Explore chapters and articles related to this topic
Bleeding, severe pelvic infection,and ectopic pregnancy
Published in David K. Gardner, Ariel Weissman, Colin M. Howles, Zeev Shoham, Textbook of Assisted Reproductive Techniques, 2017
Dicker et al. described three cases of severe intraabdominal bleeding from ovarian puncture sites during OPU, leading to acute abdominal complications (1). In two of the patients, symptoms developed three hours after OPU (hemoglobin 9.0 g/100 mL and 8.1 g/100 mL, respectively), and laparoscopic drainage and hemostasis were sufficient. The third patient became symptomatic after four hours (hemoglobin 7.3 g/100 mL) and required exploratory laparotomy and hemostasis in addition to the transfusion of four units of blood as a life-saving procedure. Later, Battaglia et al. (18) reported severe intraabdominal bleeding from the surfaces of both ovaries in a patient with coagulation factor XI deficiency. As expected, the patient became symptomatic three hours after OPU and required laparotomy, partial resection of stuffed ovaries, and hemostasis. Physicians should be aware of the presence of concomitant coagulopathy and might therefore consider intense coagulation factor replacement before or during abdominal exploration.
Plasma Protein Function in Hemostasis
Published in Genesio Murano, Rodger L. Bick, Basic Concepts of Hemostasis and Thrombosis, 2019
In the initial step of the intrinsic coagulation sequence, Factor XII (a surface-sensitive single polypeptide chain protein with a molecular weight of about 80,000) is converted to Factor XIIα by cleavage of one (or more) internal peptide bonds, resulting in two chains linked by disulfide bridge(s).82 The heavy (amino terminal) chain contains surface-binding sites. The light (carboxyterminal) chain contains the active (proteolytic) site (Figure 18).82 Factor XII can be “activated” in several ways.82-87 Collagen or vascular basement membranes (exposed upon injury), phospholipids (from platelets), or washed, activated platelets themselves can serve as a surface. Factor XII, once bound to a negatively charged surface, has minimal ability to activate prekallikrein (see Section IV. Kinin Generation) and coagulation Factor XI. This activity is enhanced by HMW kininogen. The small quantities of kallikrein that are formed in this fashion then serve to enzymatically convert more Factor XII to the active form.82,88 This latter reaction is also enhanced by HMW kininogen and constitutes a positive feedback mechanism. Furthermore, Factor XIIα and/or fragments thereof82 formed by extensive acitvation, will further activate more prekallikrein to kallikrein in the presence of HMW kininogen. It appears that HMW kininogen serves not only as the precursor of “kinins”, but also as a linkage for Factor XI and prekallikrein to the exposed surface, where they are activated by surface-bound Factor XIIα. Once activated, Factor XIα remains localized at the site of activation, whereas kallikrein circulates free in plasma88 (Figures 19 and 20). Similarly to the prothrombin, Factor X, and Factor IX activation complex, the “surface” seems to function as a stage upon which all of the components can interact.17,88,93 Most likely, several pathways of activation are operative in this early (intrinsic) phase of coagulation, and the qualitative and quantitative aspects of the reactions are undoubtedly reflected in the mode and degree of activation. Figure 21 summarizes the coagulation sequence.
Investigational drugs for ischemic stroke: what’s in the clinical development pipeline for acute phase and prevention?
Published in Expert Opinion on Investigational Drugs, 2022
Maria Giulia Mosconi, Maurizio Paciaroni, Walter Ageno
Despite the proven benefit-risk profile for DOACs, when compared to VKAs, patients prescribed with DOACs still have a residual risk for developing strokes and systemic embolism; moreover, even though DOACs have a lower associated incidence of sICHs, compared to VKAs, there is still a non-negligible risk for both major and clinically relevant non-major bleeding. To this regard, ongoing studies are focused on developing inhibitors of the activated-coagulation factor XI (FXIa) and these results are expected to have a lower bleeding risk. Likewise, data on coagulation factors deficiency, both in animal models and in humans, reported that FXI-deficiency has a non-significant incidence in terms of bleeding events and a lower risk of ischemic events. Recent clinical research has focused on assessing the combined antithrombotic benefit and reduced bleeding risk of selective inhibition for coagulation factors in the intrinsic cascade; leaving the extrinsic and common pathways of thrombin generation intact for hemostasis [58,59].
Atrial fibrillation and stroke
Published in Expert Review of Cardiovascular Therapy, 2023
Sylvia E. Choi, Dimitrios Sagris, Andrew Hill, Gregory Y.H. Lip, Azmil H. Abdul-Rahim
Nevertheless, the risk of bleeding remains an impediment to the use of and adherence to OAC. There exists developing evidence that activated coagulation factor XI (factor XIa) may provide a target for a next-generation NOAC with advantages over conventional factor X inhibitors in terms of lower risk of major bleeding. A recent randomized Phase II dose-finding study of asundexian, a direct inhibitor of factor XIa, observed significantly lower rates of bleeding with asundexian compared to apixaban in patients with AF [216]. The trial paves the way for larger studies exploring the efficacy, safety, and incidence of major bleeding events in factor XIa inhibition in patients with AF at risk of stroke.
Normal activated partial thromboplastin time in Chinese patients with mild hemophilia B
Published in Hematology, 2020
Xiong Wang, Ning Tang, Na Shen, Yaowu Zhu, Yanjun Lu, Linna Gao
FIX is a vitamin K-dependent protease, circulating as a 461 amino acid precursor. FIX is activated by activated coagulation factor XI (FXI) or tissue factor-activated coagulation factor VII (FVII) via sequential cleavage at p.Arg191-Ala192 and p.Arg226-Val227, and secreted into plasma as a mature, 415-residue activated protein. Activated FIX cleaves coagulation factor X (FX) at p.Arg182-Ser183 and p.Arg234-Ile235 combined with coagulation factor VIII (FVIII), resulting in its activation and participating in the intrinsic blood coagulation pathway [4]. FIX is encoded by the F9 gene located on Xq27.1, and the F9 gene comprises 8 exons with a 2780-bp transcript.