作者：Allison Gandey
出處：WebMD醫學新聞
March 10, 2010 — 一項新研究顯示，使用warfarin患者在接受組織胞漿素酶活化劑（tPA）治療急性缺血性中風後，發生腦出血的風險較高。
這項令人驚奇的發現對目前的執業提出質疑。
主要作者，伊利諾州芝加哥Rush大學醫學中心的Shyam Prabhakaran醫師向Medscape神經學表示，有鑑於過去沒有證據顯示使用warfarin病患接受tPA治療的安全性，這項研究提供未來要進行研究時更多的考慮與激勵。
Prabhakaran醫師指出，並無已發表的數據提到有關使用warfarin治療患者接受tPA的安全性。這些病患被使用tPA治療中風的國家神經疾病與中風機構研究、歐洲聯合急性中風研究排除，而目前warfarin使用者越來越多。
除此之外，美國心臟醫學會與美國中風醫學會所發表的治療指引容許正在使用口服抗凝血藥物，且基礎國際校正比值（INR）低於1.7的患者靜脈注射tPA。
這項新研究線上發表於3月8日的神經學誌，研究者們報告接受warfarin治療患者，即使INR在安全範圍，仍然有較高的中風風險。
在美國，估計心房顫動的盛行率為近3百萬人，預估在2050年時將會加倍，研究者們指出，中風病患使用抗凝血藥物的盛行率並非少數。
研究者們研究107位接受tPA治療的急性缺血性中風患者，這些病患中，12.1%正在使用warfarin。
整體有症狀腦出血機率為6.5%。Prabhakaran醫師的研究團隊對這個數字感到非常驚訝，使用warfarin患者的風險幾乎高了10倍。
表格-有症狀腦出血機率
預後 | 試驗前使用 warfarin ， % | 未使用 warfarin ， % | P 值 |
中風 | 30.8 | 3.2 | .004 |
研究者們表示，即使校正包括年齡、心房顫動、國家衛生研究機構中風指標分數以及INR等相關共變項後，中風風險仍是較高的。
研究者們假設tPA的血栓溶解作用可能會被warfarin的抗凝血作用增加。這項組合有較高的打通血管機率，但也可能造成梗塞組織再灌流出血。
他們表示，使用warfarin可能是心因性中風患者的一個指標，代表這些病患更容易發生出血且梗塞體積較大。
Prabhakaran醫師承認還有必須擔心的理由，這項研究應該用於產生更多假設、同時也需要做更多的研究。
這項研究由國家神經疾病與中風機構贊助。研究者們表示已無相關資金上的往來。
Warfarin-Treated Patients at Higher Risk for ICH Following tPA for Stroke
By Allison Gandey
Medscape Medical News
March 10, 2010 — Patients taking warfarin are more likely to have an intracerebral hemorrhage after treatment of an acute ischemic stroke with tissue plasminogen activator (tPA), a new study suggests.
The surprising finding is calling current practice into question.
"Given there is a lack of prior evidence on the safety of tPA in patients taking warfarin, this study should give some pause and encourage further study," lead investigator Shyam Prabhakaran, MD, from Rush University Medical Center in Chicago, Illinois, told Medscape Neurology.
Dr. Prabhakaran points out there are no published data assessing the safety of tPA among warfarin-treated patients. These patients were excluded from the National Institute of Neurological Disorders and Stroke and European Cooperative Acute Stroke Study trials of tPA for stroke, and yet warfarin users represent an increasing group of patients.
This study should give some pause and encourage further study.
Still, American Heart Association and American Stroke Association guidelines permit intravenous tPA use in patients taking oral anticoagulants with a baseline international normalized ratio (INR) less than 1.7.
In this new study, published online March 8 in Archives of Neurology, the investigators report that warfarin-treated patients are at higher risk for stroke despite INRs in a safe range.
With the estimated prevalence of atrial fibrillation in the United States approaching 3 million and expected to double by 2050, the researchers point out that the prevalence of anticoagulant use among stroke patients is not trivial.
Investigators studied 107 ischemic stroke patients treated with tPA. Of these, 12.1% were taking warfarin at baseline.
The overall rate of symptomatic intracerebral hemorrhage was 6.5%. Dr. Prabhakaran says that his team was surprised to see that this rate was nearly 10-fold higher among patients taking warfarin.
Table. Risk of Symptomatic Intracerebral Hemorrhage
| Outcome | Warfarin at Baseline, % | No Warfarin, % | P Value |
| Stroke | 30.8 | 3.2 | .004 |
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The researchers report that the stroke risk remained high even after adjusting for relevant covariates, including age, atrial fibrillation, National Institutes of Health Stroke Scale score, and INR.
The investigators propose that the fibrinolytic effects of tPA may be enhanced by the anticoagulant effects of warfarin. Higher recanalization rates with this combination may lead to a greater rate of reperfusion hemorrhage into infarcted tissue.
They suggest that warfarin use may also be a marker for patients with cardioembolic stroke in whom hemorrhagic transformation is more common and infarct volume is greater.
Dr. Prabhakaran acknowledges that although there is reason to be concerned, this work should be considered hypothesis generating, and further study is necessary.
This study was funded by the National Institute of Neurological Disorders and Stroke. The researchers have disclosed no relevant financial relationships.
Arch Neurol. Published online March 8, 2010.
