scholarly journals Puncture site bleeding complications in patients with Clopidogrel hyper-response

2020 ◽  
pp. 58-65
Author(s):  
Nedeljković Žarko ◽  
Vukasinović Ivan ◽  
Majstorović Branisalva ◽  
Milosević Medenica Svetlana ◽  
Milićević Mihailo ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Antiplatelet Therapy ◽  
Femoral Artery ◽  
Low Molecular Weight Heparin ◽  
Dual Antiplatelet Therapy ◽  
Platelet Reactivity ◽  
Thrombus Formation ◽  
Bleeding Complications ◽  
Low Molecular Weight ◽  
Increased Risk

Dual antiplatelet therapy (clopidogrel and acetylsalicylic acid) is a standard for the embolization of planned intracranial aneurysms with CNS stent due to the possibility of stent thrombus formation. All anti-aggregation drugs, including those listed, have bleeding as a side effect. Three patients with aneurysm had an elevated response to antiplatelet therapy with clopidogrel, which was confirmed by a multiplate test on the "VerifyNow" system. After reducing the dose of clopidogrel or after interrupting it, with the introduction of low molecular weight heparin for the duration of five days, aneurysms were successfully resolved by intracranial implantation of the stent. Perioperative angiograms and postoperative CT angiograms have verified hematomas at the place of punction of the femoral artery. Bleeding was resolved by the femoral artery suture by a vascular surgeon. All patients were discharged home without further complications and with dual antiplatelet therapy. By measuring the platelet function in vitro, the degree of inhibition of platelet activity achieved by the action of the drug can be assessed. A specific test can identify those patients who are highly responsive to the drug with increased platelet reactivity and the possibility of increased risk of bleeding. Our suggestion is to reduce the dosage of clopidogrel or to leave it out for 24 hours with preventive doses of low molecular weight heparin or to change the strategy of treatment of intracranial aneurysm, i.e. avoiding implantation of CNS stent.

Anti-Xa Potentiating Effect Of Low Molecular Weight Heparin

1981 ◽  
Author(s):  
W Junker ◽  
J Harenberg ◽  
F Fussi ◽  
K Mattes ◽  
R Zimmermann ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Intestinal Mucosa ◽  
Low Molecular Weight Heparin ◽  
Bleeding Complications ◽  
Low Molecular Weight ◽  
Chromogenic Substrate ◽  
Clotting Time ◽  
Blood Samples ◽  
Increased Risk

Recently special attention has been drawn to bleeding complications of commercial heparins in patients with increased risk for haemorrhages. Alternative heparin preparations with high antithrombotic and low haemostaseological properties have been developed. We now report on a new low molecular weight (LMW) heaprin (mean MW 5000, 85 USP/mg), which has been obtained by depolymerisation of a heparin from pig intestinal mucosa (mean MW 15000, 154 USP/mg).In vitro the anti-Xa-activity (chromogenic substrate S2222) was 15% higher for the LMW heparin in a range of 0.01-2.0 USP/ml plasma. No difference was seen on the anti-IIa-activity (thrombin clotting time)and the aPTT for both heparins in the same range. Both Heparins were injected s.c. in a dose of 100, 50 and 25 USP/kg bodyweight into each of six volunteers randomly at weekly intervalIs. The pharmacodynamic effects were controlled for 6-10 hrs by 8-12 blood samples in relation to the dose applied. Increasing dosis the effects of each heparin increased in all test systems. The anti- Xa-activity of LMW heparin was somewhat higher at 100 and 25 USP/kg. At 50 USP/kg the effect of LMW heaprin was in the same range as 100 USP/kg of the original preparation (MW 15000). The factor Ila activity and aPTT were not influenced differently by the two heparins at each dose.The data indicate, that the LMW heparin presented here may have a more pronounced antithrombotic property by a specific anti-Xa-activity than the compaired commercial heparin. This effect is most pronounced at doses, which have only small haemostaseological effects.

Thromboprophylaxis in medical patients: the role of low-molecular-weight heparin

2004 ◽  
Vol 92 (07) ◽  
pp. 3-12 ◽  
Author(s):  
Timothy Norris ◽  
Turpie Alexander
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Meta Analysis ◽  
Bleeding Complications ◽  
Low Molecular Weight ◽  
Medical Patients ◽  
Once Daily ◽  
Vte Prophylaxis ◽  
Increased Risk ◽  
Consensus Statements

SummaryMany hospitalised medical patients are at increased risk of venous thromboembolism (VTE). Consensus statements recommend that such patients be assessed for risk of VTE on admission to hospital and receive thromboprophylaxis where appropriate. However, VTE prophylaxis is not widely used in medical patients. One explanation is that assessing medical patients’ risk of VTE is complicated. The risk depends not only on the current illness but also on multiple intrinsic factors, and a variety of strategies for identifying patients who should receive thromboprophylaxis have been suggested. Thromboprophylaxis with unfractionated heparin (UFH) has proved to be effective in reducing the incidence of deep-vein thrombosis and overall mortality in medical patients. Clinical trial evidence, including a meta-analysis, suggests that thromboprophylaxis with low-molecular-weight heparin (LMWH) is at least as effective as with UFH, and also has the advantage of fewer bleeding complications. In particular, two large, randomised clinical trials – Prophylaxis in Medical Patients with Enoxaparin (MEDENOX) and Prospective Evaluation of Dalteparin Efficacy for Prevention of VTE in Immobilized Patients Trial (PREVENT) – showed that thromboprophylaxis with the LMWHs enoxaparin (40 mg s.c. once daily) or dalteparin (5,000 IU once daily) is more effective than placebo and well tolerated in medical patients. In addition, the Thromboembolism-Prevention in Cardiopulmonary Diseases with Enoxaparin (THE-PRINCE) trial showed that enoxaparin treatment was as effective as UFH. These studies provide solid evidence for the widespread use of thromboprophylaxis in medical patients.

scholarly journals PREVENTion of CLots in Orthopaedic Trauma (PREVENT CLOT): a randomised pragmatic trial protocol comparing aspirin versus low-molecular-weight heparin for blood clot prevention in orthopaedic trauma patients

BMJ Open ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. e041845
Author(s):  
Robert V O'Toole ◽  
Deborah M Stein ◽  
Katherine P Frey ◽  
Nathan N O'Hara ◽  
Daniel O Scharfstein ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Pragmatic Trial ◽  
Bleeding Complications ◽  
Wound Complications ◽  
Low Molecular Weight ◽  
Trauma Patients ◽  
Orthopaedic Trauma ◽  
Vte Prophylaxis ◽  
Increased Risk

Introduction Patients who sustain orthopaedic trauma are at an increased risk of venous thromboembolism (VTE), including fatal pulmonary embolism (PE). Current guidelines recommend low-molecular-weight heparin (LMWH) for VTE prophylaxis in orthopaedic trauma patients. However, emerging literature in total joint arthroplasty patients suggests the potential clinical benefits of VTE prophylaxis with aspirin. The primary aim of this trial is to compare aspirin with LMWH as a thromboprophylaxis in fracture patients. Methods and analysis PREVENT CLOT is a multicentre, randomised, pragmatic trial that aims to enrol 12 200 adult patients admitted to 1 of 21 participating centres with an operative extremity fracture, or any pelvis or acetabular fracture. The primary outcome is all-cause mortality. We will evaluate non-inferiority by testing whether the intention-to-treat difference in the probability of dying within 90 days of randomisation between aspirin and LMWH is less than our non-inferiority margin of 0.75%. Secondary efficacy outcomes include cause-specific mortality, non-fatal PE and deep vein thrombosis. Safety outcomes include bleeding complications, wound complications and deep surgical site infections. Ethics and dissemination The PREVENT CLOT trial has been approved by the ethics board at the coordinating centre (Johns Hopkins Bloomberg School of Public Health) and all participating sites. Recruitment began in April 2017 and will continue through 2021. As both study medications are currently in clinical use for VTE prophylaxis for orthopaedic trauma patients, the findings of this trial can be easily adopted into clinical practice. The results of this large, patient-centred pragmatic trial will help guide treatment choices to prevent VTE in fracture patients. Trial registration number NCT02984384.

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.

Neutralization of a Low Molecular Weight Heparin (LHN-1) and Conventional Heparin by Protamine Sulfate in Rats

1986 ◽  
Vol 56 (03) ◽  
pp. 318-322 ◽  
Author(s):  
V Diness ◽  
P B Østergaard
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Thrombus Formation ◽  
Experimental Models ◽  
Protamine Sulfate ◽  
Low Molecular Weight ◽  
Antithrombotic Effect ◽  
Higher Doses

SummaryThe neutralization of a low molecular weight heparin (LHN-1) and conventional heparin (CH) by protamine sulfate has been studied in vitro and in vivo. In vitro, the APTT activity of CH was completely neutralized in parallel with the anti-Xa activity. The APTT activity of LHN-1 was almost completely neutralized in a way similar to the APTT activity of CH, whereas the anti-Xa activity of LHN-1 was only partially neutralized.In vivo, CH 3 mg/kg and LHN-1 7.2 mg/kg was given intravenously in rats. The APTT and anti-Xa activities, after neutralization by protamine sulfate in vivo, were similar to the results in vitro. In CH treated rats no haemorrhagic effect in the rat tail bleeding test and no antithrombotic effect in the rat stasis model was found at a protamine sulfate to heparin ratio of about 1, which neutralized APTT and anti-Xa activities. In LHN-1 treated rats the haemorrhagic effect was neutralized when APTT was close to normal whereas higher doses of protamine sulfate were required for neutralization of the antithrombotic effect. This probably reflects the fact that in most experimental models higher doses of heparin are needed to induce bleeding than to prevent thrombus formation. Our results demonstrate that even if complete neutralization of APTT and anti-Xa activities were not seen in LHN-1 treated rats, the in vivo effects of LHN-1 could be neutralized as efficiently as those of conventional heparin. The large fall in blood pressure caused by high doses of protamine sulfate alone was prevented by the prior injection of LHN-1.

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.

Comparison of Continuation of Low-Molecular-Weight Heparin versus Switching to Unfractionated Heparin in the Peripartum

2019 ◽  
Vol 37 (03) ◽  
pp. 304-312 ◽  
Author(s):  
Christopher A. Enakpene ◽  
Kristina N. Pontarelli ◽  
Micaela Della Torre
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Health Science ◽  
Bleeding Complications ◽  
Low Molecular Weight ◽  
Science System ◽  
University Of Illinois ◽  
Therapeutic Anticoagulation ◽  
The University

Objective This study aimed to determine whether switching from low-molecular-weight heparin (LMWH) to unfractionated heparin (UFH) or its continuation in the peripartum affected anesthesia choice or bleeding complications. Study Design A retrospective cohort study of 189 anticoagulated pregnant women who delivered at the University of Illinois at Chicago Hospital and Health Science System from 2005 to 2016. Demography, anesthesia choice, and bleeding complications were compared between the two groups. Results There were 138 (73%) women on LMWH versus 51 (27%) who switched from LMWH to UFH during the peripartum. The demographics were similar, 123 women were on prophylactic: 81 (66%) were on LMWH and 42 (34%) switched to UFH. Of the 66 women on therapeutic anticoagulation, 57 (86%) continued on LMWH, while 9 (14%) switched to UFH. No difference in neuraxial anesthesia type received: 42 (82.4%) versus 108 (79.7%) women (odds ratio: 1.20, 95% confidence interval [CI]: 0.52–2.73, p = 0.837). Bleeding complications more than 1,000 mL, 6 versus 10% (relative risk [RR]: 0.58, 95% CI: 0.17–1.94, p = 0.380) and relaparotomy due to hemoperitoneum, 2% in either group (RR: 0.9, 95% CI: 0.10–8.48, p = 0.930) were similar in the two groups regardless of time of last injection. Conclusion Anesthesia type and rate of bleeding complications were similar between women on LMWH and UFH during the peripartum.

EXPERIMENTAL THROMBUS FORMATION AND HAEMOSTASIS OF DIFFERENT LOW MOLECULAR WEIGHT HEPARINS AND DOSAGES

1987 ◽  
Author(s):  
R A Zimmerman ◽  
C T Rieger ◽  
K Hübner ◽  
C W Harenber ◽  
W Kübler
Keyword(s):  
Molecular Weight ◽  
Thrombus Formation ◽  
Factor Xa ◽  
Bleeding Complications ◽  
Maximum Effect ◽  
Low Molecular Weight ◽  
Antithrombotic Effect ◽  
Low Molecular Weight Heparins ◽  
Antithrombotic Activity ◽  
Thrombosis Model

Low molecular weight heparin induces a higher anti factor Xa (a-Xa) and a lower antithrombin activity in plasma in comparison to conventional heparin. From this constellation a more pronounced antithrombotic effect and a minor incidence of bleeding Complications has been suggested.Therefore the antithrombotic activity of heparins was studied in a standardized experimental thrombosis model in rabbits. Three low molecular weight heparins with a mean molecular weight of 4.200 (heparin I),4.000 (heparin II),4.600 Dalton (heparin III) and standard heparin were tested at different dosages in 120 experiments. In the first series the dose of 60 anti Xa units (a-Xa U) given initially and 60 a-Xa U/kg/h induced a reduction of the thrombus size by 40 % (heparin I),37 % (heparin II) and 53 % (heparin III) and a prolongation of the aPTT to 45 (heparin I),66 (heparin II) and 79 sec (heparin III). The a-Xa activity was minor than 0.1 U/ml. In the second series heparins were given to aim at an a-Xa activity of 0.2-0.3 U/ml. Thereby the thrombus formation could be reduced by 84 % (heparin I), 62 % (heparin II) and 39 % (heparin III). aPTT and a-Xa activity were measured at 65.5 sec and 0.22 a-Xa U/ml (heparin I),67.3 sec and 0.3 a-Xa U/ml (heparin II) and 67.5 and 0.31 a-Xa U/ml (heparin III),respectively. In the third series the increase of the a-Xa activity to more than 0.3 U/ml showed no further reduction of the thrombus formation by heparin I, while heparins II and III already at this level reachedthe antithrombotic activity of heparin I.Our data on three different low molecular weight heparins demonstrate that already a heparin level ranging at a minimal a-Xa activity induces a clear and statistically significant antithrombotic effect. A higher heparin dosage with higher a-Xa activity increases the antithrombitic effect. At a level of 0.2-0.3 a-Xa U/ml an obvious and maximum effect could be reached, but the further elevation of the a-Xa activity produced no further antithrombotic action.

Sign in / Sign up

Export Citation Format

Share Document