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World Neurosurgery Jul 2020The chronic subdural hematoma (cSDH)-Drain trial compared recurrence rates and clinical outcome associated with the use of subperiosteal drain (SPD) and subdural drain... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The chronic subdural hematoma (cSDH)-Drain trial compared recurrence rates and clinical outcome associated with the use of subperiosteal drain (SPD) and subdural drain (SDD) after burr-hole drainage for cSDH. This subgroup analysis aimed to determine whether one drain type is preferable for patients treated with platelet inhibitors (PI) or anticoagulants (AC).
METHODS
This subanalysis included 133 patients treated with PI/AC of the 220 patients from the preceding cSDH-Drain trial. For these patients the association between the drain type used and recurrence rates, mortality, as well as clinical outcome at 6 weeks and 12 months follow-up were analyzed using a logistic regression analysis model. Additionally, recurrence rates, clinical outcome, and mortality were assessed for each PI or AC type separately.
RESULTS
The insertion of SPD was associated with 7.35% recurrence rates compared to 13.85% with SDD in patients treated with PI or AC (OR 0.41, 95% CI 0.06-2.65, P = 0.36). Outcome measurements and mortality did not differ significantly between both groups at 6-week and 12-month follow-up. In addition, there was no statistically significant association between drain type and recurrence rate or mortality when comparing data for each PI or AC type. At 24 hours postoperatively, significantly more patients under phenprocoumon and natrium-dalteparin had a Glasgow Coma Scale score between 13 and 15 in the SDD group compared with the SPD group (P = 0.006), whereaas at 6-week follow-up significantly more patients in the SDD group treated with ASA had a good modified Rankin scale score (P = 0.01). At 12 months, no significant difference in outcome measurements was seen for all PI and AC types.
CONCLUSIONS
In patients treated with PI or AC, the insertion of SPD after burr-hole drainage of cSDH showed comparable recurrence, mortality, and long term outcome rates when compared with SDD.
Topics: Aged; Aged, 80 and over; Anticoagulants; Drainage; Female; Hematoma, Subdural, Chronic; Humans; Male; Periosteum; Platelet Aggregation Inhibitors; Recurrence; Subdural Space; Treatment Outcome; Trephining
PubMed: 32247794
DOI: 10.1016/j.wneu.2020.03.134 -
European Stroke Journal Dec 2019The aim of the present European Stroke Organisation guideline document is to provide clinically useful evidence-based recommendation on reversal of anticoagulant...
The aim of the present European Stroke Organisation guideline document is to provide clinically useful evidence-based recommendation on reversal of anticoagulant activity VKA (warfarin, phenprocoumon and acenocoumarol), direct factor II (thrombin) inhibitors (dabigatran etexilat) and factor-Xa-inhibitors (apixaban, edoxaban and rivaroxaban) in patients with acute intracerebral haemorrhage. The guideline was prepared following the Standard Operational Procedure for a European Stroke Organisation guideline document and according to GRADE methodology. As a basic principle, we defined use of oral anticoagulation pragmatically: oral anticoagulation use is assumed by positive medical history unless relevant anticoagulant activity is regarded unlikely by medical history or has been ruled out by laboratory testing. Overall, we strongly recommend using prothrombin complex over no treatment and fresh-frozen plasma in patients on VKA plus vitamin K. We further strongly recommend using idarucizumab in patients on dabigatran and make a recommendation for andexanet alfa in patients on rivaroxaban and apixaban over no treatment. We make a weak recommendation on using high-dose prothrombin complex concentrate (50 IU/kg) for all patients taking edoxaban and for patients on rivaroxaban or apixaban in case andexanet alfa is not available. We recommend against using tranexamic acid and rFVIIa, outside of trials. The presented treatment recommendations aim to normalise coagulation, there is no or only indirect data on effects on functional outcome or mortality, and only little data from randomised controlled trials.
PubMed: 31903428
DOI: 10.1177/2396987319849763 -
BMC Pediatrics Jun 2019Neonatal renal vein thrombosis is a recognised cause of renal and inferior caval vein atresia (IVCA). However, the long-term impact of the condition is underrecognized... (Review)
Review
BACKGROUND
Neonatal renal vein thrombosis is a recognised cause of renal and inferior caval vein atresia (IVCA). However, the long-term impact of the condition is underrecognized with a high burden of morbidity for the patient, especially in adulthood. IVCA has been shown to be an independent risk factor for deep venous thrombosis (DVT) with a high risk of recurrence. The acronym KILT for kidney and inferior vena cava anomaly with leg thrombosis summarizes the pathological situation.
CASE PRESENTATION
We present the case of a 40-year-old patient with pain in the right lower limb resulting from acute thrombophlebitis. No risk factors could be identified. His history was remarkable with two episodes of deep venous thrombosis first of the left, then the right leg 22 years earlier; at that time also, no risk factor was identified. Because of the idiopathic character of that thrombosis, the patient remained on long-term anticoagulation with phenprocoumon. The present thrombophlebitis occurred while the INR was not therapeutic in the preceding weeks. A CT with contrast showed atresia of the inferior vena cava and of the right kidney, and presence of numerous collaterals. A thorough medical history revealed a renal vein thrombosis as a neonate. Anticoagulation was intensified, and stent placement became necessary after a further 2 years.
DISCUSSION AND CONCLUSIONS
KILT syndrome is a rare but underrecognized condition. Complications may arise in young adulthood only, and it is of prime importance to instruct parents of the pediatric patient of the possible consequences of renal vein thrombosis and to assure guidance from the treating physicians throughout adulthood. Diagnosis of IVCA is by CT with contrast or by MRI, and lifelong anticoagulation may be necessary. Since the KILT syndrome is widely underdiagnosed, we challenge the clinicians to keep it in mind when confronted with thrombophlebitis or thrombosis of the young, male and with no other identifiable risk factors for deep vein thrombosis.
Topics: Abbreviations as Topic; Adult; Anticoagulants; Follow-Up Studies; Humans; Infant, Newborn; Kidney; Leg; Male; Pain; Phenprocoumon; Renal Veins; Syndrome; Thrombophlebitis; Time Factors; Tomography, X-Ray Computed; Vascular Malformations; Vena Cava, Inferior; Venous Thrombosis
PubMed: 31170948
DOI: 10.1186/s12887-019-1567-7 -
Interactive Cardiovascular and Thoracic... Jun 2022Oral anticoagulation prior to emergency surgery is associated with an increased risk of perioperative bleeding, especially when this therapy cannot be discontinued or...
OBJECTIVES
Oral anticoagulation prior to emergency surgery is associated with an increased risk of perioperative bleeding, especially when this therapy cannot be discontinued or reversed in time. The goal of this study was to analyse the impact of different oral anticoagulants on the outcome of patients who underwent emergency surgery for acute type A aortic dissection (ATAAD).
METHODS
This was a single-centre retrospective study of patients treated with oral anticoagulation at the time of surgery for ATAAD. Outcomes of patients on new oral anticoagulant (NOAC) therapy were compared to respective outcomes of patients on Coumadin. Additionally, a survival analysis was performed comparing these 2 groups with patients who were operated on with no prior anticoagulation.
RESULTS
Between January 2013 and April 2020, a total of 437 patients (63.8 ± 11.8 years, 68.4% male) received emergency surgery for ATAAD; 35 (8%) were taking oral anticoagulation at the time of hospital admission: 20 received phenprocoumon; 14, rivaroxaban; and 1, dabigatran. Compared to Coumadin, NOAC was associated with a greater need for blood-product transfusions and haemodynamic compromise. Operative mortality was 53% in the NOAC group and 30% in the Coumadin group. A 5-year survival analysis showed no significant difference between the NOAC and the Coumadin group (P = 0.059). Compared to 402 patients treated during the study period without anticoagulation, patients taking NOAC had significantly worse survival (P = 0.001), whereas that effect was not observed in patients undergoing surgery who were taking Coumadin (P = 0.99).
CONCLUSIONS
Emergency surgery for ATAAD in patients taking NOAC is associated with high morbidity and mortality. NOAC are a major risk factor for uncontrollable bleeding and haemodynamic compromise. New treatment strategies must be defined to improve surgical outcomes in these high-risk patients.
Topics: Administration, Oral; Aortic Dissection; Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Male; Retrospective Studies; Warfarin
PubMed: 35258082
DOI: 10.1093/icvts/ivac037 -
Cancers Jan 2022Stereotactic radiosurgery (SRS) is a well-established treatment modality for brain metastases (BM). Given the manifold implications of metastatic cancer on the body,...
BACKGROUND
Stereotactic radiosurgery (SRS) is a well-established treatment modality for brain metastases (BM). Given the manifold implications of metastatic cancer on the body, affected patients have an increased risk of comorbidities, such as atrial fibrillation (AF) and venous thromboembolism (VTE), which includes pulmonary embolism (PE) and deep-vein thrombosis (DVT). These may require therapeutic anticoagulant therapy (ACT). Limited data are available on the risk of intracranial hemorrhage (ICH) after SRS for patients with BM who are receiving ACT. This bi-institutional analysis aimed to describe the bleeding risk for this patient subgroup.
METHODS
Patients with ACT at the time of single-fraction SRS for BM from two institutions were eligible for analysis. The cumulative incidence of ICH with death as a competing event was assessed during follow-up with magnetic resonance imaging or computed tomography.
RESULTS
Forty-one patients with 97 BM were included in the analyses. The median follow-up was 8.2 months (range: 1.7-77.5 months). The median and mean BM volumes were 0.47 and 1.19 cubic centimeters, respectively. The most common reasons for ACT were PE (41%), AF (34%), and DVT (7%). The ACT was mostly performed utilizing phenprocoumon (37%), novel oral anticoagulants (32%), or low-molecular-weight heparin (20%). Nine BM from a group of five patients with ICH after SRS were identified: none of them caused neurological or any other deficits. The 6-, 12-, and 18-month cumulative bleeding incidences per metastasis were 2.1%, 12.4%, and 12.4%, respectively. The metastases with previous bleeding events and those originating from malignant melanomas were found to more frequently demonstrate ICH after SRS ( = 0.02, = 0.01). No surgical or medical intervention was necessary for ICH management, and no observed death was associated with an ICH.
CONCLUSION
Patients receiving an ACT and single-fraction SRS for small- to medium-sized BM did not seem to have a clinically relevant risk of ICH. Previous bleeding and metastases originating from a malignant melanoma may favor bleeding events after SRS. Further studies are needed to validate our reported findings.
PubMed: 35158734
DOI: 10.3390/cancers14030465 -
Saudi Journal of Biological Sciences Dec 2022COVID-19 is a progressing pandemic of coronavirus disease-2019, which had drowned the whole world in a deep sorrow sea. Uncountable deaths were extending the list of...
COVID-19 is a progressing pandemic of coronavirus disease-2019, which had drowned the whole world in a deep sorrow sea. Uncountable deaths were extending the list of deaths every single day. The present research was aimed to study the multi-target interaction of coumarins against COVID-19 using molecular docking analysis. The structure of coumarin compounds was checked for ADME and Lipinski rule of five by using SwissADME, an online tool. SARS-CoV-2 proteins such as RdRp, PLpro, Mpro and spike protein were collected from the Protein Data Bank. The molecular docking study was performed in the PyRx tool, and the molecular interactions were visualised by Discovery Studio Visualizer. All the coumarin compounds used in the study were obeyed Lipinski's rule of 5 without any violations. All the three designed derivatives of phenprocoumon, hymecromone, and psoralen were showed high binding affinity and prominent interactions with the drug target. The presence of -OH groups in the compound, His41, a catalytic dyad in Mpro, number of and the distance of hydrogen bond interactions with SARS-CoV-2 targets was accountable for the high binding attractions. The modified drug structures possess better binding efficacy towards at least three targets compared to their parent compounds. Further, molecular dynamic studies can be suggested to find the ligand-protein complex stability. The present study outcome reveals that the designed coumarins can be synthesised and examined as a potent inhibitory drug of SARS-CoV-2.
PubMed: 36187455
DOI: 10.1016/j.sjbs.2022.103458 -
Pharmaceuticals (Basel, Switzerland) Nov 2022Background: Phenprocoumon has been used as an oral anticoagulant in patients with thromboembolic disease for more than 40 years. So far its pharmacokinetics have not...
Pharmacokinetics of Phenprocoumon in Emergency Situations-Results of the Prospective Observational RADOA-Registry (Reversal Agent Use in Patients Treated with Direct Oral Anticoagulants or Vitamin K Antagonists Registry).
Background: Phenprocoumon has been used as an oral anticoagulant in patients with thromboembolic disease for more than 40 years. So far its pharmacokinetics have not been analyzed in emergency situations. Methods: Phenprocoumon-treated patients with major bleeding or urgent surgery were included in a prospective, observational registry. Phenprocoumon drug concentrations were analyzed in samples, collected as part of routine care using ultraperformance liquid chromatography tandem mass spectrometry. Moreover, anticoagulant intensity and drug half-life (t1/2) were calculated. Results: 115 patients were included. Phenprocoumon levels declined over time with a half-life of 5.27 and 5.29 days in patients with major bleedings (n = 82) and with urgent surgery (n = 33). Baseline phenprocoumon levels were 2.2 times higher in the bleeding group compared to the surgery group (1.92 vs. 0.87 ng/mL, p < 0.0001). International normalized ratio (INR) values decreased rapidly during the first 24 h. In 27.6% of patients a rebound of INR (recurrent increase > 1.5) was observed which was associated with significantly increased bleeding rates (22% vs. 4.2% in patients with or without INR rebound, p = 0.012). Conclusions: In emergency situations, the long half-life of phenprocoumon may cause INR rebound and associated recurrent bleedings. Optimal management may need to include repeated vitamin K supplementation over days.
PubMed: 36422567
DOI: 10.3390/ph15111437 -
Clinical Otolaryngology : Official... Feb 2018Treatment of epistaxis in patients on anticoagulants is challenging and associated with higher admission rates and longer hospital stays compared with patients without... (Comparative Study)
Comparative Study
OBJECTIVES
Treatment of epistaxis in patients on anticoagulants is challenging and associated with higher admission rates and longer hospital stays compared with patients without anticoagulation. However, there is little information about epistaxis in patients taking new direct oral anticoagulants such as rivaroxaban compared with patients on traditional vitamin K antagonists such as phenprocoumon.
DESIGN
Retrospective cohort study.
SETTING
The study was conducted at the emergency department of the University Hospital Inselspital, Bern, Switzerland.
PARTICIPANTS
All admissions to the emergency department of the University Hospital Inselspital, Bern, Switzerland from 1st July 2012 to 30th June 2016 with non-traumatic epistaxis on anticoagulant therapy with phenprocoumon or rivaroxaban were included.
MAIN OUTCOME MEASURES
We compared clinical outcome parameters (admission rates, length of hospital stay and mortality) for both anticoagulant groups.
RESULTS
We included 440 patients with epistaxis, 123 (28%) on rivaroxaban and 317 (72%) on phenprocoumon. Fewer hospital admissions and shorter hospital stays were found in patients under rivaroxaban (12 (10.4%) vs 57 (18.0%) patients, P=.033; 0.7±2.2 vs 1.5±3.7 days, P=.011) compared with phenprocoumon. Anterior epistaxis was more common in the rivaroxaban group in contrast to posterior epistaxis in patients on phenprocoumon (74 (60.2%) vs 139 (43.8%) patients, P=.002; 7 (5.7%) vs 39 (12.3%) patients, P=.042).
CONCLUSIONS
Our data suggests that epistaxis on direct oral anticoagulation with rivaroxaban is associated with shorter hospital stays and fewer hospital admissions than epistaxis on vitamin K antagonist phenprocoumon.
Topics: Aged; Anticoagulants; Epistaxis; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Incidence; Length of Stay; Male; Patient Admission; Phenprocoumon; Retrospective Studies; Risk Assessment; Rivaroxaban; Switzerland
PubMed: 28510336
DOI: 10.1111/coa.12904 -
Medicine Nov 2016Oral anticoagulants and painkillers, some with an additional effect on the coagulation system, are widely used and are therefore prone to abuse and (intentional)...
RATIONALE
Oral anticoagulants and painkillers, some with an additional effect on the coagulation system, are widely used and are therefore prone to abuse and (intentional) overdose. We report the case of a patient with a massive mixed anticoagulant intoxication.
PATIENT CONCERNS
The patient had ingested 1960 mg rivaroxaban, 31.5 mg phenprocoumon, 1425 mg diclofenac, and 21,000 mg metamizole in suicidal intention.
DIAGNOSES
Massive mixed anticoagulant overdose.
INTERVENTIONS
The patient was closely monitored. The phenprocoumon overdose was treated by the administration of vitamin K and PCC.
OUTCOMES
Despite the massive inhibition of the coagulation system, the patient did not experience bleeding apart from a slight gross hematuria.
LESSONS
Despite the ingestion of a massive amount of rivaroxaban, the plasma levels were not as high as feared, due to the ceiling effect of rivaroxaban absorption. Elimination occurred according to the half-life of rivaroxaban and was not unduly prolonged by the ingested quantity.
Topics: Anticoagulants; Cyclooxygenase Inhibitors; Diclofenac; Factor Xa Inhibitors; Humans; Male; Phenprocoumon; Rivaroxaban; Young Adult
PubMed: 27858919
DOI: 10.1097/MD.0000000000005343 -
British Journal of Clinical Pharmacology Aug 2014Adherence to the generally complex regimen of coumarin derivatives is vital in order to keep patients in the adequate International Normalized Ratio range. Patients'...
AIMS
Adherence to the generally complex regimen of coumarin derivatives is vital in order to keep patients in the adequate International Normalized Ratio range. Patients' beliefs about medicines are associated with the level of therapy adherence. Our first aim was to assess beliefs about coumarins. Secondly, we compared the beliefs about coumarins with the beliefs about other cardiovascular drugs.
METHODS
The Beliefs about Medicines Questionnaire was used to assess medication beliefs. The questionnaire was completed by new users of coumarins indicated for venous thromboembolism or atrial fibrillation. A necessity score and a concerns score were calculated for all patients. The analyses were repeated for users of antihypertensive drugs or statins (not using coumarins).
RESULTS
Three hundred and twenty patients were included in the analysis of the beliefs about coumarins. The mean necessity score was 15.3, the concerns score 12.3 and the necessity-concerns differential 3.0. Patients with venous thromboembolism (n = 71) had higher necessity scores than patients with atrial fibrillation (n = 249; 16.8 vs. 14.9, P < 0.001). The mean necessity score in 493 users of other cardiovascular drugs was 16.1, the concerns score 13.5 and the necessity-concerns differential 2.6. The necessity score was higher in chronic cardiovascular drug users (n = 192) than in new users (n = 301; 17.9 vs. 14.9, P < 0.001).
CONCLUSIONS
Coumarin users score higher on the necessity scale than on the concerns scale, which is also the case in users of other cardiovascular drugs. Patients with atrial fibrillation have a less positive attitude towards these drugs than patients with venous thromboembolism, and could therefore benefit more from specific attention.
Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Cardiovascular Diseases; Data Interpretation, Statistical; Female; Humans; International Normalized Ratio; Male; Middle Aged; Netherlands; Patient Compliance; Patient Medication Knowledge; Phenprocoumon; Surveys and Questionnaires
PubMed: 24528215
DOI: 10.1111/bcp.12346