Heparin is an effective treatment for preventing liver failure after hepatectomy.

BACKGROUND: Posthepatectomy liver failure (PHLF) is one of the most important causes of death following liver resection. Heparin, an established anticoagulant, can protect liver function through a number of mechanisms, and thus, prevent liver failure. AIM: To look at the safety and efficacy of heparin in preventing hepatic dysfunction after hepatectomy. METHODS: The data was extracted from Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) v1. 4 pinpointed patients who had undergone hepatectomy for liver cancer, subdividing them into two cohorts: Those who were injected with heparin and those who were not. The statistical evaluations used were unpaired t-tests, Mann-Whitney U tests, chi-square tests, and Fisher's exact tests to assess the effect of heparin administration on PHLF, duration of intensive care unit (ICU) stay, need for mechanical ventilation, use of continuous renal replacement therapy (CRRT), incidence of hypoxemia, development of acute kidney injury, and ICU mortality. Logistic regression was utilized to analyze the factors related to PHLF, with propensity score matching (PSM) aiming to balance the preoperative disparities between the two groups. RESULTS: In this study, 1388 patients who underwent liver cancer hepatectomy were analyzed. PSM yielded 213 matched pairs from the heparin-treated and control groups. Initial univariate analyses indicated that heparin potentially reduces the risk of PHLF in both matched and unmatched samples. Further analysis in the matched cohorts confirmed a significant association, with heparin reducing the risk of PHLF (odds ratio: 0.518; 95% confidence interval: 0.295-0.910; P = 0.022). Additionally, heparin treatment correlated with improved short-term postoperative outcomes such as reduced ICU stay durations, diminished requirements for respiratory support and CRRT, and lower incidences of hypoxemia and ICU mortality. CONCLUSION: Liver failure is an important hazard following hepatic surgery. During ICU care heparin administration has been proved to decrease the occurrence of hepatectomy induced liver failure. This indicates that heparin may provide a hopeful option for controlling PHLF.

Feasibility of atezolizumab and bevacizumab combination regimens in patients with hepatocellular carcinoma and lung cancer taking direct oral anticoagulants.

AIM: Atezolizumab and bevacizumab (Atezo/Bev) combination immunotherapy regimens and direct oral anticoagulants (DOACs) are both associated with bleeding. Therefore, combining Atezo/Bev regimens with DOACs may exacerbate the bleeding risk. This study investigated the feasibility of the Atezo/Bev regimen in patients taking DOACs. METHODS: This retrospective study included 141 patients with unresectable hepatocellular carcinoma (HCC) or advanced lung cancer (LC) treated with Atezo/Bev regimens. Patients who used antithrombotic agents other than DOACs were excluded. Bleeding events during the Atezo/Bev regimen were analyzed. RESULTS: The incidence rates of bleeding of any grade in the DOAC (n = 11) and no antithrombotic agent (NAA) (n = 130) groups were 9.1% and 10.8%, respectively, with no significant differences. Moreover, no significant difference was found in the frequency of bleeding of grade ≥3 between the DOAC and NAA groups. No patients in the DOAC group discontinued the Atezo/Bev regimen because of severe bleeding. Although serum albumin levels, with a hazard ratio (HR) of 0.298 (95% confidence interval [CI]: 0.105-0.847), independently contributed to bleeding events (p = 0.023), DOAC administration did not (HR: 1.357; 95% CI: 0.157-10.54; p = 0.770). Among only patients with HCC (n = 59), none of the five patients taking DOACs experienced bleeding events. A high albumin-bilirubin score (HR: 9.083, 95% CI: 1.118-73.76) was associated with bleeding events (p = 0.039). CONCLUSIONS: DOACs did not have a considerable effect on bleeding events in the Atezo/Bev regimens for HCC or LC. Under careful surveillance for bleeding, Atezo/Bev regimens may be feasible in patients receiving DOACs.

Antithrombotic therapy for durable left ventricular assist devices: protocol for a living systematic review with indirect comparison/network meta-analysis.

BACKGROUND: Left ventricular assist devices (LVADs) have emerged as a successful treatment option for patients with end-stage heart failure. Compared with the best medical therapy, LVADs improve survival and enhance functional capacity and quality of life. However, two major complications compromise this patient population's outcomes: thrombosis and bleeding. Despite technological innovations and better hemocompatibility, these devices alter the rheology, triggering the coagulation cascade and, therefore, require antithrombotic therapy. Anticoagulation and antiplatelet therapies represent the current standard of care. Still, inconsistency in the literature exists, especially whether antiplatelet therapy is required, whether direct oral anticoagulants can replace vitamin K antagonists and even whether phosphodiesterase type 5 inhibitors with their antithrombotic effects could be added to the regimen of anticoagulation. METHODS AND ANALYSIS: We will perform a living systematic review with network meta-analysis and indirect comparison between current antithrombotic therapies, which have and have not been directly compared within clinical trials and observational studies. We will systematically search the following electronic sources: Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica Database (EMBASE). We will exclusively examine studies published in English from 2016 to the present. Studies conducted before 2016 will be omitted since our primary focus is evaluating continuous flow devices. Two independent reviewers will assess the articles by title, abstract and full text; any disagreement will be resolved through discussion, and a third reviewer will be involved if necessary. The Cochrane Risk of Bias tool will be used to assess the risk of bias. We will then conduct a pairwise meta-analysis; if the assumption of transitivity is satisfied, we will proceed with network meta-analysis using Bayesian methodology. ETHICS AND DISSEMINATION: Formal ethical approval is not required as no primary data are collected. This systematic review and network meta-analysis will delineate the risks of stroke, thromboembolic events, pump thrombosis, gastrointestinal bleeding and mortality in patients equipped with LVADs who are subjected to various antithrombotic regimens. The findings will be disseminated via a peer-reviewed publication and presented at conference meetings. This will enhance clinical practice and guide future research on anticoagulation strategies within this distinct patient cohort. PROSPERO REGISTRATION NUMBER: CRD42023465288.

Clinical guidance for unfractionated heparin dosing and monitoring in critically ill patients.

INTRODUCTION: Unfractionated heparin is a widely used anticoagulant in critically ill patients. It has a well-established safety profile and remains an attractive option for clinicians due to its short half-life and reversibility. Heparin has a unique pharmacokinetic profile, which contributes to significant inter-patient and intra-patient variability in effect. The variability in anticoagulant effect combined with heparin's short half-life mean close monitoring is required for clinical efficacy and preventing adverse effects. To optimize heparin use in critically ill patients, effective monitoring assays and dose adjustment strategies are needed. AREAS COVERED: This paper explores the use of heparin as an anticoagulant and optimal approaches to monitoring in critically ill patients. EXPERT OPINION: Conventional monitoring assays for heparin dosing have significant limitations. Emerging data appear to favor using anti-Xa assay monitoring for heparin anticoagulation, which many centers have successfully adopted as the standard. The anti-Xa assay appears have important benefits relative to the aPTT for heparin monitoring in critically ill patients, and should be considered for broader use.

Efficacy and safety of antithrombotic therapy for preventing and treating pediatric thromboembolic disease: a systematic review.

This review used traditional and network meta-analyses (NMA) to conduct a comprehensive study of antithrombotic therapies in children with thromboembolic disease. We searched the PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov databases from their inception to 26 February, 2023. And we finally included 16 randomized controlled trials. In the prevention of thromboembolic events (TEs), the use of anticoagulants had a low risk of TEs (relative risk (RR) 0.73, 95% CI 0.56 to 0.94) and a high risk of minor bleeding (RR 1.43, 95% CI 1.09 to 1.86) compared with no anticoagulants. In the treatment of TEs, direct oral anticoagulants (DOACs) were not inferior to standard anticoagulation in terms of efficacy and safety outcomes. In NMA, rivaroxaban and apixaban showed the lowest risk for TEs and major or clinically relevant nonmajor bleeding. According to the overall assessment of efficacy and safety, dabigatran may be the best choice for children with thromboembolic disease. The results of our study will provide references and suggestions for clinical drug selection.

[Heparin-Induced Thrombocytopenia].

The extensive use of therapeutic doses of heparin to prevent thrombosis in critically ill patients with COVID-19 during the pandemic has led to an increased incidence of bleeding and heparin-induced thrombocytopenia (HIT). In addition, the introduction of the AstraZeneca and Johnson&Johnson vaccines against COVID-19 into clinical practice was associated with the development of a rare but very severe, adverse thrombotic complication, vaccine-induced immune thrombotic thrombocytopenia (VITT). Thrombotic complications of VITT turned out to be similar to HIT both clinically and pathophysiologically. HIT is a potentially fatal immune-mediated adverse drug response that results in emergence of antibodies that activate platelets in the presence of heparin. HIT is characterized by a high incidence of venous and arterial thromboses, often with fatal outcomes. Currently, there are clearly defined international guidelines for the diagnosis, treatment and prevention of HIT. In case of thrombotic complications, non-heparin anticoagulants should be used.

[How to generate recommendations for venous thromboprophylaxis in health institutions?] / Cómo generar recomendaciones de tromboprofilaxis venosa en instituciones de salud.

Venous thromboembolism disease (VTE) prevention strategy has to be constantly updated based on new evidence that is generated every year. Each institution must have a formal and active prevention policy against VTE and must develop guidelines or standards for thromboprophylaxis (TP) according to the local reality. During this process of adapting a guideline to the region and the generation of hospital recommendations, we must always consider the available local resources, the thromboembolic and hemorrhagic risk of the patients, even after discharge, and also their considerations and preferences. Adherence to local TP recommendations is one of the most important items evaluated by organizations that measure institutional quality. Individualized prophylaxis should consider personal and family history of VTE, the use of validated risk assessment models or RAMs for thrombosis and bleeding events, as well as the special characteristics of each patient. Ideally, each center's own statistics should be available for decision-making. Extrapolating guidelines from developed countries could have a negative impact, if we ignore our hospital's reality. In this document we will find practical tools for health institutions that will allow them to prepare recommendations or guidelines for adequate VTE prophylaxis.

La prevención de la enfermedad tromboembólica venosa (ETV) es motivo de continua actualización en función de nueva evidencia que se genera permanentemente. Cada institución debe contar con una estrategia activa de prevención contra la ETV y debe generar normas de tromboprofilaxis (TP) de acuerdo con la realidad local. Durante este proceso de adaptación de una guía a la región debemos siempre tener en cuenta los recursos locales disponibles, el riesgo tromboembólico y hemorrágico propio del paciente, de la enfermedad por la que se encuentra internado (ya sea clínica o quirúrgica) y las consideraciones o preferencias del paciente. La tasa de adherencia a recomendaciones locales de TP es uno de los indicadores de excelencia más importantes evaluados en organismos que califican la calidad de una institución de salud. Las medidas de profilaxis que propongamos para los centros de salud, deben ser individualizadas para cada paciente, tienen que considerar antecedentes personales y familiares del enfermo y utilizar modelos de evaluación de riesgo validados de trombosis y de sangrado. También deben incluir a la población con riesgo de trombosis persistente luego del alta. Lo ideal es tener estadísticas propias de cada nosocomio para la toma de decisiones de cómo implementar una correcta TP. Extrapolar guías de los países desarrollados a nuestro ámbito podría tener un impacto negativo, si no se conoce la propia realidad. En este documento encontraremos herramientas prácticas para las instituciones de salud de la región, que les permita orientarse al momento de confeccionar recomendaciones para una adecuada TP.

[Translation into French and republication of: "Central venous catheter associated upper extremity deep vein thrombosis in cancer patients: Diagnosis and therapeutic management"]. / Traduction et republication de : « Thrombose veineuse profonde du membre supérieur associée à un cathéter veineux central chez les patients cancéreux : diagnostic et prise en charge thérapeutique ¼.

Catheter-related thrombosis (CRT) is a relatively frequent and potentially fatal complication arising in patients with cancer who require a central catheter placement for intravenous treatment. In everyday practice, CRT remains a challenge for management; despite its frequency and its negative clinical impact, few data are available concerning diagnosis and treatment of CRT. In particular, no diagnostic studies or clinical trials have been published that included exclusively patients with cancer and a central venous catheter (CVC). For this reason, many questions regarding optimal management of CRT remain unanswered. Due to the paucity of high-grade evidence regarding CRT in cancer patients, guidelines are derived from upper extremity DVT studies for diagnosis, and from those for lower limb DVT for treatment. This article addresses the issues of diagnosis and management of CRT through a review of the available literature and makes a number of proposals based on the available evidence. In symptomatic patients, venous ultrasound is the most appropriate choice for first-line diagnostic imaging of CRT because it is noninvasive, and its diagnostic performance is high (which is not the case in asymptomatic patients). In the absence of direct comparative clinical trials, we suggest treating patients with CRT with a therapeutic dose of either a LMWH or a direct oral factor Xa inhibitor, with or without a loading dose. These anticoagulants should be given for a total of at least 3 months, including at least 1 month after catheter removal following initiation of therapy.

[Interference of oral anti-Xa anticoagulants during monitoring of unfractionated heparin treatments: practical and future attitudes]. / Interférence des anticoagulants oraux directs anti-Xa lors de la surveillance des traitements par héparine non-fractionnée : attitudes pratiques et à venir.

Contrary to direct oral anticoagulants (DOAC), unfractionated heparin (UFH) requires daily monitoring when administered at therapeutic dose. At present, UFH monitoring is preferably carried out by measuring plasma anti-Xa activity, however, in patients previously treated with an anti-Xa DOAC and switched to UFH, there is a high risk of DOAC interfering with the measurement of UFH anti-Xa activity. Residual anti-Xa DOAC in the sample can lead to an overestimation of the anticoagulant activity attributed to heparin and thus to incorrect anticoagulation. This risk of interference should not be overlooked because interference may occur even at concentration of DOAC below the hemostatic safety threshold and can last several days. To overcome this issue, several alternatives are being studied. This note provides an update on anti-Xa DOAC interference and different strategies available in current practice. It also underlines the importance of communication between biologists and clinicians on anticoagulant treatments received by patients.

[Is monitoring of anti-factor Xa levels required for low molecular weight heparin prophylaxis of venous thromboembolism in critically ill patients?]

The incidence and mortality of venous thromboembolism (VTE) are high in critically ill patients, and there is still a risk of VTE and bleeding after the use of fixed-dose low molecular weight heparin (LMWH) for prophylaxis. The level of anti-factor Xa is not up to standard after LMWH prophylaxis in patients with surgery or trauma. The condition of critically ill patients is complicated, and the proportion of patients with low antithrombin III is high, which can affect the prophylactic efficacy of LMWH and contribute to VTE occurrence. There is currently no consensus on whether adjusting LMWH dose according to anti-factor Xa levels can reduce VTE occurrence in critically ill patients. High-quality multicenter randomized controlled studies are needed in the future to establish new approaches for precise prevention of VTE in critically ill patients.

Citrate and low-dose heparin combined anticoagulation in pediatric continuous renal replacement therapy.

There remains no optimal anticoagulation protocol for continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in pediatric patients with elevated D-dimer levels. We aimed to assess the effects of different anticoagulation strategies on the risk of CRRT filter clotting in these patients. Pediatric patients undergoing CRRT were retrospectively grouped based on pre-CRRT D-dimer levels and anticoagulant: D-RCA group (normal D-dimer, RCA only, n = 22), D+ RCA group (elevated D-dimer, RCA only, n = 50), and D+ RCA+ systemic heparin anticoagulation (SHA) group (elevated D-dimer, RCA combined with SHA, n = 55). The risk of filter clotting and incidence of bleeding were compared among the groups. Among the groups, the D+ RCA+ SHA group had the longest filter lifespan; further, the incidence of bleeding was not increased by concurrent use of low-dose heparin for anticoagulation. Moreover, concurrent heparin anticoagulation was associated with a decreased risk of filter clotting. Contrastingly, high pre-CRRT hemoglobin and D-dimer levels and post-filter ionized calcium level > 0.4 mmol/L were associated with an increased risk of filter clotting. RCA combined with low-dose heparin anticoagulation could reduce the risk of filter clotting and prolong filter lifespan without increasing the risk of bleeding in patients with elevated D-dimer levels undergoing CRRT.

Unilateral retrobulbar haemorrhage in a cat secondary to suspected anticoagulant rodenticide intoxication.

A 6-month-old intact female mixed-breed kitten presented with severe exophthalmos of the left eye. Periocular lesions, including subconjunctival haemorrhage, third eyelid protrusion, and left eyelid oedema, were detected in the absence of globe retropulsion. The left intraocular pressure was increased, and ocular ultrasonography revealed ipsilateral retrobulbar fluid. Coagulation panels were markedly prolonged and severe anaemia was detected. Ultrasound-guided retrobulbar centesis performed to decrease intraocular pressure yielded blood. Based on the history and clinical findings, anticoagulant rodenticide intoxication was suspected. Treatment included partial tarsorrhaphy and the administration of topical antibiotics, artificial tears, and vitamin K1. Fresh whole blood and fresh frozen plasma were transfused for supportive therapy. Coagulation parameters improved after 7 days of hospitalisation. The periocular lesions resolved within 14 days, despite persistent optic nerve damage and blindness. This case report raises the possibility that anticoagulant rodenticide toxicity may result in retrobulbar haemorrhage in the absence of other typical cavitary bleeding. Although uncommon, anticoagulant rodenticide toxicity should be considered in cats with retrobulbar haemorrhage.

Special Issue "Genetic, Functional and Therapeutic Aspects of Procoagulant and Anticoagulant Factors".

Pro- and anticoagulant factors are core components of hemostasis [...].

Time-in-therapeutic-range defined warfarin and direct oral anticoagulants in atrial fibrillation: a Nationwide Cohort Study.

BACKGROUND: Little is known how individual time-in-therapeutic-range (TTR) impacts the effectiveness and safety of warfarin therapy compared to direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF). OBJECTIVE: To compare the effectiveness and safety of standard dose DOACs to warfarin in patients with AF, while categorizing warfarin treated patients into quartiles based on their individual TTR. MATERIALS AND METHODS: We conducted a nationwide study including all patients with new-onset AF between 2011 and 2018 in Finland. Hazard ratios (HR) were calculated using Cox regression analysis with the inverse probability of treatment weighted method to assess the risks of ischaemic stroke (IS), intracranial haemorrhage (ICH) and mortality for users of apixaban (n = 12,426), dabigatran (n = 4545), rivaroxaban (n = 12,950) and warfarin (n = 43,548). RESULTS: The median TTR for warfarin users was 72%. Compared to the second best TTR quartile (reference), the risk of IS was higher in the two poorest TTR quartiles, and lower in the best TTR quartile and on rivaroxaban [2.35 (95% confidence interval, 1.85-2.85), 1.44 (1.18-1.75), 0.60 (0.47-0.77) and 0.72 (0.56-0.92)]. These differences were non-significant for apixaban and dabigatran. HR of ICH was 6.38 (4.88-8.35) and 1.87 (1.41-2.49) in the two poorest TTR groups, 1.44 (1.02-1.93) on rivaroxaban, and 0.58 (0.40-0.85) in the best TTR group compared to the reference group. Mortality was higher in the two poorest TTR groups and lowest in the best TTR group. CONCLUSIONS: The outcome was unsatisfactory in the two lowest TTR quartiles - in half of the patients treated with warfarin. The differences between the high TTR groups and standard dose DOACs were absent or modest.

A Comparison Between Fondaparinux Sodium and Low-Molecular-Weight Heparin in Preventing Patients Undergoing Hip Replacement from Deep Vein Thrombosis.

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.

Quality control, safety assessment and preparation approaches of low molecular weight heparin.

Low Molecular Weight Heparins (LMWHs) are well-established for use in the prevention and treatment of thrombotic diseases, and as a substitute for unfractionated heparin (UFH) due to their predictable pharmacokinetics and subcutaneous bioavailability. LMWHs are produced by various depolymerization methods from UFH, resulting in heterogeneous compounds with similar biochemical and pharmacological properties. However, the delicate supply chain of UFH and potential contamination from animal sources require new manufacturing approaches for LMWHs. Various LMWH preparation methods are emerging, such as chemical synthesis, enzymatic or chemical depolymerization and chemoenzymatic synthesis. To establish the sameness of active ingredients in both innovator and generic LMWH products, the Food and Drug Administration has implemented a stringent scientific method of equivalence based on physicochemical properties, heparin source material and depolymerization techniques, disaccharide composition and oligosaccharide mapping, biological and biochemical properties, and in vivo pharmacodynamic profiles. In this review, we discuss currently available LMWHs, potential manufacturing methods, and recent progress for manufacturing quality control of these LMWHs.

Overview of the current procedures in synthesis of heparin saccharides.

Natural heparin, a glycosaminoglycan consisting of repeating hexuronic acid and glucosamine linked by 1 â†’ 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.

[Impaired hemostasis in elderly and senile patients with mesenteric thrombosis in COVID-19.]

In the treatment of coronavirus infections, it is important not only to understand the course of the disease, but also to understand what is happening in the human body, especially in the circulatory system, that is, which disorders lead to deterioration and further complications. Hemostasis disorder in COVID-19 plays an important role in the etiology and clinical manifestations of the disease. The ability to identify factors and risk groups for the development of thrombotic complications, the ability to dynamically interpret peripheral blood parameters and coagulograms, knowledge of diagnostic criteria for possible hemostasis disorders (for example, DIC syndrome, sepsis-associated coagulopathy, antiphospholipids, hemophagocytosis and hypercoagulation syndrome) are necessary to determine the indications for the test. Differentiated prescribing of clinically justified therapy (including anticoagulants and blood components) is important, which determines the complexity of treatment and prognosis for patients with COVID-19. This article is a review of the literature on the topic of hemostasis disorders in elderly and senile patients with mesenteric thrombosis in COVID 19 over the past few years.

Construction of warfarin population pharmacokinetics and pharmacodynamics model in Han population based on Bayesian method.

The purpose of this paper is to study the genetic polymorphisms of related gene loci (CYP2C9*3, VKORC1-1639G > A) based on demographic and clinical factors, and use the maximum a posterior Bayesian method to construct a warfarin individualized dose prediction model in line with the Chinese Han population. Finally, the built model is compared and analyzed with the widely used models at home and abroad. In this study, a total of 5467 INR measurements are collected from 646 eligible subjects in our hospital, and the maximum a posterior Bayesian method is used to construct a warfarin dose prediction that conforms to the Chinese Han population on the basis of the Hamberg model. The model is verified and compared with foreign models. This study finds that body weight and concomitant use of amiodarone have a significant effect on the anticoagulant effect of warfarin. The model can provide an effective basis for individualized and rational dosing of warfarin in Han population more accurately. In the performance of comparison with different warfarin dose prediction models, the new model has the highest prediction accuracy, and the prediction percentage is as high as 72.56%. The dose predicted by the Huang model is the closest to the actual dose of warfarin. The population pharmacokinetics and pharmacodynamics model established in this study can better reflect the distribution characteristics of INR values after warfarin administration in the Han population, and performs better than the models reported in the literature.

Role of prescribed medication in the development of iron deficiency anaemia in adults-a case-control study.

OBJECTIVE: To estimate the strength of association between exposure to selected classes of prescribed medications and the risk of developing iron deficiency anaemia (IDA), specifically considering oral anticoagulants (OACs), antidepressants, antiplatelet agents, proton pump inhibitors (PPIs) and non-steroidal anti-inflammatories. DESIGN: A case-control study involving the analysis of community repeat prescriptions among subjects referred with IDA, and unmatched controls referred as gastroenterology fast-tracks for other indications. Multivariable logistic regression modelling was used to calculate ORs for the association between IDA presentation and each medication class, adjusted for age, sex and coprescribing. For those classes showing significance, it was also used to calculate risk differences between those in the IDA group with or without haemorrhagic lesions on investigation. RESULTS: A total of 1210 cases were analysed-409 in the IDA group, and 801 in the control group. Significant associations were identified between presentation with IDA and long-term exposure to PPIs (OR 3.29, 95% CI: 2.47 to 4.41, p<0.001) and to OACs (OR 2.04, 95% CI: 1.29 to 3.24, p=0.002). IDA was not associated with long-term exposure to any of the other three drug classes. In contrast to the relationship with PPIs, the association with OACs was primarily in the IDA sub-group with haemorrhagic lesions. CONCLUSION: Long-term exposure to PPIs and OACs are independently associated with the risk of developing IDA. There are grounds for considering that these associations may be causal, though the underlying mechanisms probably differ.