Arteropathies, Microcirculation and Vasculitis
Mary N. Sheppard in Practical Cardiovascular Pathology, 2022
Together, acute venous and arterial thrombosis accounts for the most common causes of death in developed countries. This mortality obviously depends on location and acuity of thrombosis, with myocardial infarction and cerebrovascular accident (CVA) or stroke accounting for the highest proportion of thrombosis-associated death in the US and UK. The cause of thrombosis is multifactorial. As noted, thrombosis occurs when there is an imbalance in endogenous anticoagulation and haemostasis through a complex pathophysiological mechanism. Historically, three common factors predispose to thrombosis: (1) damage to the endothelial lining of the vessel wall, (2) a hypercoagulable state and (3) arterial or venous blood stasis. These three factors are known by the eponym ‘Virchow's triad’ described by Rudolf Virchow in 1856. In larger vessels, the complications are well known but in smaller vessels and capillaries, the pathology is complicated by the complex haematological clinical entities and the microscopic nature of the pathology leading to confusion for pathologists.
Inflammation
George Feuer, Felix A. de la Iglesia in Molecular Biochemistry of Human Disease, 2020
Platelets are the fundamental elements involved in the formation of a hemostatic plug from circulating blood. When the wall of the vessel is injured, platelets adhere to structures of the subendothelial layer which includes collagen, some types of basement membrane, and the microfibrils around elastin.32,231,325 Platelets accumulate around the injured endothelial cells, or if the endothelium is exposed, they adhere to thrombin.118 Collagen causes a release of the granular content of platelets.32 The structural feature of collagen interactions with platelets include enhanced affinity between platelets and collagen and subsequent adherence, platelet spreading, and activation of arachidonic acid metabolism leading to thromboxane A2 synthesis, platelet aggregation, and finally, discharge of platelet granules. Part of the polypeptide chain of the monomeric collagen is required for the platelet-collagen association which initiates the arachidonate pathway.307
Phospholipids and the Clotting Process
E. Nigel Harris, Thomas Exner, Graham R. V. Hughes, Ronald A. Asherson in Phospholipid-Binding Antibodies, 2020
The most likely source of procoagulant phospholipid to stimulate tenase and prothrombinase activity in vivo are platelet membrane phospholipids. Indeed, platelets can accelerate factor Xa and thrombin formation by virtue of binding and promoting assembly of the coagulation factors of the tenase and prothrombinase complex. Moreover, platelets participate in the formation of a hemostatic plug by forming an aggregate in response to vascular injury. Platelet activation not only involves aggregation of cells, but this process is also accompanied by secretion of subcellular components, which can contribute to thrombus formation. Since activated platelets may more efficiently accelerate tenase and prothrombinase activity, thrombin and thus fibrin formation remains restricted to where platelet aggregation occurs. This localized restriction is thought to prevent massive thrombosis that might otherwise occur in the circulatory system even after a minor injury.
Hirudin versus citrate as an anticoagulant for ROTEM platelet whole blood impedance aggregometry in thrombocytopenic patients
Published in Platelets, 2023
Wasanthi Wickramasinghe, Bhawani Yasassri Alvitigala, Thisarika Perera, Panduka Karunanayake, Saroj Jayasinghe, Senaka Rajapakse, Praveen Weeratunga, Ananda Wijewickrama, Roopen Arya, Klaus Goerlinger, Lallindra Viranjan Gooneratne
Platelets play a crucial role in hemostasis.1 The rotational thromboelastometry (ROTEM) platelet module used together with the ROTEM delta device (TEM Innovations GmbH, Munich, Germany) assesses platelet aggregation by whole blood impedance aggregometry and displays platelet aggregation graphically and numerically.2 3.2% sodium citrate is the most widely used and conveniently available anticoagulant for platelet function tests (PFTs), although its chelation of ionized calcium in blood affects platelet function by the inhibition of platelet aggregation since intra-platelet calcium concentration is an important modulator of platelet function.3 Moreover, as a result of reduction in calcium levels, citrated samples have resulted in low reproducibility and sensitivity to tests associated with thrombin activation of platelets.4 The non-calcium chelating anticoagulant hirudin which was introduced subsequently, is a polypeptide present in the leech (Hirudo medicinalis) having a strong and direct antithrombin activity by inhibiting the conversion of fibrinogen to fibrin. Hence, hirudin maintains the physiological milieu of the sample.5 Thrombin-receptor activating peptide-6 is used in platelet function testing in order to provide a standardized activation.6–8
Computational modeling of hypercoagulability in COVID-19
Published in Computer Methods in Biomechanics and Biomedical Engineering, 2023
Ge Zhu, Susree Modepalli, Mohan Anand, He Li
The human blood coagulation cascade is a complex biochemical process (Schenone et al. (2004)). The primary function of human blood coagulation is to minimize blood loss during vascular injury due to physical trauma. Hemostasis refers to the process by which the body controls blood loss after an injury by secreting enzymes to form a clot and cover the injury sites. The human body maintains homeostasis by maintaining balance among three major hemostatic processes: vasodilation, blood coagulation and clot dissolution. The excessive progress of any of these three hemostatic processes can lead to abnormal hemostasis and potentially fatal consequences. For example, lack of sufficient concentration of coagulation factors (hemophilia) or abnormal fibrinolysis (Francis (1989)) can lead to rapid blood loss (Zimmerman and Valentino (2013)) and excessive generation of prothrombotic factors can lead to undesired blood clotting (thrombosis)(Zoller et al. (1999)). Both hemophilia and thrombosis can lead to fatalities. As a result, maintaining hemostasis is key to maintaining healthy physiology.
Application of anti-Xa assay in monitoring unfractionated heparin therapy in contemporary antithrombotic management
Published in Expert Review of Hematology, 2023
Michael Safani, Steve Appleby, Ryan Chiu, Emmanuel J Favaloro, Emanuel T. Ferro, Jimmy Johannes, Milan Sheth
The coagulation pathways represent a cascade of events intended to provide a balance between procoagulant and anticoagulant processes and maintain hemostasis. Primary hemostasis consists of platelet activation, aggregation, and thrombus formation and aims to form a plug at the site of exposed endothelial cells due to tissue damage. Secondary hemostasis, as measured by the pathology laboratory, conventionally comprises three coagulation pathways. The intrinsic pathway is activated by endothelial damage and collagen exposure and includes factors I, II, IX, X, XI, and XII. The extrinsic pathway is activated by release of tissue factor by damaged endothelium and includes factors I, II, VII, and X. The common pathway consists of factors I, II, V, VIII, X. The intrinsic and extrinsic pathways converge to form a common pathway and at a specific point to activate fibrinogen to form fibrin polymer. In vivo, the final stages of primary and secondary hemostasis are marked by binding of fibrin polymers to platelets to secure and stabilize the platelet plug [37–41].