Low Molecular Weight Heparin Regimen Research Articles

Abstract 12891: Protocol Driven Therapeutic Efficacy of Intravenous Unfractionated Heparin in the Current Era

Introduction: Despite years of refining algorithms, intravenous (IV) unfractionated heparin (UFH) is associated with many limitations in the inpatient setting. Low-molecular-weight heparin (LMWH) has shown to be equivalent to UFH in the treatment of acute venous thromboembolic disease (VTE), and demonstrated superiority in acute coronary syndrome (ACS). LMWH has less pharmacokinetic variability, a longer plasma half-life, and is associated with fewer complications. UFH also requires frequent activated partial thromboplastin time (aPTT) monitoring, affecting hospital resources. The objectives of this study were to assess the real-word therapeutic impact of routine IV UFH use in the setting of a hospital-based algorithm, evaluate the number of patients eligible for substitution with LMWH, and estimate the cost differential. Hypothesis: Methods: Adult patients who received greater than 24 hours of IV UFH from 8/1/21 to 9/30/21 (n=174), were included in this retrospective evaluation. A random sample of 100 of these 174 patients was analyzed for aPTT results in hours 25-48. These 100 patients were also considered for theoretical substitution with LMWH. Ineligibility for substitution included intermittent and continuous renal replacement therapy (RRT), creatinine clearance less than 30 mL/min, and a planned invasive procedure within 24 hours. Fiscal analyses were also done. Results: Among 519 aPTTs drawn from these 100 patients, 348 (67%) were not within the hospital therapeutic range. The most common indications for anticoagulation were ACS and acute VTE. Eighty-one percent of patients on UFH were eligible for LMWH substitution. Ineligibility was most commonly secondary to renal dysfunction. Estimated drug acquisition costs were similar, but overall cost was lower with LMWH due to decreased laboratory testing, nurse/patient contact time, and infusion supplies. Conclusions: In spite of current hospital-based algorithms and electronic order sets to minimize variability, achieving a therapeutic aPTT during the day after UFH initiation, remained elusive. The majority of patients receiving IV UFH were eligible for substitution with LMWH. Patients who qualify, should be placed on the simpler and more reliable antithrombotic LMWH regimen.

The Safety and Efficacy of Low-Molecular-Weight Heparin in Pregnant Women With Rheumatic Heart Disease and Valves Replacement.

Background: In patients with rheumatic heart disease (RHD) and prosthetic valve replacement, the risk of thromboembolic complications is the highest during and immediately after pregnancy. Therapeutic anticoagulation during this period is crucial to minimize the risk of thromboembolic complications. The use of low-molecular-weight heparin (LMWH) remains an off-label indication. The type of anticoagulants used, dosing regimens, target anti-Xa levels, and frequency of anti-Xa monitoring are highly variable in the pregnant population and have been derived from pilots, observational studies, and empirical evidence. Herein, in a real-world setting, we sought to examine the efficacy and safety of variable anticoagulation options with a focus on LMWH in the management of RHD-related valvular disease in pregnant women.Methods: This study is a retrospective study conducted at a large university-affiliated tertiary care center (King Saud University Medical City) between January 2011 and February 2020. All pregnant women with RHD who had heart valve replacements were reviewed. Patient data were extracted for demographic information, baseline characteristics, anticoagulation type, and primary outcomes. Primary endpoints were thromboembolic events, hemorrhagic complications, and fetal outcomes.Results: A total of 744 pregnancies in 149 women were identified. The mean age ± SD of the women was 43.8 ± 12 years. A total of 86 women (58%) were on the LMWH regimen, 35 women (23%) were on LMWH and warfarin regimen, and 28 women (19%) were on unfractionated heparin (UFH) and warfarin regimen. Overall, thromboembolic events developed in five (0.7%) pregnancies. Of those, two were in the LMWH group, two were in the LMWH and warfarin group, and one was in the UFH and warfarin group. In addition, significant hemorrhagic complications occurred in five pregnancies. Of these, two occurred in the LMWH group, two in the LMWH and warfarin group, and one in the UFH and warfarin group. No adverse maternal and fetal outcomes were noted.Conclusion: This study presents the largest retrospective study of variable anticoagulation options in pregnant women with RHD and prosthetic valve replacement. LMWH is both safe and effective in preventing major thromboembolic complications compared to other forms of anticoagulation used during pregnancy.

Postoperative management of antithrombotic medication in microvascular head and neck reconstruction: a comparative analysis of unfractionated and low-molecular-weight heparin

PurposeFree flap reconstruction is a valuable technique to preserve function in oncological head and neck surgery. Postoperative graft thrombosis is a dreaded risk. This study aims to compare low-dose unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) in perioperative thrombosis prophylaxis.MethodsThis is a retrospective analysis of 266 free flaps performed at our academic center. A comparison was made between 2 patient groups, based on their respective postoperative prophylaxis protocols either with UFH (n = 87) or LMWH (n = 179). Primary endpoints were the frequency of transplant thrombosis and the number of flap failures. Secondary endpoints were the occurrence of peri- and postoperative complications.ResultsThe flap survival rate was 96.6% and 93.3% for the groups UFH and LMWH, respectively (P = 0.280). The rate of postoperative bleeding requiring revision was 4.6% and 6.7% for each group, respectively (P = 0.498). We found a hematoma formation in 4.6% and 3.9% (P = 0.792).ConclusionThe free-flap survival rate using low-dose UFH seems to be equivalent to LMWH regimens without compromising the postoperative outcome. Consequently, for risk-adapted thrombosis prophylaxis, either LMWH or UFH can be administrated.

Incidence and outcomes of catheter related thrombosis (CRT) in patients with acute leukemia using a platelet-adjusted low molecular weight heparin regimen.

Patients with acute leukemia frequently develop catheter-related thrombosis (CRT) despite concurrent thrombocytopenia. The incidence, treatment and outcomes of this complication are poorly documented. We undertook this study todetermine the incidence of CRT in patients with acute leukemia and assess the safety and effectiveness of a treatment strategy using a platelet-adjusted low molecular weight heparin (LMWH) dosing protocol. Patients (18years and older) with newly diagnosed acute leukemia from January 2014 to December 2015 who received central venous catheters were included. The clinical data were reviewed up to 12months from acute leukemia diagnosis to capture objectively documented CRT events. The outcome events including recurrent venous thromboembolism (VTE), bleeding events, infectious or mechanical complications, and death were reported up to 3months from the time of CRT diagnosis. The incidence of CRT among 214 patients was 10.7% (23 patients) in the first 12 months after acute leukemia diagnosis. Among 18 patients who were treated with anticoagulation, 14 (78%) received reduced LMWH dosing due to concurrent thrombocytopenia. There were no recurrent VTE episodes, but 3 patients experienced bleeding events while on anticoagulation. Fifteen patients (83%) completed a minimum of 3 months anticoagulation. Twelve patients (52%) experienced an infectious complication, which was the main reason for catheter removal. Deaths occurred in 2 patients, related to underlying acute leukemia during 3 months period following CRT. Symptomatic CRT is frequent in patients with acute leukemia. Platelet-adjusted LMWH dosing may be effective and well tolerated despite thrombocytopenia.

Maternal and Fetal Outcomes of Anticoagulation in Pregnant Women With Mechanical Heart Valves

BackgroundAnticoagulation for mechanical heart valves during pregnancy is essential to prevent thromboembolic events. Each regimen has drawbacks with regard to maternal or fetal risk. ObjectivesThis meta-analysis sought to estimate and compare the risk of adverse maternal and fetal outcomes in pregnant women with mechanical heart valves who received different methods of anticoagulation. MethodsStudies were identified using a Medline search including all publications up to June 5, 2016. Study inclusion required reporting of maternal death, thromboembolism, and valve failure, and/or fetal spontaneous abortion, death, and congenital defects in pregnant women treated with any of the following: 1) a vitamin K antagonist (VKA) throughout pregnancy; 2) low-molecular-weight heparin (LMWH) throughout pregnancy; 3) LMWH for the first trimester, followed by a VKA (LMWH and VKA); or 4) unfractionated heparin for the first trimester, followed by a VKA (UFH and VKA). ResultsA total of 800 pregnancies from 18 publications were included. Composite maternal risk was lowest with VKA (5%), compared with LMWH (16%; ratio of averaged risk [RAR]: 3.2; 95% confidence interval [CI]: 1.5 to 7.5), LMWH and VKA (16%; RAR: 3.1; 95% CI: 1.2 to 7.5), or UFH and VKA (16%; RAR: 3.1; 95% CI: 1.5 to 7.1). Composite fetal risk was lowest with LMWH (13%; RAR: 0.3; 95% CI: 0.1 to 0.8), compared with VKA (39%), LMWH and VKA (23%), or UFH and VKA (34%). No significant difference in fetal risk was observed between women taking ≤5 mg daily warfarin and those with an LMWH regimen (RAR: 0.9; 95% CI: 0.3 to 2.4). ConclusionsVKA treatment was associated with the lowest risk of adverse maternal outcomes, whereas the use of LMWH throughout pregnancy was associated with the lowest risk of adverse fetal outcomes. Fetal risk was similar between women taking ≤5 mg warfarin daily and women treated with LMWH.

P.59 Therapeutic versus prophylactic low molecular weight heparin regimen during pregnancy: the incidence of treatment complications

P.59 Therapeutic versus prophylactic low molecular weight heparin regimen during pregnancy: the incidence of treatment complications

Comparison of the Effectiveness and Safety of Low-Molecular Weight Heparin Versus Unfractionated Heparin Anticoagulation After Heart Valve Surgery

Although unfractionated heparin (UFH) is used routinely after heart valve surgery at many institutions, cardiovascular surgery patients have a particularly high risk for developing heparin-induced thrombocytopenia (HIT). The aim of this study was to compare the efficacy and safety of low-molecular-weight heparin (LMWH) or UFH after heart valve surgery by conducting a retrospective evaluation of consecutive cardiovascular surgery patients in whom the LMWH dalteparin (n = 100) was used as the postoperative anticoagulant. This group was compared to an earlier group of patients who received UFH (n = 103). The main outcomes included the efficacy of the anticoagulant regimens (determined by the incidence of valve thrombosis, arterial thromboembolic events, and venous thromboembolic events) and the safety (determined by major bleeding, HIT, thrombotic events in HIT-positive cases, and death). Overall, there were for fewer thrombotic events in the LMWH-treated group (4% vs 11%, p = 0.11). There was a higher rate of bleeding events in the UFH-treated group (10% vs 3%, p = 0.08). Six patients in the UFH-treated group developed HIT, 4 of whom had thrombotic events (HIT with thrombosis). In the LMWH-treated group, 3 patients developed HIT, 1 of whom had HIT with thrombosis. In conclusion, in this study, an LMWH regimen after heart valve surgery was effective and safe, with fewer thrombotic, bleeding, HIT, and HIT with thrombosis events.

Long-Term Use of Different Doses of Low-Molecular-Weight Heparin Versus Vitamin K Antagonists in the Treatment of Venous Thromboembolism

We evaluated whether the incidence of recurrent venous thromboembolic events (VTEs) during and after therapy differs for patients treated with full or reduced doses of low-molecular-weight heparin (LMWH) used long term compared with vitamin K antagonists (VKAs). We identified randomized studies of long-term treatment with LMWH or VKA by searching MEDLINE, EMBASE, BIOSIS, and PASCAL. Seventeen studies were included, with 4,002 patients. In the assessment at 12 months of 1,957 patients without cancer, the recurrence rates of VTE in the LMWH/VKA groups were 8.3%/7.6% in the studies using full doses and 12.3%/12.1% in those using prophylactic doses. However, combined analysis after treatment to 1 year showed a nonsignificant (NS) trend to lower recurrent symptomatic VTE in favor of VKA (RR = 1.46, 95% CI 0.96-2.23). In 1,292 patients with cancer the recurrence rates of VTE in the LMWH/VKA groups were 6.5%/17.9% (p = 0.005) in the studies using full doses, 7.1%/13.4% (p = 0.002) in the studies using intermediate doses, and 14.3%/19.1% (p = NS) in the studies using prophylactic doses. Furthermore, the recurrences of VTE after discontinuation of treatment in the LMWH/VKA groups were 1.6%/9.5% (RR = 0.25, 95% CI 0.06-1.1) in 252 patients with full doses and 12%/7.4% (RR = 1.49, 95% CI 0.3-7.48) in 52 patients with prophylactic doses. In this population with cancer, the full-treatment LMWH regimen did not produce more major bleeding events than intermediate or prophylactic doses (5.1% vs. 6.3% or 8.1%, respectively). Full-dose LMWH for 3-6 months is as safe as intermediate and prophylactic doses for the long-term treatment of deep vein thrombosis. In patients with cancer it appears that there is an excess of VTE recurrence after treatment with prophylactic doses that does not occur with full therapeutic doses.

Efficacy and safety of once daily low molecular weight heparin (tinzaparin sodium) in high risk pregnancy

Low molecular weight heparin (LMWH) is widely regarded as the anticoagulant treatment of choice for the prevention and treatment of venous thromboembolism during pregnancy. However, previous studies have demonstrated that the pharmacokinetic profiles of LMWH vary significantly with increasing gestation. Consequently, it remains unclear whether LMWH regimens recommended for use in nonpregnant individuals can be safely extrapolated to pregnant women. The aims of this study were to assess the safety and the efficacy of tinzaparin sodium (Innohep) administered only once daily during pregnancy. A systematic retrospective review identified a cohort of 37 high-risk pregnancies which had been managed using tinzaparin 175 IU/kg once daily. In 26 cases, the index pregnancy had been complicated by development of an acute venous thromboembolism (17 deep vein thrombosis and nine pulmonary embolism). For each individual, case notes were examined and data extracted using a predetermined questionnaire. No episodes of recurrent venous thromboembolism were identified amongst this cohort of pregnancies managed using once daily LMWH administration. However, two unusual thrombotic complications were observed, including a parietal infarct in one patient, and a postpartum cerebral venous thrombosis in another. Once daily tinzaparin was well tolerated, with no cases of heparin-induced thrombocytopaenia, symptomatic osteoporosis, or foetal malformations. Tinzaparin dose modification based upon peak anti-Xa levels occurred in 45% of the cases examined. The present study is the largest study to have examined the clinical efficacy of once daily LMWH for use in pregnant women at high risk of venous thromboembolism. Our data support the safety and efficacy of antenatal tinzaparin at a dose of 175 IU/kg. In order to determine whether this once daily regimen provides equivalent (or indeed greater) thromboprophylaxis to twice daily LMWH regimens during pregnancy will require highly powered direct comparative studies.

Primary percutaneous coronary intervention for ST-elevation myocardial infarction using an intravenous and subcutaneous enoxaparin low molecular weight heparin regimen

Enoxaparin use in PCI has been investigated, however its role in primary PCI is less known. To evaluate the role of combination IV + SC enoxaparin in primary PCI in STEMI. 83 consecutive patients with STEMI who underwent primary PCI between January 1, 2005 and January 15, 2008 were included. Anticoagulation was based on our institution's STEMI protocol; either IV + SC enoxaparin, or IV unfractionated heparin (UFH). Clinical endpoints included MACE, bleeding and net adverse cardiac events (NACE). 45 patients received UFH and 37 received IV + SC enoxaparin. There was no difference in the rate of mortality, MACE, or NACE. There was a trend toward more TIMI major and GUSTO moderate and severe bleeding in the UFH group. Application of IV + SC enoxaparin strategy for primary PCI in STEMI appears both safe and efficacious. A prospective randomized trial will be necessary to evaluate the safety and efficacy more thoroughly.

Dose-Escalated Low Molecular Weight Heparin Provides Effective Anticoagulation for Women with Mechanical Heart Valves during Pregnancy: A Single-Centre Experience.

Effective anticoagulation for women with mechanical heart valves during pregnancy remains a major challenge. The use of standard dosage low molecular weight heparin (LMWH) is associated with an unacceptable incidence of morbidity and mortality for this patient group. In this prospective audit of anticoagulation management, we report pregnancy outcome for a cohort of women with mechanical heart valves, who received anticoagulation with a higher dosage LMWH regimen. We audited 12 consecutive pregnancies in 10 women (mean age 27.8 (18–41) years) with mechanical heart valves (mitral 4, aortic 2, aortic and mitral 2, systemic tricuspid AV valve 2). Past obstetric history (on warfarin) included 6 fetal losses: 2 miscarriages <12 weeks and 4 terminations including one therapeutic at 22 weeks gestation because of an intracerebral fetal haemorrhage. In 11/12 pregnancies treated with LMWH, warfarin was discontinued at <6 weeks and in 1/12 at 8 weeks. LMWH (dalteparin 7, enoxaparin 5) +/− low-dose aspirin (4) was then started at full therapeutic dosage (subcutaneous 12 hourly) with regular monitoring to maintain anti-Xa levels at 1.0–1.2U/mL (0.8–1.2 in the first 4/12 pregnancies). This necessitated stepwise increases in LMWH with median doses (12 hourly) pre-delivery 11,750IU for dalteparin and 95mg for enoxaparin, representing a median 47.7% increase over initial dosage. 11/12 pregnancies on LMWH resulted in live births (median BW 2.5 kg (range 1.0–3.7) at median gestation 36 (range 26–38 weeks) with 1 IUFD at 37 weeks. One patient had non-fatal valve-related thrombosis at 26 weeks associated with a sub-therapeutic anti-Xa level (0.64 U/ml). Of note, she had a past history of pulmonary embolism and was heterozygous for the G20210A prothrombin gene mutation. There were no other valve-related thrombotic events. Minor bleeding occurred during 3 pregnancies. There were 5 major bleeding episodes in 4 patients: 3 antepartum (1 with placenta praevia) and 1 post-partum haemorrhage plus 1 abdominal wound haematoma. Our data suggest that in this patient group escalated dose LMWH provides effective anticoagulation. These patients require meticulous anticoagulant monitoring and close surveillance for bleeding and thrombotic complications within a multidisciplinary setting, with urgent intervention when indicated.

Towards evidence-based guidelines for the prevention of venous thromboembolism: systematic reviews of mechanical methods, oral anticoagulation, dextran and regional anaesthesia as thromboprophylaxis

To assess the benefits in terms of reductions in the risks of deep vein thrombosis (DVT) and of pulmonary embolism (PE), and hazards in terms of major bleeding, of: (i) mechanical compression; (ii) oral anticoagulants; (iii) dextran; and (iv) regional anaesthesia (as an alternative to general anaesthesia) in surgical and medical patients. Electronic databases, search of Antithrombotic Trialists' Collaboration database, contact with trialists and manufacturers. All trials identified as fitting the selection criteria were independently assessed. The primary outcomes were DVT, PE and major bleeding events, and proximal venous thrombosis (PVT) and fatal PE were secondary outcomes. Trials were subdivided into those that had assessed a method as the only means of thromboprophylaxis ('monotherapy') and those that had assessed the effects of adding a method to another form of thromboprophylaxis ('adjunctive therapy'). Mechanical compression methods reduced the risk of DVT by about two-thirds when used as monotherapy and by about half when added to a pharmacological method. These benefits were similar irrespective of the particular method used (graduated compression stockings, intermittent pneumatic compression or footpumps) and were similar in each of the surgical groups studied. Mechanical methods reduced the risk of PVT by about half and the risk of PE by two-fifths. Oral anticoagulants, when used as monotherapy, reduced the risk of DVT and of PVT by about half, and this protective effect appeared similar in each of the surgical groups studied. There was an apparently large four-fifths reduction in the role of PE, but not only was the magnitude of this reduction statistically uncertain, but also pulmonary embolism was reported by a minority of trials, so it may be subject to selection bias. Oral anticoagulant regimens approximately doubled the risk of major bleeding and appeared less effective at preventing DVT than heparin regimens, although were associated with less major bleeding. Dextran reduced the risk of DVT and of PVT by about half, again irrespective of the type of surgery, but too few studies had reported PE to provide reliable estimates of effect on this outcome. Dextran appeared to be less effective at preventing DVT than the heparin regimens studied. Dextran was associated with an increased risk of bleeding, but too few bleeds had occurred for the size of this excess risk to be estimated reliably. Compared with general anaesthesia, regional anaesthesia reduced the risk of DVT by about half, and this benefit appeared similar in each of the surgical settings studied. Regional anaesthesia was associated with less major bleeding than general anaesthesia. In the absence of a clear contraindication (such as severe peripheral arterial disease), patients undergoing a surgical procedure would be expected to derive net benefit from a mechanical compression method of thromboprophylaxis (such as graduated compression stockings), irrespective of their absolute risk of venous thromboembolism. Patients who are considered to be at particularly high risk of venous thromboembolism may also benefit from a pharmacological thromboprophylactic agent, but since oral anticoagulant and dextran regimens appear less effective at preventing DVT than standard low-dose unfractionated heparin or low molecular weight heparin regimens, they may be less suitable for patients at high risk of venous thromboembolism, even though they are associated with less bleeding. Whenever feasible, the use of regional anaesthesia as an alternative to general anaesthesia may also provide additional protection against venous thromboembolism. There is little information on the prevention of venous thromboembolism among high-risk medical patients (such as those with stroke), so further randomised trials in this area would be helpful.

Deep Venous Thrombosis and Pulmonary Embolism in Neurosurgery: A Review of the Risks and Benefits of Prophylaxis

Background : In neurosurgery and spine surgery in particular, the unique risks and benefits of utilizing different prophylaxis regimens against deep venous thrombosis (DVT) and pulmonary embolism (PE) must be carefully weighed. Our aim was to comprehensively review the safety and efficacy of different regimens of prophylaxis against DVT and PE in neurosurgical cranial and spinal studies.Methods : Patients undergoing cranial or spinal procedures may receive one or more types of prophylaxis; elastic stockings (ES), intermittent pneumatic compression stockings (IPC), low dose unfractionated subcutaneous heparin (typically 5000 U q12h), and/or low dose low molecular weight heparin alternatives. The incidence of DVT, PE, and hemorrhage, particularly for those receiving low dose fractionated or low molecular weight heparin, were reviewed.Results : IPC stockings appeared to be very effective, particularly in spinal surgical series where the frequency of DVT/PE remained lower than in cranial studies. Although the addition of low dose unfractionated subcutaneous or low dose low molecular weight heparin regimens further decreased the frequency of DVT and PE, it carried a 2%-4% risk of major postoperative hemorrhage.Conclusions : Intermittent compression stocking prophylaxis (IPC) alone provide adequate prophylaxis against DVT and PE in most patients undergoing spinal procedures. The “value added” of low dose unfractionated subcutaneous or low dose low molecular weight heparin regimens regarding further reduction in the incidence of DVT and PE, poses the significant risk of major postoperative hemorrhage.

Postoperative Melagatran/Ximelagatran for the Prevention of Venous Thromboembolism following Major Elective Orthopaedic Surgery

To examine the influence of timing of postoperative initiation of subcutaneous melagatran followed by oral ximelagatran, and of risk factors for venous thromboembolism (VTE; including deep vein thrombosis [DVT] and pulmonary embolism [PE]) and bleeding complications, on the efficacy and safety of this regimen, compared with preoperative enoxaparin sodium, following total hip replacement (THR) or total knee replacement (TKR) surgery. Statistical analyses of efficacy and safety in subgroups of the METHRO III intention-to-treat population. Main efficacy outcome measures were major VTE (proximal DVT, PE or VTE-related death) and total VTE (distal or proximal DVT, fatal or non-fatal PE). The main safety outcome measures were blood transfusion, severe bleeding events, blood loss, bleeding-related adverse events and need for reoperation. In the combined THR and TKR population, melagatran initiated 4 - <8 hours postoperatively was non-inferior to enoxaparin sodium with respect to the risks of total VTE (absolute risk reduction [ARR] 0; 95% confidence interval [CI] -4.4, 4.4) and major VTE (ARR -0.63; 95% CI -2.94, 1.67). The rate of major VTE was unaffected by the different risk factors. In the combined THR and TKR population, blood transfusion requirements were lower with melagatran/ximelagatran than enoxaparin sodium (odds ratio 0.83; 95% CI 0.71, 0.96; p = 0.016). Melagatran/ximelagatran initiated 4 - <8 hours postoperatively provided a comparable level of protection against total and major VTE to preoperative enoxaparin sodium. Major VTE rates and safety were consistent across different patient subgroups. Subcutaneous melagatran followed by fixed-dose oral ximelagatran offers an alternative to the standard European low molecular-weight heparin regimen in a wide range of patients.

Thrombophilies et pathologies vasculaires placentaires. Revue de la littérature

Purpose. – Hereditary thrombophilia as antiphospholipid syndrome (APS) may represent a new risk factor for placental vascular diseases. Current knowledge and key points. – General screening for biological abnormalities related to thrombophilia is poorly associated with placental vascular diseases and therefore, may be unwarranted. Women with an history of thrombotic diseases may be at risk for late fetal loss or preeclampsia. Adverse obstetric outcomes are particularly high despite anticoagulation regimens in patients with APS. A high frequency for biological abnormalities related to thrombophilia was detected in pregnancies complicated by late fetal loss in comparison with controls. However, no beneficial strategy prevention was clearly reported and therefore, a selective testing was actually debated for these patients. Future prospects and projects. – Searching for acceptable treatment alternatives in patients with APS in order to reduce the high rate for pregnancy complications which may be persistent despite anticoagulation regimens. To determine by controlled studies the role for a prophylactic low molecular weight heparin regimens in patients with haemostatic abnormalities and previous pregnancy complications.

Fondaparinux, the first selective factor Xa inhibitor.

Fondaparinux (Arixtra, Sanofi-Synthelabo, Paris, France) is a pentasaccharide that selectively inhibits factor Xa; it is the first of a new class of synthetic antithrombotic agents. Fondaparinux has a linear pharmacokinetic profile allowing once-daily subcutaneous administration. Absence of metabolism, complete bioavailability, and lack of nonspecific binding in plasma contribute to the predictability of its effect. Fondaparinux has been approved for use in the prophylaxis of venous thromboembolism following orthopedic surgery. In this setting, it was found to reduce VTE risk by more than 50% in comparison with the low molecular weight heparin enoxaparin, with an incidence of clinically important bleeding not significantly different from that of standard low molecular weight heparin regimens. Furthermore, 4 weeks of prophylaxis with fondaparinux after hip fracture surgery was shown to reduce the risk of venous thromboembolism by 96% compared with 1-week prophylaxis. Finally, the efficacy and safety of fondaparinux in the treatment of venous thromboembolism and acute coronary syndromes appears promising.

Perioperative low molecular weight heparin regimen to prevent deep vein thrombosis and heart ischaemy in patients operated on gynaecologically

International Journal of Gynecology & ObstetricsVolume 70, Issue S2 p. B82-B82 Experimental drug therapy Perioperative low molecular weight heparin regimen to prevent deep vein thrombosis and heart ischaemy in patients operated on gynaecologically A. Cyrkowicz, A. CyrkowiczSearch for more papers by this author A. Cyrkowicz, A. CyrkowiczSearch for more papers by this author First published: 10 December 2003 https://doi.org/10.1016/S0020-7292(00)85180-2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume70, IssueS22000Pages B82-B82 RelatedInformation

Comparison of a once Daily with a twice Daily Subcutaneous Low Molecular Weight Heparin Regimen in the Treatment of Deep Vein Thrombosis

SummaryBackground: Clinical trials have been performed to compare with standard heparin a once or a twice daily regimen of low-molecular-weight heparin but no direct comparison has been done between these two low-molecular-weight heparin regimens in terms of efficacy and safety with a long-term clinical evaluation.Methods: Patients with proximal deep vein thrombosis, confirmed by venography were randomly assigned to either nadroparin (10,250 AXa IU/ml) twice daily or nadroparin (20,500 AXa IU/ml) once daily for at least 5 days. Regimens were adjusted to bodyweight. Oral anticoagulants were started on day 1 or 2 and continued for 3 months. Patients were followed up for 3 months. The composite outcome of venous thromboembolism and death possibly related to pulmonary embolism was the primary measure of efficacy. Major bleeding was the principal measure of safety. The study was designed to show equivalence between the two regimens.Results: Recurrent thromboembolic events or death possibly related to pulmonary embolism were reported in 13 patients in the once daily group (4.1%) and in 24 patients of the twice daily group (7.2%): (absolute difference 3.1% in favor of the once daily regimen; 95% confidence interval -6.6%, +0.5%). Major bleeding episodes during nadroparin treatment occurred in 4 (1.3%) and 4 patients (1.2%) in the once and twice daily groups, respectively.Conclusions: A nadroparin regimen of one injection per day is at least as effective and safe as the same total daily dose divided over two injections for the treatment of acute deep vein thrombosis.

Use of Single Dose Low-Molecular-Weight Heparin in Long Hemodialysis

Low-molecular-weight (LMW) heparin has recently been used for anti-coagulation in maintenance hemodialysis. The LMW heparin was administered as a single bolus in hemodialysis that usually lasted for four hours or less. The regimen for administering LMW heparin in hemodialysis of longer duration (5 hours or more) is not well documented and manufacturers recommend a supplementary dose equivalent to one-quarter of the initial dose to be given at 4 hours after the commencement of hemodialysis. In this study, we explored whether administering a single dose of LMW heparin is feasible in hemodialysis of longer duration. Maintenance five-hour hemodialysis sessions were performed in nine uremic patients with two different heparin regimens: single dose of LMW heparin (nadroparin) 12,500 ICU AXa at the beginning of dialysis or a priming dose of nadroparin 10,000 ICU AXa at the beginning of dialysis followed by a supplementary dose of nadroparin 2,500 ICU AXa at the beginning of the fifth hour of dialysis. Clots in the airtraps or clotting of the dialyser were not observed in hemodialysis with the single dose heparin regimen. The anti-Xa activities at different time intervals during dialysis were above the therapeutic range of 0.5 U/ml except towards the end of the hemodialysis treatment. There was no difference between anti-Xa activities determined in dialysis sessions using two different regimens of LMW heparin at any individual time interval. The anti-thrombotic effect determined by the area under the time response curve for anti-Xa activity was comparable in the two LMW heparin regimens. Hence, our findings suggest a single bolus dose of LMW heparin (nadroparin) at 12,500 ICU AXa provides adequate, safe, and effective anti-coagulation for five-hour hemodialysis. This practice is convenient and avoids the necessity of administering a double dose of LMW heparin.