新近的研究發現，血小板在人體所扮演之角色越來越為重要，從以前所認知的凝血功能中不可或缺的一環，到近幾年來發現它在發炎反應中亦佔有舉足輕重的地位。
不管是凝血或是發炎反應，血小板參與其中的第一步驟就是要被刺激活化。許多分子或化學物質被發現可以活化血小板，造成後續的形變、附著、分泌與凝集。目前被發現的血小板膜表面接受器越來越多，各自有其不同的影響及功能，使血小板在人體內與其他相關細胞間形成一個被嚴密調控的交互作用網絡。藉著測量不同的化學產物或物理表現，我們可以知道血小板的哪一條路徑可能被活化。
本研究在探討出目前在台灣重症照護單位被廣為使用的鎮靜兼具止痛藥物–Precedex (右美托咪啶，dexmedetomidine)，是否會活化血小板，或加強血小板活化反應，進而可能加重病人的發炎反應。截至目前為止，並無類似的研究報告。我們的研究發現，右美托咪啶會加強血小板對其他已知活化物質 (如ADP) 的反應，包括血小板的活化指標，例如platelet aggregation、P-selectin、platelet-leukocyte aggregate、[Ca2+]i 、ATP等，並利用甲型交感受器抑制劑 (alpha antagonist) 來證明右美托咪啶對血小板的作用是經由活化血小板的甲型交感受器而來。最後，我們比較重症單位的患者在使用右美托咪啶前後的血小板數，藉此初步釐清此藥物實際使用在人體的可能影響。
綜合本系列實驗的結果，我們證實右美托咪啶在體外會透過活化甲二型交感受器 (alpha-2 receptor) 而加強二磷酸腺苷對血小板活化及凝集的程度。而此結果可能可以部分解釋在重症患者身上使用此藥物後，我們所發現的血小板數會有稍微降低的趨勢。故我們建議臨床上在重症患者使用右美托咪啶時，應該小心此作用，以避免造成更多的血小板凝集、活化、及可能的後續發炎反應。
As an integral part in hemostasis, platelet has also been proved to play an important role in inflammation.
Platelet activation was the very first step to participate in either hemostasis or inflammation. Many factors or molecules have been demonstrated as platelet stimulants. More and more platelet receptors were then discovered as well. The complicated networks of these receptor functions were composed of several distinct pathways. We could measure the different chemical products or physical phenomenons and thereby study the possible pathways in which were involved.
In Taiwan, Precedex (dexmedetomidine) was used, as a sedative agent with analgesic effect, more and more frequently in ICU and operating room. In this study, we were the first to described that dexmedetomidine might have pro-aggregatory effect on platelet in vitro. We used several indicators of platelet activation, such as platelet aggregation, P-selectin, platelet-leukocyte aggregate, [Ca2+]i, and ATP, to measure the effect of dexmedetomidine on ADP-induced platelet aggregation and activation. Moreover, we used alpha antagonists to prove the above effect was through the activation of alpha-2 receptor on platelets. Then we compared the platelet counts before and after use of dexmedetomidine on ICU patients to preliminarily find out it’s possible effects in vivo.
In this series of experiments, we have proved that dexmedetomidine could enhance ADP-induced platelet activation and aggregation through alpha-2 receptor in vitro. We should be cautious about prescribing dexmedetomidine for the patients with high risk of thromboembolism or inflammatory diseases.
