A Comparison of Fibrinolysis of Clots from Venipuncture

止血血凝块的溶解是由一系列复杂的生化途径协调的，并被调节以允许血凝块随着伤口愈合而消失。如果血块溶解得太快，伤口可能会再出血。纤维蛋白溶解的研究传统上集中在通过无创伤静脉穿刺获得的血液上，尽管这样的样品缺乏可能由血管外组织贡献的任何组分，而血管外组织是止血凝块天然存在的地方。因此，我们比较了静脉穿刺获得的血液和手指针刺获得的血液的体外裂解率，手指针刺在出血过程中穿过血管外组织。将凝块孵育2-48小时，并通过测量血清中的蛋白水解分解产物来监测其降解。我们发现手指针刺血凝块溶解速度明显快于静脉穿刺血凝块。我们已经分析了手指针刺和静脉穿刺样本中已知参与纤维蛋白溶解的所有蛋白质，但没有发现两者之间的显着差异。假设基质金属蛋白酶（MMPs）可能有助于手指针刺凝块的溶解，我们在首次获得血液样本时添加了这些酶的抑制剂。抑制剂通过不同方式改变手指针刺血栓的溶解率，但对静脉穿刺血栓的溶解作用不明显。我们将通过分析特定MMP的样本来追踪这一证据。如果我们能鉴定出在手指针刺血中起作用的特定酶或抑制剂，我们将在未确诊的出血性疾病患者中寻找这些蛋白质的异常。

The lysis of hemostatic blood clots is orchestrated by a complex array of biochemical pathways and regulated to allow the clot to disappear as a wound heals. If a clot dissolves too quickly, the wound may rebleed. The study of fibrinolysis has traditionally focused on blood obtained by atraumatic venipuncture, although such samples lack any components that might be contributed by the extravascular tissue, which is where hemostatic clots naturally exist. Therefore, we have compared the in vitro lysis rate of blood obtained by venipuncture and blood obtained by fingerstick, which passes through extravascular tissue in the process of bleeding. Clots are incubated for 2-48 hours, and their degradation is monitored by measuring proteolytic breakdown products in the serum. We have found that fingerstick clots lyse significantly faster than clots of venipuncture blood. We have assayed fingerstick and venipuncture samples for all the proteins known to be involved in fibrinolysis but have not found significant differences between the two. With the hypothesis that matrix metalloproteinases (MMPs) might be contributing to the lysis of fingerstick clots, we have added inhibitors of these enzymes to the blood samples when they are first obtained. The inhibitors change the lytic rate of fingerstick clots in different ways but have no obvious effect on the lysis of venipuncture clots. We will pursue this line of evidence by assaying samples for specific MMPs. If we can identify specific enzymes or inhibitors that are operative in fingerstick blood, we will look for abnormalities in these proteins in patients with undiagnosed bleeding disorders.