Occurrence of thrombosis and haemorrhage, relationship with anti‐Xa, anti‐IIa activities, and D‐dimer plasma levels in patients receiving a low molecular weight heparin, enoxaparin or tinzaparin, to prevent deep vein thrombosis after hip surgery

Abstract

Summary. Studies in experimental animal models and in patients receiving low molecular weight heparin (LMWH) to prevent thromboembolic events after surgery have not demonstrated a clear relationship between anti-Xa and anti-IIa activities in plasma and either bleeding or prevention of thrombosis. The relationship between these clinical outcomes and ex vivo anti-Xa and anti-IIa activities, activated partial thromboplastin time (APTT) and D-dimers were evaluated in 440 patients undergoing total hip replacement and given prophylaxis once daily with a LMWH (tinzaparin or enoxaparin) in a multicentre doubleblind randomized study. 221 patients received 4500 anti-Xa IU of tinzaparin; 219 patients received 40 mg (4000 anti-Xa IU) of enoxaparin. Both regimens were administered subcutaneously once daily. Blood samples for anti-IIa, antiXa, D-dimers levels and APTT were taken at baseline, on day 1, day 5 and on the day of discharge (days 8-14) and clinical assessments were performed daily until day 14. All patients had bilateral venography between days 8 and 14.All coagulation tests were performed in central laboratories. A significant correlation was observed between anti-IIa activity and anti-Xa activity and the dose of each LMWH injected. The anti-Xa activity was significantly higher with enoxaparin and the anti-IIa activity was significantly higher with tinzaparin. No clear relationship between these two activities and the clinical outcomes was observed. This was also true with regards to APTT. Before and after surgery, Ddimers were significantly higher in patients with deep vein thrombosis (DVT) than in those without DVT but had no predictive value. Interestingly, a significant post-operative increase of D-dimers persisted in both groups of patients during the whole observation period, possibly suggesting that a longer duration of prophylactic treatment may be appropriate.

Effect of the anti‐factor Xa and anti‐factor IIa activities of low‐molecular‐weight heparins upon the phases of thrombin generation

“…It is well established that measurement of anti-FXa activity is not mandatory for monitoring anticoagulant treatment, as anti-FXa plasma levels in treated patients do not correlate well with clinical outcome (thrombosis or bleeding). That aside, some controversy exists regarding the credibility of this test in the monitoring of LMWH treatment in patients with acute coronary syndromes [13][14][15]. In some patients (i.e.…”

Coagulation Day 2010: an Austrian survey on the routine of thromboprophylaxis in intensive care

“…In this context it needs to be born in mind that target ranges are different for different LMWHs, and that it is still unknown if targets derived from pharmacological studies in healthy volunteers are indeed applicable to the critically ill population with major, heterogeneous and unpredictable modifications in pharmacokinetics and pharmacodynamics, as well as changes in haemostatic competence. Another problem is the only weak relationship between anti-Xa activity and clinical occurrence of symptomatic and asymptomatic VTE [18][19][20]. However, determination of anti-Xa activity is recommended if renal elimination of LMWH is impaired [2].…”

Reversal of low-molecular-weight heparin-induced bleeding in patients with pre-existing hypercoagulable states with human recombinant activated factor VII concentrate

“…Furthermore, the results of laboratory assays are not closely predictive of or correlated with the clinical propensity to bleed with LMWH or to excessively clot with RFVIIa [25]. The anti-Xa assay is conventionally used to assess the anticoagulant effect in vitro for LMWH, which, in contrast to unfractionated heparin, typically does not influence the aPTT.…”