Introduction
The article ‘mechanisms of thrombus formation are authored by Bruce Furie and Barbara C. Furie is a 2008 publication in the New England Journal of Medicine, volume 359 from page 938 to 949. In this article, Furie and Furie (p. 938) attempt to describe the various ways in which thrombosis occurs, by examining the process of platelet activation leading to blood coagulation and the eventual formation of a thrombus. While the authors of this article provide an elaborate process of thrombus formation, they do not give an exhaustive mechanism. This is evident given several questions that have remained unanswered more so on membrane surfaces necessary for complex assembly and the process of activating certain enzymes and factors required in thrombus formation.
Article summary
In this article, the authors heavily depend on knowledge gathered from animal studies, more so with mouse models, to explain the thrombosis process as well as provide new possible explanations for the process. It is understood that disruption of the endothelium is a trigger to thrombus formation since the platelets are activated by the exposed collagen. Thrombin is also activated by exposure to tissue factors once the endothelium is injured. Using genetically modified mice, researchers have been able to identify two pathways that lead to platelet activation. The first pathway involves exposing subendothelial collagen, with platelet glycoprotein VI interacting with collagen found in the exposed blood vessel as well as platelet glycoprotein lb-V-IX interacting with von Willebrand factor collagen. It is important to note that this pathway does not require thrombin for platelet activation to occur. In the second pathway, platelet activation is initiated by thrombin from tissue factors. In this case, it is not necessary to have the endothelium disrupted and factors such as the glycoprotein VI or the von Willebrand are not essential. Also notable is that not all platelets that adhere to the wall are activated. A proteolytic cascade is involved in the generation of thrombin, which subsequently activates platelets and thrombus formation by cleaving protease-activated receptor 4. In this pathway, no explanation is given as to how platelets gather at the site of injury.
Furie and Furie (p. 942) mention that the thrombosis process does not involve adherence of all platelets on the developing thrombus, and instead some platelets adhere while others do not adhere to. When platelet integrin αIIbβ3 is activated enzymatically, platelets then start being recruited at the thrombus. Through a cascade of events, platelet-platelet affinity is enhanced and in the process, the thrombus is stabilized. It is, therefore, speculated that receptors that mediate the adherence of platelets are very important in platelet activation and thrombus formation. Despite the findings from animal models on thrombus formation, the authors of this article conclude that it is important to identify the components of factor XI activation in the formation of thrombosis.
Personal Reaction
This article is a commendable publication on the process of thrombosis given the detailed explanation of the possible mechanisms through which the process occurs. The authors of the article have explored up-to-date findings on this topic as evidenced by their reliance on findings from genetically modified mice. In addition, the article has explored both pathways that are believed to be the pathways to platelet activation and subsequent thrombus formation. As such, the reader is given all the available possibilities of the mechanism of thrombosis without biasing on a specific pathway. As such, the article provokes the reader’s curiosity more so in understanding how thrombus formation can occur even without vessel injury, which is viewed as the principal pathway to platelet activation. This article is also resourceful in that it explains the thrombus formation process in a non-complicated way, making it easy for the reader to understand and make conclusions. For instance, the authors have not used a lot of jargon that complicates the topic, despite the fact that this is a topic that can be explained using jargon. This article, therefore, communicates its contents easily and explicitly. The process of thrombus is for instance explained sequentially, starting with platelet activation, enhancement of the thrombus, blood coagulation, and finally the formation of a stable thrombus.
Despite this article has provided as much information on the thrombus formation process as possible, it is still unable to address some pertinent questions regarding thrombus formation. For instance, the authors still pose questions regarding the process by which some factors involved in thrombin formation are activated as well as cell surface interactions in platelet activation. As such, the article can be viewed as not providing more than what is already known regarding the thrombosis process. The article can therefore be summarized as more mind-provoking than one that reports new findings. It is however commendable that the authors acknowledge the need to advance research on this topic and more so transfer successfully in vitro experiments as well as successful experiments on animal models to be human beings, which would be of great help in curbing the thrombosis process. Given this, the article can be overall said to be useful for providing a platform for understanding the thrombosis process.
Reference
Furie, Bruce and Furie, Barbara C. Mechanisms of thrombus formation. New England Journal of Medicine, 359; 2008:938-949.