Christensen Thomas Decker
Department of Cardiothoracic and Vascular Surgery & Clinical Institute, Aarhus University Hospital, Skejby, Aarhus N, Denmark.
Dan Med Bull. 2011 May;58(5):B4284.
Oral anticoagulation therapy (OAT) with coumarins (vitamin K-antagonists) is prescribed for both prophylactic and therapeutic use to patients at increased risk of thromboembolism. OAT has a narrow therapeutic index, and monitoring is based on the International Normalized Ratio (INR) conventionally determined on citrated plasma obtained by venepuncture. Based on the INR measurements, health care providers determine the appropriate dose of coumarins (e.g. warfarin (Marevan). Optimised management of OAT improves the quality of treatment. Patient self-management (PSM) is a new concept where the patient takes an active part in his or her own treatment. PSM in OAT implies that the patient analyses a drop of blood using a portable coagulometer (INR-monitor). The coagulometer displays the INR, which the patient uses for coumarins dosage. It is still not clarified which subset of patients (in terms of indication for OAT, age, co-morbidity etc.) that potentially will benefit from PSM, and how large this potential effect is. A precondition for a correct dosage of coumarins is a correct estimation of the INR, and the method and apparatus used for providing the INR measurements is in this context essential. The coagulometers used for PSM have not been investigated adequately in terms of precision and agreement, so this is warranted. INR has proven adequate for adjusting dosages. It is doubtful that the level of INR reflects the overall haemostatic capacity or thrombotic potential of individual patients. Measurement of continuous calibrated automated thrombin generation (CAT) and coagulation factors activities may serve as a more sensitive and global haemostatic parameter and potentially with better performance in predicting risk of complications in patients on OAT. We found that the clotting activity of coagulation factors II, VII, IX, and X and CAT exhibited no variability over a 6-week period. The activity of the coagulation factors and CAT was significantly associated with the INR, so these two tests can be used concomitantly and/or interchangeably with the INR. Approximately 50% of the total variability of the coagulation factor activities and CAT was reflected by the INR, whereas the remaining variability was within the subject (patient). Coagulation factor activities and CAT can therefore potentially be used to provide further information to the risk of bleeding and thromboembolism, since almost 50% of the variability within the subject is not displayed in the INR value. Yet it remains uncertain if this method can predict complications in individual patients on OAT. Larger clinical trials with a longer follow-up period, preferably using clinical endpoints, are needed in order to draw any firm conclusions regarding the clinical consequences. However, measurement of coagulation factor activities and CAT may improve measurement of coagulation activity in patients prescribed OAT beyond the parameters currently clinically available. The CoaguChek S and XS coagulometers used for PSM were found to have an adequate precision. Regarding the accuracy, the INR measurements tended to be lower on the coagulometers, compared with the laboratory. A large proportion of the measurements on the coagulometers deviated more than 15% from the laboratory measurements. However, only one laboratory was used for comparison and the original WHO method (gold standard) for estimating INR was not used. Furthermore, the inherent limitations of the INR have to be taken into consideration, and the results have to be viewed in this context. The accuracy of the coagulometers seems in this respect acceptable and they can be used in a clinical setting. However, external quality control is essential. In the observational studies, it was found that PSM was feasible and provides satisfactory treatment quality for various indications and in a wide range of patient age. In a randomised controlled trial, using a documented blinded composite endpoint, PSM was found to provide a treatment quality that was at least as good as that provided by conventional management. Additionally it was found, that training and implementation of PSM lead to a smaller variance in INR measurements, a higher median INR and a higher dose of coumarins compared to that obtained for conventionally managed patients. Further evidence was provided in a systematic review and meta-analysis, where it was documented, that PSM appears at least as good as and possibly better than conventional management in highly selected patients.
对于血栓栓塞风险增加的患者，会使用香豆素类（维生素K拮抗剂）进行口服抗凝治疗（OAT），用于预防和治疗。OAT的治疗指数较窄，监测基于通过静脉穿刺获取的枸橼酸盐血浆常规测定的国际标准化比值（INR）。基于INR测量结果，医疗保健人员确定香豆素类（如华法林（可迈丁））的合适剂量。优化的OAT管理可提高治疗质量。患者自我管理（PSM）是一个新概念，即患者积极参与自身治疗。OAT中的PSM意味着患者使用便携式凝血仪（INR监测仪）分析一滴血液。凝血仪显示INR，患者用其来确定香豆素类药物的剂量。目前仍未明确哪些患者亚组（就OAT适应症、年龄、合并症等而言）可能从PSM中获益，以及这种潜在效果有多大。正确估算INR是正确使用香豆素类药物剂量的前提条件，在此背景下，用于提供INR测量结果的方法和仪器至关重要。用于PSM的凝血仪在精度和一致性方面尚未得到充分研究，因此有必要进行研究。已证明INR足以用于调整剂量。怀疑INR水平是否反映个体患者的整体止血能力或血栓形成潜力。连续校准自动凝血酶生成（CAT）和凝血因子活性的测量可能作为更敏感和全面的止血参数，并且在预测接受OAT患者的并发症风险方面可能具有更好的表现。我们发现凝血因子II、VII、IX和X的凝血活性以及CAT在6周内没有变化。凝血因子活性和CAT与INR显著相关，因此这两项检测可与INR同时使用和/或相互替代。凝血因子活性和CAT总变异性的约50%由INR反映，而其余变异性存在于个体（患者）内部。因此，凝血因子活性和CAT可能潜在地用于提供关于出血和血栓栓塞风险的更多信息，因为个体内部近50%的变异性未在INR值中体现。然而，该方法能否预测接受OAT的个体患者的并发症仍不确定。需要进行更大规模、随访期更长的临床试验，最好使用临床终点，以便就临床后果得出任何确凿结论。然而，凝血因子活性和CAT的测量可能会改善接受OAT患者凝血活性的测量，超出目前临床可用的参数范围。发现用于PSM的CoaguChek S和XS凝血仪具有足够的精度。关于准确性，与实验室相比，凝血仪上的INR测量值往往较低。凝血仪上很大一部分测量值与实验室测量值的偏差超过15%。然而，仅使用了一个实验室进行比较，且未使用估计INR的原始WHO方法（金标准）。此外，必须考虑INR的固有局限性，并在此背景下看待结果。在这方面，凝血仪的准确性似乎是可以接受的，并且可用于临床环境。然而，外部质量控制至关重要。在观察性研究中，发现PSM是可行的，并且对于各种适应症和广泛年龄范围的患者都能提供令人满意的治疗质量。在一项随机对照试验中，使用记录的盲法复合终点，发现PSM提供的治疗质量至少与传统管理提供的质量一样好。此外，还发现，与传统管理的患者相比，PSM的培训和实施导致INR测量的变异性更小、INR中位数更高以及香豆素类药物剂量更高。在一项系统评价和荟萃分析中提供了进一步的证据，其中记录了在高度选择的患者中，PSM似乎至少与传统管理一样好，甚至可能更好。
