Prevention of Venous Thrombosis in Cancer Patients: A randomized, Double-Blind Study Comparing Two Different Dosages of Low-Molecular Weight Heparin.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1977-1977 ◽  
Author(s):  
Sabine Eichinger ◽  
Ludwig Traby ◽  
Alexandra Kaider ◽  
Peter Quehenberger ◽  
Paul Alexander Kyrle
Keyword(s):  
Molecular Weight ◽  
Venous Thrombosis ◽  
Cancer Patients ◽  
Low Molecular Weight Heparin ◽  
Thrombin Generation ◽  
Low Molecular Weight ◽  
Coagulation Activation ◽  
Double Blind ◽  
Once Daily ◽  
D Dimer

Abstract Background: Cancer patients are at increased risk of venous thrombosis (VT). In surgical cancer patients a dose of about 5000 anti factor Xa (aXa) units of low molecular weight heparin (LMWH) prevents VT at acceptable safety with regard to bleeding. We hypothesize that non-surgical cancer patients at risk of VT could benefit from a higher LMWH dose. Methods: We conducted a randomized, double-blind trial in 49 hospitalised non-surgical cancer patients with risk factors of VT. Patients received either enoxaparin 40 mg or 80 mg once daily subcutaneously. Outcome variables were markers of coagulation activation (D-Dimer), thrombin generation (peak thrombin level) and aXa levels determined in venous blood before enoxaparin on day 1 to 4 and 2, 4, and 6 hours after enoxaparin on day 1. D-Dimer was determined by enzyme immunoassay (Asserachrom® D-Di, Roche, Germany), and thrombin generation by use of a commercially available fluorogenic assay (Technothrombin TGA, Vienna, Austria). Results: 22 patients were randomized to enoxaparin 40 mg and 27 to 80 mg. On day 1, D-dimer levels [median (range)] before administration of enoxaparin (=baseline) were elevated in both groups [40 mg: 957.0 ng/ml (254.1–4419.6); 80 mg: 1054.9 ng/ml (197.0–14761.0)]. D-Dimer levels only slightly decreased 6 hours after enoxaparin in both groups (p=0.001). D-Dimer baseline levels in the 80 mg group were significantly lower on day 4 [1785.6 ng/ml (128.4–13742.5)] than on day 1 (p=0.01), while in the 40 mg group no difference was seen. In patients receiving enoxaparin 40 mg, peak thrombin levels (mean±SD) at baseline were 434.8±29.7 nM and significantly decreased over time. Trough levels (171.8±30.9 nM) were reached after 4 hours. The decrease of peak thrombin levels was significantly more pronounced in the enoxaparin 80 mg group. Compared with baseline (407.8±18.9 nM), peak thrombin levels were 138.7±19.6, 86.6±19.9 and 82.8±19.9 nM after 2, 4 and 6 hours, respectively. Compared with baseline on day 1, peak thrombin levels in the 80 mg group were significantly lower on day 4 (317.5±28.3 nM; p=0.005), while no significant difference was seen in patients receiving 40 mg (p=0.5). aXa levels significantly increased with maximum levels at 4 hours in patients receiving enoxaparin 40 mg and at 6 hours in the 80 mg group. In none of the patients receiving enoxaparin 40 mg and in 3 of those receiving 80 mg, peak aXa levels exceeded 1.0 IU/ml. None of the patients had thrombotic or bleeding complications. Conclusion: Non-surgical cancer patients exhibit a state of hypercoagulability. Compared with enoxaparin 40 mg, the extent of coagulation activation and thrombin generation can be significantly reduced by doubling the dose. These findings support the hypothesis that thromboprophylaxis with a standard dose of enoxaparin 40 mg once daily might be too low to provide optimal protection from VT in non-surgical cancer patients at high thrombotic risk. Interventional studies are needed to investigate safety and efficacy of a more intense thromboprophylactic regimen in these patients.

The effects of low-molecular-weight heparin at two different dosages on thrombin generation in cancer patients.

2010 ◽  
Vol 104 (07) ◽  
pp. 92-99 ◽  
Author(s):  
Ludwig Traby ◽  
Alexandra Kaider ◽  
Rainer Schmid ◽  
Alexander Kranz ◽  
Peter Quehenberger ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Cancer Patients ◽  
Low Molecular Weight Heparin ◽  
Thrombin Generation ◽  
Low Molecular Weight ◽  
Prothrombotic State ◽  
Coagulation Activation ◽  
Thrombotic Risk ◽  
Baseline Levels ◽  
D Dimer

SummaryNon-surgical cancer patients are at high thrombotic risk. We hypothesised that the prothrombotic state is reflected by elevated thrombin generation and can be mitigated by increasing the low-molecularweight heparin (LMWH) dose. Non-surgical cancer patients were randomised to enoxaparin 40 or 80 mg. D-dimer, prothrombin fragment F1+2 (F1+2) and peak thrombin (PT) were measured 2, 4, 6 hours (h) after LMWH (day 1) and daily for 4 days. A total of 22 and 27 patients received enoxaparin 40 and 80 mg, respectively. D-dimer and F1+2 moderately decreased after 6 h in both groups. After enoxaparin 80 mg, D-dimer baseline levels [median (quartiles)] decreased from day 1 to 4 [1054.9 (549.5, 2714.0) vs. 613.0 (441.1, 1793.5) ng/ml] (p<0.0001), while no difference was seen after 40 mg. Baseline PT levels [median (quartiles)] were 426.2 nM (347.3, 542.3) (40 mg) and 394.0 nM (357.1, 448.8) (80 mg). After 80 mg, PT significantly decreased to 112.4 nM (68.5, 202.4), 57.1 nM (38.0, 101.2) and 43.6 nM (23.4, 112.8) after 2, 4 and 6 h, which was lower than after 40 mg (p=0.003). After 80 mg, PT decreased from day 1 to 4 [358.6 nM (194.2, 436.6); p=0.06] while no difference was seen after 40 mg. In conclusion, in cancer patients coagulation activation and thrombin generation is substantially increased. Peak thrombin levels are sensitive to the anticoagulant effects of LMWH at different dosages. The prothrombotic state is substantially attenuated by higher LMWH doses.

scholarly journals Low Molecular Weight Heparin Modulates Thrombin Generation in Cancer Patients Undergoing Antithrombotic Therapy for Overt Venous Thromboembolism

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1539-1539
Author(s):  
Anna Falanga ◽  
Carmen J Tartari ◽  
Marina R Marchetti ◽  
Laura Russo ◽  
Kim WFM Lambregts ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
High Risk ◽  
Cancer Patients ◽  
Low Molecular Weight Heparin ◽  
Thrombin Generation ◽  
Procoagulant Activity ◽  
Low Molecular Weight ◽  
Cancer Associated Thrombosis ◽  
D Dimer

Abstract Introduction The incidence and recurrence rate of venous thromboembolism (VTE) are increased in the cancer compared to the non-cancer population. Low molecular weight heparin (LMWH) is recommended for both initial and long-term anticoagulant therapy for cancer-associated thrombosis, being more effective and safer than vitamin K antagonist therapy. However, failure of anticoagulation with LMWH in cancer-associated thrombosis still remains significantly elevated (VTE recurrence = 9-15%). In this study we tested whether thrombin generation (TG), a global hemostatic assay, may represent a modality to evaluate the LMWH anticoagulant level in vivo and help identifying patients at high risk for VTE recurrences. In a prospective cohort of cancer patients with VTE receiving LMWH nadroparin 200 U.I./Kg once a day, we evaluated whether LMWH treatment modulated the plasma TG capacity, together with other hemostatic parameters, i.e. microparticle (MP)-associated procoagulant activity (PCA) and D-dimer levels. Second we wished to explore whether these parameters may predict for VTE recurrence and/or bleeding. Methods Fifty eight consecutive cancer patients with acute VTE were enrolled into the study. Plasma samples were obtained at the following time intervals: at the thrombotic event (T0), at 1 month LMWH therapy (T1), and at discontinuation (T2), i.e. 6 months after VTE. Patients were followed up clinically for a total 9 months to detect overt thrombotic or bleeding events. TG was measured by the CAT assay, MP-associated procoagulant activity (PCA) by the STA Procoag PPL assay, and D-dimer by HemosIL D-dimer test. Results In this study cohort, the most represented malignancies were colon (25.9%), breast (15.5%), lung (15.5%), and gastric cancer (13.8%). Thirty six patients had metastatic disease, 22 had a limited disease. The VTE sites were: subclavian (36.2%), femoro-popliteal (20.7%), pulmonary (13.8%), jugular (8.6%), and brachial (6.9%) veins. Six patients had simultaneous femoro-popliteal venous thrombosis and pulmonary embolism. At T0 patients were characterized by a procoagulant phenotype as reflected by increased TG potential, and elevated MP-associated PCA and D-dimer compared to controls. In particular, cancer patients displayed a higher levels (p<0.01) of endogenous thrombin potential (ETP) and peak of thrombin vs controls (ETP: 1612±538 vs 1210±344 nMol*min and peak: 305±123 vs 182±84 mMol). These data were accompanied by a significant increase in MP-associated PCA (i.e. shorter clotting time 58±18 vs controls 89±12 sec; p<0.01), and D-dimer plasma levels (1430±1615 vs controls 90±96 ng/ml; p<0.01). During LMWH nadroparin therapy, a significant reduction in both TG potential (ETP-T1: 1254±810 nMol*min) and D-dimer levels (397±697 ng/ml) occurred, and after LMWH discontinuation (T2), TG potential as well as D-Dimer levels rose back, becoming similar to the control values. Differently, no reduction in MP-associated PCA was observed during LMWH therapy. Twenty-seven patients (46.6%) died during follow-up because of cancer disease. No patients had VTE recurrence. The analysis according to the stage of disease showed a significant difference with a higher mortality rate among those with a metastatic stage (p < 0.01). No correlations were observed according to chemotherapy. Conclusion Our results show that LMWH therapy modulates the global thrombin generation capacity and affects the hypercoagulable state of cancer patients, whereas MP-PCA is insensitive to it. In this cohort LMWH treatment was effective (0% VTE recurrences) and safe (1 major bleeding episode). As no recurrences were observed, it was not possible to identify a predictive value for the biological parameters. It is worth to define in a large trial the clinical utility of the TG global coagulation assay to monitor LMWH anticoagulation levels in this high risk population. Disclosures No relevant conflicts of interest to declare.

A RANDOMIZED, DOUBLE BLIND STUDY OF A LOW MOLECULAR WEIGHT HEPARIN (KABI 2165) ONCE DAILY AND LOW DOSE STANDARD HEPARIN TWICE DAILY, IN THE PREVENTION OF POST OPERATIVE DEEP VEIN THROMBOSIS IN GENERAL SURGERY. A French Multicenter Trial

1987 ◽  
Keyword(s):  
Molecular Weight ◽  
Deep Vein Thrombosis ◽  
Low Molecular Weight Heparin ◽  
Low Dose ◽  
Multicenter Trial ◽  
Low Molecular Weight ◽  
Double Blind ◽  
Once Daily ◽  
Vein Thrombosis ◽  
Deep Vein

The efficacy and safety of a low molecular weight heparin (Kabi 2165) in preventing postoperative deep vein thrombosis (D.V.T.), was assessed in a double blind randomly allocated multicenter trial. 385 patients were included and analysed on a intention to treat basis. Kabi 2165 was given S.C. 24 hourly in 2 500 anti-factor Xa units and compared with standard low dose calcium heparin 5 000 i.u. S.C. 12 hourly in patients undergoing major abdominal or gynaecological surgery. The first dose was administered two hours before operation in both groups. The relevant characteristics of the patients in the two treatment groups were similar. The two groups were well matched for risk factors which could predispose to D.V.T.DVT was detected by the radioactive fibrinogen test. Venography was performed whenever a positive scan developed in a patient. Six (3,1 96) of 195 patients receiving Kabi 2165 and seven (3,7 96) of 190 patients in the standard heparin group developed D.V.T. No pulmonary embolism we re detected during the prophylactic regimens. There was no significant difference between the two groups in terms of blood loss during surgery, postoperative drainage, blood transfusion, wound haematoma. Mean hemoglobin levels and mean hematocrit values preoperatively and postoperatively (day 1 and 6) were :There were no statistically significant differences in both groups. No thrombocytopenia was reported in this study. The antifactor Xa activity was significantly higher in the Kabi 2165 group.In conclusion, Kabi 2165 once daily is as effective and safe as standard heparin twice daily in preventing postoperative D.V.T. in general surgery.

Prospective evaluation of coagulation activation in pregnant women receiving low-molecular weight heparin

2004 ◽  
Vol 91 (05) ◽  
pp. 935-940 ◽  
Author(s):  
Matthias Hoke ◽  
Paul Kyrle ◽  
Karl Philipp ◽  
Ingrid Pabinger ◽  
Alexandra Kaider ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Pregnant Women ◽  
Low Molecular Weight Heparin ◽  
Activated Protein C ◽  
Normal Pregnancy ◽  
Coagulation System ◽  
Control Group ◽  
Low Molecular Weight ◽  
Coagulation Activation ◽  
D Dimer

SummaryPregnancy is a major risk factor for venous thromboembolism (VTE), and low-molecular weight heparin (LMWH) seems to be safe and effective in pregnant women. Normal pregnancy is accompanied by a state of hypercoagulability, indicated by an increase in markers of coagulation activation. In a prospective cohort study, we followed 61 women who received LMWH thromboprophylaxis throughout pregnancy because of a history of VTE, hereditary thrombophilia and/or previous pregnancyrelated complications. The control group consisted of 113 healthy pregnant women without antithrombotics. D-Dimer, prothrombin fragment F1+2 (F1+2) and the resistance to activated protein C (APC-ratio) were measured in all women during the first, second and third trimester. Patients and controls did not significantly differ with regard to baseline characteristics and pregnancy outcome. A (recurrent)VTE was seen in one patient despite LMWH. D-Dimer levels significantly increased among patients and controls during pregnancy (p <0.0001), and were significantly higher among patients compared with the controls (p <0.0001) [395 ng/ml (95% CI 340-458) and 249 ng/ml (95%CI 234-266); 710 ng/ml (95% CI 602-838) and 475 ng/ml (95% CI 431-523); 1089 ng/ml (95% CI 931-1273) and 822 ng/ml (95% CI 741-911); respectively]. Levels of F1+2 significantly increased while the APC-ratio significantly decreased during pregnancy among patients and controls. Despite LMWH, pregnancy is accompanied by a substantial activation of the coagulation system.

Sign in / Sign up

Export Citation Format

Share Document