Comparision Between Activated Partial Thromboplastin Time Versus Anti-Xa Activity in Heparin Monitoring
Status:
Unknown status
Trial end date:
2018-10-30
Target enrollment:
Participant gender:
Summary
Background:
Unfractionated heparin (UFH) is a sulfated polysaccharide extracted from porcine intestinal
mucosa that enhances the inhibitory activity of the natural anticoagulant antithrombin
towards most activated clotting factors (F), particularly FXa and FIIa (thrombin) . Despite
the growing interest for low molecular weight derivatives (LMWH), UFH is still widely used
for different indications including the treatment of acute thrombosis including venous
thromboembolism, coronary syndromes (ACS), and other thrombotic diseases. UFH is administered
by parenteral route either intravenous (IV) or sub-cutaneous (SC).Actually, there is evidence
that the risk of recurrence of thrombosis is increased when heparin levels fells below the
lower limit of the therapeutic range, while the hemorrhagic risk increases with heparin
levels above the upper limit of the therapeutic range. Moreover, the anticoagulant response
to UFH is highly variable for one individual to another. As the clinical efficacy of heparin
is dependent on maintaining an anticoagulant effect above a minimum level, careful laboratory
monitoring of UFH treatment is mandatory. For that purpose, two options are offered to the
clinicians: i) to evaluate either the prolongation of a global clotting assay, the activated
partial thromboplastin time (aPTT) and ii) to measure the heparin-enhanced inhibitory
activity of AT toward purified activated factors such as FIIa and FXa using chromogenic
substrate-based assays. UFH therapy is still widely monitored by the aPTT, a global clotting
assay, that reflects the ability of heparin to enhance the inhibitory activity of AT against
FIIa, FXa, and other activated factors. The therapeutic range of aPTT prolongation is highly
dependent on the reagent and analyzer used. As the consequence, it must be defined by each
laboratory in its own technical conditions (for each reagent batch) to correlate with heparin
levels between 0.20 and 0.40 U/mL (protamine sulfate titration), corresponding to anti-FXa
activity between 0.30 and 0.70 IU/mL. In that connection, the prolongation of aPTT
corresponding to antiFXa activity between 0.30 - 0.70 IU/mL is highly variable depending of
the reagents e.g.between 1.6 - 2.7 x control for weakly sensitive reagents and between 3.7 -
6.2 x control for highly sensitive reagents. The use of aPTT has advantages as it is
easy-to-perform, quick, inexpensive but faces numerous challenges due to the significant
influence of the technical conditions (reagent/instrument) on the test result, to lot-lot
variation in reagent sensitivity, to the need of studies to evaluate the therapeutic range,
to limited therapeutic range, and also to non-specific prolongation in the case of lupus
anticoagulant, factors deficiency, inhibitors or shortening in the case of high factor
levels, particularly FVIII.In contrast, the use of chromogenic anti-Xa assays has many
advantages particularly a published therapeutic range for UFH i.e. between 0.30 and 0.70
IU/mL, a specificity to its interaction with AT (no Heparin Cofactor II interference by using
bovine FIIa or short incubation time) and faces few challenges such as limited availability
in some area and a cost that is slightly higher than that of aPTT. In addition, anti-Xa
assays allow accurate measurement of all heparin(s) derivatives and particularly LMWHs and
fondaparinux.
Since the first reports in the mid-eighties, some small sized studies have compared the two
monitoring strategies mainly retrospectively designed (7-11). Even though, one single
prospective randomized management study evaluated the comparison between the two monitoring
strategies with clinical end-points i.e. recurrence of thrombosis and bleeding complication
in a cohort of 131 patients with VTE . All concluded to a trend toward higher, or at least
similar, safety/efficacy/efficiency when patients were monitored using antiXa activity vs.
aPTT. Even though differences were not significant due to the lack of power of these studies.