Ensuring Sustainability of Continuous Kidney Replacement Therapy in the Face of Extraordinary Demand: Lessons From the COVID-19 Pandemic.

With the exponential surge in patients with coronavirus disease 2019 (COVID-19) worldwide, the resources needed to provide continuous kidney replacement therapy (CKRT) for patients with acute kidney injury or kidney failure may be threatened. This article summarizes subsisting strategies that can be implemented immediately. Pre-emptive weekly multicenter projections of CKRT demand based on evolving COVID-19 epidemiology and routine workload should be made. Corresponding consumables should be quantified and acquired, with diversification of sources from multiple vendors. Supply procurement should be stepped up accordingly so that a several-week stock is amassed, with administrative oversight to prevent disproportionate hoarding by institutions. Consumption of CKRT resources can be made more efficient by optimizing circuit anticoagulation to preserve filters, extending use of each vascular access, lowering blood flows to reduce citrate consumption, moderating the CKRT intensity to conserve fluids, or running accelerated KRT at higher clearance to treat more patients per machine. If logistically feasible, earlier transition to intermittent hemodialysis with online-generated dialysate, or urgent peritoneal dialysis in selected patients, may help reduce CKRT dependency. These measures, coupled to multicenter collaboration and a corresponding increase in trained medical and nursing staffing levels, may avoid downstream rationing of care and save lives during the peak of the pandemic.

Postoperative Bleeding After Change in Heparin Supplier: A Cardiothoracic Center Experience.

OBJECTIVE: Unfractionated heparin is a mixture of glycosaminoglycans with different pharmacologic and pharmacokinetic properties. The literature suggests that blood loss after cardiac surgery is related to both elevated postoperative heparin concentrations and the potency of different heparin brands. DESIGN: An audit of the observed increase in the incidence of cardiac surgery-related bleeding after change in heparin supplier. Patient characteristics were compared between groups before and after a change in heparin brands. SETTING: Tertiary cardiothoracic center. PARTICIPANTS: All patients undergoing cardiac surgery between August 1, 2011, and April 30, 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred eighty patients underwent surgery before a change in heparin brands and 216 after a change. Their preoperative and intraoperative characteristics were similar. Postoperative chest tube drainages and blood transfusions were significantly greater after the change in heparin brands (postoperative chest drainage 476.8 ± 393.1 v 344.8 ± 323.2 mL/6 h and 1,062.2 ± 738.8 v 841.8 ± 567.4 mL/24 h, respectively; both p < 0.001) despite the administration of larger amounts of protamine, fresh frozen plasma/platelet transfusions, and cryoprecipitate. Heparin recirculation within 24 hours of bypass was noted in about 70% of the samples tested using either anti-factor X activity or the thromboelastography ratio between nonheparinase R and heparinase-modified R and was not associated with the heparin brand. The likelihood ratio chi-square test for nested models identified an added predictive value of the heparin brand when included as a predictor of bleeding (chest drainage >800 mL/6 h) in a model comprising recirculation, assessed using either an elevated anti-factor X activity or ratio between nonheparinase R and heparinase-modified R. CONCLUSION: It is likely that the observed increase in postoperative bleeding was related to the pharmacologic properties of the new heparin brand rather than a higher incidence of heparin recirculation.

How to define the relative contraindications to oral anticoagulant therapy.

There is currently a lack of consensus on which anticoagulant therapy contraindications should be considered "absolute" and which should be considered "relative". Guidelines do not clearly identify absolute and relative contraindications to anticoagulant therapy. Recent guidelines on AF of the European Society of Cardiology underline the relevance of several factors and their use in scores, leaving anyway space to the clinical judgment of the physician. A high bleeding risk score should generally not result per se in a contraindication to anticoagulant therapy. Rather, bleeding risk factors should be identified and treatable factors corrected. A combined use of a more hierarchical classification of the different bleeding risk factors and the risk scores probably represents the best approach to maximize the benefit of anticoagulant therapy in various clinical settings.

[A Survey of the Use of Direct Oral Anticoagulants in Patients' Possession at the Time of Hospitalization].

The dose of direct oral anticoagulants (DOACs) must be determined based on package insert recommendations. There are reports on the rate of inappropriate DOAC dose usage defined as a dose deviating from the approved dose in the package insert but no reports on factors that led to such deviations. Thus, patients who were admitted to the Suzuka Kaisei Hospital between 1 April 2016 and 31 March 2017 were chosen as subjects. Moreover, the factors that during hospitalization led to dose deviation from the package-insert DOAC dose were retrospectively examined. The characteristics of patients administered doses deviating from the package insert were compared with those of patients in the appropriate-dose group. The finding was that the proportion concomitantly administered antiplatelet agents was higher in the underdose group. In contrast, deviations from the recommended dose did not occur when DOACs were combined with CYP3A4 inhibitors or P-glycoprotein (P-gp) inhibitors. It was suggested that increase in the risk of hemorrhage by antiplatelet agents in combination with oral anticoagulants could explain deviations from the stipulated DOAC dose. In addition, a higher proportion of patients in the overdose group showed depressed Ccr, and gastrointestinal bleeding. In future, it will be necessary to propose principle-based dose changes for patients administered doses deviating from the package insert. If an underdose is administered, it is important to make a dose change that takes the concomitant drugs into consideration.

Synthesis, anticoagulant and PIVKA-II induced by new 4-hydroxycoumarin derivatives.

The action of the coumarin-type drugs and related compounds is reviewed to their VKOR antagonistic effects. In our study, twenty 3-pyridinyl, pyrimidinyl and pyrazolyl-4-hydroxycoumarin derivatives were synthesized. A comparative in vivo (CT, PT determination) and in vitro (measurement of PIVKA-II levels) anticoagulant study with respect to warfarin showed that the synthesized compounds have different anticoagulant activities, the most prospective compounds were the 3-pyrazolyl-4-hydroxycoumarin derivatives.

A survey of precision diagnosis and management capacity of pulmonary embolism in 90 hospitals of China.

OBJECTIVE: To conduct a survey of diagnostic facility and therapeutic capability of Pulmonary thromboembolism (PE) in 90 hospitals throughout China. METHOD: It was a cross-sectional study among the participating hospitals of the National Key Research & Development Program of China-the Precision Research of Standardized Management and Application of Pulmonary Thromboembolism to obtain the equipment and application of radiological facility to diagnose PE, laboratory tests for thrombophilia, coagulation function and the availability of anticoagulants and thrombolysis agents. RESULTS: CT pulmonary arteriography is capable in all 90 hospitals, 71.11% of the hospitals could perform ventilation/perfusion scintigraphy, 24.44% of the hospitals do not routinely perform right heart evaluation by echocardiography. Protein C and protein S activity can be detected in half of the hospitals and warfarin pharmacogenomics tests can be conducted in 40 hospitals. Immune turbidimetry was used as the detection method of D-dimer in 72.37% hospitals. About 81.11% of participating hospitals were equipped with new novel oral anticoagulants, all of which were equipped with Rivaroxaban. CONCLUSION: The hospitals are capable for standardized diagnosis and management PE, while the capability of precise stratification, coagulation function tests, thrombophilia screening and pharmacogenomics requires further improvement.

Imminent risk of a global shortage of heparin caused by the African Swine Fever afflicting the Chinese pig herd.

Most of the unfractionated and low-molecular-weight heparins available worldwide are produced by Chinese companies from porcine mucosa. China is the world's largest producer of pork and thus has plenty of raw material to produce heparins. However, the deadly African Swine Fever (ASF) outbreaks afflicting China since August 2018 may cause extensive losses to the pig herd, with serious consequences for the global supply of heparins. In 2008, a sudden shortage of heparin's raw material resulting from a viral disease in Chinese pigs prompted adulterations responsible for 80 deaths and hundreds of adverse events. This incident revealed the fragility of such a supply chain, which is mostly based on raw material from a single animal from a single country. A worldwide introduction of bovine mucosa heparins manufactured in different countries certainly is a feasible way to mitigate eventual shortages of these life-saving anticoagulants caused by local veterinary problems such as the ASF threatening China now.

Gender-related differences in presentation and treatment of patients with non-valvular atrial fibrillation: results from RAMSES study.

OBJECTIVE: Gender is an important feature in the management of atrial fibrillation (AF). This study investigated gender-related differences in patients with AF in Turkey. METHODS: As a part of RAMSES (ReAl-life Multicenter Survey Evaluating Stroke prevention strategies in Turkey, NCT02344901) study, information of the patients with AF who successively applied to the hospital was analyzed. This cross-sectional, multicenter, nationwide observational study enrolled 6264 non-valvular AF (NVAF) outpatients (55.9% women) from Turkey. RESULTS: Compared with men, women with NVAF were older (71 years [range: 65-78 years] vs. 70 years [range: 62-77 years]; p<0.001), had lower frequency of coronary artery disease (22.0% vs. 38.3%; p<0.001) and congestive heart failure (18.2% vs. 27.2%; p<0.001). Women had higher median CHA2DS2-VASc score (4 [range: 3-5] vs. 3 [range: 2-4]; p<0.001), but similar HAS-BLED score (2 [range: 1-2] vs. 2 [range: 1-2]; p=0.141) when compared with men. Anticoagulant therapy use was higher in women (74.5% vs. 69.9%; p<0.001). Analysis of anticoagulation therapy use revealed that 68.5% of men and 61.6% of women (p=0.204) who had low risk for stroke (CHA2DS2-VASc score: 0 [male], 1 [female]) received anticoagulation therapy, and 30.5% of the men. Meanwhile, 25.3% of the women (p<0.001) with high risk for stroke (CHA2DS2-VASc score: ≥1 [male], ≥2 [female]) had not received any anticogulant therapy. CONCLUSION: Although women with NVAF receive better treatment than men, anticoagulation therapy is suboptimal in large proportion of men and women, with underuse in high-risk patients and overuse in low-risk patients. There is an urgent need to improve optimization of anticoagulation in patients with NVAF.

New oral anticoagulants-TURKey (NOAC-TURK): Multicenter cross-sectional study.

OBJECTIVE: New oral anticoagulants (NOACs) are increasingly used both for prevention of stroke in non-valvular atrial fibrillation (NVAF) and the treatment of venous thromboembolism (VTE). In this study, we aimed to evaluate the current patterns of NOACs treatment in Turkey. Moreover, demographic and clinical parameters and bleeding and/or embolic events under NOACs treatment were analyzed. METHODS: The New Oral Anticoagulants-TURKey (NOAC-TURK) study was designed as a multicenter cross-sectional study. A total of 2,862 patients from 21 different centers of Turkey under the treatment of NOACs for at least three months were included in this study. Demographic, clinical, and laboratory characteristics of study participants with their medications used were obtained through the NOAC-TURK survey database. Additional necessary medical records were obtained from electronic health records of participating centers. RESULTS: Of the 2. 862 patients, 1.131 (39.5%) were male and the mean age was 70.3±10.2 years. Hypertension was found as the most frequent comorbidity (81%). The most common indication for NOACs was permanent atrial fibrillation (83.3%). NOACs were mainly preferred because of inadequate therapeutic range or overdose during warfarin usage. The most frequent complication was bleeding (n=217, 7.6%), and major bleeding was observed in 1.1% of the patients. Embolic events were observed in 37 patients (1.3%). Rivaroxaban and dabigatran were both more preferred than apixaban. Almost half of the patients (47.6%) were using lower doses of NOACs, which is definitely much more than expected. CONCLUSION: The NOAC-TURK study showed an important overview of the current NOACs treatment regimens in Turkey. Although embolic and bleeding complications were lower than or similar to previous studies, increased utilization of low-dose NOACs in this study should be considered carefully. According to the results of this study, NOACs treatment should be guided through CHA2DS2-VASc and HASBLED scores to ensure more benefit and less adverse effects in NVAF patients.

[Preferences of surgeons in total knee and hip arthroplasty, and operating room facilities in Turkey: a survey]. / Türkiye'de total diz ve kalça artroplastisinde cerrahlarin tercihleri ve ameliyathane olanaklari: Bir anket.

OBJECTIVES: This study aims to determine the pre- and postoperative approaches of orthopedic surgeons and operative room environment facilities in total knee arthroplasty (TKA) and total hip arthroplasty (THA) in Turkey. MATERIALS AND METHODS: Data for this study were collected through a questionnaire completed by 234 physicians randomly identified from the database of Turkish Society of Orthopedics and Traumatology. The questionnaire comprised 19 questions investigating the operative room environment, demographic characteristics of surgeons, laboratory and radiologic analyses required by surgeons in pre- and postoperative patient evaluation, and management of postoperative complications. RESULTS: In Turkey, 48% of the operating rooms where TKA and THA are performed lack laminar airflow, while 35% lack HEPA filters. Only 20.5% of surgeons continue antibiotic prophylaxis for postoperative 24 hours. Low molecular weight heparins are the most preferred anticoagulant (86%) for thromboembolism prophylaxis. While all surgeons perform primary TKA or THA, only 63.7% perform revision TKA or THA. Of the surgeons, 84.6% do not recommended antibiotic prophylaxis before dental or urologic procedures in patients who were performed TKA or THA. CONCLUSION: In Turkey, although consensus has been built on many issues regarding TKA and THA, different approaches are adopted based on academic position, duration of specialty, and employer institution.

The Disconnect Between Novel Oral Anticoagulant Eligibility and Provincial Drug Coverage: An Albertan Anticoagulation Clinic Audit.

Canadian practice guidelines for nonvalvular atrial fibrillation (NVAF) recommend that most patients receive a novel oral anticoagulant (NOAC) in preference to warfarin to prevent stroke, but not all patients have insurance that covers NOACs. The gap between optimal therapy and drug coverage is unknown. We retrospectively assessed eligibility for NOACs in patients with NVAF at our single-centre anticoagulation clinic and ascertained whether provincial drug coverage would be in place. Most patients (89%-95%) were eligible, but only 39%-41% qualified for drug coverage. Our findings suggest most Albertans with NVAF might not have drug coverage for optimal medical therapy for stroke prevention.

Patterns of oral anticoagulants use in atrial fibrillation.

BACKGROUND: Novel oral anticoagulants are available for the management of atrial fibrillation and are considered more convenient to use than warfarin. OBJECTIVE: The main objective of this study was to describe patterns of oral anticoagulant use in the 6 months period following the availability of dabigatran at our hospital. METHODS: A cross-sectional study was conducted in a single University hospital in the province of Québec, Canada. Medical records of subjects on oral anticoagulants for atrial fibrillation that were hospitalized between October 1st, 2011 and March 31th, 2012 were reviewed. Type of use (prevalent, incident and switch) and patient's characteristics of warfarin and dabigatran users were compared using Chi-squared and T-tests. RESULTS: In the 6-month period following dabigatran availability in the hospital, 59 patients (13%) were on dabigatran and 388 (87%) on warfarin. Mean CHADS2 score, mean age and mean number of chronic medications were lower in the dabigatran group. The percentage of patients with coronary artery disease was lower and renal function was higher in the dabigatran group. CONCLUSION: Dabigatran use remained low in the first 6 months period following the approval of dabigatran at our hospital, which could be explained by limited data on the efficacy and safety of this agent in subjects with multiple comorbidities.

Overview of anticoagulant drugs for the future.

More efficacious, safer, and easier to use anticoagulants are under development. Multiple agents have been shown to be effective in ex vivo or animal thrombosis models and several have progressed to clinical studies. Investigators have not yet determined if pharmaceuticals that inhibit coagulation factor activity earlier in the cascade (for example, inhibitors of tissue factor/factor VIIa, factor IXa, or Xa) are superior to those that block the cascade at a later point. Orally bioavailable drugs for the long-term treatment of thrombotic disorders, particularly those that do not require monitoring, are needed and are under development. Local delivery of anticoagulants or genes modulating anticoagulant control at sites of increased thrombogenicity, such as in diseased arteries, is a promising treatment modality that may decrease systemic bleeding problems. Much about the initiating pathophysiologic events leading to venous thrombotic disease needs to be elucidated before such local therapy can be tested in the venous vasculature. While awaiting better anticoagulants to become routinely available, we need to improve patient management with existing drugs by instituting anticoagulation clinics, promoting patient self-monitoring, and improving efforts to educate patients and health care providers about the use of anticoagulant drugs.

"The end of good luck''--long-term survival without anticoagulation: a case report and review of the literature.

Long-term anticoagulation in patients with metallic prosthetic valve disease is required according to current guidelines. We describe a patient with a functioning mitral mechanical valve without anticoagulation for 27 years. A 46-year-old man admitted to the emergency department with complains of palpitation. The patient had a mitral valve replacement because of severe mitral stenosis. He discontinued warfarin treatment 1 month after surgery because of the unavailability of this drug in Turkey. Transthoracic echocardiography revealed functioning metalic mitral valve with a mean gradient of 9 mm Hg. Fluoroscopy showed normal excursions of the mechanical mitral valve. Transesophageal echocardiography was performed and revealed fresh thrombus formation in the left atrial appendix. Admission international normalized ration (INR) level was 1.79. Due to the higher INR level and long-term survival, genetic analysis of warfarin polymorphism was performed. There was a homozygous mutation in the vitamin K epoxide reductase complex 1 (VKORC1) 1173C>T and 1639G>A genotypes. The possible explanations of long-term survival and baseline higher INR level were linked to the mutation in warfarin metabolism. We also briefly review the literature.