scholarly journals Thrombin generation assay identifies individual variability in responses to low molecular weight heparin in pregnancy: implications for anticoagulant monitoring

2014 ◽  
Vol 168 (5) ◽  
pp. 719-727 ◽  
Author(s):  
Pratima Chowdary ◽  
Despoina Adamidou ◽  
Anne Riddell ◽  
Saman Aghighi ◽  
Anja Griffioen ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Thrombin Generation ◽  
Individual Variability ◽  
Low Molecular Weight ◽  
Thrombin Generation Assay ◽  
In Pregnancy

Differential inhibition of thrombin generation by vitamin K antagonists alone and associated with low-molecular-weight heparin

2009 ◽  
Vol 102 (07) ◽  
pp. 42-48 ◽  
Author(s):  
Grigoris T. Gerotziafas ◽  
Charlotte Dupont ◽  
Alex C. Spyropoulos ◽  
Mohamed Hatmi ◽  
Meyer M. Samama ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Vitamin K ◽  
Low Molecular Weight Heparin ◽  
Thrombin Generation ◽  
Vitamin K Antagonists ◽  
Low Molecular Weight ◽  
Plasma Samples ◽  
Thrombin Generation Assay ◽  
International Normalised Ratio ◽  
Inhibition Of Thrombin

SummaryVitamin K antagonists (VKA) treatment starts with co-administration of low-molecular-weight heparin (LMWH). The anticoagulation induced by the two drugs is still not well determined. In the present study we used thrombin generation assay to evaluate the hypo-coagulation induced by treatment with VKA and by the combination of VKA with LMWH. Tissue factor triggered thrombin generation in platelet-poor plasma was assessed in samples from 15 healthy volunteers, 97 samples from patients treated with VKA and 41 samples from patients receiving enoxaparin and VKA. Patients were classified according to international normalised ratio (INR) level (<2, 2–3 and >3).In plasma samples from patients treated with VKA having INR 2–3 the inhibition of thrombin generation reached 50% compared to controls. In samples with INR>3 this inhibition was 80%. In samples from patients receiving both LMWH and VKA, thrombin generation was significantly decreased compared to the controls and VKA group. In samples with an INR 2–3 obtained from patients treated with LMWH and VKA, the inhibition of thrombin generation was similar to that observed in samples with an INR>3 obtained from VKA treated patients. Thrombin generation assay is sensitive to detect the global the anticoagulant effect produced by the association of LMWH and VKA. For equal INR dual anticoagulant treatment induces significantly more profound inhibition of thrombin generation compared to treatment with VKA alone. The clinical relevance of this observation merits to be studied in prospective studies in patients with defined indications of anticoagulant therapy.

Thrombin generation and low-molecular-weight heparin prophylaxis in pregnant women with thrombophilia

2015 ◽  
Vol 113 (02) ◽  
pp. 283-289 ◽  
Author(s):  
Anna Selmeczi ◽  
Rachel E. J. Roach ◽  
Csaba Móré ◽  
Zoltán Batta ◽  
Jolán Hársfalvi ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Pregnant Women ◽  
Low Molecular Weight Heparin ◽  
Thrombin Generation ◽  
Factor Xa ◽  
Peak Effect ◽  
Low Molecular Weight ◽  
Endogenous Thrombin Potential ◽  
Increased Risk ◽  
Optimal Approach

SummaryPregnancy is associated with increased risk of venous thromboembolism, especially in the presence of thrombophilia. However, there is no consensus on the optimal approach for thromboprophylaxis in this population. Recent evidence suggests that thrombin generation correlates with the overall procoagulant state of the plasma. Our aim was to evaluate thrombin generation in a prospective cohort of thrombophilic pregnant women, and investigate the effectiveness of low-molecular- weight heparin (LMWH) prophylaxis in pregnancy. Women with severe (n=8), mild (n=47) and no (n=15) thrombophilia were followed throughout their pregnancies. Thrombin generation was evaluated in each trimester as well as five days and eight weeks postpartum (as a reference category). In women undergoing LMWH prophylaxis, thrombin generation and anti-Factor-Xa activity were measured just before and 4 hours after administration (peak effect). Thrombin generation was determined using Technothrombin TGA assay system. For the analysis, median peak thrombin and endogenous thrombin potential were used. Peak thrombin and endogenous thrombin potential were increased during pregnancy compared to the non-pregnant state with the highest results in the severe thrombophilia group. In women receiving LMWH prophylaxis a decrease was observed in thrombin generation at peak effect but over the progression of pregnancy the extent of this decrease reduced in a stepwise fashion. Our results show that thrombin generation demonstrates the hypercoagulable state in thrombophilic pregnancies. In addition, we found the effect of LMWH prophylaxis to progressively decrease with advancing stages of pregnancy.

Thrombosis and embolism in pregnancy

2020 ◽  
pp. 206-212
Author(s):  
Ian A. Greer
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Objective Assessment ◽  
Fold Increase ◽  
Low Molecular Weight ◽  
Thoracic Imaging ◽  
Mortality And Morbidity ◽  
First Choice ◽  
Daily Risk ◽  
In Pregnancy

Venous thromboembolism (VTE) is a leading cause of maternal mortality and morbidity. Prophylaxis and management of VTE in pregnancy can impact mortality and morbidity. The overall reported incidence of gestational VTE ranges from 0.5 to 2.2 per 1000 maternities with a relative 5–10-fold increase in risk during pregnancy, increasing to a daily risk of 15–35-fold in the puerperium, compared with non-pregnant women of similar age. Risk factors inform the use of thromboprophylaxis usually with low-molecular-weight heparin, which has a better safety profile than unfractionated heparin. VTE can occur at any time in pregnancy, but over 50% of events occur prior to 20 weeks’ gestation. As clinical diagnosis is unreliable, objective assessment is required when there is clinical suspicion of an event. Less than 10% of clinically suspected cases of VTE are confirmed on objective testing. Compression duplex ultrasonography is the first-line investigation for suspected gestational deep venous thrombosis and thoracic imaging with ventilation–perfusion scanning is required for suspected pulmonary embolism. Low-molecular-weight heparin is usually the first choice treatment for gestational VTE based on safety and efficacy.

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.

OC-10 Effect of low molecular weight heparin (LMWH) on thrombin generation in cirrhotic patients

2011 ◽  
Vol 43 ◽  
pp. S68
Author(s):  
K.I. Rodriguez ◽  
V. Rossetto ◽  
C. Radu ◽  
P. Dabrilli ◽  
S. Gavasso ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Thrombin Generation ◽  
Low Molecular Weight ◽  
Cirrhotic Patients
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