Miscellaneous: Dextran, Dermatan Sulfate, Low Molecular Weight Heparinoids (Org 10172), Pentosan Polysulfate (Sp54), Defibrinating Agents (Ancrod And Reptilase)
Hau C. Kwaan, Meyer M. Samama in Clinical Thrombosis, 2019
Heparin, heparan sulfate, and dermatan sulfate (DS) are the only glycosaminoglycans which possess the iduronate residue.15 DS has anticoagulant activity similar to other compounds already discussed, but this specific activity is low. DS has a molecular weight of about 25 kDa. In vitro, on a gravimetric basis, 70 times more DS is needed than heparin to give similar anticoagulant activity as tested by the activated partial thromboplastin time. When Factor Xa is added to normal plasma, thrombin generation is inhibited by DS, by the same conditions as its amidolytic activity. Factor IIa (thrombin), but not Factor Xa, is also inhibited.16,17 The antithrombin activity of DS is dependent on the presence of heparin cofactor II, but not antithrombin III. Heparin cofactor II forms a stable equimolar complex with thrombin. The speed of the formation of this complex is 1000 times greater when DS is present. Platelet factor 4 can inhibit the function of DS activity. In contrast, histidinerich glycoprotein can inhibit antithrombin activity of heparin in the presence of DS.18,21
Thrombosis, heparin and laboratory monitoring of heparin therapy
John Edward Boland, David W. M. Muller in Interventional Cardiology and Cardiac Catheterisation, 2019
Following spontaneous or chemically induced lysis of a thrombus, thrombin may become exposed to circulating blood, leading to activation of platelets and coagulation factors and culminating in further thrombosis. The antithrombin activity of heparin is limited for three major reasons. First, residual thrombus contains thrombin bound to fibrin, which is poorly accessible to the heparin-ATIII complex and requires about 20 times more heparin for inactivation compared to unbound thrombin. Second, platelet-rich arterial thrombus releases large amounts of platelet factor 4, which inhibits heparin. Third, the fibrin II monomer, formed by the action of thrombin on fibrinogen, is also an inhibitor of heparin. Hirudin, a naturally occurring compound derived from leech saliva, has antithrombin properties and is at least 10 times smaller than the heparin-ATIII complex. It has no natural inhibitors. As such, it is more accessible to thrombin bound to fibrin, and may prove to have a clinically useful role in this situation.
Orthopaedic Pharmacology
Manoj Ramachandran, Tom Nunn in Basic Orthopaedic Sciences, 2018
Haemorrhage: less with LMWHs than with heparin. Bleeding with heparin can normally be controlled by stopping its administration, but in severe cases protamine sulphate (a basic peptide that combines with the acidic heparin) may be required.Heparin-induced thrombocytopenia (HIT): caused by heparin-dependent immunoglobulin G (IgG) antibodies binding to platelet factor 4 (PF4). The heparin–PF4–IgG immune complex binds to platelets causing platelet activation, which accelerates coagulation reactions and generates thrombin.Osteoporosis: when used long term.Allergic reaction, bruising at the injection site.
Evaluation of blood collection methods and anticoagulants for platelet function analyses on C57BL/6J laboratory mice
Published in Platelets, 2020
Alexandra Grill, Klytaimnistra Kiouptsi, Cornelia Karwot, Kerstin Jurk, Christoph Reinhardt
Apart from choosing the appropriate target, the choice of anticoagulant is essential for further usage of the collected platelets. When whole blood is treated with anticoagulating substances, e.g. heparin, the anticoagulation will influence the experiments and might be inappropriate for assays that require unaffected coagulation. Heparin is widely used for its ability to interact with thrombin, accelerating the formation of thrombin-antithrombin complexes [17]. However, the interaction with other platelet proteins (e.g. platelet factor 4) could induce side effects on the functional integrity of the platelets and thereby cause platelet pre-activation. Moreover, inhibition of coagulation can be achieved by chelation of calcium ions required for the binding of clotting factors to phosphatidylserine or phosphatidylethanolamine on the outer membrane leaflet of activated blood cells [18]. Ethylenediaminetetraacetic acid (EDTA) is a commonly used anticoagulant that inhibits coagulation efficiently and irreversibly [19]. In contrast, citrate-containing compounds have the advantage that they allow re-calcification, if desired. Therefore, the citrate treated and re-calcified blood samples can be used in functional platelet and coagulation assays, e.g. in thromboelastometry (ROTEM®) measurements [20].
The COVID-19 pandemic: viral variants and vaccine efficacy
Published in Critical Reviews in Clinical Laboratory Sciences, 2022
Marco Ciotti, Massimo Ciccozzi, Massimo Pieri, Sergio Bernardini
Thrombotic events and thrombocytopenia have been reported following vaccination with AstraZeneca ChAdOx1 nCov-19 vaccine. These rare and in some cases fatal adverse reactions were described mainly in young women, median age 36 years old [43]. The thrombotic events manifested 5–16 days after vaccination and included cerebral venous thrombosis, pulmonary embolism, splanchnic-vein thrombosis, and other thrombotic manifestations. Six patients died and five had disseminated intravascular coagulation. Platelet-activating antibodies against platelet factor 4 (PF4) mediates this rare complication that resembles autoimmune heparin induced thrombocytopenia [43]. The same complication occurred in an individual who received the Johnson & Johnson/Janssen vaccine (Ad26.COV2. S) 14 days after vaccination. Considering that both AstraZeneca and Janssen use vaccines based on nonreplicating adenoviral vector suggests that this rare event of immune thrombotic thrombocytopenia might be triggered by adenoviral vector vaccines [44]. A hypothesis is that complexes form between polyanionic groups induced by the vector and PF4 or antibodies generated by the inflammatory response to the vaccine and cross-react with platelets and PF4.
Immunopathology of COVID-19 and its implications in the development of rhino-orbital-cerebral mucormycosis: a major review
Published in Orbit, 2022
Tarjani Vivek Dave, Akshay Gopinathan Nair, Joveeta Joseph, Suzanne K Freitag
Platelets are one of the key cells in the innate immune response. While their primary role is in hemostasis, another important role is in the immune response against pathogens, by inhibiting their dissemination through the circulation, which could increase the severity of infection.46 Platelets help in fighting microbes by producing antimicrobial peptides such as platelet factor 4.47 Typical hematologic features of COVID-19 include thrombocytopenia, lymphopenia, and neutrophilia.48 NK cells modulate the immune response that is mounted when a pathogen is encountered. There is a reduction in the number of NK cells and blunting of the effector functions of NK cells in COVID-19.46 This results in a decrease in the clearance of infected and activated cells and also results in an unabated elevation of toxic inflammatory markers.46 Previous literature has clearly shown that SARS-CoV can cause infection of the dendritic cells (DC). This can lead to an upregulation of inflammatory chemokines following a very poor antiviral cytokine expression.49,50 Dendritic cells play a prime role in specific T-cell responses, cytokine production, and antigen presentation.49 In patients with COVID-19, a loss of DC function could lead to delayed response of the immune system.