Thrombin generation assays for optimizing low molecular weight heparin dosing in pregnant women at risk of thrombosis - response to Ismailet al

2015 ◽  
Vol 172 (4) ◽  
pp. 643-644 ◽  
Author(s):  
Pratima Chowdary ◽  
Anne Riddell ◽  
Collen Hamid ◽  
Alex Gatt
Keyword(s):  
At Risk ◽  
Molecular Weight ◽  
Pregnant Women ◽  
Low Molecular Weight Heparin ◽  
Thrombin Generation ◽  
Low Molecular Weight

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.

Thrombin Generation and Low Molecular Weight Heparin Prophylaxis In Pregnant Women With Thrombophilia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1140-1140
Author(s):  
Anna Selmeczi ◽  
Rachel E. J. Roach ◽  
Csaba More ◽  
Zoltan Batta ◽  
Gyorgy Pfliegler ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Pregnant Women ◽  
Low Molecular Weight Heparin ◽  
Thrombin Generation ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Inherited Thrombophilia ◽  
Endogenous Thrombin Potential ◽  
Before And After ◽  
The Difference

Abstract Introduction Pregnancy is associated with an increased risk of venous thromboembolism (VTE) which is even more pronounced in the presence of inherited thrombophilia. Despite the well-established relation between thrombophilic pregnancies and VTE, there is no consensus on the optimal approach for thromboprophylaxis in this population. There is growing evidence that thrombin generation correlates with the overall procoagulant state of the plasma leading to elevated thrombosis risk. The aim of this study was to evaluate thrombin generation over the course of pregnancy in women with inherited thrombophilia compared to healthy pregnant women. We also aimed to investigate the effectiveness of low molecular weight heparin (LMWH) prophylaxis in pregnancy by measuring thrombin generation and anti-Factor-Xa activity. Methods In this cohort study women with severe (n=8) and mild (n=47) thrombophilia were followed throughout their pregnancies. In addition, healthy pregnant women (n=15) were recruited as control subjects. Thrombin generation was evaluated in each trimester as well as 5 days after delivery and 8 weeks postpartum (baseline). In order to assess the effect of LMWH therapy at each stage of the pregnancy, thrombin generation and anti-Factor-Xa activity were measured just before and 4 hours after administration of the drug (peak and trough effect). Thrombin generation was determined using Technothrombin TGA assay system, and the results were evaluated with the provided software. For analysis, the median peak thrombin and endogenous thrombin potential were determined. The anti-Factor-Xa activity was measured by a commercially available chromogenic assay. Results In all the 3 study groups, both peak thrombin and endogenous thrombin potential were increased over the course of pregnancy compared to the non-pregnant state. Peak thrombin and endogenous thrombin potential were higher in the severe thrombophilia group than in the other 2 groups in every trimester and also after delivery. There was no distinct difference in thrombin generation between the mild group and the controls. In women undergoing LMWH prophylaxis a decrease was observed in both the peak thrombin and endogenous thrombin potential after the drug was administered. Over the course of pregnancy the extent of this decrease reduced in a stepwise fashion. The difference between the 2 measurements (before and after LMWH) was smallest in the third trimester and increased again after delivery. Anti-Factor-Xa activity appeared to be enhanced at the peak effect of LMWH. However, the difference between the anti-Factor-Xa activity before and after LMWH administration remained unchanged over the progression of pregnancy. None of the women suffered from VTE or had any bleeding complications during the observation period. Conclusions Our results show that thrombin generation is increased during pregnancy, with higher levels in women with severe thrombophilic defects. In addition, our data demonstrate a decrease in the effect of LMWH with advancing stages of pregnancy. Until now no studies evaluated prospectively the effect of LMWH prophylaxis on thrombin generation over pregnancy. Our findings contribute to the ongoing debate about the necessity and intensity of thromboprophylaxis during pregnancy, providing new information about the coagulable state of mild and severe thrombophilic pregnant women. The decreasing antithrombotic effect of LMWH over pregnancy suggests a need for dose adjustment in late gestational weeks. Furthermore, our results imply that thrombin generation as a global coagulation test may demonstrate more sensitively the effect of LMWH than the anti-Factor-Xa activity assay. Disclosures: No relevant conflicts of interest to declare.

Thrombocytopenia in pregnant women with thrombophilia treated with low-molecular-weight heparin

2019 ◽  
Vol 1 (67) ◽  
pp. 30
Author(s):  
Melinda-Ildiko Mitranovici ◽  
Smaranda Ilea ◽  
Mihai Morariu ◽  
Daniel Mureşan ◽  
Izabella Petre
Keyword(s):  
Molecular Weight ◽  
Pregnant Women ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight

Anti-factor Xa Plasma Levels in Pregnant Women Receiving Low Molecular Weight Heparin Thromboprophylaxis

2008 ◽  
Vol 112 (4) ◽  
pp. 884-889 ◽  
Author(s):  
Nathan S. Fox ◽  
S Katherine Laughon ◽  
Samuel D. Bender ◽  
Daniel H. Saltzman ◽  
Andrei Rebarber
Keyword(s):  
Molecular Weight ◽  
Pregnant Women ◽  
Plasma Levels ◽  
Low Molecular Weight Heparin ◽  
Factor Xa ◽  
Low Molecular Weight

The Relationship between Use of Low Molecular Weight Heparin during Pregnancy and Risk of Peripartum Adverse Events: A Meta-Analysis

2021 ◽  
Vol 8 (11) ◽  
Author(s):  
Xiaorong Y ◽  
◽  
Shan L ◽  
Shengji S ◽  
Tao S ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Adverse Events ◽  
Pregnant Women ◽  
Low Molecular Weight Heparin ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Premature Delivery ◽  
Low Molecular Weight ◽  
Significant Difference ◽  
Fetal Complications

Introduction: To summarize the trials investigated on relationship between low molecular weight heparin use during pregnancy and peripartum adverse events. Meta-analysis was performed to evaluate the effect of Low Molecular Weight Heparin (LMWH) on maternal and fetal complications. Methods: Electronic research was performed in Cochrane Library, MEDLINE and EMBASE through October 2020. The primary outcome was the incidence of maternal and fetal complications during peripartum period. RevMan 5.3 was used for data analysis. Results: 11 articles were finally included. Meta-analysis showed there was no significant difference in abortion, premature delivery, stillbirth, preeclampsia and postpartum hemorrhage events between pregnant women who used LMWH and those who not. Conclusion: Using LMWH in pregnant women does not increase pregnancy related maternal and fetal complications.

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.

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.

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