Activated Partial Thromboplastin Time Monitoring of Unfractionated Heparin Therapy: Issues and Recommendations

Marlar, Richard A.; Clément, Bernadette; Gausman, Jana N.

doi:10.1055/s-0036-1581128

Cited by 38 publications

(34 citation statements)

References 29 publications

(129 reference statements)

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“…This therapeutic target dates from work in 1972 and has never been confirmed in large clinical studies [ 128 ]. Since then, the number of reagents used for the APTT has exponentially increased, the sensitivity of which is very different both to heparin and biological interference (including several proteins of the acute phase) [ 129 – 131 ]. Therefore, calculation of the APTT ratio corresponding to an anti-Xa activity between 0.3 and 0.7 IU/mL would be recommended for each analyzer and each new batch of reagents.…”

Section: Anticoagulation - Laboratory Monitoringmentioning

confidence: 99%

Management of the thrombotic risk associated with COVID-19: guidance for the hemostasis laboratory

Hardy¹,

Lecompte

Douxfils

et al. 2020

Thrombosis J

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Coronavirus disease 2019 (COVID-19) is associated with extreme inflammatory response, disordered hemostasis and high thrombotic risk. A high incidence of thromboembolic events has been reported despite thromboprophylaxis, raising the question of a more effective anticoagulation. First-line hemostasis tests such as activated partial thromboplastin time, prothrombin time, fibrinogen and D-dimers are proposed for assessing thrombotic risk and monitoring hemostasis, but are vulnerable to many drawbacks affecting their reliability and clinical relevance. Specialized hemostasis-related tests (soluble fibrin complexes, tests assessing fibrinolytic capacity, viscoelastic tests, thrombin generation) may have an interest to assess the thrombotic risk associated with COVID-19. Another challenge for the hemostasis laboratory is the monitoring of heparin treatment, especially unfractionated heparin in the setting of an extreme inflammatory response. This review aimed at evaluating the role of hemostasis tests in the management of COVID-19 and discussing their main limitations.

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Section: Anticoagulation - Laboratory Monitoringmentioning

confidence: 99%

Management of the thrombotic risk associated with COVID-19: guidance for the hemostasis laboratory

Hardy¹,

Lecompte

Douxfils

et al. 2020

Thrombosis J

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“…First, the sample size was small, given the single-center study. Second, aPTT values differ between institutions and assay methods 7 , 40 , 41 . Third, the protocols of heparin therapy after cardiac surgery vary depending on the institution, and our aPPT targets and low heparin dose requirements present unique limiting generalizability 42 – 44 .…”

Section: Discussionmentioning

confidence: 99%

“…We also estimated the variance explained, adjusting for the APTT in each model and regressing the effect of APTT, as APTT could also be influenced by multiple factors and variabilities could be due to APTT itself 7 . All statistical analyses were two-sided, and a P value of < 0.05 was considered significant.…”

Section: Methodsmentioning

confidence: 99%

Individual variation in unfractionated heparin dosing after pediatric cardiac surgery

Hikino

Koido

Ide

et al. 2020

Sci Rep

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We aimed to identify attributing factors to the interindividual variabilities of the infusion rates in unfractionated heparin therapy. We included patients who required unfractionated heparin therapy to achieve the target APTT after cardiac surgery between May 2014 and February 2018. Fifty-nine patients were included, of whom 8 underwent Blalock-Taussig shunt; 27, Glenn procedure; 19, Fontan procedure; 3, mechanical valve replacement; and 2, Rastelli procedure. Previously reported variables that influenced the response to unfractionated heparin treatment were initially compared, which included age; weight; sex; type of surgery; platelet count; fibrinogen, antithrombin III, total protein, albumin, alanine transaminase, and creatinine levels; and use of fresh frozen plasma. The type of surgical procedure was found to be significantly associated with the differences in heparin infusion rate (P = 0.00073). Subsequently, the variance explained by these factors was estimated through a selection based on the minimum Akaike information criterion value; models constructed by various combinations of the surgery types were compared. The model including the Blalock-Taussig shunt, Glenn procedure, and mechanical valve replacement showed the highest summed variance explained (29.1%). More than 70% of the interindividual variability in initial heparin maintenance dosing was unexplained.

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“… 15 Because large differences exist between different reagents and platforms, each laboratory should ideally determine the aPTT target range based on a corresponding anti-Xa activity of 0.3 to 0.7 IU/mL. 16 17 In our laboratory, UFH is monitored using the aPTT with a HTR of 50 to 80 s, based on an aPTT ratio of 1.5 to 2.5. We utilize two different instruments for the aPTT: the Sysmex CS2100i (optical clot detection and the default instrument) and the Stago STA-R Max 2 (mechanical clot detection).…”

Section: Introductionmentioning

confidence: 99%

Monitoring of Unfractionated Heparin in Severe COVID-19: An Observational Study of Patients on CRRT and ECMO

Streng

Delnoij

Mulder

et al. 2020

TH Open

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Objective Severe cases of coronavirus disease 2019 (COVID-19) can require continuous renal replacement therapy (CRRT) and/or extracorporeal membrane oxygenation (ECMO). Unfractionated heparin (UFH) to prevent circuit clotting is mandatory but monitoring is complicated by (pseudo)-heparin resistance. In this observational study, we compared two different activated partial thromboplastin time (aPTT) assays and a chromogenic anti-Xa assay in COVID-19 patients on CRRT or ECMO in relation to their UFH dosages and acute phase reactants. Materials and Methods The aPTT (optical [aPTT-CS] and/or mechanical [aPTT-STA] clot detection methods were used), anti-Xa, factor VIII (FVIII), antithrombin III (ATIII), and fibrinogen were measured in 342 samples from 7 COVID-19 patients on CRRT or ECMO during their UFH treatment. Dosage of UFH was primarily based on the aPTT-CS with a heparin therapeutic range (HTR) of 50–80s. Associations between different variables were made using linear regression and Bland–Altman analysis. Results Dosage of UFH was above 35,000IU/24 hours in all patients. aPTT-CS and aPTT-STA were predominantly within the HTR. Anti-Xa was predominantly above the HTR (0.3–0.7 IU/mL) and ATIII concentration was >70% for all patients; mean FVIII and fibrinogen were 606% and 7.5 g/L, respectively. aPTT-CS correlated with aPTT-STA (r 2 = 0.68) with a bias of 39.3%. Correlation between aPTT and anti-Xa was better for aPTT-CS (0.78 ≤ r 2 ≤ 0.94) than for aPTT-STA (0.34 ≤ r 2 ≤ 0.81). There was no general correlation between the aPTT-CS and ATIII, FVIII, fibrinogen, thrombocytes, C-reactive protein, or ferritin. Conclusion All included COVID-19 patients on CRRT or ECMO conformed to the definition of heparin resistance. A patient-specific association was found between aPTT and anti-Xa. This association could not be explained by FVIII or fibrinogen.

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Activated Partial Thromboplastin Time Monitoring of Unfractionated Heparin Therapy: Issues and Recommendations

Cited by 38 publications

References 29 publications

Management of the thrombotic risk associated with COVID-19: guidance for the hemostasis laboratory

Management of the thrombotic risk associated with COVID-19: guidance for the hemostasis laboratory

Individual variation in unfractionated heparin dosing after pediatric cardiac surgery

Monitoring of Unfractionated Heparin in Severe COVID-19: An Observational Study of Patients on CRRT and ECMO

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