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Haematological problems
Published in Catherine Nelson-Piercy, Handbook of Obstetric Medicine, 2020
The bleeding time is prolonged. APTT may be prolonged, and vWF and factor VIII may be reduced. A functional measure of vWF is obtained with a ristocetin cofactor, although this does not necessarily correlate to the bleeding risk.
Critical Appraisal of Animal Models for Antibiotic Toxicity
Published in Adorjan Aszalos, Modern Analysis of Antibiotics, 2020
Patricia D. Williams, Girard H. Hottendorf
The liability of bleeding disorders associated with penicillins and cephalosporins has been assessed in clinical trials in humans. Though Johnson and coworkers have reported relevant experiments in dogs [137], mechanistic studies havebeen performed largely in human volunteers. The following tests are usually performed to study coagulation and platelet function: bleeding time, platelet count, blood clotting time, prothrombin time, thrombin clotting time, fibrinogen levels, and platelet adhesiveness and aggregation. Although it cannot beargued that the human is the most valid animal model for human risk assessment, there is a need to identify appropriate human surrogates for the pre-clinical evaluation of these toxicities. Valid preclinical screens must be developed that will provide a means for selecting against these toxic properties early in drug development. Pharmacokinetic and metabolic criteria willbe particularly important in developing a hypoprothrombinemic model sincetwo factors relevant to these criteria may be involved in the pathogenesis:(1) biliary excretion resulting in eradication of vitamin K-producing micro-organisms [49], and (2) liberation of the methyltetrazolethiol side chain common to antibiotics causing this disorder [69].
Glycogenosis type I – von Gierke disease
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Allopurinol is used to lower the concentration of urate to normal levels. A starting dose of 10 mg/kg was recommended. In patients requiring surgery, the bleeding time should be determined. If it is prolonged, it may be improved by 24–48 hours of IV glucose or L-deamino-8-D-arginine vasopressin (DDAVP) [108]. Angiotensin converting enzyme inhibitors have been recommended [105] for hypertension. Hypertriglyceridemia has been treated with nicotinic acid or fibrates [105].
Hemostasis-on-a-chip / incorporating the endothelium in microfluidic models of bleeding
Published in Platelets, 2023
Yumiko Sakurai, Elaissa T. Hardy, Wilbur A. Lam
Bleeding disorders (i.e. hemophilia and von Willebrand disease) affect hemostasis, and affected patients may exhibit various degrees of bleeding problems. Historically, patients with a suspected bleeding disorder underwent a “bleeding time test” to directly assess the patient’s bleeding risk. This test includes small incisions on the patient’s arm and recording the time when the bleeding stops [1] but the procedure is difficult to control and is invasive. Currently, the bleeding time test has largely been replaced by assays using blood collected through a venipuncture, assessing the risks of abnormal bleeding and blood clotting. Specifically, the assays include prothrombin and partial thromboplastin time, platelet function assays, and various viscoelastic tests. The assays can be performed as point-of-care in clinical settings [2–4] where timely assessment is needed in the emergency department, surgery, trauma involving hemorrhagic shock, and more recently, COVID-19-associated coagulopathy [5]. They can determine the patient’s hemostatic competence more precisely but other critical factors that control hemostasis in the body may be omitted. For example, the fluid dynamics of blood flow and blood interaction with the cells composing the vasculatures, i.e. endothelial cells and the underlying matrix. Additionally, the assays can determine the risk of the blood clotting through direct observation of platelet behaviors and coagulation, but bleeding risks are only indicated by the lack of or the reduced amount of activity. There is no direct observation of “bleeding” and hemostasis to assess patient’s hemostatic competence.
Solid self nano-emulsifying system for the enhancement of dissolution and bioavailability of Prasugrel HCl: in vitro and in vivo studies
Published in Pharmaceutical Development and Technology, 2021
Mai Khanfar, Suhair Al-Nimry, Shatha Attar
The bleeding time was measured according to a previous study (Dejana et al. 1979; Liu et al. 2012). Four groups of rats (n = 3 for each group) were used. Group I represent the control group (no treatment), in group II, rats received the raw material of PHCl (pure drug), group III, received PHCl S-SNEDDS formulation and group IV, received the commercial drug (Lexar ® of 5 mg). Groups (II, III) received the drug by oral gavage in a dose of 1 mg/kg using flexible feeding tubes, while the rats in group IV received an equivalent dose to 1 mg/kg of the commercial drug (Lexar®) tablets by oral gavage after crushing the tablets into a fine powder, and dissolving them in water. After one hour of receiving treatments, rats were anesthetized with ether; positioned in prone situation in a rodent restrainer device. The distal 10-mm segment of the tail was amputated with a scalpel. The tails were immediately immersed in a 50-ml tube containing isotonic saline pre-warmed in a water bath to 37 °C. The position of the tail was vertical with the tip positioned about 2 cm below the body horizon. Bleeding time was determined using a stop clock.
Thromboelastography versus bleeding time for risk of bleeding post native kidney biopsy
Published in Renal Failure, 2020
Amir Gal-Oz, Amitay Papushado, Ilya Kirgner, Shmuel Meirsdorf, Doron Schwartz, Idit Francesca Schwartz, Asia Zubkov, Ayelet Grupper
The risk of bleeding has led to standard screening of the primary hemostasis before a renal biopsy is performed [10], although no strong evidence exists to support this practice. While a bleeding time (BT) test is considered to be standard practice for the assessment of platelet function in uremic patients [11], it requires technical expertise, has questionable reproducibility and accuracy, and poorly predicts clinical bleeding risks [12–15]. Although there are no randomized prospective studies evaluating the use of a BT test in the setting of a percutaneous renal biopsy, observational studies have demonstrated a higher bleeding complication rate in those patients with abnormal test results [16–21]. Other series, however, report no increased risk [22,23], so the value of this practice remains to be debated [22,24]. Platelet function analyzer-100 (PFA-100) test measures activated platelets and is more sensitive in comparison with the bleeding time for bleeding disorders. However, it was not found to be useful in predicting bleeding post kidney biopsy [25,26].