BOSTON (EGMN) – A point-of-care assay that assesses platelet inhibition levels may be helpful for rapidly identifying trauma patients who might not respond to platelet reversal therapies or antiplatelet management, reported Dr. Vishal Bansal.

In a prospective study of 46 trauma patients who reported taking the platelet inhibitor clopidogrel, nearly 30% had no platelet inhibition, and another 30% had minimal or low platelet inhibition, said Dr. Bansal of the department of surgery at the University of California at San Diego.

“Unlike warfarin, which has been well established to increase morbidity and mortality from trauma, typically in TBI [traumatic brain injury], and where INR [international normalized ratio] can help guide management, in [clopidogrel] that is not the case,” said Dr. Bansal at the annual meeting of the American Association for the Surgery of Trauma. “The effects in the trauma patient are less well known, managing platelet inhibition is difficult and often not standardized, and managing these patients is often based solely on history.”

Nearly 30% of patients on clopidogrel are thought to have some degree of resistance to the drug, and the U.S. Food and Drug Administration in March 2010 required the manufacturer to include a boxed warning about the drug’s reduced efficacy in poor metabolizers. Patients with genetic variations in the cytochrome P450 system, particularly in cytochrome P2C19 (CYP2C19), may be unable to metabolize the drug into its active metabolite.

The investigators sought to determine the degree of platelet inhibition in trauma patients on clopidogrel, employing a point-of-care assay developed for detecting platelet inhibition levels in cardiovascular patients (VerifyNow P2Y12).

All trauma patients seen at their center in 2009 were asked by prehospital personnel and trauma team members whether they took clopidogrel. Blood samples were obtained by arterial or venous puncture from patients who reported taking the drug, and the samples were assayed. The assay results are expressed in P2Y12 reaction units and in the percentage of platelet inhibition within 30 minutes.

Of 2,520 patients admitted directly to the trauma unit, 84 were identified as using clopidogrel, and of these, 46 had their blood assayed. The mean patient age was 75.9 years, mean injury severity score was 7.0, and mean Glasgow Coma Scale score was 14.2.

The primary mechanism of injury was falling in 40 patients (86.9%), a car crash in 4 (8.7%), and being struck by a car in 2 (4.3%). The mean INR on admission was 1.1, and the mean systolic blood pressure was 146.8 mm Hg. Fourteen patients (30.4%) used aspirin concomitantly with clopidogrel.

Thirteen patients (28.2%) were found to have no platelet inhibition, and 10 (21.7%) had low levels of inhibition (between 0% and 20% inhibition). Four patients (8.7%) had inhibition levels between 20% and 30%, and 19 (41.3%) had inhibition levels greater than 30%.

In all, 17 patients (36.9%) had platelet inhibition from 0% to 10%, levels considered by the American College of Cardiology to be subtherapeutic, Dr. Bansal said.

Two patients had subdural hemorrhage – one in the 0% inhibition group, and one in the greater than 30% group.

“We concluded that the P2Y12 point-of-care platelet inhibition assay determined that a significant number of patients had no measurable platelet inhibition. These patients may be nonresponders, noncompliant, or simply not being treated with clopidogrel. It is unlikely that platelet reversal therapies or antiplatelet management algorithms will be beneficial in this group of patients,” Dr. Bansal said.

He acknowledged that the study was limited by the small sample size and by a lack of information about the correlation between percentage of platelet inhibition and risks of increased hemorrhagic complications.

“If we can correlate this, similar to INR, I think we can effectively manage these patients. And finally, we need to assess whether platelet transfusion or [desmopressin] administration can be monitored and optimized by measuring posttherapy percentage of platelet inhibition,” he added.

However, invited discussant Dr. C. Clay Cothren, trauma surgeon and chief of surgical oncology at Denver Health Medical Center, cautioned that assay results don’t always correlate with clinical findings.

“One of the clear points in reading the cardiology literature on this topic is the difficulty in applying platelet-function testing in a clinical setting. There is no agreement on the optimal test, much less the optimal test value which correlates with an optimal clinical response. In fact, none of the available assays have an established range for clopidogrel responsiveness,” she said.

A finding of clopidogrel nonresponsiveness is therefore test-dependent, and there are currently no clinical guidelines to support the use of platelet function testing to clinically manage patients and their antiplatelet therapy, she added.

The study had no industry support, and neither the authors nor Dr. Cothren reported any conflicts of interest.

Copyright (c) 2010 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

波士顿(EGMN) ——加州大学圣地亚哥分校外科系Vishal Bansal博士在美国创伤外科学会年会上报告称，应用血小板抑制水平即时分析方法可有助于快速鉴定对抗血小板治疗无反应的创伤患者。

 

此前认为近30%的患者对氯吡格雷存在一定程度的抵抗，但对创伤患者的情况知之甚少。为此，研究者应用一种血小板抑制功能即时检测方法(VerifyNow P2Y12)确定服用氯吡格雷创伤患者的血小板抑制水平。

 

研究者对46例服用氯吡格雷的创伤患者进行了血样分析。患者平均年龄75.9岁，平均创伤严重程度评分为7.0，格拉斯哥昏迷量表得分为14.2。创伤原因为坠落的有40例(86.9%)、汽车碰撞4例(8.7%)、车祸被撞2例(4.3%)。住院时平均INR为1.1，平均收缩压为146.8 mmHg。14例(30.4%)同时服用阿司匹林。

 

分析结果显示，13例(28.2%)未见血小板抑制反应，10例(21.7%)为低水平抑制(0～20%)，4例(8.7%)抑制水平为20%～30%，19例(41.3%)抑制水平大于30%。总之，近30%患者未见血小板抑制作用，而另外30%患者呈现较低的血小板抑制作用；17例(36.9%)抑制水平为0~10%，属于美国心脏病学会认为的治疗剂量不足。

 

未能检测到血小板抑制功能的患者不可能从抗血小板治疗中受益，因此P2Y12血小板抑制功能即时检测方法确定氯吡格雷无反应性患者意义重大，有助于调整患者抗血小板治疗方案。

 

但有学者评论称，由于目前对于血小板功能最佳检测方法和最佳检测指标尚未达成共识，与临床疗效的相关性也有待研究，因此尚没有临床指南支持血小板功能检测用于调整临床患者处置及抗血小板治疗。

 

研究者声称无利益冲突披露。

 

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