Continuous administration of LMWH in critical patients: a contribution to the monitoring of hemocoagulation

Objective

To monitor hemocoagulation in patients with systemic inflammation while continually i.v. administering LMWH, plus dosage adjustment, while trying to reflect on coagulation changes, mainly regarding the values of anti-Xa and Ddim.

Background

LMWH is used in the prophylaxis of as well as therapy of DVT, in the prevention of thrombus formation in extra-corporal circulation through CRRT, in the therapy of unstable angina pectoris and non-Q myocardial infarction, and in the therapy of stroke. We have asked ourselves the question of whether the same administration routine could be applied in critically ill patients where we assume a pronounced prothrombotic state. Critically ill patients commonly demonstrate hyperfibrinogenemy, reactive thromobocytosis, and changes of the plasmatic coagulation system. Due to the favourable therapeutic potential of LMWH, we decided on a continual i.v. administration of enoxaparin as well as hemocoagulation monitoring.

Materials and methods

The study included patients with an expected length of stay >48 hours and with no contraindication to anticoagulation therapy. We monitored the coagulation parameters INR, aPTT, TT, FBG, AT, Ddim, PLT count, leukocyte count, anti-Xa, vWfF level, PLT activation, and the dosage of LMWH within the past 24 hours. The patients were divided into two groups: with SOFA <5 and with SOFA≥ 5. The initial daily dose of LMWH was administered based on the patient's weight. Dose modifications were carried out so that the anti-Xa level would be between 0.2 and 0.5 IU/ml and/or the Ddim count would demonstrate a steady (in the standard levels) or falling (in elevated levels) tendency. Flow cytometry was used for quantification of blood cells carrying the CD61 antigen (i.e. platelet identification), out of which those that carried CD62 antigen on the surface were selected (i.e. activated platelets).

Results

Preliminary evaluation includes 10 patients, 109 sets of measuring. The average dose of LMWH was 490 IU anti-Xa/ 24 hours (8.05 IU anti-Xa/kg/24 hours, respectively). The average value of anti-Xa was 0.21 IU/ml. The average value of activated PLT was 53.16%, within the 16–97% range. The increased activity of the coagulation system as well as the endothelium (the level of vWF reached 482% on average, within the 185–825% range) correlated (P = 0.001) with the intensity of systemic inflammation (CRP, leucocytes), especially in patients with SOFA score ≥ 5.

Conclusion

Monitoring vWF levels and the number of activated platelets indicates a prothrombotic potential of the hemocoagulation system in critically ill patients. The established methods of administering LMWH quite probably do not correspond with the prothrombotic activation of the coagulation system in these patients. As it turns out, it will be necessary to carry out much more research.