Fondaparinux: An effective bridging strategy in heparin-induced thrombocytopenia and mechanical circulatory support

Gellatly, Rochelle; Leet, Angeline; Brown, Kathryn E.

doi:10.1016/j.healun.2013.07.015

Cited by 17 publications

(13 citation statements)

References 5 publications

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“…33 The other was successfully switched to biventricular assist device without complications. 47 Plasma Multiple regression analyses revealed that the TT predicted 54% of argatroban and 42% of lepirudin levels, but no significant impact was seen for PT or aPTT. The aPTT-guided monitoring of DTI therapy leads to a high percentage of patients with inaccurate plasma levels, hence resulting with either undertreatment or overtreatment.…”

Section: Dtismentioning

confidence: 93%

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Heparin‐induced thrombocytopenia complicating extracorporeal membrane oxygenation support: Review of the literature and alternative anticoagulants

Pollak

2019

Journal of Thrombosis and Haemostasis

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Heparin‐induced thrombocytopenia (HIT) is a life‐threatening prothrombotic, immune‐mediated complication of unfractionated heparin and low molecular weight heparin therapy. HIT is characterized by moderate thrombocytopenia 5‐10 days after initial heparin exposure, detection of platelet‐activating anti‐platelet factor 4/heparin antibodies and an increased risk of venous and arterial thrombosis. Extracorporeal membrane oxygenation (ECMO) is a form of mechanical circulatory support used in critically ill patients with respiratory or cardiac failure. Systemic anticoagulation is used to alleviate the thrombotic complications that may occur when blood is exposed to artificial surfaces within the ECMO circuit. Therefore, when HIT complicates patients on ECMO support, it is associated with a high thrombotic morbidity and mortality. The risk for HIT correlates with the accumulative dosage of heparin exposure. In ECMO patients receiving continuous infusion of heparin for circuit patency, the risk for HIT is not neglected and must be thought of in the differential diagnosis of the appropriate clinical and laboratory circumstances. The following article reviews the current knowledge in HIT complicating ECMO patients and the alternative anticoagulation options in the presence of HIT.

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Section: Dtismentioning

confidence: 93%

“…One adult had no complications and was weaned after 7 days but treatment included plasmapheresis, which may have influenced the outcome . The other was successfully switched to biventricular assist device without complications …”

Section: Treatment Of Hitmentioning

confidence: 99%

Heparin‐induced thrombocytopenia complicating extracorporeal membrane oxygenation support: Review of the literature and alternative anticoagulants

Pollak

2019

Journal of Thrombosis and Haemostasis

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“…Suspicion of HIT was raised in patients on ECLS by various factors including a decrease in platelet count by >50% (5-9), thrombotic event(s) (6,9,10), change in postoperative status (6), duration of ECLS support >72 hours (11) and intermediate to high 4Ts score (>3) (6,12). The cutoff criterion for HIT suspicion was not always specified or uniform for every institution.…”

Section: Definitionsmentioning

confidence: 99%

“…H-PF4 antibody enzyme-linked immunosorbent assay (ELISA) was performed as a screening test for HIT (13,14), where optical density (OD) values of equal to or greater than 0.4 was considered positive. Following a positive screening test, the diagnosis was usually confirmed by either functional assays, such as serotonin release assay (SRA) (6,8,(15)(16)(17) or heparin induced platelet aggregation assay (HIPA) (5,18,19), or a strong clinical suspicion of HIT with subsequent recovery of thrombocytopenia following heparin discontinuation (8,10,(20)(21)(22)(23)(24). High positive ELISA test result (e.g., OD >1.0) alone was sometimes considered sufficient to confirm the diagnosis of HIT (6,25).…”

Section: Definitionsmentioning

confidence: 99%

Heparin-induced thrombocytopenia during extracorporeal life support: incidence, management and outcomes

Choi

Luc

Weber

et al. 2019

Ann. Cardiothorac. Surg.

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Background: Heparin-induced thrombocytopenia (HIT) is a severe antibody-mediated reaction leading to transient prothrombosis. However, its incidence in patients on extracorporeal life support (ECLS) is not well described. The aim of this systematic review was to report the incidence of HIT in patients on ECLS, as well as compare the characteristics and outcomes of HIT in patients undergoing veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and veno-venous ECMO (VV-ECMO). Methods: An electronic search was performed to identify all studies in the English literature examining outcomes of patients with HIT on ECLS. All identified articles were systematically assessed using specific inclusion and exclusion criteria. Random effects meta-analysis as well as univariate analysis was performed. Results: Of 309 patients from six retrospective studies undergoing ECLS, 83% were suspected, and 17% were confirmed to have HIT. Due to the sparsity of relevant retrospective data regarding patients with confirmed HIT on ECLS, patient-based data was subsequently collected on 28 patients from case reports and case series. Out of these 28 patients, 53.6% and 46.4% of them underwent VA-ECMO and VV-ECMO, respectively. Patients on VA-ECMO had a lower median platelet count nadir (VA-ECMO: 26.0 vs. VV-ECMO: 45.0 per µL, P=0.012) and were more likely to experience arterial thromboembolism (VA-ECMO: 53.3% vs. VV-ECMO: 0.0%, P=0.007), though there was a trend towards decreased likelihood of experiencing ECLS circuit oxygenator thromboembolism (VA-ECMO: 0.0% vs. VV-ECMO: 30.8%, P=0.075) and thromboembolism necessitating ECLS device or circuit exchange (VA-ECMO: 13.3% vs. VV-ECMO 53.8%, P=0.060). Kaplan-Meier survival plots including time from ECLS initiation reveal no significant differences in survival in patients supported on VA-ECMO as compared to VV-ECMO (P=0.300). Conclusions: Patients who develop HIT on VA-ECMO are more likely to experience more severe thrombocytopenia and arterial thromboembolism than those on VV-ECMO. Further research in this area and development of standardized protocols for the monitoring, diagnosis and management of HIT in patients on ECLS support are warranted.

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“…Results obtained for fondaparinux showed that whatever the used methodology (current and improved), the presence of fondaparinux could impact the tests, except for the higher dilution (ie, Biophen ® DiXaI ® [1:50]) (Figure . Although a switching between fondaparinux and betrixaban is unlikely, the increase in the concentration of the buffer could be one possibility to avoid this interference. However, we have to keep in mind that even if some chromogenic anti‐Xa assays are specific for direct factor Xa inhibitors, none of these are able to discriminate between direct factor Xa inhibitors which may be a problem when no information on the drug taken by the patients is available…”

Section: Discussionmentioning

confidence: 99%

Development of new methodologies for the chromogenic estimation of betrixaban concentrations in plasma

Siriez

Evrard

Dogné

et al. 2019

Int J Lab Hematology

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Introduction Chromogenic anti‐Xa assays are the most appropriate tests to estimate the amount of betrixaban in plasma but the sensitivity of available tests is limited and improvements are needed to encompass the on‐therapy range. Methods Betrixaban was spiked at concentrations ranging from 0 to 500 ng/mL in plasma from healthy donors. Three commercial tests were used (Biophen®DiXaI®, STA®Liquid Anti‐Xa, and HemosIL®Liquid Anti‐Xa), and adaptation of their sample dilution scheme was performed. These new methodologies were also tested on plasma spiked with amounts of unfractionated heparin (UFH), low molecular weight heparins (LMWH), or fondaparinux covering the on‐therapy ranges to evaluate their sensitivity to indirect factor Xa inhibitors. Results Results showed concentration‐dependent decreases in OD/min inversely proportional to the dilutions. While modifications improve the sensitivity of these tests to betrixaban (eg, ½*OD/min of 502 ng/mL [95% CI: 495‐508 ng/mL] for Biophen®DiXaI® [1:50] is reduced to 51 ng/mL [95% CI: 50‐52 ng/mL] for improved Biophen®DiXaI® [1:5]), results also showed an increased sensitivity to indirect factor Xa inhibitors, except for Biophen®DiXaI® which remains insensitive to UFH and LMWH. Conclusions Results showed that the improvement of current chromogenic anti‐Xa methodologies enhances the sensitivity of these assays to betrixaban but also to indirect factor Xa inhibitors. This lack of specificity may lead to overestimation of betrixaban concentrations in patients bridged with heparins. To avoid this cross‐interference, the use of the Biophen®DiXaI® may be a solution except for fondaparinux which remains active even in the presence of the Biophen®DiXaI®’s specific buffer. For the other chromogenic assays, the conception and validation of specific buffer is required.

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Fondaparinux: An effective bridging strategy in heparin-induced thrombocytopenia and mechanical circulatory support

Cited by 17 publications

References 5 publications

Heparin‐induced thrombocytopenia complicating extracorporeal membrane oxygenation support: Review of the literature and alternative anticoagulants

Heparin‐induced thrombocytopenia complicating extracorporeal membrane oxygenation support: Review of the literature and alternative anticoagulants

Heparin-induced thrombocytopenia during extracorporeal life support: incidence, management and outcomes

Development of new methodologies for the chromogenic estimation of betrixaban concentrations in plasma

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