstract
The clinical course of heparin-induced thrombocytopenia (HIT) may be separated into five sequential phases: 1. suspected HIT, 2. acute HIT, 3. subacute HIT A, 4. subacute HIT B, and 5. remote HIT. Each phase confronts the clinician with a unique set of management questions. In this review, the phases of HIT are defined and key management questions associated with each phase are discussed. Among patients with Suspected HIT, I use the 4Ts score to determine which patients have a sufficiently high probability of HIT to justify discontinuation of heparin and initiation of a non-heparin parenteral anticoagulant. An algorithm for selecting an appropriate non-heparin anticoagulant based on the patient's clinical stability, renal and hepatic function, drug availability, and physician comfort is provided. In patients with Acute HIT, I generally avoid prophylactic platelet transfusion and inferior vena cava filter insertion because of a potential increased risk of thrombosis. I perform 4-limb screening compression ultrasonography. In patients with symptomatic thromboembolism or asymptomatic proximal deep-vein thrombosis, I treat with anticoagulation for three months. In patients without thrombosis, I discontinue anticoagulation upon platelet count recovery. I do not transition patients to an oral anticoagulant until platelet count recovery (i. e. Subacute HIT A). I increasingly choose direct oral anticoagulants over vitamin K antagonists in this setting because of their greater convenience and safety. In Subacute HIT B and Remote HIT, I use heparin for cardiovascular surgery, whereas I use bivalirudin in patients with Acute HIT and Subacute HIT A in whom surgery cannot be delayed.
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8.
Heparins in cancer-associated venous thrombosis.
Krasiński, Z, Krasińska, B, Dzieciuchowicz, Ł, Urbanek, T, Gabriel, M
Polskie Archiwum Medycyny Wewnetrznej. 2016;(6):419-29
Abstract
A close causal relationship between cancer and venous thrombosis gives rise to questions about the effect of treatment modalities, in particular of the administered drugs, in patients with cancer-related venous thrombosis. An increased risk of chemotherapy-associated venous thromboembolism (VTE) has been well documented, while the effect of heparins used in VTE treatment on the disease course and prognosis in cancer patients has not been fully elucidated. This paper discusses the outcomes of the studies conducted so far investigating the role of heparins, in particular, low-molecular-weight heparins (LMWHs), in the prevention of thrombosis in cancer patients. It also focuses on such aspects of the treatment for cancer-associated VTE as treatment duration and drugs used. The paper summarizes the often discrepant results of long-term therapies with various LMWH products, emphasising that in this specific case the class effect is rather unlikely. It also presents the possible effects of heparins administered as part of cancer treatment, and points to the effects of LMWHs on cancer that are not related to an antithrombotic effect. On the 100th anniversary of heparin discovery, it can be said that heparin is irreversibly connected with thrombosis in the course of cancer.
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9.
Anticoagulants (extended duration) for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair.
Forster, R, Stewart, M
The Cochrane database of systematic reviews. 2016;(3):CD004179
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Abstract
BACKGROUND The optimal duration of thromboprophylaxis after total hip or knee replacement, or hip fracture repair remains controversial. It is common practice to administer prophylaxis using low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) until discharge from hospital, usually seven to 14 days after surgery. International guidelines recommend extending thromboprophylaxis for up to 35 days following major orthopaedic surgery but the recommendation is weak due to moderate quality evidence. In addition, recent oral anticoagulants that exert effect by direct inhibition of thrombin or activated factor X lack the need for monitoring and have few known drug interactions. Interest in this topic remains high. OBJECTIVES To assess the effects of extended-duration anticoagulant thromboprophylaxis for the prevention of venous thromboembolism (VTE) in people undergoing elective hip or knee replacement surgery, or hip fracture repair. SEARCH METHODS The Cochrane Vascular Information Specialist searched the Specialised Register (last searched May 2015) and CENTRAL (2015, Issue 4). Clinical trials databases were searched for ongoing or unpublished studies. SELECTION CRITERIA Randomised controlled trials assessing extended-duration thromboprophylaxis (five to seven weeks) using accepted prophylactic doses of LMWH, UFH, vitamin K antagonists (VKA) or direct oral anticoagulants (DOAC) compared with short-duration thromboprophylaxis (seven to 14 days) followed by placebo, no treatment or similar extended-duration thromboprophylaxis with LMWH, UFH, VKA or DOACs in participants undergoing hip or knee replacement or hip fracture repair. DATA COLLECTION AND ANALYSIS We independently selected trials and extracted data. Disagreements were resolved by discussion. We performed fixed-effect model meta-analyses with odds ratios (ORs) and 95% confidence intervals (CIs). We used a random-effects model when there was heterogeneity. MAIN RESULTS We included 16 studies (24,930 participants); six compared heparin with placebo, one compared VKA with placebo, two compared DOAC with placebo, one compared VKA with heparin, five compared DOAC with heparin and one compared anticoagulants chosen at investigators' discretion with placebo. Three trials included participants undergoing knee replacement. No studies assessed hip fracture repair.Trials were generally of good methodological quality. The main reason for unclear risk of bias was insufficient reporting. The quality of evidence according to GRADE was generally moderate, as some comparisons included a single study, low number of events or heterogeneity between studies leading to wide CIs.We showed no difference between extended-duration heparin and placebo in symptomatic VTE (OR 0.59, 95% CI 0.35 to 1.01; 2329 participants; 5 studies; high quality evidence), symptomatic deep vein thrombosis (DVT) (OR 0.73, 95% CI 0.39 to 1.38; 2019 participants; 4 studies; moderate quality evidence), symptomatic pulmonary embolism (PE) (OR 0.61, 95% CI 0.16 to 2.33; 1595 participants; 3 studies; low quality evidence) and major bleeding (OR 0.59, 95% CI 0.14 to 2.46; 2500 participants; 5 studies; moderate quality evidence). Minor bleeding was increased in the heparin group (OR 2.01, 95% CI 1.43 to 2.81; 2500 participants; 5 studies; high quality evidence). Clinically relevant non-major bleeding was not reported.We showed no difference between extended-duration VKA and placebo (one study, 360 participants) for symptomatic VTE (OR 0.10, 95% CI 0.01 to 1.94; moderate quality evidence), symptomatic DVT (OR 0.13, 95% CI 0.01 to 2.62; moderate quality evidence), symptomatic PE (OR 0.32, 95% CI 0.01 to 7.84; moderate quality evidence) and major bleeding (OR 2.89, 95% CI 0.12 to 71.31; low quality evidence). Clinically relevant non-major bleeding and minor bleeding were not reported.Extended-duration DOAC showed reduced symptomatic VTE (OR 0.20, 95% CI 0.06 to 0.68; 2419 participants; 1 study; moderate quality evidence) and symptomatic DVT (OR 0.18, 95% CI 0.04 to 0.81; 2459 participants; 2 studies; high quality evidence) compared to placebo. No differences were found for symptomatic PE (OR 0.25, 95% CI 0.03 to 2.25; 1733 participants; 1 study; low quality evidence), major bleeding (OR 1.00, 95% CI 0.06 to 16.02; 2457 participants; 1 study; low quality evidence), clinically relevant non-major bleeding (OR 1.22, 95% CI 0.76 to 1.95; 2457 participants; 1 study; moderate quality evidence) and minor bleeding (OR 1.18, 95% CI 0.74 to 1.88; 2457 participants; 1 study; moderate quality evidence).We showed no difference between extended-duration anticoagulants chosen at investigators' discretion and placebo (one study, 557 participants, low quality evidence) for symptomatic VTE (OR 0.50, 95% CI 0.09 to 2.74), symptomatic DVT (OR 0.33, 95% CI 0.03 to 3.21), symptomatic PE (OR 1.00, 95% CI 0.06 to 16.13), and major bleeding (OR 5.05, 95% CI 0.24 to 105.76). Clinically relevant non-major bleeding and minor bleeding were not reported.We showed no difference between extended-duration VKA and heparin (one study, low quality evidence) for symptomatic VTE (OR 1.64, 95% CI 0.85 to 3.16; 1279 participants), symptomatic DVT (OR 1.36, 95% CI 0.69 to 2.68; 1279 participants), symptomatic PE (OR 9.16, 95% CI 0.49 to 170.42; 1279 participants), major bleeding (OR 3.87, 95% CI 1.91 to 7.85; 1272 participants) and minor bleeding (OR 1.33, 95% CI 0.64 to 2.76; 1279 participants). Clinically relevant non-major bleeding was not reported.We showed no difference between extended-duration DOAC and heparin for symptomatic VTE (OR 0.70, 95% CI 0.28 to 1.70; 15,977 participants; 5 studies; low quality evidence), symptomatic DVT (OR 0.60, 95% CI 0.11 to 3.27; 15,977 participants; 5 studies; low quality evidence), symptomatic PE (OR 0.91, 95% CI 0.43 to 1.94; 14,731 participants; 5 studies; moderate quality evidence), major bleeding (OR 1.11, 95% CI 0.79 to 1.54; 16,199 participants; 5 studies; high quality evidence), clinically relevant non-major bleeding (OR 1.08, 95% CI 0.90 to 1.28; 15,241 participants; 4 studies; high quality evidence) and minor bleeding (OR 0.95, 95% CI 0.82 to 1.10; 11,766 participants; 4 studies; high quality evidence). AUTHORS' CONCLUSIONS Moderate quality evidence suggests extended-duration anticoagulants to prevent VTE should be considered for people undergoing hip replacement surgery, although the benefit should be weighed against the increased risk of minor bleeding. Further studies are needed to better understand the association between VTE and extended-duration oral anticoagulants in relation to knee replacement and hip fracture repair, as well as outcomes such as distal and proximal DVT, reoperation, wound infection and healing.
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Pharmacotherapy of heparin-induced thrombocytopenia: therapeutic options and challenges in the clinical practices.
Al-Eidan, FA
Journal of vascular nursing : official publication of the Society for Peripheral Vascular Nursing. 2015;(1):10-20
Abstract
Heparin-induced thrombocytopenia (HIT) is an immune response to heparin associated with significant morbidity and mortality in hospitalized patients if unidentified as soon as possible, owing to thromboembolic complications involving both arterial and venous systems. Early diagnoses based on a comprehensive interpretation of clinical and laboratory information improves clinical outcomes. Management principles of strongly suspected HIT should not be delayed for laboratory result confirmation. Treatment strategies have been introduced including new, safe, and effective agents. This review summarizes the clinical therapeutic options for HIT addressing the use of parenteral direct thrombin inhibitors and indirect factor Xa inhibitors as well as the potential non-vitamin K antagonist oral anticoagulants.