MERCURIC ION RECALCIFICATION TIME (RT) MONITORS ANTICOAGULANT EFFECT OF LOW MOLECULAR WEIGHT HEPARIN

SummaryBridging anticoagulation with low-molecular-weight heparin (LMWH) is common in patients who require temporary interruption of warfarin before surgery or a procedure, but whether such patients have a residual anticoagulant effect just before a procedure is not known. Consecutive patients who received bridging anticoagulation with LMWH had anti-Xa levels measured just before a procedure. The proportion of patients with a residual anticoagulant effect, defined as an anti-Xa level ≥0.10 IU/ml, was determined. Multivariable regression analysis identified predictors of a residual anticoagulant effect, expressed as an odds ratio (OR) and corresponding 95% confidence interval (CI). A pre-procedure residual anticoagulant effect was detected in 12 of 73 (16%) patients overall, in 11 of 37 (30%) patients who received therapeutic-dose LMWH, and in 1 of 36 patients (3%) who received low-dose LMWH. Receiving therapeutic- dose LMWH (OR = 118.8; 95% CI: 5.8, 999.9), and increasing age (OR = 4.0; 95% CI: 1.3, 12.5) were predictors of a residual pre-procedure anticoagulant effect. In patients who require bridging anticoagulation with LMWH, a residual anticoagulant effect from LMWH is detected in 1 of 6 patients, and receiving therapeutic-dose LMWH is the strongest predictor of such an effect.

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Relationship between ex vivo anti-proteinase (factor Xa and thrombin) assays and in vivo anticoagulant effect of very low molecular weight heparin, CY222

British Journal of Haematology ◽

10.1111/j.1365-2141.1988.00335.x ◽

2008 ◽

Vol 70 (3) ◽

pp. 335-340

Author(s):

C. J. Tew ◽

D. A. Lane ◽

E. Thompson ◽

H. Ireland ◽

J. R. Curtis

Keyword(s):

Molecular Weight ◽

Low Molecular Weight Heparin ◽

Ex Vivo ◽

Factor Xa ◽

Anticoagulant Effect ◽

Low Molecular Weight

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Suppression of Markers of Thrombin Generation and Inflammation in Patients Receiving Low Molecular Weight Heparin Compared to Unfractionated Heparin for TEE-Guided Cardioversion of Atrial Fibrillation.

Blood ◽

10.1182/blood.v110.11.3621.3621 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3621-3621

Author(s):

Debra Hoppensteadt ◽

Jawed Fareed ◽

Allan Klein ◽

Susan Jasper ◽

Carolyn Apperson-Hansen ◽

...

Keyword(s):

Atrial Fibrillation ◽

Molecular Weight ◽

Unfractionated Heparin ◽

Low Molecular Weight Heparin ◽

Thrombin Generation ◽

Anticoagulant Activity ◽

Anticoagulant Effect ◽

Low Molecular Weight ◽

Blood Samples ◽

Markers Of Inflammation

Abstract Introduction: Atrial fibrillation (AF) represents a cardiovascular syndrome which can lead to embolic stroke. Several AF clinical trials have shown a decrease risk of stroke with anticoagulation using warfarin. Currently, there are two approaches for anticoagulation in AF patients. For outpatients, warfarin is used with an INR goal 2.0–3.0. For inpatients requiring cardioversion, unfractionated heparin (UFH, IV) is used as a bridge to therapeutic warfarin. More recently, anticoagulation with a low molecular weight heparin, enoxaparin, has been reported to give a more predictable anticoagulant response than UFH in TEEguided cardioversion. The present study compares the markers of inflammation and thrombin generation in patients included in the ACUTE II study. Methods: This was a randomized multicenter trial of 155 patients from 17 clinical sites, the anticoagulant activity of LMWH (enoxaparin, 1 mg/kg sc bid, Sanofi-Aventis, n=76) was compared to that of UFH (APTT 1.5 – 2.5 x control, n=79). Blood samples were drawn at enrollment (baseline), day 2 (peri cardioversion) and day 4 in both groups. Day 2 and day 4 samples were taken 3–4 hours after the injection of LMWH in patients in the LMWH group. Blood samples were evaluated for inflammation: C-reactive protein (CRP), CD 40 ligand (CD 40L), monocyte chemotactic protein 1 (MCP-1) and anticoagulant effect: thrombin antithrombin complex (TAT) and prothrombin fragment (F 1.2). Results: The APTT and anti-Xa levels indicated therapeutic anticoagulation was achieved (previously reported). In addition, both TAT and F1.2 levels were increased at baseline and were significantly decreased with LMWH (p<0.01) in comparison to UFH. The CRP, CD40L, MCP-1 were decreased after treatment in both groups of patients. These results suggest that AF patients treated with LMWH demonstrate a stronger anticoagulant effect as measured by a significant reduction in the markers of thrombin generation. Furthermore, anticoagulation with either UFH of LMWH results in a decrease in inflammation which was not different between groups. Conclusion: In the ACUTE II trial, anticoagulation with LMWH in AF patients may be a better alternate than UFH during TEE-guided cardioversion due to a a stronger anticoagulant.

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Anticoagulant Effects of the Low-Molecular-Weight Heparin Certoparin in Combination with Phenprocoumon in Patients with Recent Atrial Fibrillation Undergoing Cardioversion

Blood ◽

10.1182/blood.v112.11.4057.4057 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4057-4057

Author(s):

Job Harenberg ◽

Jolanta Wierdack ◽

Christel Weiss ◽

Christina Giese ◽

Claudia Abletshauser ◽

...

Keyword(s):

Atrial Fibrillation ◽

Molecular Weight ◽

Low Molecular Weight Heparin ◽

Electrical Cardioversion ◽

Anticoagulant Effect ◽

Low Molecular Weight ◽

Clinical Effects ◽

Recent Onset ◽

D Dimer

Abstract Patients with recent onset of atrial fibrillation (AF) receive anticoagulation with low-molecular-weight heparin (LMWH) and coumarin targeted at an INR of 2 to 3. Recently, LMWH is given alone before cardioversion followed by coumarin. At present, no method is available to determine the combined effect of LMWH and coumarin in order to get information on the in vivo anticoagulant status of these patients. Patients with recent onset of AF (n=200) received 8.000 IU LMWH certoparin bid upon entry into the study. Phenprocoumon was started after electrical cardioversion. LMWH was stopped after 2 days within therapeutic INR range of phenprocoumon. The clincial data have been published (Clin Res Cardiol 2008). Blood samples were drawn from patients before LMWH administration (visit 1, V1), before start of phenprocoumon (V4) and after reaching the desired INR range and before stopping LMWH (V5) to determine a set of anticoagulant parameters. The study was accepted by the local ethics committees and patients gave written informed consent. Activated partial thromboplastin time, chromogenic factor Xa assay, heptest time values, prothrombinase-induced clotting time and tissue factor pathway inhibitor demonstrated the anticoagulant effect of certoparin at V4 and V5. Results of these parameters differed between V1 and V4 as well as between V1 and V5 (all p<0.001) but not between V4 and V5. Prothrombin time was prolonged at V5 versus V1 and V4 (both p<0.001). D-Dimer and prothrombinfragment F1+2 significantly decreased from V1 to V4 and from V4 to V5 (all p<0.001). Endogenous thrombin potential assay (ETP) was inhibited stronger at V4 compared to V1, and at V5 compared to V4 (both p<0.001). D-Dimer, F1+2 and ETP are the parameters reflecting the combined anticoagulant effect of certoparin and phenprocoumon while overlapping anticoagulation with these compounds in patients with recent AF for electrical cardioversion. The clinical effects on thromboembolic or bleeding incidences remain to be determined.

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Low molecular weight heparin: A closer look at its anticoagulant effect

Journal of Laboratory and Clinical Medicine ◽

10.1016/j.lab.2004.07.003 ◽

2004 ◽

Vol 144 (2) ◽

pp. 56-57

Keyword(s):

Molecular Weight ◽

Low Molecular Weight Heparin ◽

Anticoagulant Effect ◽

Low Molecular Weight

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Anticoagulant Effect at the Time of Epidural Catheter Removal in Patients Receiving Twice-daily or Once-daily Low-molecular-weight Heparin and Continuous Epidural Analgesia after Orthopedic Surgery

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613150 ◽

2002 ◽

Vol 88 (07) ◽

pp. 37-40 ◽

Cited By ~ 21

Author(s):

Krystyna Kinnon ◽

Mark Crowther ◽

James Douketis

Keyword(s):

Molecular Weight ◽

Epidural Analgesia ◽

Epidural Catheter ◽

Orthopedic Surgery ◽

Low Molecular Weight Heparin ◽

Anticoagulant Effect ◽

Catheter Removal ◽

Low Molecular Weight ◽

Once Daily ◽

Continuous Epidural Analgesia

SummaryIn patients who receive co-administered low-molecular-weight heparin (LMWH) and continuous epidural analgesia (CEA) after orthopedic surgery, there is concern about an increased risk of a spinal epidural hematoma. The practice of twice-daily LMWH dosing in North America might, in part, account for the greater number of epidural hematomas reports compared to Europe where once-daily LMWH is used. We performed a prospective cohort study in patients who had orthopedic surgery and received co-administered LMWH and CEA. We investigated the trough anticoagulant effect, as measured by an anti-Xa heparin level, at the time of epidural catheter removal in patients who received twice-daily or once-daily LMWH. Twenty-five patients who received enoxaparin, 30 mg twice-daily, and 25 patients who received dalteparin, 5,000 IU once-daily, had anti-Xa heparin levels measured on the second or third post-operative day at the time of epidural catheter removal. In patients who received twice-daily enoxaparin, or once-daily dalteparin, the anti-Xa heparin level was measured, on average, 10.4 h and 21.8 h, respectively, after the preceding LWMH dose. All 25 patients who received once-daily LMWH had an anti-Xa heparin level <0.10 U/ml at the time of catheter removal. Of 25 patients who received twice-daily LMWH, the anti-Xa heparin level at the time of catheter removal was >0.20 U/ml in 5 patients (P = 0.050), and >0.10 U/ml in 7 patients (P = 0.009). We conclude that in patients who are receiving co-administered LMWH and CEA after orthopedic surgery, twice-daily but not once-daily LMWH administration is more likely to be associated with a clinically important anticoagulant effect at the time of epidural catheter removal.

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