Monitoring Treatments with Unfractionated Heparin: CTAD Must Be Used Instead of Citrate as the Anticoagulant Solution When Using Partial-Draw Collection Tubes.
Authors: Toulon Pierre A. , Abecassis Lién , Smahi Motalib , Ternisien Catherine 
Published: October 2019

Abstract
Abstract 2091
Poster Board II-68
Collecting small volumes of blood may be necessary, particularly in pediatrics, or in case of difficult or recurrent sampling. The aim of this multicenter study, involving four hemostasis laboratories, was to compare hemostasis test results in plasma samples obtained using partial- and full-draw evacuated polymer collection tubes containing 0.109 M sodium citrate (1 vol./9 vol.) as the anticoagulant solution (VenoSafeTM, Terumo Europe, Leuven, Belgium). For that purpose, blood was collected into one full- and one partial-draw tube from patients on vitamin K antagonists (VKA, n=100), unfractionated heparin (UFH, n=89), or a low molecular weight derivative (LMWH, n=52), as well as from 136 untreated patients, including 13 hemophiliacs. Routine coagulation tests i.e. PT/INR, aPTT, fibrinogen, and factor V, as well as factor VIII and anti-FXa activity when applicable, were measured using the routine techniques at each participating center. In addition, plasma PF-4 level, evaluated using an ELISA, was investigated in a subset of 36 healthy controls. In untreated patients incl. hemophiliacs as well as in those on either VKA or LMWH, no significantly relevant discrepancy (Bland-Altman) was found between tests results obtained using full- and partial-draw tubes. In contrast, anti-FXa activity in patients on UFH was significantly lower in partial- than in full-draw tubes [median=0.33 IU/mL (range: 0.00-1.11) vs. 0.39 (range: 0.05-1.32) respectively, p<0.0001]. Similarly, aPTT was significantly shorter in partial- than in the full-draw tubes, whereas other test results were not significantly different in the two tubes. That discrepancy was likely to be related to higher amount of PF4 released in plasma after increased platelet activation in partial-draw than in full-draw tubes [392 U/mL (range: 138-971) vs. 177 (range: 52-460) respectively, n=36; p<0.005)]. To further support that hypothesis, blood was collected, from 101 patients on UFH and from 104 untreated patients, into one partial-draw collection tube containing CTAD, a mixture of citrate and inhibitors of platelet activation, as the anticoagulant solution and one full-draw citrated tube, obtained from the same manufacturer. Comparison performed according to Bland-Altman of anti-FXa obtained in the two tubes failed to demonstrate any relevant difference, with a mean bias of +0.02 IU/mL that was identical throughout the measuring range of values [median=0.22 IU/mL (range: 0.06-1.16) vs. 0.20 (range: 0.03-1.15) respectively, n=101]. Moreover, in those patients on UFH, aPTT and other routine coagulation tests were not significantly different in the two tubes and the same applied to test results obtained in the plasma from untreated patients. These results suggest that samples collected into partial-draw citrated tubes allow accurate routine coagulation testing in all patients but those requiring UFH assessment, in which their use could lead to a significant underestimation of anticoagulation. In such cases, partial-draw tubes containing CTAD could be validly used to monitor heparin therapy, as well as to perform routine coagulation testing.

Disclosures:
No relevant conflicts of interest to declare.