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Cureus May 2023Spontaneous retroperitoneal hematomas are a rare yet potentially devastating occurrence associated with antiplatelet and anticoagulant therapies. We present a case of a...
Spontaneous retroperitoneal hematomas are a rare yet potentially devastating occurrence associated with antiplatelet and anticoagulant therapies. We present a case of a spontaneous retroperitoneal hematoma post-operatively after a total hip arthroplasty surgery performed under a midline approach spinal anesthetic. A 79-year-old male with a BMI of 25.72 kg/m presented for anterior total hip arthroplasty. A midline approach with an uncomplicated spinal anesthetic was performed. On the night of postoperative day 0, the patient received a prophylactic dose of dalteparin. The patient reported back pain, contralateral leg numbness, and weakness that began overnight on postoperative day 0. A computed tomography (CT) scan confirmed a 10 cm, contralateral retroperitoneal hematoma. The patient underwent interventional radiology embolization followed by surgical evacuation and demonstrated improvement in the neurologic function of his affected leg. Despite the rarity of a spontaneous retroperitoneal hematoma formation in the perioperative period, it could be simultaneously evaluated when performing an MRI to rule out spinal hematoma if a patient suffers a post-op neurologic deficit after a neuraxial technique. Understanding the evaluation and timely treatment of patients at risk for a perioperative retroperitoneal hematoma could help clinicians prevent a permanent neurologic deficit.
PubMed: 37193095
DOI: 10.7759/cureus.38971 -
Fundamental & Clinical Pharmacology Oct 2023Augmented renal clearance (ARC) is a pathophysiological phenomenon that can occur in critically ill patients, leading to enhanced renal function. It is defined as a...
Augmented renal clearance (ARC) is a pathophysiological phenomenon that can occur in critically ill patients, leading to enhanced renal function. It is defined as a creatinine clearance of >130 mL/min/1.73 m . ARC can lead to subtherapeutic levels of renally cleared drugs and subsequent treatment failure. In COVID-19, it has only been described in the literature in a few cases. We present the case of a 38-year-old critically ill patient with COVID-19 who developed ARC with an initial clearance of 226 mL/min/1.73 m , persisting for 30 days. He required high doses of sedatives and neuromuscular blocking agents, as well as increased doses of vancomycin and dalteparin, to reach adequate serum levels. This case emphasizes the importance for clinicians to consider ARC in the dosing of all renally cleared drugs, including antibiotics, low molecular weight heparins, and sedatives, to prevent subtherapeutic drug levels and treatment failure.
Topics: Male; Humans; Adult; Critical Illness; COVID-19; Creatinine; Anti-Bacterial Agents; Vancomycin
PubMed: 37161707
DOI: 10.1111/fcp.12916 -
Case Reports in Cardiology 2023A 45-year-old woman was admitted with severe pain in the right leg and dyspnea. Her medical history included previous endocarditis, biological aortic valve replacement,...
A 45-year-old woman was admitted with severe pain in the right leg and dyspnea. Her medical history included previous endocarditis, biological aortic valve replacement, and intravenous drug abuse. She was febrile but did not have any focal signs of infection. Blood tests showed raised infectious markers and troponin levels. Electrocardiogram showed sinus rhythm without signs of ischemia. Ultrasound revealed thrombosis of the right popliteal artery. The leg was not critically ischemic, and therefore, treatment with dalteparin was chosen. Transesophageal echocardiography showed an excrescence on the biological aortic valve. Empiric treatment for endocarditis was started with intravenous vancomycin, gentamicin, and oral rifampicin. Blood cultures subsequently grew . On day 2, treatment was changed to intravenous cloxacillin. Due to the comorbidity, the patient was not a candidate for the surgical treatment. On day 10, the patient developed moderate expressive aphasia and weakness in the right upper limb. Magnetic resonance imaging showed micro-embolic lesions scattered across both hemispheres of the brain. Treatment was changed from cloxacillin to cefuroxime. On day 42, infectious markers were normal, and echocardiography showed regression of the excrescence. Antibiotic treatment was stopped. Follow-up on day 52 did not show any signs of active infection. However, on day 143, the patient was readmitted with cardiogenic shock due to aortic root fistulation to the left atrium. She quickly deteriorated and died.
PubMed: 37013024
DOI: 10.1155/2023/4624492 -
Shock (Augusta, Ga.) Apr 2023Introduction: Cell-free DNA (CFDNA) has emerged as a prognostic biomarker in patients with sepsis. Circulating CFDNA is hypothesized to be associated with histones in...
Introduction: Cell-free DNA (CFDNA) has emerged as a prognostic biomarker in patients with sepsis. Circulating CFDNA is hypothesized to be associated with histones in the form of nucleosomes. In vitro, DNA activates coagulation and inhibits fibrinolysis, whereas histones activate platelets and are cytotoxic to endothelial cells. Previous studies have targeted CFDNA or histones in animal models of sepsis using DNase I or heparins, respectively, which has reduced inflammatory and thrombosis markers, thereby improving survival. In this study, we explored the possibility that the combination of DNase I and a low-molecular weight heparin (LMWH) may be a better therapeutic approach than monotherapy in a murine model of abdominal sepsis. Methods: C57Bl/6 mice (8-12 weeks old, both sexes) were subjected to either cecal ligation and puncture or sham surgery. Mice were given antibiotics, fluids, and either saline, DNase I (intraperitoneally, 20 mg/kg/8 h), LMWH (dalteparin, subcutaneously 500 IU/kg/12 h), or a combination of both (n = 12-31). Mice were monitored over 72 h for survival. Organs and blood were harvested for analysis. Levels of LMWH, CFDNA, IL-6, citrullinated histone-H3, thrombin-antithrombin complexes, and protein C were measured in plasma. Results: Administration of either DNase I (81.8%) or LMWH (83.3%, prophylactic range of 0.12 ± 0.07 IU/mL achieved) improved the survival of septic mice compared with saline- (38.7%) and combination-treated mice (48.8%, P < 0.05). Combination-treated mice also showed a small but insignificant improvement in survival compared with saline-treated cecal ligation and puncture mice. Monotherapies may be improving survival by reducing blood bacterial loads, citrullinated histone-H3, and thrombin-antithrombin complexes, and improving protein C levels. Conclusions: Compared with saline- and combination-treated mice, administration of monotherapies to septic mice improved survival. These findings suggest that there may be a negative drug-drug interaction between DNase I and LMWH when DNase I is administered intraperitoneally in a murine model of polymicrobial abdominal sepsis.
Topics: Male; Female; Mice; Animals; Heparin, Low-Molecular-Weight; Histones; Protein C; Deoxyribonuclease I; Thrombin; Disease Models, Animal; Endothelial Cells; Sepsis; Intraabdominal Infections; Antithrombins; Mice, Inbred C57BL
PubMed: 36852972
DOI: 10.1097/SHK.0000000000002095 -
Medicina (Kaunas, Lithuania) Feb 2023Even though low-molecular-weight heparin (LMWH), including dalteparin, has a critical role in portal vein thrombosis (PVT) treatment in liver cirrhosis (LC) patients,...
Even though low-molecular-weight heparin (LMWH), including dalteparin, has a critical role in portal vein thrombosis (PVT) treatment in liver cirrhosis (LC) patients, the predictive factors and the proper dose of dalteparin for PVT treatment and relapse have not yet been investigated. This retrospective study evaluated the records of LC patients receiving dalteparin from July 2013 to June 2019. The odds ratio (OR) and adjusted OR were calculated from univariate and multivariable analyses, respectively. Among data from 121 patients, the overall recanalization rate of all patients was 66.1% (80 patients). No history of variceal bleeding (OR 4.6, 95% CI: 1.88-11.43) and the case of newly developed thrombus before dalteparin treatment (OR 3.2, 95% CI: 1.24-8.08) were predictive factors associated with increased treatment response. Relapse of PVT occurred in 32 out of 80 patients (40%) who showed a recanalization. The risk of relapse was 3.1-3.9 times higher in those who took more than three months or more than six months from the diagnosis of PVT to dalteparin treatment compared to those who took less than these durations, respectively. In the dosing regimen, patients with the kg-based dosing regimen showed 2.6 times better response than those with the fixed dosing regimen. However, no difference in bleeding complications was observed. In the dosing regimen, the kg-based regimen that was the same as the venous thromboembolism regimen was a better option for the efficacy and safety of dalteparin therapy. Additionally, when treating PVT in LC patients, careful monitoring is recommended for patients with predictive factors for treatment response and relapse of PVT.
Topics: Humans; Heparin, Low-Molecular-Weight; Anticoagulants; Portal Vein; Dalteparin; Retrospective Studies; Liver Cirrhosis; Venous Thrombosis; Thrombosis; Recurrence
PubMed: 36837493
DOI: 10.3390/medicina59020292 -
TH Open : Companion Journal To... Jan 2023Thrombocytopenia is common among critically ill sepsis patients, while they also hold an increased risk for thromboembolic events. Thus, the choice of anticoagulant...
Thrombocytopenia is common among critically ill sepsis patients, while they also hold an increased risk for thromboembolic events. Thus, the choice of anticoagulant prophylaxis for this patient population is challenging. We investigated the effect of low-molecular-weight heparin (dalteparin) and direct thrombin inhibitor (argatroban) on the hemostasis in blood from sepsis patients with new-onset thrombocytopenia. Thrombocytopenia was defined as a platelet count drop of ≥30% and/or from >100 × 10 /L to 30 to 100 × 10 /L within 24 hours prior to inclusion. We included five healthy individuals and ten patients. Analyses of thrombin generation (Calibrated Automated Thrombogram), thrombin-antithrombin (TAT) complex levels, prothrombin fragment 1+2 (F1+2), and rotational thromboelastometry (ROTEM) were performed. Based on dose-response relationships investigated in healthy blood, patient samples were spiked with prophylactic (0.25 IU/mL) and therapeutic (0.75 IU/mL) dalteparin and low (0.25 µg/mL) and high (0.50 µg/mL) argatroban concentrations, each with a sample without anticoagulant. In patients, the endogenous thrombin potential was markedly lower in therapeutic dalteparin samples than in samples without anticoagulant [median (range): 29 (0-388) vs. 795 (98-2121) nM × min]. In high argatroban concentration samples, thrombin lag time was longer than in samples without anticoagulant [median (range): 15.5 (10.5-20.2) versus 5.3 (2.8-7.3) min]. Dalteparin and argatroban both increased clotting time but did not affect maximum clot firmness in the ROTEM INTEM assay. Six patients had elevated TAT and eight patients had elevated F1 + 2. In conclusion, dalteparin mainly affected the amount of thrombin generated and argatroban delayed clot initiation in critically ill sepsis patients with new-onset thrombocytopenia. Neither anticoagulant affected clot strength.
PubMed: 36751302
DOI: 10.1055/a-2000-6576 -
BJOG : An International Journal of... May 2023The Accelerating Innovation for Mothers project established a new database of candidate medicines under development between 2000 and 2021 for five pregnancy-related...
OBJECTIVE
The Accelerating Innovation for Mothers project established a new database of candidate medicines under development between 2000 and 2021 for five pregnancy-related conditions, including fetal growth restriction. The objective was to assess medicines for fetal growth restriction and their potential for clinical use globally.
DESIGN
Landscape analysis.
SETTING
Global (focus on low- and middle-income countries, LMICs).
SAMPLE
Drugs, dietary supplements and biologics under investigation for prevention or treatment of fetal growth restriction.
METHODS
A research pipeline database of medicines was created through searching AdisInsight, PubMed and various grant and clinical trial databases. Analysis of clinical and preclinical candidates were descriptive.
MAIN OUTCOMES MEASURES
Fetal growth restriction candidates in clinical development were identified and ranked as high, medium or low potential based on prespecified criteria, including efficacy, safety and accessibility.
RESULTS
Of the 444 unique candidates in the database across all five pregnancy-related conditions, 63 were for fetal growth restriction. Of these, 31 were in clinical development (phases I, II or III) and 32 were in preclinical development. Three candidates, aspirin, l-arginine and vitamin D, were ranked as having high potential as preventive agents. There were no high-potential candidates for treating fetal growth restriction, although five candidates were ranked as having medium potential: allylestrenol, dalteparin, omega-3 fatty acids, tadalafil, and United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP).
CONCLUSIONS
l-Arginine, aspirin and vitamin D are promising, high-potential preventative agents for fetal growth restriction. Based on the medicines pipeline, new pharmacological agents for fetal growth restriction are unlikely to emerge in the near future.
Topics: Pregnancy; Female; Humans; Fetal Growth Retardation; Maternal Health; Pregnancy Complications; Aspirin; Vitamins; Vitamin D; Arginine
PubMed: 36655375
DOI: 10.1111/1471-0528.17392 -
BMC Musculoskeletal Disorders Jan 2023Tranexamic acid (TXA) has been widely applied in total knee arthroplasty (TKA) to significantly reduce perioperative blood loss and improve knee function recovery in... (Randomized Controlled Trial)
Randomized Controlled Trial
Effectiveness of different antithrombotic agents in combination with tranexamic acid for venous thromboembolism prophylaxis and blood management after total knee replacement: a prospective randomized study.
BACKGROUND
Tranexamic acid (TXA) has been widely applied in total knee arthroplasty (TKA) to significantly reduce perioperative blood loss and improve knee function recovery in patients after surgery. The choice of antithrombotic agents for venous thromboembolism (VTE) prevention after TKA is controversial. Therefore, this study aimed to compare the effects of different antithrombotic agents on patients after primary unilateral TKA in the context of applied TXA.
METHODS
A total of 180 patients undergoing primary unilateral TKA from October 2020 to December 2021 were included in this study. All patients were given an intraoperative drip of 60 mg/kg TXA. Thereafter, patients were divided into three groups (n = 60 each). Baseline data were comparable among the three groups. The average follow-up time was 3.02 ± 0.09 months. Group 1 enrolled patients receiving oral rivaroxaban (RA) at 10 mg, Group 2 included patients who received subcutaneous Dalteparin sodium at 2500 IU, while Group 3 included patients taking oral aspirin (ASA) at 100 mg. Patients in all the three groups received treatment once a day for 30 days at 12 h postoperatively. The primary outcomes in this study were post-treatment drainage volume and thrombotic complication rate. The secondary outcomes included hematologic parameters, transfusion rate, intraoperative blood loss, total blood loss (TBL), and bleeding complication rate.
RESULTS
The average drainage volume after treatment was significantly lower in Group 3 than in Group 1 and Group 2 (205.2 ± 69.0 vs 243.4 ± 72.5 vs 295.4 ± 72.5 ml, P < 0.001), and there was a significant difference between Group 1 and Group 2 (243.4 ± 72.5 mL vs 295.4 ± 72.5 mL, P < 0.001). The blood transfusion rate of Group 2 dramatically increased compared with Group 1 and Group 3 (20.0% vs 6.7% vs 5.0%, P = 0.01). The bleeding complication rate in Group 1 apparently increased relative to Group 2 and Group 3 (26.7% vs 10.0% vs 8.3%, P = 0.008). Besides, there was no significant difference in the thrombotic complication rate among the three groups.
CONCLUSION
Under the background of TXA application, ASA, RA, and Dalteparin sodium were all effective on preventing VTE after TKA. In addition, ASA effectively reduced post-treatment Hemoglobin (Hb) loss, drainage volume, TBL, transfusion rate, and bleeding complications compared with RA and Dalteparin sodium.
TRIAL REGISTRATION
The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2200060169). Date of Registration: 21/05/2022.
Topics: Humans; Tranexamic Acid; Arthroplasty, Replacement, Knee; Venous Thromboembolism; Fibrinolytic Agents; Antifibrinolytic Agents; Dalteparin; Prospective Studies; Blood Loss, Surgical; Rivaroxaban; Anticoagulants; Postoperative Hemorrhage
PubMed: 36600227
DOI: 10.1186/s12891-022-06117-8 -
Medicinski Glasnik : Official... Feb 2023Aim To determine differences between reviparin and dalteparin treatment in patients with extracapsular hip fractures treated with intramedullary nailing and their...
Comparative analysis of the effects of dalteparin and reviparin on perioperative blood loss in patients with extracapsular hip fractures treated with intramedullary nailing.
Aim To determine differences between reviparin and dalteparin treatment in patients with extracapsular hip fractures treated with intramedullary nailing and their effects on perioperative blood loss and early postoperative recovery. Methods Retrospective comparative study included 68 patients with extracapsular hip fracture who were divided into dalteparin and reviparin group. Medical records were used to obtain demographic data, laboratory parameters, haemoglobin and haematocrit levels, platelet count, mortality rate and medical complications. Results Out of total 68 patients, 31 were in reviparin and 37 in dalteparin group. Mean age of patients was 70.5 (±14.4) and 76.8 (±8.4) years in reviparin and dalteparin group, respectively (p=0.071). Median values of haemoglobin levels on the first postoperative day were lower in dalteparin group compared to reviparin group (p=0.012). On the first postoperative day haematocrit values were also lower in dalteparin than in reviparin group (p=0.015). Both groups showed an increase in platelet count on the first postoperative day, but without significant difference (p=0.084). There was no statistically significant difference in intrahospital mortality between the groups (6.4% vs. 2.7%; p=0.588). One case of pulmonary embolism was detected in the dalteparin group. Conclusion Low-molecular-weight heparin is the drug of choice in patients with hip fractures for thromboprophylaxis. Due to non-antithrombin-mediated actions, reviparin and dalteparin could have different effects on perioperative blood loss. Both dalteparin and reviparin are safe and effective agents for thromboprophylaxis in patients with proximal femur fractures.
PubMed: 36435999
DOI: 10.17392/1526-22 -
Cardiovascular Drugs and Therapy Jun 2024As of July 2022, the COVID-19 pandemic has affected over 555 million worldwide confirmed cases and caused more than 6.3 million deaths. The studies showed that the...
Promising Drug Fondaparinux for the Treatment of COVID-19: an In Silico Analysis of Low Molecular Weight Heparin, Direct Oral Anticoagulant, and Antiplatelet Drug Interactions with Host Protease Furin.
PURPOSE
As of July 2022, the COVID-19 pandemic has affected over 555 million worldwide confirmed cases and caused more than 6.3 million deaths. The studies showed that the D-dimer levels were increased in non-survivors compared to survivors and heparin treatment has begun to be administered to the patients in severe clinics. As we knew that the entrance of SARS-CoV-2 to the host cell needs to be facilitated by host proteases; we published our hypothesis that heparin as a serine protease inhibitor may block the interaction between spike protein receptor-binding domain and host proteases. In our study, we aimed to investigate the interactions between not only heparins but also other antiplatelet and anticoagulant drugs including fondaparinux.
METHODS
In this study, docking studies were carried out to evaluate the interactions between low molecular weight heparins (LMWHs) (enoxaparin, dalteparin, tinzaparin), direct oral anticoagulant, and antiplatelet drugs with host proteases. Molecular docking studies were performed by using Schrödinger molecular modeling software. 3D structures of the ligands were obtained from the 2D structures by assigning the OPLS-2005 force field using the Maestro 12.7. The 3D crystal structure of the furin complexed with an inhibitor, 2,5-dideoksistreptamin derivative, was extracted from the Protein Data Bank (PDB ID: 5MIM). Docking studies were carried out using the Grid-based Ligand Docking with Energetics module of the Schrödinger Software.
RESULTS
The docking studies revealed that fondaparinux was the most relevant molecule to interact with furin with a docking score of - 12.74. It showed better interaction than the natural ligand of furin with an increased score compared to the docking score of - 8.155 of the natural ligand. AnaGA*IsA structure representing LMWH structure has shown a docking score of - 11.562 which was also better than the score of the natural ligand of furin.
CONCLUSION
Our findings have shown that LMWHs and fondaparinux can be used for their possible antiviral effects in COVID-19 patients. Our results have shown that in accordance with heparin and LMWH, fondaparinux can also be a candidate for "drug repurposing" in COVID-19 therapy, not only because of their anticoagulant but also possible antiviral effects.
Topics: Fondaparinux; Humans; Molecular Docking Simulation; Anticoagulants; COVID-19 Drug Treatment; Platelet Aggregation Inhibitors; Heparin, Low-Molecular-Weight; Furin; SARS-CoV-2; COVID-19; Computer Simulation; Drug Interactions
PubMed: 36401727
DOI: 10.1007/s10557-022-07406-z