319: IDENTIFICATION OF PSEUDO-HEPARIN RESISTANCE IN CRITICALLY ILL PATIENTS WITH COVID-19

The current study aims to evaluate whether prophylactic anticoagulation using argatroban or an increased dose of unfractionated heparin (UFH) is effective in achieving the targeted activated partial thromboplastin time (aPTT) of more than 45 s in critically ill heparin-resistant (HR) patients. Patients were randomized either to continue receiving an increased dose of UFH, or to be treated with argatroban. The endpoints were defined as achieving an aPTT target of more than 45 s at 7 h and 24 h. This clinical trial was registered on clinicaltrials.gov (NCT01734252) and on EudraCT (2012-000487-23). A total of 42 patients, 20 patients in the heparin and 22 in the argatroban group, were included. Of the patients with continued heparin treatment 55% achieved the target aPTT at 7 h, while only 40% of this group maintained the target aPTT after 24 h. Of the argatroban group 59% reached the target aPTT at 7 h, while at 24 h 86% of these patients maintained the targeted aPTT. Treatment success at 7 h did not differ between the groups (p = 0.1000), whereas at 24 h argatroban showed significantly greater efficacy (p = 0.0021) than did heparin. Argatroban also worked better in maintaining adequate anticoagulation in the further course of the study. There was no significant difference in the occurrence of bleeding or thromboembolic complications between the treatment groups. In the case of heparin-resistant critically ill patients, argatroban showed greater efficacy than did an increased dose of heparin in achieving adequate anticoagulation at 24 h and in maintaining the targeted aPTT goal throughout the treatment phase.

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Efficacy of Argatroban in Critically Ill Patients with Heparin Resistance: A Retrospective Analysis

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0034-1398382 ◽

2015 ◽

Vol 41 (01) ◽

pp. 061-067 ◽

Cited By ~ 12

Author(s):

Benjamin Treichl ◽

Mirjam Bachler ◽

Ingo Lorenz ◽

Barbara Friesenecker ◽

Elgar Oswald ◽

...

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Primary Objective ◽

University Hospital ◽

Thrombin Inhibitor ◽

Clinical Aspects ◽

Surgical Intensive Care ◽

Heparin Resistance ◽

The Mean ◽

Prophylactic Anticoagulation

The patients who do not respond even to very high dosages of heparin are assumed to suffer from heparin resistance. The aim of this study was to investigate whether critically ill patients suffering from heparin resistance generally have low antithrombin III (AT) levels, and if the direct thrombin inhibitor argatroban in that case can be an effective option to achieve prophylactic anticoagulation. The study was conducted at the Department for General and Surgical Intensive Care Medicine at the University Hospital Innsbruck. We retrospectively included all patients between 2008 and 2012, who received argatroban because of poor response to high-dosage heparin prophylaxis. The period under observation lasted in total for 9 days, 2 days of anticoagulation with unfractionated heparin (UFH) and 7 days with argatroban. The primary objective was to investigate if after 7 (± 1) hours of switching to argatroban the activated partial thromboplastin time (aPTT) levels were in a prophylactic range of 45 to 55 seconds. Further objectives were to assess the AT level, side effects such as bleeding or thromboembolism, platelet count, correlation between organ function and argatroban dose as well as any need for allogeneic blood products. The study population, consisting of 5 women and 15 men with a mean (± standard deviation, SD) age of 54.6 ± 16.3 years, differed in many clinical aspects. A median (interquartile range) heparin dose of 1,000, 819 to 1,125 IU/h was administered for 2 days and failed in providing a prophylactic anticoagulation measured by the aPTT. The mean aPTT level with heparin treatment was 38.5 seconds (± 4.7) its change within that period was not significant. After switching to argatroban, the mean increase of the aPTT levels in all study patients amounted from 38.5 to 48.3 seconds (p < 0.001). The rise in aPTT clearly reaches sufficient prophylactic anticoagulant levels. The maintenance of prophylactic aPTT levels was achieved over the period of 1 week. There was neither a correlation found between low-AT levels and occurrence of heparin resistance, nor between the simplified acute physiology score II and the administered argatroban dose (r = −0.224, p = 0.342). The results of the present study indicate that argatroban is an effective alternative therapy, especially in critically ill patients, to achieve prophylactic anticoagulation when heparin resistance occurs.

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Heparin Resistance in ECMO and the Role of Direct Thrombin Inhibitors: A Case Report

University of Western Ontario Medical Journal ◽

10.5206/uwomj.v89i2.10242 ◽

2021 ◽

Author(s):

Mohsyn Imran Malik ◽

Dr. Roman Nepomuceno ◽

Dr. Dave Nagpal

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Therapeutic Potential ◽

Standard Procedure ◽

Thrombin Inhibitors ◽

Thrombin Inhibitor ◽

Direct Thrombin Inhibitors ◽

Bleeding Events ◽

Heparin Resistance

Extracorporeal membrane oxygenation (ECMO) is a potentially life-saving technology that can provide timely support to those failing to oxygenate their blood, either due to cardiac or respiratory related illnesses. However, ECMO also requires a careful hemostatic balance due to the thrombotic nature of the external circuit and the potential for bleeding events while anticoagulated. Current standard procedure for anticoagulating patients on ECMO is the use of unfractionated heparin. Despite its widespread use, many patients still face bleeding and/or clotting complications during their admission, some resulting in disastrous consequences. One possible etiology for this ineffectiveness is due to the mechanism by which heparin works via antithrombin (AT) and the AT deficiency of a critically ill patients. In this case study, we discuss the use of an alternative anticoagulant, a direct-thrombin inhibitor (DTI) in a patient cannulated to ECMO, which is independent of AT. The case study follows their course while on ECMO, focusing on relevant hemostatic measures. We further demonstrate the therapeutic potential for DTIs in place of UFH in ECMO patients, and the need for further research into anticoagulation strategies in critically ill patients.

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