Quality of oral anticoagulation control in Chinese patients with non-valvular atrial fibrillation: a prospective controlled study

Abstract

Objective

The sex, age, medical history, treatment, tobacco use, race risk (SAMe-TT₂R₂) Score; the sex, age, medical history, treatment, tobacco use, genotype combination (SAMe-TT₂G₂) Score; and the so-called modified SAMe-TT₂R₂ scores have been proposed to predict the anticoagulation quality for patients with non-valvular atrial fibrillation (NVAF). The data from a prospective controlled study is used to validate the SAMe-TT₂R₂ and SAMe-TT₂G₂ scores in Chinese NVAF patients treated with warfarin and to evaluate the association of factors with time in therapeutic range (TTR) to predict the quality of oral anticoagulation control.     

Systematic review of drug–drug interactions between rifamycins and anticoagulant and antiplatelet agents and considerations for management

Rifamycins (rifampin, rifabutin, and rifapentine) play an essential role in the treatment of mycobacterial and some nonmycobacterial infections. They also induce the activity of various drug transporting and metabolizing enzymes, which can impact the concentrations and efficacy of substrates. Many anticoagulant and antiplatelet (AC/AP) agents are substrates of these enzymes and have narrow therapeutic indices, leading to risks of thrombosis or bleeding when coadministered with rifamycins. The objective of this systematic review was to evaluate the effects on AC/AP pharmacokinetics, laboratory markers, and clinical safety and efficacy of combined use with rifamycins. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidance was performed. The PubMed, Embase, and Web of Science databases were queried for English-language reports on combination use of rifamycins and AC/AP agents from database inception through August 2021. The 29 studies identified examined warfarin (n = 17), direct oral anticoagulants (DOACs) (n = 8), and antiplatelet agents (n = 4) combined with rifampin (n = 28) or rifabutin (n = 1). Eleven studies were case reports or small case series; 14 reported on pharmacokinetic or laboratory markers in healthy volunteers. Rifampin-warfarin combinations led to reductions in warfarin area under the curve (AUC) of 15%–74%, with variability by warfarin isomer and study. Warfarin dose increases of up to 3–5 times prerifampin doses were required to maintain coagulation parameters in the therapeutic range. DOAC AUCs were decreased by 20%–67%, with variability by individual agent and with rifampin versus rifabutin. The active metabolite of clopidogrel increased substantially with rifampin coadministration, whereas prasugrel was largely unaffected and ticagrelor saw decreases. Our review suggests most combinations of AC/AP agents and rifampin are problematic. Further studies are required to determine whether rifabutin or rifapentine could be safe alternatives for coadministration with AC/AP drugs.     

Utility of INR For Prediction of Delayed Intracranial Hemorrhage Among Warfarin Users with Head Injury

BackgroundIncidence of delayed intracranial hemorrhage (DICH) in patients on warfarin has been controversial. No previous literature has reported the utility of international normalized ratio (INR) in predicting traumatic DICH.ObjectivesUtilizing INR to risk stratify head trauma patients who may be managed without repeat imaging.MethodsThis was a retrospective study at a Level II trauma center. All patients on warfarin with head injuries from March 2014 to December 31, 2017 were included. Each patient underwent an initial head computed tomography scan (HCT) and subsequent repeat HCT 12 h after. Patients presenting > 12 h after head injury received only one HCT. Two blinded neuroradiologists reviewed each case of DICH. Statistical analysis evaluated Glasgow Coma Scale (GCS), Injury Severity Score (ISS), heart rate, systolic blood pressure (SBP), age, and platelet count.ResultsThere were 395 patients who qualified for the protocol; 238 were female. Average age was 79 years. Seventy-seven percent of patients underwent repeat HCT. Five resulted in DICH (INR 2.6–3.0), three of which might have been present on initial HCT; incidence rate of 0.51–1.27%. One patient required neurosurgical intervention. Among 80 patients with INR < 2, no DICH was identified, resulting in high sensitivity, but with a wide confidence interval; sensitivity of 100% (95% confidence interval [CI] 47.8–100), specificity 21% (95% CI 16.6–28.9). Correlation of factors: ISS (p = 0.039), GCS (p = 0.978), HR (p = 0.601), SBP (p = 0.198), age (p = 0.014), and platelets (p = 0.281).ConclusionNo patient with INR < 2 suffered DICH, suggesting that warfarin users presenting with INR < 2 may be managed without repeat HCT. For INR > 2, patients age and injury severity can be used for shared decision-making to discharge home with standard head injury precautions and no repeat HCT.     

The effect of oral anticoagulant therapy on aptt results from a bedside coagulation monitor

Objective. The Ciba Corning 512 coagulation monitor (CC512) can be used to monitor heparin therapy by performing an activated partial thromboplastin time (APTT) at the patient’s bedside. This study was designed to compare the CC512 results to results using the laboratory system. The relative sensitivities of both systems to the effect of oral anticoagulant therapy also was investigated.Methods. Activated partial thromboplastin times were performed with both the CC512 and laboratory system on 74 specimens from patients receiving IV heparin therapy, and on 14 specimens from patients on warfarin only. Heparin assays were performed on 43 of the specimens from the heparinized patients.Results. When a patient was receiving heparin only, the APTT results of the CC512 proved to be similar to existing laboratory methods. The CC512 APTT results of patients on warfarin only were markedly prolonged, whereas the laboratory APTTs were only slightly affected.Conclusion. The CC512 results were comparable to the laboratory system. However, the CC512 APTT was more sensitive to the effect of warfarin than the laboratory APTT system used in this study. CC512 APTT results on a patient receiving both oral and intravenous anticoagulation could be misleading. The authors wish to thank D.M. O’Brien and the nursing staff of the Coronary Care Unit for providing CC512 data and laboratory specimens, and I. Smith for the preparation of graphics. We also wish to thank Australian Diagnostics Corporation, which provided consumables.     

Chinese herbs and warfarin potentiation by 'Danshen'

Drug interactions with warfarin can be dangerous and although common drug interactions are now well recognized those with Chinese herbs are not widely appreciated. 'Danshen' is a herbal medicine often used for various complaints, particularly cardiovascular, in the Chinese community. We report a case of danshen-induced overcoagulation with severe and dangerous abnormalities of clotting in a patient with rheumatic heart disease.     

Chemical and statistical considerations in the determination of partition coefficients of weakly ionizable drugs and poisons

Equations have been developed that relate the concentration (or a parameter directly proportional to concentration, such as optical absorbance) of a weakly ionizable solute in a water-immiscible phase, in equilibrium with an aqueous phase, to the pH of the aqueous phase, the partition coefficient of the unionized solute and the phase volume ratio. These relationships have been used in the design of experimental methods for determining partition coefficients, which require measurement of solute concentration in only one phase. Data obtained in this way permit ready recognition of deviations from assumptions made in the development of the model; these assumptions include insolubility of the ionized solute in the water-immiscible phase and lack of interaction between buffer components and solute. Conditions for optimal liquid—liquid extraction of weakly ionizable solutes are more easily recognized. With these techniques, the negative logarithm of the acid dissociation constant (pK′_a) and the logarithm of the octanol—water partition coefficient (log P) have been measured for warfarin (pK′_a = 5.15 ± 0.04; log P = 2.82 ± 0.06), strychnine (pK′_a = 8.29 ± 0.02; log P = 2.23 ± 0.04), phenol (pK′_a = 9.88 ± 0.02; log P = 1.75 ± 0.05), procaine (pK′_a = 8.11 ± 0.04; log P = 1.10 ± 0.08), and ephedrine (pK′_a = 9.92 ± 0.01; log P = 1.65 ± 0.04) at 21°C.     

Breast fat necrosis secondary to warfarin-induced calciphylaxis,a rare mimicker of breast cancer: A case report and a review of literature

Breast fat necrosis (BFN) is usually a benign inflammatory response to breast trauma. However, an extremely rare cause of fat necrosis is calciphylaxis, a calcification of small- and medium-sized arteries causing thrombosis and ischemia. It is classified into (A) uremic (B) nonuremic-induced calciphylaxis. Calciphylaxis has been reported to be encountered in different parts of the body. However, to the best of our knowledge there is only one case in the English literature of BFN 2ry to warfarin-induced calciphylaxis. We report a 65-year-old female, known case of atrial fibrillation on warfarin, presented with a left breast mass of 4-month duration. The mass was painful and progressively enlarging. Examination of the left breast showed 7 × 4 cm mass, spanning from 10-2 o'clock, free from surrounding structures, with preserved overlying skin. However, the mass was not visualized on mammogram. Ultrasound showed a left breast lobulated hypoechoic mass containing a hyperechoic component. Biopsy showed fat necrosis. After 1 month, she presented with ulceration of the overlying skin. After wide local excision, histopathology demonstrated a calciphylaxis-induced fat necrosis. Considering the patient's background, the diagnosis was BFN secondary to warfarin-induced calciphylaxis. Hence, the warfarin was shifted to Rivaroxaban, 6 months follow-up showed no evidence of recurrence. In conclusion, the rarity of nonuremic calciphylaxis is reflected on the delay of diagnosis in some of the reported cases and the lack of grading system used to guide the management of such difficult wounds. However, keeping a high index of suspicion is important whenever such wounds are encountered with presence of risk factors other than end-stage kidney disease.     

低危非瓣膜病心房颤动患者抗栓疗效分析

目的:比较低危非瓣膜病心房颤动(AF)患者华法林和阿司匹林的疗效,以明确抗栓治疗的最佳策略。方法:资料来源于华法林(目标INR 2．0～3．0)与阿司匹林(150～160mg／d)的前瞻性随机对照研究,参考国际指南中关于非瓣膜病AF血栓栓塞高危因素的建议,低危分层标准为不具备任何一项高危因素:脑卒中病史、年龄大于75岁、糖尿病、心肌梗死、超声心动图EF小于40％。分析低危亚组中阿司匹林与华法林组血栓栓塞和出血事件。结果:低危亚组患者306例,平均年龄(61．9±9．3)岁,男性194例(63．4％),孤立性AF 41例(13．4％)。随访时间中位数19个月。服用阿司匹林患者发生血栓栓塞事件5例,华法林组仅1例,但统计学没有显著差异(P=0．219)。患者共发生出血事件11例,其中严重出血仅在华法林组有1例。华法林组总出血发生率高于阿司匹林组但没有统计学差异(P=0．288)。血栓栓塞和严重出血事件的联合终点[9例(5．6％)比3例(2．1％)P=0．146]两组间也没有差异。结论:不具有血栓栓塞高危因素的低危非瓣膜病AF患者,抗血小板药物阿司匹林与口服抗凝药物的疗效相似,但阿司匹林的剂量还需进一步研究。     

华法林预防非瓣膜性心房颤动老年患者脑栓塞

目的观察不同抗凝强度华法林预防非瓣膜病心房颤动（简称房颤）老年患者脑栓塞的效果及出血不良事件。方法264例非瓣膜病房颤老年患者随机分为两组，分别给予华法林抗凝强度国际标准化比值（INR）1．7-2.2（低强度组，152例）和INR2．3—3.0（中强度组，112例）抗凝治疗。观察两组脑栓塞并发症及出血事件发生率。结果低强度组患者脑栓塞年发生率为2．2％，与中强度组患者的1.9％比较差异无统计学意义（x^2=0．115，P〉0．05）。低强度组患者的严重出血事件年发生率为0．7％，与中强度组患者的1.0％比较差异无统计学意义（x^2=0．254。P〉0．05），但低强度组患者轻微出血事件印发生率3．6％明显低于中强度组患者10．7％（x^2=4．086，P〈0．05）。结论华法林抗凝强度INR1.7-2．2能明显降低老年非瓣膜病房颤脑栓塞发生率，INR2．3—3．0时轻微出血事件增加。