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Cardiovascular Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Tinzaparin is a heparin that is used to treat DVT and prevent DVT in high risk individuals. The frequency of birth defects was not increased following first trimester exposure to tinzaparin among 699 infants (Kallen, 2019).
Can Recurrent Pregnancy Loss Be Prevented by Antithrombotic Agents?
Published in Howard J.A. Carp, Recurrent Pregnancy Loss, 2020
Audrey A. Merriam, Michael J. Paidas
A prospective study by Fawzy et al. showed a 33% improvement in the enoxaparin-treated arm compared to the control arm [31]. A more recent randomized trial by Shaaban et al. with 300 women showed a significantly improved pregnancy continuation rate and live birth rate in women treated with tinzaparin 4500 IU/d. This study was well designed, and all participants had complete follow-up to pregnancy loss or delivery [32].
Haematological conditions
Published in David M. Luesley, Mark D. Kilby, Obstetrics & Gynaecology, 2016
The LMWHs commonly used in the UK include enoxaparin, dalteparin or tinzaparin. Due to altered pharmacokinetics in pregnancy, both enoxaparin and dalteparin are usually given as a twice-daily dose to begin with, with some centres reducing to a once-daily intermediate dose after 2–4 weeks, if symptoms and signs are resolving. Tinzaparin is given once daily. LMWH therapy does not require monitoring with anti-factor Xa levels, except for extremes of weight, renal disease or if VTE has occurred while on LMWH, when they may be helpful to guide dosing. Although the test is limited by lack of standardisation and wide inter-laboratory variation, in-house experience allows reasonable interpretation of the assay result and the activity level is considered therapeutic at 0.5–1.2 U/mL 3 hours after injection. Unfractionated heparin may be preferred if the acute thrombotic event occurs near term, as the half-life is short and it can be continued for longer before delivery. It is also more easily monitored, readily reversed and not a concern in renal impairment.
Critical appraisal of evidence for anti-Xa monitoring and dosing of low-molecular-weight heparin in renal insufficiency
Published in Expert Review of Clinical Pharmacology, 2022
M. P. H. van den Broek, Marjon V. Verschueren, C. A. J. Knibbe
From a pharmacokinetic point of view, monitoring peak concentrations as a proxy for drug accumulation of a solely renally excreted drug in patients with renal insufficiency seems to be less sensitive than monitoring trough concentrations [36]. Moreover, there is increasing awareness that trough anti-Xa concentrations might be a more suitable safety and efficacy parameter [14,37]. Lim et al. observed in patients with CrCl > 60 ml/min on once-daily dosed tinzaparin mean steady-state trough concentrations of 0.15 (standard deviation (SD) 0.12) IU/mL, which implies that 95% (+2 SD) of the patients had trough anti-Xa concentrations below 0.4 IU/mL [35]. For twice-daily dosed enoxaparin, Al-Sallami found a doubling of the bleeding risk of patients with trough anti-Xa concentrations above 0.5 IU/mL [37]. These trough anti-Xa concentrations could potentially be used as an upper limit to monitor LMWH accumulation and, subsequently, to adjust LMWH doses. Finally, given the increased LMWH half-life in patients with severe renal insufficiency, steady-state trough concentrations can be expected 5–7 days after initiation of treatment. However, to prevent accumulation in these patients, trough concentrations could already be monitored 3–4 days after initiation of treatment to avoid prolonged overtreatment, but one should be aware that steady-state has not yet been achieved at this time.
Antithrombotic therapy for venous thromboembolism in patients with cancer: expert guidance
Published in Expert Opinion on Pharmacotherapy, 2018
Davide Imberti, Claudio Cimminiello, Marcello Di Nisio, Marco Marietta, Hernan Polo Friz, Walter Ageno
The randomized comparison of LMWH versus oral anticoagulant therapy for the prevention of recurrent VTE in patients with cancer (CLOT) trial randomized 676 patients with cancer to dalteparin or warfarin [11]. Dalteparin was more effective than warfarin (recurrent VTE, 9% versus 16%, p = 0.002) with no significant difference in bleeding or mortality. No significant difference was seen between LWHW and warfarin in the CANTHANOX study with respect to the composite endpoint of VTE recurrence and major bleeding [14]. In the CATCH trial [12], tinzaparin showed a non-statistically significant reduction in the composite primary outcome (recurrent DVT, fatal or nonfatal pulmonary embolism, and incidental VTE). There were no differences in major bleeding, but a significant reduction in clinically relevant non-major bleeding was observed with tinzaparin.
Advances in new drug therapies for the management of sickle cell disease
Published in Expert Opinion on Orphan Drugs, 2018
Kenneth I. Ataga, Payal C. Desai
In addition to their anticoagulant effects, heparins are known to inhibit adhesive interactions via P-selectin [87,88]. Sevuparin is a derivative of low-molecular-weight heparin that retains the P-selectin-binding domain of heparin but largely lacks anticoagulant properties [89]. Sevuparin binds to P- and L-selectins, thrombospondin, fibronectin and von Willebrand factor and inhibits the adhesion of sickle RBCs to stimulated cultured endothelial cells in vitro [89]. In addition, sevuparin prevents vaso-occlusion and normalizes blood flow in a mouse model of SCD vaso-occlusion [89]. A phase II clinical trial of sevuparin for the management of acute vaso-occlusive crisis is ongoing (NCT02515838), the primary end point being the time to resolution of vaso-occlusive crisis. In a multicenter study with 253 patients, tinzaparin at its usual therapeutic dose was reported to decrease the total number of hospital days, the overall number of days with pain crisis and the number of days of the most severe pain scores compared with placebo [90]. However, it is uncertain whether the observed benefit of tinzaparin was due to its anticoagulant or its anti-adhesive effect. Furthermore, issues regarding standard of care and potential study bias make the study difficult to interpret [91]. A phase II, pilot feasibility study of unfractionated heparin (NCT02098993) and a phase 3, randomized, placebo-controlled study of tinzaparin in acute chest syndrome are ongoing (NCT02580773).