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Cardiovascular Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
No studies are published of human use of thrombolytics (e.g., streptokinase or urokinase) during the first trimester. A review of 172 pregnant women who used thrombolytics compiled from published reports found no increase in congenital anomalies and a pregnancy loss rate of 5.8 percent (Turrentine et al., 1995). However, exposures to the thrombolytics varied from 9 weeks to 40 weeks. Hemorrhagic complications occurred in 8 percent of the women. Among more than 140 infants exposed to heparin during the first trimester, the frequency of congenital anomalies was not increased (Chan et al., 2000). Among 119 infants exposed to heparin in the first trimester in the Swedish birth Defects Registry, the frequency of birth defects was not increased (Kallen, 2019). For low molecular weight heparin findings are similar from a literature review identified more than 440 infants exposed to low molecular weight heparins during pregnancy. The review included nearly 200 infants whose mothers were treated during the first trimester; no congenital anomalies were reported (Sanson et al., 1999). This is a case of ascertainment bias result because seven to 10 infant birth defects were expected in the absence of any drug exposure.
Pregnancy-Related Proteins Detected by Their Biological Activities
Published in Gábor N. Than, Hans Bohn, Dénes G. Szabó, Advances in Pregnancy-Related Protein Research, 2020
The presence of an urokinase inhibitor in placenta homogenates was first reported by Kawano et al.131 It also inhibited PA extracted from tissues.132 The primary structure of human placental type PAI has recently been determined by cDNA cloning and sequencing. The translated amino acid sequence consisted of 415 amino acids, corresponding to a 46,600 Da protein. The sequence was related to members of the serpin gene family, particularly ovalbumin and also to PAI-1.129 Very recently it was shown by Kiso et al.133 that PAI-2 is identical to the immunochemically detected placental protein 10 (PP10) which has been isolated from human term placentas and characterized by Bohn and Kraus in 1979134 (see Chapter 2).
Acquired Bleeding Disorders Associated with the Character of the Surgery
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
William A. Rock, Robert F. Baugh
Excessive bleeding in urological surgery is frequently confined to prostate surgery. Occasionally, renal surgery or renal trauma can result in life-threatening hemorrhage. In both cases the operative site which is actively bleeding forms clots which are in turn lysed by the urokinase in urine. Urokinase is a potent plasminogen activator, which converts plasminogen to plasmin, the active enzyme. Bleeding continues as all clots are lysed. The use of epsilon-aminocaproic acid or tranexamic acid blocks the activation of plasminogen. This use is not without controversy (160). Nonetheless, the antifibrinolytic agents have been useful in stopping or slowing the blood loss in prostate surgery (161–164).
Intraventricular haemorrhage due to re-ruptured arteriovenous malformation cleared with tissue plasminogen activator administered through a pre-existing ventriculoperitoneal shunt
Published in British Journal of Neurosurgery, 2023
Fotis G. Souslian, Eric S. Nussbaum, Puja D. Patel
Pharmacological thrombolysis shows promise as a means of preventing shunt obstruction in the context of IVH. Administration of intraventricular t-PA or urokinase has been reported to prevent clotting, clear blood at a faster rate, and improve survival rates in patients with IVH.5–7,16,17 There are important differences between the scheme used here and that used in other studies. CLEAR-IVH injected t-Pa and left the ventricles without drainage for one hour before opening drainage again, whereas in the present case, the shunt was patent throughout. The multicenter randomized controlled trial (CLEAR III) delivered 1 mg intraventricular alteplase delivered in up to 12 doses, 8 hours apart, in 500 IVH patients with an EVD, demonstrating a larger volume of blood removed and significantly lower rates of mortality compared to a control group.8 This type of procedure should be performed with caution, as frequent injections into EVDs may introduce a significant risk for infections. In the present case, we injected 6 doses of t-PA through the EVDs and a single direct injection into the shunt reservoir. It is thought that this not only prevented a shunt malfunction, but also bypassed the need for shunt revision surgery, leading to an impressive patient recovery. It can be argued that EVD placement may have not been necessary, and that instead, t-PA may have been injected into the shunt reservoir upon readmission.
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
Another agent under investigation in several studies is modified urokinase. The PROACT II was a RCT on treatment with intra-arterial recombinant pro-urokinase (IA r-proUK) + heparin within 6 h of acute ischemic stroke onset caused by middle-cerebral artery occlusion, and reported a significantly improved clinical outcome at 90 days, compared to heparin [84]. Mutant pro-urokinase is being investigated in the DUMAS study (NCT04256473), a phase 2 RCT where mutant pro-urokinase is infused IV after a small bolus of alteplase, compared with IV alteplase alone, in patients diagnosed with AIS within 4.5 h from symptom onset and no eligibility for endovascular treatment. Urokinase is also under investigation in the TRUST study (NCT04420351) where patients with minor stroke, within 6 h from symptoms onset, in the experimental arm will receive IV urokinase, as compared to antiplatelet standard treatment.
Prevention, treatment, and risk factors of deep vein thrombosis in critically ill patients in Zhejiang province, China: a multicenter, prospective, observational study
Published in Annals of Medicine, 2021
Li Li, Jia Zhou, Liquan Huang, Junhai Zhen, Lina Yao, Lingen Xu, Weimin Zhang, Gensheng Zhang, Qijiang Chen, Bihuan Cheng, Shijin Gong, Guolong Cai, Ronglin Jiang, Jing Yan
The treatment of DVT was conducted according to the 2017 “Guidelines for the Diagnosis and Treatment of Deep Vein Thrombosis (Third Edition)” by the Chinese Society of Vascular Surgery of the Chinese Medical Association and the 2018 Chinese Thoracic Society “Guidelines for the Diagnosis, Treatment, and Prevention of Pulmonary Thromboembolism.” The patients were treated with one drug among UFH, LMWH, and vitamin K antagonists. Moreover, the therapy was changed according to the condition of the patient. The initial dose of UFH was 80–100 U/kg/h intravenously, and then 10–20 U/kg/h intravenously. Afterward, it was adjusted according to the activated partial thromboplastin activity every 4–6 h to extend it to 1.5–2.5 times the normal control value. LMWH was administered according to the bodyweight at a dose of 100 U/kg once every 12 h, subcutaneously. The initial dose of vitamin K antagonists, such as warfarin, was 3.0–5.0 mg/d, starting with 2.5–3.0 mg for patients >75 years old and at high haemorrhage risk. Thrombolysis therapy included streptokinase, urokinase, and recombinant human tissue plasminogen activator (rt-PA), each used alone. The loading dose of streptokinase was 250,000 U intravenously for 30 min, followed by a maintenance intravenous infusion of 100,000 U/h for 12–24 h. The loading dose of urokinase was 4400 U/kg intravenously for 10 min, followed by 2200 U/kg/h continuous intravenous drip for 12 h. The dose of rt-PA was 50 mg, infused continuously for 2 h.