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Dopamine in the Immune and Hematopoietic Systems
Published in Nira Ben-Jonathan, Dopamine, 2020
Interactions between the dopaminergic and the coagulation systems were also suggested by some of the results of a study that examined serum proteins in patients with PD using quantitating proteomics [78]. The expression level of 8 proteins that included sero-transferrin and clusterin increased, while the expression level of 18 proteins, including complement component 4B, apolipoprotein A-I, alpha-2-antiplasmin, and coagulation factor V decreased. Alpha 2-antiplasmin is a serine protease inhibitor responsible for inactivating plasmin, an important enzyme that participates in fibrinolysis. Coagulation Factor V interacts with other clotting proteins such as activated factor X and prothrombin to increase the production of thrombin, the key hemostatic enzyme that converts soluble fibrinogen to a fibrin clot.
Coagulation Theory, Principles, and Concepts
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
Alpha-2-antiplasmin is the principal inhibitor of plasmin and is structurally related to antithrombin III. It has three major functional properties: (a) the inhibition of plasmin, (b) interference with the binding of plasminogen to fibrin, and (c) incorporation into a fibrin clot by cross-linking to the alpha chains of fibrin by the action of factor XIIIa (99–101). During clot formation approximately 20% of the alpha-2-antiplasmin cross-links to fibrin. Because of this a normal blood clot will not lyse spontaneously, despite the presence of clot-bound tPA. Clot bound alpha-2-antiplasmin is more effective in preventing clot dissolution than is the free plasma alpha-2-antiplasmin.
Clinical Toxicology of Snakebite in Asia
Published in Jürg Meier, Julian White, Handbook of: Clinical Toxicology of Animal Venoms and Poisons, 2017
A woman was bitten on the foot by a 50 cm long specimen of T. kanburiensis while searching for bamboo shoots on a hill near to where the type specimen was collected in 192722. She developed severe pain and swelling which eventually involved the whole limb and the right flank (Figure 56), bruising of the calf, tender popliteal lymph nodes, recurrent shock probably attributable to hypovolaemia, peripheral leucocytosis, anaemia and a mild coagulopathy (hypofibrinogenaemia, elevated fibrin(ogen) degradation products and modest reduction in plasminogen and alpha-2 antiplasmin without thrombocytopenia). She was treated conservatively and was fit to leave hospital after four days. Such serious symptoms in a healthy young woman suggest that, in the absence of the specific antivenom, bites by this species could prove fatal in very young, very old or debilitated patients.
Bothrops snakebites in the Amazon: recovery from hemostatic disorders after Brazilian antivenom therapy
Published in Clinical Toxicology, 2020
Sâmella Silva de Oliveira, Eliane Campos Alves, Alessandra dos Santos Santos, Elizandra Freitas Nascimento, João Pedro Tavares Pereira, Iran Mendonça da Silva, Jacqueline Sachett, Hiochelson Najibe dos Santos Ibiapina, Lybia Kássia Santos Sarraf, Jorge Carlos Contreras Bernal, Luciana Aparecida Freitas de Sousa, Mônica Colombini, Hedylamar Oliveira Marques, Marcus Vinicius Guimarães de Lacerda, Ana Maria Moura-da-Silva, Hui Wen Fan, Luiz Carlos de Lima Ferreira, Ida Sigueko Sano Martins, Wuelton Marcelo Monteiro
In Bothrops envenomation, hypofibrinogenemia returned to normal within 24 h after beginning antivenom therapy [35]. In our study, low fibrinogen and high FDP levels were almost totally normal within 24 h after beginning antivenom therapy when compared to reference values. The median concentration of D-dimer on admission showed a gradual decrease after antivenom therapy. High D-dimer reported on admission suggests that intravascular thrombin formation contributes to the coagulation disorders in Bothrops snakebites in this region by converting fibrinogen to fibrin and activating factor XIII. Plasmin cleaves cross-linked fibrin by activating factor XIII and generates D-dimer [36]. Inhibition of the fibrinolytic system at the plasmin level is a function exerted by alpha 2-antiplasmin [37]. In our study, patients showed low levels of alpha 2-antiplasmin within the first 24 h after antivenom therapy, indicating that its intravascular consumption is induced by plasmin formation [36,37]. These levels returned to normal values on discharge, accompanied by normalization of fibrinogen and FDP levels.
Do we still need cryoprecipitate? Cryoprecipitate and fibrinogen concentrate as treatments for major hemorrhage — how do they compare?
Published in Expert Review of Hematology, 2018
Alex Novak, Simon J. Stanworth, Nicola Curry
The content of fibrinogen in fibrinogen concentrate is considerably more standardized than in cryoprecipitate, which varies from 3–30 g/L depending on differences in the manufacturing process and variability between blood donors [12]. Furthermore, the high concentration of fibrinogen concentrate allows relatively large doses to be administered to the patient in a small volume. However in the guidance for use of fibrinogen concentrates in perioperative bleeding published by the International Society on Thrombosis and Haemostasis, Godier et al. note that there are several reasons why fibrinogen supplementation alone may not be of benefit, including the use of a single coagulation factor to treat a coagulopathy characterized by a decrease in all factors [40]. Cryoprecipitate is rich in VWF, fibronectin, FVIII, and FXIII and contains significant amounts of a2-antiplasmin and antithrombin, and it is unclear what if any advantage these additional pro-coagulant factors might add – low levels of both VWF and FXIII have been identified in major trauma patients [41]. Alpha-2 antiplasmin levels are often low in trauma as well and replacement with cryoprecipitate hypothetically may mitigate the known fibrinolytic processes accompanying trauma hemorrhage [42].
Testing strategies used in the diagnosis of rare inherited bleeding disorders
Published in Expert Review of Hematology, 2023
Alpha 2 antiplasmin (plasmin inhibitor) deficiency: Fibrinolytic inhibitors such as epsilon aminocaproic acid or tranexamic acid will falsely raise alpha 2 antiplasmin levels. Inter-laboratory variation in test results complicates the diagnosis. In the aforementioned survey, alpha-2 plasmin inhibitor activity, results of testing on normal plasma demonstrated that 5/101 (5%) of responding laboratories classified the sample as borderline abnormal or abnormal. Results of testing on an abnormal low control plasma were classified as normal or borderline normal by 3/101 (3%) (personal communication from Piet Meijer, Ph.D., ECAT Foundation)