Initial anticoagulation in patients with pulmonary embolism: thrombolysis, unfractionated heparin, LMWH, fondaparinux, or DOACs?

Abstract

The initial treatment of haemodynamically stable patients with pulmonary embolism (PE) has dramatically changed since the introduction of low molecular weight heparins (LMWHs). With the recent discovery of the direct oral anticoagulant drugs (DOACs), initial treatment of PE will be simplified even further. In several large clinical trials it has been demonstrated that DOACs are not inferior to standard therapy for the initial treatment of PE, and because of their practicability they are becoming the agents of first choice. However, many relative contraindications to DOACs were exclusion criteria in the clinical trials. Therefore, LMWHs will continue to play an important role in initial PE treatment and in some cases there still is a role for unfractionated heparin (UFH). In this review we will give an overview of the biophysical, pharmacokinetic and pharmacodynamic properties of anticoagulants currently available for the initial management of PE. In addition, we will provide a comprehensive overview of the indications for the use of UFH, LMWHs and DOACs in the initial management of PE from a pharmacokinetic/-dynamic point of view.

Analysis of Partial Thromboplastin Times in Patients With Pulmonary Embolism During the First 48 Hours of Anticoagulation With Unfractionated Heparin

“…The dosing of UFH is weight‐based: the standard dose is an intravenous 80 unit/kg bolus followed by an infusion started at 18 units/kg/hour, titrated to a target activated partial thromboplastin time (aPTT) of 1.5 to 2.5 times the control range or an anti‐Xa level of 0.3 to 0.7 μ/mL . Although this “standard dose” has been developed, UFH has long been known to have unpredictable pharmacokinetics and thus far only one small study ( n = 45) has explored the efficacy of this standard dose in patients with acute PE, finding only 22% of aPTT values within the reference range …”

“…[4][5][6]10 The dosing of UFH is weight-based: the standard dose is an intravenous 80 unit/kg bolus followed by an infusion started at 18 units/kg/hour, titrated to a target activated partial thromboplastin time (aPTT) of 1.5 to 2.5 times the control range or an anti-Xa level of 0.3 to 0.7 l/mL. [11][12][13][14][15][16] Although this "standard dose" has been developed, UFH has long been known to have unpredictable pharmacokinetics [17][18][19] and thus far only one small study (n = 45) has explored the efficacy of this standard dose in patients with acute PE, finding only 22% of aPTT values within the reference range. 20 Goals of This Investigation Therefore, given the expansion of PERTs worldwide and the unpredictable pharmacokinetics of UFH, we sought to determine the proportion of PERT patients at our institution treated with UFH who achieved a therapeutic aPTT within 48 hours of UFH initiation.…”

Антикоагулянты В Терапии Тромбоэмболии Легочной Артерии В Госпитальном Периоде: Рекомендации, Возможности, Подходы К рациональному Выбору. Место Фондапаринукса

“…При этом нелеченая ТЭЛА ведет к летальному исходу в 30 % случаев, тогда как вовремя распознанная и леченая -только в 8 % [4,5]. В настоящее время [6] отсутствуют доказательства, что низкомолекулярный гепарин (НМГ)/фондапаринукс (Ф) или парентеральные антикоагулянты (ПАК) имеют прямое действие на уже сформировавшиеся тромбы. Но прерывание коагуляционного каскада облегчает эндогенный фибринолиз и растворение тромба в большие в сравнении с тромболитической терапией (ТЛТ) сроки.…”

“…Это прерывание роста и образования свежих тромбов имеет критически важное значение не только в лечении, но и в профилактике рецидивов ТЭЛА, поскольку такие тромбы механически неустойчивы, легко отрываются и ведут к повторным эмболиям. Вазодилатирующие и антибронхоспастические свойства парентеральных антикоагулянтов никогда специально не изучались, однако они могут иметь дополнительный позитивный эффект [6]. НМГ/Ф сравнивались с нефракционированным гепарином (НФГ) в ряде специально спланированных исследований.…”

Pulmonary Embolism and Unfractionated Heparin: Time to End the Roller Coaster Ride

“…Despite these explanations, the preference for UFH is at odds with professional guidelines and published data. UFH, in contrast to LMWH, is notorious for its unpredictable pharmacokinetics from its small volume of distribution and variable half‐life due to a wide‐ranging molecular weight, two‐phased elimination, and extensive binding to plasma proteins . As a result, UFH is within the therapeutic range only 22% of the time in patients with acute PE .…”