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.

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.

Effects of a Low Molecular Weight Heparin (Fragmin®) and of Unfractionated Heparin on Coagulation Activation at the Site of Plug Formation In Vivo

1994 ◽  
Vol 72 (06) ◽  
pp. 831-835 ◽  
Author(s):  
Sabine Elchinger ◽  
Michael Wolzt ◽  
Malgorzata Nieszpaur-Los ◽  
Barbara Schneider ◽  
Klaus Lechner ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Bleeding Time ◽  
Venous Blood ◽  
Coagulation System ◽  
Low Molecular Weight ◽  
Coagulation Activation

SummaryThe clinical benefits of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) have been shown in many trials. However, the mode of action of heparin has not been fully elucidated. Thus, we wanted to study the effects of UFH and LMWH in vivo by measuring coagulation activation markers in blood obtained directly from a vascular injury site. In a double-blind, randomized, 3-way, cross-over study 18 healthy volunteers were given UFH (150 U/kg s.c.) and 2 doses of LMWH [35 U/kg s.c. (low dose, Id), 75 U/kg s.c. (high dose, hd)]. Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT) and fibrinopeptide A (FPA) were measured in bleeding time blood and in venous blood before and after drug application. In addition, the effects of UFH and LMWH on in vitro coagulation tests were studied. Compared to base line, UFH and both IdLMWH and hdLMWH caused significant reductions of F1+2, TAT and FPA in bleeding time blood at 2 h. A marked effect of UFH and of hdLMWH was also seen at 5 h. The inhibition of FPA generation was more pronounced after hdLMWH compared to IdLMWH. In venous blood, UFH and LMWH caused reductions of F1+2, but not of TAT and FPA. In vitro, UFH predominantly affected the anti-IIa assays (activated partial thromboplastin time, thrombin time) and LMWH mainly the anti-Xa test system. Using a technique that investigates the activated coagulation system in vivo, a time- and dose dependent inhibitory effect of heparin on coagulation activation was detectable. Therefore, in our experimental setting a preferential inhibition of a particular portion of the coagulation system by one of the two heparin preparations was not detectable.

scholarly journals Changes in Coagulation and Fibrinolysis in Post-Cesarean Section Parturients Treated With Low Molecular Weight Heparin

2020 ◽  
Vol 26 ◽  
pp. 107602962097880
Author(s):  
Ziwei Liu ◽  
Chixiang Liu ◽  
Mei Zhong ◽  
Fang Yang ◽  
Hongtian Chen ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Cesarean Section ◽  
Pregnant Women ◽  
Vaginal Delivery ◽  
Low Molecular Weight Heparin ◽  
Dynamic Equilibrium ◽  
Low Molecular Weight ◽  
Spontaneous Vaginal Delivery ◽  
D Dimer ◽  
Coagulation And Fibrinolysis

Background: Cesarean section is an independent risk factor for Venous thromboembolism (VTE). Low molecular weight heparin (LMWH) is extensively used for VTE prophylaxis after cesarean section. In this study, the effects of LMWH on coagulation and fibrinolysis after cesarean section and its clinical value were explored by studying the changes in laboratory indicators. Methods: Antepartum and postpartum peripheral blood of 44 pregnant women who underwent vaginal delivery and 44 pregnant women who underwent cesarean section treated per routine with LMWH thromboprophylaxis on the first day post-operatively were collected for the following tests: D-dimer; thrombotic markers such as thrombomodulin (TM), thrombin-antithrombin complex (TAT), α2-plasmin inhibitor-plasmin complex (PIC), and tissue plasminogen activator inhibitor complex (t-PAIC); thromboelastography. Results: Compared to the antepartum levels, PIC increased, TM, TAT, and t-PAIC decreased significantly in the parturients after a spontaneous vaginal delivery. Compared to the antepartum levels, parturients routinely treated with LMWH after cesarean section had higher PIC levels and lower D-dimer, TAT, and t-PAIC levels. Compared with parturients after vaginal delivery, parturients treated with LMWH after cesarean section had higher levels of TM, R, and MA, while there was no significant differences in the levels of D-dimer, TAT, PIC, t-PAIC, K, angle, LY30, and CI. Conclusion: The coagulation and fibrinolytic systems in gravidas and parturients are in a high level of dynamic equilibrium. The levels of coagulation and fibrinolytic system activation were similar in parturients who were routinely treated with LMWH after cesarean section compared with parturients after a spontaneous vaginal delivery.

Thrombogenesis in Thrombophilic Pregnancy: Evaluation of Low-Molecular-Weight Heparin Prophylaxis

2017 ◽  
Vol 137 (4) ◽  
pp. 201-206 ◽  
Author(s):  
Roberto Simeone ◽  
Roberta Giacomello ◽  
Germano Bruno ◽  
Sergio Parco ◽  
Natalia Maximova ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Pregnant Women ◽  
Low Molecular Weight Heparin ◽  
Factor V Leiden ◽  
Control Group ◽  
Low Molecular Weight ◽  
Factor V ◽  
Protein C Deficiency ◽  
Factor V Leiden Mutation ◽  
Heparin Prophylaxis

The aim of this study is to investigate thrombogenesis and the hypercoagulable changes in pregnant women affected by thrombophilia who received low-molecular-weight heparin (LWMH) prophylaxis. We included 21 pregnant women affected by thrombophilia treated with LWMH and 20 nontreated normal pregnant women as the control group. The sample group of thrombophilic pregnant women included different conditions (factor V Leiden mutation, protein C deficiency, protein S deficiency, antiphospholipid antibodies syndrome, and combined defects). Three blood samples were collected during pregnancy (i.e., at 16, 20, and 24 weeks) and tested for activated partial thromboplastin time and prothrombin fragment F1 + 2 (F1 + 2); anti-FXa activity was tested only in treated thrombophilic pregnant women. F1 + 2 levels progressively increased during pregnancy in both study groups. However, the F1 + 2 increase in women exposed to heparin prophylaxis was significantly lower than that in normal pregnant women in all 3 measurements carried out during gestation (p < 0.05); a statistically significant inverse correlation between F1 + 2 levels and anti-Xa activity (R = -0.8575, p < 0.05) was observed in treated women during pregnancy. Our findings suggest that F1 + 2 in addition to anti-Xa measurement could be used to adjust LWMH prophylaxis, at least in high-risk pregnant women.

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.

Systemic Thrombin Generation and Activity Resistant to Low Molecular Weight Heparin Administered Prior to Streptokinase in Patients with Acute Myocardial Infarction

1997 ◽  
Vol 77 (01) ◽  
pp. 057-061 ◽  
Author(s):  
Dennis W T Nilsen ◽  
Lasse Gøransson ◽  
Alf-Inge Larsen ◽  
Øyvind Hetland ◽  
Peter Kierulf
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Molecular Weight ◽  
Body Weight ◽  
Low Molecular Weight Heparin ◽  
Troponin T ◽  
Bleeding Complications ◽  
Control Group ◽  
Low Molecular Weight ◽  
Creatine Kinase Mb

SummaryOne hundred patients were included in a randomized open trial to assess the systemic factor Xa (FXa) and thrombin inhibitory effect as well as the safety profile of low molecular weight heparin (LMWH) given subcutaneously in conjunction with streptokinase (SK) in patients with acute myocardial infarction (MI). The treatment was initiated prior to SK, followed by repeated injections every 12 h for 7 days, using a dose of 150 anti-Xa units per kg body weight. The control group received unfractionated heparin (UFH) 12,500 IU subcutaneously every 12 h for 7 days, initiated 4 h after start of SK infusion. All patients received acetylsalicylic acid (ASA) initiated prior to SK.Serial blood samples were collected prior to and during the first 24 h after initiation of SK infusion for determination of prothrombin fragment 1+2 (Fl+2), thrombin-antithrombin III (TAT) complexes, fibrinopeptide A (FPA) and cardiac enzymes. Bleeding complications and adverse events were carefully accounted for.Infarct characteristics, as judged by creatine kinase MB isoenzyme (CK-MB) and cardiac troponin T (cTnT), were similar in both groups of patients.A comparable transient increase in Fl+2, TAT and FPA was noted irrespective of heparin regimen. Increased anti-Xa activity in patients given LMWH prior to thrombolytic treatment had no impact on indices of systemic thrombin activation.The incidence of major bleedings was significantly higher in patients receiving LMWH as compared to patients receiving UFH. However, the occurrence of bleedings was modified after reduction of the initial LMWH dose to 100 anti-Xa units per kg body weight.In conclusion, systemic FXa- and thrombin activity following SK-infusion in patients with acute MI was uninfluenced by conjunctive LMWH treatment.

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

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.

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