-
Circulation Reports Jun 2024Factor Xa inhibitors, such as rivaroxaban, are increasing the convenience of treatment for deep vein thrombosis (DVT). Limited evidence exists regarding clot evaluation...
Factor Xa inhibitors, such as rivaroxaban, are increasing the convenience of treatment for deep vein thrombosis (DVT). Limited evidence exists regarding clot evaluation at 3 months after treatment for DVT. We retrospectively analyzed the clinical course of symptomatic proximal DVT in patients who received 3 months of anticoagulation treatment at our hospital. Patients treated with the rivaroxaban single-drug approach were classified as group A (n=42). Patients treated with unfractionated heparin (UFH) or subcutaneous fondaparinux followed by vitamin K antagonist comprised group B (n=60) as an historical cohort. The quantitative ultrasound thrombosis (QUT) score was used to quantify clot burden before and after treatment. No significant differences were observed in patient characteristics between the groups. Serum D-dimer levels in both groups significantly improved after treatment. Clot volume assessed using QUT also reduced significantly in both groups. The QUT score in groups A and B improved from 7.5 [4.8, 12.0] to 3.0 [1.8, 5.0; P=0.000] and 7.0 [4.0, 9.8] to 3.0 [2.0, 5.0; P=0.000], respectively. The change in QUT (∆QUT) was significantly greater in group A compared with group B (-4.5 [-8.25, -2.0] vs. -2.0 [-6.0, 0.0]; P=0.005). We were able to demonstrate the effectiveness of DVT treatment using rivaroxaban over a period of 3 months from onset, in terms of clot regression evaluated using the QUT score.
PubMed: 38860185
DOI: 10.1253/circrep.CR-24-0042 -
Cureus May 2024Cerebral venous thrombosis (CVT) is a cerebrovascular condition characterized by cerebral venous sinus thrombosis, resulting in venous infarction. The condition can...
Multifaceted Cerebral Venous Thrombosis With Extensive Intra-cerebral Hemorrhage in a Young Man With Mitral Valve Replacement Due to Thrombosis and IgA Nephropathy: A Challenging Case Report From Saudi Arabia.
Cerebral venous thrombosis (CVT) is a cerebrovascular condition characterized by cerebral venous sinus thrombosis, resulting in venous infarction. The condition can manifest through a range of signs and symptoms such as headaches, benign intracranial hypertension, subarachnoid hemorrhage, localized neurological deficits, seizures, unexplained changes in consciousness, and meningoencephalitis. Its causes are linked to numerous different conditions and factors. We report a complicated case and course of antiphospholipid antibody syndrome in a young patient. The case began two years prior, involving a 33-year-old man who had chronic kidney disease due to IgA nephropathy, pneumonia, and a large mass on his native mitral valve. He developed deep vein thrombosis (DVT) in his upper limb, for which he was prescribed warfarin. He was transferred to our hospital with a five-day history of severe headaches followed by a decrease in consciousness and seizures requiring intubation. He was found to have a subdural hematoma with a high international normalized ratio (INR). He underwent hematoma evacuation and a right decompressive craniotomy. CT of the brain via CT venography revealed intracerebral haemorrhage along with ischemic infarction in the right frontal-parietal and temporal lobes and cerebral venous thrombosis. He was treated with heparin infusion but later developed heparin-induced thrombocytopenia (HIT) and was switched to fondaparinux. Plasma exchange and intravenous methylprednisolone were given. His hospital course was complicated by recurrent infections, a new left intraparenchymal hemorrhage with intraventricular extension, and the need for extra ventricular drainage (EVD). The diagnosis of antiphospholipid antibody syndrome was confirmed. This case report provides invaluable insights into managing a complex scenario that requires balanced decisions between anticoagulation in the context of severe ICH and the necessity of immunosuppressive therapy. The emphasis is on the significance of using a personalized and multidisciplinary strategy to address CVT situations and their issues.
PubMed: 38854275
DOI: 10.7759/cureus.60016 -
International Journal of Biological... Jun 2024Low molecular weight heparin and synthetic mimetics such as fondaparinux show different binding kinetics, protease specificity, and clinical effects. A combination of...
Low molecular weight heparin and synthetic mimetics such as fondaparinux show different binding kinetics, protease specificity, and clinical effects. A combination of allosteric and template-mediated bridging mechanisms have been proposed to explain the differences in rate acceleration and specificity. The difficulty in working with heterogeneous heparin species has rendered a crystallographic interpretation of the differences in antithrombin activation between mimetics and natural heparin inaccessible. In this study, we examine the allosteric changes in antithrombin caused by binding fondaparinux, enoxaparin and depolymerized natural heparins using millisecond hydrogen deuterium exchange mass spectrometry (TRESI-HDX MS) and relate these conformational changes to complex stability in the gas phase using collision induced unfolding (CIU). This exploration reveals that in addition to the dynamic changes caused by fondaparinux, long chain heparins reduce structural flexibility proximal to Arg393, the cleavable residue in the reactive centre loop of the protein. These local changes in protein dynamics are associated with an increase in overall complex stability that increases with heparin chain length. Ultimately, these results shed light on the molecular mechanisms underlying differences in activity and specificity between heparin mimetics and natural heparins.
PubMed: 38838881
DOI: 10.1016/j.ijbiomac.2024.132868 -
Journal of Musculoskeletal & Neuronal... Jun 2024Total hip arthroplasty (THA) is a highly successful and effective surgery for improving hip functions and relieving pain. However, the lower extremities are prone to... (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVES
Total hip arthroplasty (THA) is a highly successful and effective surgery for improving hip functions and relieving pain. However, the lower extremities are prone to deep vein thrombosis (DVT) and swelling after surgery, thereby delaying recovery. In this study, we investigated the preventive effects of fondaparinux sodium (FS) and low-molecular-weight heparin (LMWH) on DVT of the lower extremity after THA.
METHODS
Firstly, 60 patients who underwent THA at the First Affiliated Hospital of Wannan Medical College from March 2020 to December 2020 were included. Next, the patients were randomly divided into an LMWH group (n = 30) and an FS group (n = 30). Then, the indexes related to DVT were compared between both groups.
RESULTS
Specifically, the differences in baseline data, such as age, gender and body mass index (BMI), between the two groups were not statistically significant. The postoperative weight bearing time of patients in the FS group was much shorter than that in the LMWH group.
CONCLUSION
Subcutaneous injection of FS not only exhibits superior effects to LMWH in preventing DVT after THA but also has a correlation with reducing the risk of thrombosis and improving patient symptoms.
Topics: Humans; Arthroplasty, Replacement, Hip; Heparin, Low-Molecular-Weight; Fondaparinux; Male; Female; Venous Thrombosis; Middle Aged; Aged; Anticoagulants; Postoperative Complications
PubMed: 38826001
DOI: No ID Found -
Carbohydrate Polymers Sep 2024Natural heparin, a glycosaminoglycan consisting of repeating hexuronic acid and glucosamine linked by 1 → 4 glycosidic bonds, is the most widely used anticoagulant.... (Review)
Review
Natural heparin, a glycosaminoglycan consisting of repeating hexuronic acid and glucosamine linked by 1 → 4 glycosidic bonds, is the most widely used anticoagulant. To subvert the dependence on animal sourced heparin, alternative methods to produce heparin saccharides, i.e., either heterogenous sugar chains similar to natural heparin, or structurally defined oligosaccharides, are becoming hot subjects. Although the success by chemical synthesis of the pentasaccharide, fondaparinux, encourages to proceed through a chemical approach generating homogenous product, synthesizing larger oligos is still cumbersome and beyond reach so far. Alternatively, the chemoenzymatic pathway exhibited exquisite stereoselectivity of glycosylation and regioselectivity of modification, with the advantage to skip the tedious protection steps unavoidable in chemical synthesis. However, to a scale of drug production needed today is still not in sight. In comparison, a procedure of de novo biosynthesis in an organism could be an ultimate goal. The main purpose of this review is to summarize the current available/developing strategies and techniques, which is expected to provide a comprehensive picture for production of heparin saccharides to replenish or eventually to replace the animal derived products. In chemical and chemoenzymatic approaches, the methodologies are discussed according to the synthesis procedures: building block preparation, chain elongation, and backbone modification.
Topics: Heparin; Glycosylation; Anticoagulants; Animals; Oligosaccharides
PubMed: 38823902
DOI: 10.1016/j.carbpol.2024.122220 -
Journal of Vascular Surgery. Venous and... May 2024The aim of this study was to assess the utilization of surgical interventions in patients diagnosed with superficial vein thrombosis (SVT) and its potential association...
OBJECTIVE
The aim of this study was to assess the utilization of surgical interventions in patients diagnosed with superficial vein thrombosis (SVT) and its potential association with the occurrence of venous thromboembolism (VTE) and bleeding events.
METHODS
INSIGHTS-SVT, a prospective, non-interventional, multicenter study in Germany, investigated the management and outcomes of patients with acute SVT who received conservative and/or invasive treatments at the discretion of the treating physician.
RESULTS
Among the 872 patients with 12-month data, 657 had medical therapy only, and 215 patients underwent vascular surgery (70 within three months of SVT diagnosis, 136 between months 4 and 12, and 9 had an intervention in both periods). The most commonly performed procedures included endovenous thermal ablation (EVTA), ligation of the saphenofemoral or saphenopopliteal junction (SFJ/SPJ), and vein stripping. The primary outcome of symptomatic VTE was observed in 5.8% of conservatively treated patients and 6.3% of those who underwent surgical intervention. Additionally, the secondary outcome of recurrent or extended SVT was documented in 4.7% of conservatively treated patients and 5.3% of invasively treated patients. Bleeding events occurred in 1.4% of conservatively treated patients and 2.1% of surgically treated patients. These differences were statistically not significant. Furthermore, our analysis indicated a potential protective effect associated with surgical treatments, such as ligation of the SFJ/SPJ, stripping and EVTA, concerning the endpoint of VTE for patients when applied after 3 months from the index SVT event.
CONCLUSIONS
In line with previous research, our study suggests that surgical interventions are not frequently employed in the management of SVT, although they may be warranted in select cases. Nevertheless, additional research is essential to gain a deeper understanding of the indications, criteria and benefit of surgical interventions in the treatment of SVT.
PubMed: 38821188
DOI: 10.1016/j.jvsv.2024.101917 -
BMC Surgery May 2024To compare the efficacy of nadroparin and fondaparinux sodium for prevention of deep vein thromboembolism (DVT) in lower extremities after total hip arthroplasty (THA)... (Comparative Study)
Comparative Study
Comparison of efficacy of nadroparin and fondaparinux sodium for prevention of deep vein thromboembolism in lower extremities after total hip arthroplasty and total knee arthroplasty: a retrospective study of 592 patients.
OBJECTIVES
To compare the efficacy of nadroparin and fondaparinux sodium for prevention of deep vein thromboembolism (DVT) in lower extremities after total hip arthroplasty (THA) and total knee arthroplasty (TKA).
METHODS
A total of 592 patients were enrolled in the study. Clinical data of patients who underwent total hip arthroplasty (THA) and total knee arthroplasty (TKA) in our hospital from December 2021 to September 2022 were retrospectively collected, which mainly included patients' general information, surgery-related information, and DVT-related information. The patients were categorized into the nadroparin group(n = 278) and the fondaparinux sodium group(n = 314) according to the types of anticoagulants used. Anticoagulant therapy began 12-24 h after operation and continued until discharge. DVT prevalence between two groups was compared. The Statistical Package for Social Sciences (SPSS) software version 25 (SPSS, Armonk, NY, USA) was used for statistical analysis.
RESULTS
The prevalence of DVT in the nadroparin group and the fondaparinux sodium group was 8.3% (23/278) and 15.0% (47/314), respectively(p = 0.012). Statistical analysis showed that nadroparin group showed a lower prevalence of thrombosis than fondaparinux group (OR = 1.952, P = 0.012). Subgroup analyses showed that nadroparin group had a lower prevalence of DVT than fondaparinux group in some special patients groups such as female patients (OR = 2.258, P = 0.007), patients who are 65-79 years old (OR = 2.796, P = 0.004), patients with hypertension (OR = 2.237, P = 0.042), patients who underwent TKA (OR = 2.091, P = 0.011), and patients who underwent combined spinal-epidural anesthesia (OR = 2.490, P = 0.003) (P < 0.05).
CONCLUSION
Nadroparin may have an advantage over fondaparinux sodium in preventing DVT in lower extremities after THA and TKA.
Topics: Humans; Fondaparinux; Female; Male; Retrospective Studies; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Nadroparin; Middle Aged; Venous Thromboembolism; Aged; Anticoagulants; Postoperative Complications; Lower Extremity; Treatment Outcome
PubMed: 38762739
DOI: 10.1186/s12893-024-02440-0 -
Cureus Apr 2024This article presents a case of a multimorbid 63-year-old woman with chronic kidney disease and heparin-induced thrombocytopenia (HIT). Following the insertion of a...
This article presents a case of a multimorbid 63-year-old woman with chronic kidney disease and heparin-induced thrombocytopenia (HIT). Following the insertion of a central venous catheter, she developed phlegmasia cerulea dolens (PCD) in her left arm, a rare and severe complication of deep vein thrombosis (DVT). Given the severity of the case, adapting to anticoagulant contraindications or unavailability, management with catheter-directed thrombolysis and mechanical thrombectomy was made. It is concluded that catheter-directed thrombolysis and mechanical thrombectomy are valuable therapeutic alternatives in critical situations where treatment options are limited.
PubMed: 38738034
DOI: 10.7759/cureus.57987 -
Journal of Cardiothoracic Surgery Apr 2024Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome is a severe adverse drug reaction marked by delayed hypersensitivity reactions causing skin and...
BACKGROUND
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome is a severe adverse drug reaction marked by delayed hypersensitivity reactions causing skin and systemic complications. DRESS diagnosis is challenging due to the variety of clinical presentations and symptom overlap with other conditions. The perioperative period in these patients requires precise pharmacological strategies to prevent complications associated with this syndrome. The treatment of DRESS induced by unfractionated heparin during cardiopulmonary bypass (CPB) surgery presents some challenges that must be considered when selecting an anticoagulant to avoid side effects. In this case, bivalirudin, a direct thrombin inhibitor, is indicated as an alternative to heparin in patients undergoing CPB. However, in contrast to heparin/protamine, there is no direct reversal agent for bivalirudin.
CASE PRESENTATION
We report the case of an 11-year-old male diagnosed with native aortic valve endocarditis and thrombosis in his left lower extremity. During valvular replacement surgery, systemic unfractionated heparin was administered. Postoperatively, the patient developed fever, eosinophilia and pruritic rash. Warm shock and elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels followed, leading to the diagnosis of DRESS syndrome. Treatment with methylprednisolone resulted in complete resolution of symptoms. Seven years later, the patient was readmitted due to insufficient anticoagulation and a thrombus in the prosthetic aortic valve, presenting a recurrent DRESS episode due to the administration of unfractionated heparin, which was later replaced with low-molecular-weight heparin during hospitalization. Treatment with corticosteroids and antihistamines was initiated, resulting in the resolution of this episode. Ultimately, the patient required the Ross procedure. During this intervention the anticoagulation strategy was modified, unfractionated heparin was replaced with bivalirudin during the procedure and fondaparinux was administered during the postoperative period. This resulted in stable transaminases levels and no eosinophilia.
CONCLUSION
The severity of DRESS Syndrome underscores the importance of early recognition, heightened monitoring, and a comprehensive approach tailored to each patient's needs. This particular case highlights the significance of this approach and may have a substantial clinical impact since it provides alternatives to heparin, such as bivalirudin and fondaparinux, in the anticoagulation strategy of CPB for patients who have a hypersensibility reaction to this medication; thus, enhancing clinical outcomes by minimizing risks linked to adverse drug reactions.
Topics: Male; Humans; Child; Heparin; Fondaparinux; Drug Hypersensitivity Syndrome; Anticoagulants; Hirudins; Eosinophilia; Peptide Fragments; Anesthetics; Recombinant Proteins
PubMed: 38632589
DOI: 10.1186/s13019-024-02722-x -
Frontiers in Pharmacology 2024Thromboembolic disease is associated with a high rate of disability or death and gravely jeopardizes people's health and places considerable financial pressure on... (Review)
Review
Thromboembolic disease is associated with a high rate of disability or death and gravely jeopardizes people's health and places considerable financial pressure on society. The primary treatment for thromboembolic illness is anticoagulant medication. Fondaparinux, a parenteral anticoagulant medicine, is still used but is confusing due to its disparate domestic and international indications and lack of knowledge about its usage. Its off-label drug usage in therapeutic settings and irrational drug use are also common. The aim of this guideline is to enhance the judicious clinical application of fondaparinux by consolidating the findings of evidence-based research on the drug and offering superior clinical suggestions. Seventeen clinical questions were developed by 37 clinical pharmacy experts, and recommendations were formulated under the supervision of three methodologists. Through methodical literature searches and the use of recommendation, assessment, development and evaluation grading techniques, we gathered evidence. This guideline culminated in 17 recommendations, including the use of fondaparinux for venous thromboembolism (VTE) prevention and treatment, perioperative surgical prophylaxis, specific diseases, special populations, bleeding and overdose management. For different types of VTE, we recommend first assessing thrombotic risk in hospitalized patients and then administering the drug according to the patient's body mass. In surgical patients in the perioperative period, fondaparinux may be used for VTE prophylaxis, but postoperative use usually requires confirmation that adequate hemostasis has been achieved. Fondaparinux may be used for anticoagulation prophylaxis in patients hospitalized for oncological purposes, in patients with atrial fibrillation (AF) after resuscitation, in patients with cirrhosis combined with portal vein thrombosis (PVT), in patients with antiphospholipid syndrome (APS), and in patients with inflammatory bowel disease (IBD). Fondaparinux should be used with caution in special populations, such as pregnant female patients with a history of heparin-induced thrombocytopenia (HIT) or platelet counts less than 50 × 10/L, pregnant patients with a prethrombotic state (PTS) combined with recurrent spontaneous abortion (RSA), and children. For bleeding caused by fondaparinux, dialysis may partially remove the drug. The purpose of this guideline is to provide all healthcare providers with high-quality recommendations for the clinical use of fondaparinux and to improve the rational use of the drug in clinical practice. Currently, there is a lack of a dedicated antidote for the management of fondaparinux. The clinical investigation of activated prothrombin complex concentrate (APCC) or recombinant activated factor VII (rFⅦa) as potential reversal agents is still pending. This critical gap necessitates heightened scrutiny and research emphasis, potentially constituting a novel avenue for future inquiries into fondaparinux sodium. A meticulous examination of adverse events and safety profiles associated with the utilization of fondaparinux sodium will contribute significantly to a more comprehensive understanding of its inherent risks and benefits within the clinical milieu.
PubMed: 38529183
DOI: 10.3389/fphar.2024.1352982