Diurnal Rhythm in Anticoagulant Effect of Heparin during a Low Dose Constant Rate Infusion

Abstract

SummaryThe objective of the study was to investigate possible diurnal rhythms in coagulation tests during a continuous intravenous infusion of unfractionated heparin. Six volunteers participated in the study, which was divided in a treatment (500 U heparin/h for 30 h) and a control experiment. Under basal conditions, no rhythm was found in coagulation tests. During heparin treatment, APTT, thrombin clotting time and anti-Xa activity showed a greater anticoagulant effect at night, with a striking decrease in the morning.In a search for the explanation of this phenomenon we looked for diurnal variations in the urinary excretion of heparin, in the plasma concentrations of antithrombin III and platelet factor 4, and in the effect of heparin added to the plasma samples in vitro. None of these studies provided the explanation.

Effect of Thrombolytic Therapy on Platelet Expression and Plasma Concentration of PECAM-1 (CD31) in Patients With Acute Myocardial Infarction

“…Another meaningful issue is an obvious concern for a possible diurnal variation of PECAM-1 in normal controls, which were described earlier for the fibrinolytic system 29 and platelet serotonin transport 30 but not for platelet aggregability 31 and membrane ␣ 2 -adrenoceptor expression 32 or eicosanoid urinary excretion. 33 Diurnal variations are important because there is clear clinical evidence of circadian patterns in myocardial ischemic episodes.…”

Antifactor Xa Levels versus Activated Partial Thromboplastin Time for Monitoring Unfractionated Heparin

“…3,12 Limitations Over time, it was realized that the performance of the aPTT is affected by preanalytic, analytic, and biologic variables (Table 1). 4,7,8,10,[13][14][15][16][17][18] Compared with antifactor Xa testing, the aPTT is impacted more frequently by preanalytic variables due to its greater fluctuations secondary to underfill of blood sample tubes and diurnal variation. 13-15, 17, 19 In terms of biologic variables, the aPTT is limited as a marker because there are clinical conditions in which the aPTT is elevated but does not correlate with bleeding or protection from thrombosis, as well as other clinical conditions that alter the aPTT response to heparin.…”

“…[28][29][30] The full effect of these preanalytic, analytic, and biologic variables was made apparent when it was determined that less than half of the variation in aPTT values in patients receiving heparin was explained by differences in heparin concentrations. 4,9,20,[31][32][33][34][35] Because these two parameters (aPTT and heparin concentration) were often not acting in concert, this lack of [13][14][15] ↑ ↔ Blood sampling in the morning (due to diurnal variation) [13][14][15] ↓ ↔ High concentration of citrate in collection tube (3.2% is standard) 4 ↓ ↓ Impaired renal function (decreased UFH elimination) 4 ↑ ↑ Liver disease (decreased clotting factor production) 8,10 ↑ ↔ Consumptive coagulopathy 8,10 ↑ ↔ Lupus anticoagulant 8,10 ↑ ↔ Deficiencies of specific clotting factors (preallikrein and factors IX, XI, and XII) 8,10 ↑ ↔ Elderly 4, 8, 10 ↑ ↔ Recent use of low-molecular-weight heparins or fondaparinux (particularly in setting of impaired renal function) 7…”

A Chronopharmacodynamic Study on Standard Heparin, a Low Molecular Weight Heparin (Nadroparin) and Danaproid: Establishing and Comparing the Daily Variations of These Drugs in Rats

“…This is in accordance with results on AXa [7], when the chromogenic method [15] is used, as we did. In contrast, daily variations of AXa and aPTT were observed [4][5][6]25] when AXa assays were based on a chronometric method [26]. Because the chronometric AXa measure represents a global coagulation time, we can suspect that both the hepatic lipoprotein lipase and the antithrombin III are participating to the AXa.…”