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Hieh-Dose Immunosuppressive Chemotherapy with Autologous Stem Cell Support for Chronic Autoimmune Thrombocytopenia
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Richard D. Huhn, Patrick F. Fogarty, Ryotaro Nakamura, Cynthia E. Dunbar
Autoimmune idiopathic thrombocytopenia (AITP) is a disorder of low platelet counts in which antibodies directed against platelet and megakaryocyte surface proteins cause platelet destruction in reticuloendothelial organs and inhibit platelet production.1,2 A compensatory increase in marrow megakaryocytes is an important diagnostic hallmark but is often not observed. Platelet destruction outpaces platelet production, leading to varying degrees of thrombocytopenia. Acute AITP is more common in children than adults and usually has a short self-limited course following an acute viral infection.3,4 Chronic AITP is more common in adults and is frequently refractory to conventional therapies.5,6 Chronic AITP is typically idiopathic (although it may be associated with a variety of other autoimmune disorders or lymphoproliferative diseases).7-12
Enzyme Kinetics and Drugs as Enzyme Inhibitors
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Plasma cells normally produce large amounts of antibodies (immunoglobulins) in response to the immune system. In case of malignant transformation this property gets lost and is substituted by the production of a single type of abnormal monoclonal or M protein (monoclonal gammopathy) not being able to fight infections. Myeloma cells may also produce too many light chains that accumulate in tissues to amyloids (light chain amyloidosis). For example, their agglomeration in the heart may cause congestive heart failure, or harm the kidney. Furthermore the exceeding growth of plasma cells in the bone marrow proceeds at the expense of normal blood-forming cells with the consequence of anemia; thrombocytopenia (a low platelet count in the blood) may lead to development of external bleeding; a decrease in the number leukocytes (leukopenia) is tantamount to an increased risk of infections.
Clinical Effects of Pollution
Published in William J. Rea, Kalpana D. Patel, Reversibility of Chronic Disease and Hypersensitivity, Volume 5, 2017
William J. Rea, Kalpana D. Patel
Symmetric peripheral gangrene and purpura fulminans are two syndromes typically associated with thrombocytopenia and coagulopathy in patients who are critically ill. Symmetric peripheral gangrene indicates predominantly acral necrosis, which affects the distal limbs (with more frequent and extensive involvement of the feet than the fingers or hands [Figure 2.20]) but sometimes also the nose, lips, ears, scalp, and genitalia.475,476 The term purpura fulminans is used when there is extensive, multicentric, nonacral skin necrosis, although patients usually have acral limb necrosis as well. Septicemia and cardiac failure are the most common underlying disorders, and patients usually have metabolic (lactic) acidosis.494,507 Although underlying infection may suggest septic embolization, the presence of pulses and findings on histopathological analyses show the role of microthrombosis associated with DIC. Most patients with symmetric peripheral gangrene have shock, but this complication can occasionally also occur in a normotensive patient with a severe systemic inflammatory state and in the absence of overt DIC.
Antithrombotic therapy after transcatheter aortic valve implantation
Published in Expert Review of Medical Devices, 2022
Antonio Greco, Marco Spagnolo, Davide Capodanno
Non-access site-related bleedings (e.g. gastrointestinal, genitourinary, neurological) display an early incidence peak and then tend to steadily accrue over time, significantly contributing to late bleedings after TAVI [61]. Transient thrombocytopenia acts as a potential risk enhancer: it is caused by a periprocedural thrombo-inflammatory state and the reduced platelet turnover typical of the elderly, and represents a marker of frailty and general impairment [68]. Interestingly, Heyde’s syndrome, also known as acquired von Willebrand factor disease type 2A, consists of gastrointestinal bleeding associated with aortic stenosis: the cleavage of high-molecular-weight multimers of von Willebrand factor by the shear stress across the stenotic aortic valve, along with systemic hypoperfusion, prolong the adenosine diphosphate closure time and lead to the development of angiodysplasia [69]. Heyde’s syndrome confers a higher risk for periprocedural bleeding, but gastrointestinal bleeding have been shown to disappear in a large proportion of patients after TAVI [70]. Importantly, this condition may also result from a moderate or severe paravalvular leak after TAVI [71].
Polynuclear Ag(I)-N-heterocyclic carbene complexes: synthesis, electrochemical and in vitro anticancer study against human breast cancer and colon cancer
Published in Journal of Coordination Chemistry, 2019
Aqsa Habib, Muhammad Adnan Iqbal, Haq Nawaz Bhatti
Breast cancer is the most substantial sort of human non-skin malignancy and the second major cause of women mortality in western countries, while human colon cancer is among the most common types of cancer and major cause of deaths all over the world [10, 11]. Numerous silver-based drugs are already in the market for treatment of both cancer types, but almost all have several side effects including allergy, fatigue, seizures, bleeding, thrombocytopenia, renal damage, alopecia, peripheral neuropathy, blood dyscrasias, hepatotoxicity and nephrotoxicity, destruction of central nervous system and oligodendrocytes [12]. The major cause of these side-effects is the fast release of Ag+ ions which in turn destroys the normal cells in addition to diseased cells during their activity [13]. The disadvantages of these market drugs have attracted the attention of researchers to introduce new metallodrugs having little or no side-effects [14–21]. Recently, gold– and silver(I)–NHC complexes have been examined for their anticancer potential against human breast cancer and colon cancer cell lines [22, 23]. Ag(I)–NHC complexes are surpassing some already available market silver-based drugs [24]. The complexes bearing various substituents have been observed to pose strong biopotential due to sustained release of Ag+ ions which depends on their electronic and steric features influencing their lipophilicity [25].
Immobilizing argatroban and mPEG-NH2 on a polyethersulfone membrane surface to prepare an effective nonthrombogenic biointerface
Published in Journal of Biomaterials Science, Polymer Edition, 2019
Yanling Dai, Siyuan Dai, Xiaohui Xie, Jianping Ning
Heparin has been extensively researched as a coating of biomaterial surfaces to inhibit thrombosis [3, 8, 18, 21, 22]. HeprAN, the membrane of the commercial Evodial dialyzer, uses improved AN69ST technology in which heparin is grafted to the membrane. Several studies show that the Evodial dialyzer can be used without the systemic administration of heparin for hemodialysis in patients with bleeding tendencies [23–27]. Although the HeprAN membrane has been proven to be non-inferior to saline infusion, the superiority of its treatment, has not been demonstrated [23, 28, 29]. Additionally, the anticoagulation effectiveness of heparin is dependent upon the patient plasma concentration of antithrombin (AT). Therefore, heparin cannot be used in patients with an AT deficiency and can only indirectly inhibit free plasma thrombin but cannot inhibit fibrin-bound thrombin [30–31]. Moreover, nonspecific binding to other molecules [32], including plasma proteins and platelet factor 4 (PF4), not only reduces the availability of heparin to bind AT but can also induce side effects [31, 33], such as heparin-induced thrombocytopenia (HIT, an adverse immune-mediated drug reaction by an anti-heparin/PF4 complex antibody), which may further increase the risk of bleeding in patients with hemorrhage complications.