Thromboembolism In High-risk Patients Research Articles

Surgical Treatment of Pancreatic Head Cancer and Perioperative Management in High Thromboembolic Risk Patients With Recent Drug-Eluting Coronary Stent Implantation

Patients with multiple coronary artery diseases, especially with recent implantation of a drug-eluting coronary stent (DES), require strong dual antiplatelet therapy and regarded as those with very high thromboembolic risks. When these patients undergo major abdominal surgery for malignancy, perioperative risks including bleeding and thromboembolic risks have to be balanced against oncological radicality. We performed successful management of 81-year-old man suffering locally advanced pancreatic head cancer detected just after recent DES implantation. Curative-intent pancreaticoduodenectomy under preoperative continuation of aspirin monotherapy is safe and feasible, and is considered to be one of the promising options for the treatment of such complicated patients.

Venous Thromboembolism in High-Risk Patients: Are We Doing Enough for Prevention?

Objectives: CEA in asymptomatic patients is recommended only when postoperative complications and mortality are kept low; but predicting CEA complications in a specific patient remains elusive. To better predict 30-day postoperative outcomes, we calculated a novel point-weight ordinal Frailty Risk Score (FRS) by an analysis of 20 preoperative risk factors based on their individual odds ratios (ORs) as predictors of postoperative complications using all vascular surgery cases in the 2005 to 2011 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database (n 1⁄4 121,015). Methods: To compare the predictive value of this calculated FRS with that of patient demographics and surgical variables alone, we examined the predictive contribution value of five levels of FRS on four outcomes (stroke, myocardial infarction [MI], and mortality), and a composite of the three outcomes in all primary asymptomatic CEAs in the 2005 to 2011 ACSNSQIP database (n 1⁄4 39,859). Results: Thirty-day mortality occurred in 273 patients (0.7%), stroke in 527 (1.3%), MI in 301 (0.8%), and the composite outcome was positive in 1008 (2.5%). We found that by itself, the FRS level was strongly and significantly associated with all four outcomes (Table). For stroke, we used only three levels of frailty because the stroke rate no longer increased after this point, and found that for the lowest vs highest frailty levels, the rate of stroke was 1.1% vs 2.4% (P < .0001). Percentage of patients that were positive for the composite outcome was 1.7% in lowest vs 15.2% in the highest FRS group (P < .0001). Conclusions: An easy-to-calculate FRS can help stratify risk based on preoperative patient characteristics and will help to identify asymptomatic patients for whom CEA is risky.

Truly low and high thromboembolic risk - impact of risk scores in real life.

BackgroundAnticoagulation therapy is followed by analysis of factors used in the CHA2DS2-VASc score and assessing the risk of bleeding (HAS-BLED).The aim of the studyThe aim of the study was to evaluate in ‘real life’ risk stratification scores in nonvalvular atrial fibrillation (AF).Material and methodsFrom 81 consecutive patients who had not yet received anticoagulation, 68 were finally enrolled after exclusion criteria. Patients were analyzed related to risk scores: CHADS2 ≥ 2 (group I) vs. CHADS2 < 2 and CHA2DS2-VASc score ≥ 2 (group II) and gender. Patients at high thromboembolic risk were treated with warfarin, after consideration of the patient's decision.ResultsAt high risk of thromboembolic complications were 61 patients (90%). In 26 subjects (43%, 15 women – 57%) indication for anticoagulation was established by CHA2DS2-VASc. When compared to CHADS2 ≥ 2, these patients were younger (72 ±10 years vs. 63 ±10 years, p = 0.0002), less frequently burdened with arterial hypertension (p = 0.03) and had lower risk in HAS-BLED (1.23 ±0.65 vs. 0.81 ±0.49, p = 0.03). Seven patients (10%) did not require anticoagulation (CHA2DS2-VASc = 0). Compared to men, women more often had ischemic stroke (2 vs. 18%, p = 0.03), but less coronary artery disease (58 vs. 25%, p = 0.005). During 18 months on warfarin, bleeding occurred in 9 patients (13%, 6 women). On dual antiplatelet therapy were 11 patients (16%). No thromboembolic complications were recorded.ConclusionsCHA2DS2-VASc and HAS-BLED schemata easily identify real low and high thromboembolic risk patients and bleeding risk. It seems that women present higher risk of bleeding, but less frequent use of antiplatelet therapy.

Comparison of Transesophageal Echocardiography Versus Computed Tomography for Detection of Left Atrial Appendage Filling Defect (Thrombus)

Patients with atrial fibrillation, who are referred for radiofrequency pulmonary vein antral isolation, frequently undergo transesophageal echocardiography (TEE) to detect and/or exclude left atrial or left atrial appendage (LAA) thrombus and cardiac computed tomographic angiography (CCTA) to define and/or evaluate left atrial and pulmonary venous anatomy. Previous studies have reported CCTA to have high sensitivity and negative predictive value (NPV) for detecting thrombus in the LAA. Previous studies determining an optimal LAA/ascending aorta (AA) Hounsfield unit (HU) density ratio for detection of LAA thrombus have been small, with limited numbers of thrombi. We thus sought to determine both the optimal cutoff for LAA HU density and LAA/AA HU density ratio in detecting LAA thrombus compared with TEE in a multicenter population. We included 84 patients who had undergone CCTA and TEE. LAA was evaluated by 64-row CCTA qualitatively (visual filling defect) and quantitatively (measurement of LAA HU density and LAA/AA HU density ratio), using a 1-cm area of interest in the same axial plane. Results were compared with TEE visualization of thrombus or spontaneous echo contrast. Qualitative identification of thrombus in LAA by CCTA compared with TEE detection of thrombus had a sensitivity of 100%, a specificity of 77.9%, a positive predictive value (PPV) of 51.6%, an NPV of 100%, and a total accuracy of 82.1%. The optimal LAA HU density cutoff for thrombus detection was 119 with a sensitivity of 88%, a specificity of 86%, PPV 56%, and an area under the curve of 0.923 (p = 0.0004). The optimal LAA/aorta HU ratio was 0.242 with a sensitivity of 87%, a specificity of 88%, a PPV of 64%, and an area under the curve of 0.921 (p = 0.0011). There is no significant difference (p = 0.72) between both areas under the curve, and both measurements improved the specificity and PPV compared with qualitative measures. Multidetector computed tomography is an imaging technique that can exclude LAA thrombus with very high NPV. Quantitative measurement of LAA HU density (cutoff 119) or LAA/aorta HU density ratio (cutoff 0.242) improves accuracy of positively detecting LAA thrombus. This technique is especially useful when delayed scanning is not performed and LAA is found incidentally after the patient scanning is complete.

One-year adherence to warfarin treatment for venous thromboembolism in high-risk patients and its association with long-term risk of recurrent events.

Warfarin is the predominant oral anticoagulant used for the prevention of recurrent venous thromboembolism (VTE) events. However, its long-term use is complicated by the need to manage the drug within a narrow therapeutic range and by possible food and drug interactions. To examine the association between 1-year adherence, measured through compliance with and persistence on warfarin treatment for VTE, and long-term risk of recurrent events among patients at high risk. Medical and pharmacy claims for patients with commercial or Medicare supplemental insurance in the Thomson Reuters MarketScan database were analyzed. Adult patients with medical claims with an associated VTE diagnosis between January 1, 2006, and March 31, 2008, were identified. The index date was defined as the date of the first observed VTE claim or the date of discharge if the index event was a hospital stay. High-risk patients (patients with cancer, or noncancer patients who did not have reversible risk factors during the 3-month period prior to the index date) who filled a warfarin prescription within 2 weeks of the index date were included. Persistence was evaluated in terms of discontinuation, defined as a 90-day gap in warfarin supply during a 1-year assessment period following the index date. Compliance was measured by the proportion of days covered (PDC) over the 1-year assessment period, with PDC less than 0.8 defined as noncompliance. Recurrent VTE events were identified as hospitalizations where VTE was the primary diagnosis after the 1-year assessment period and until patients were lost to follow-up. The association between adherence to warfarin therapy and VTE recurrence was evaluated descriptively via Kaplan-Meier curves and a Cox proportional hazards model, adjusted for patient demographic and clinical characteristics. A similar analysis using the medication possession ratio (MPR) as a measure of compliance was also performed in a subset of patients who had filled at least 2 warfarin prescriptions. The study included 8,040 VTE patients identified as being at high risk of recurrence (mean age 61 years, 59.4% male), of whom 76.9% were not compliant with warfarin therapy based on PDC, and 51.5% discontinued therapy. Among those with at least 2 warfarin prescriptions (n = 7612), 34.1% of high-risk patients were not compliant with warfarin therapy between the first and last refills based on MPR. Kaplan-Meier curves showed that patients who were compliant or continued warfarin therapy were less likely to experience a VTE event (all P less than 0.05). Noncompliant patients had a 3 times greater risk of VTE recurrence than compliant patients, based on PDC (hazard ratio [HR] = 3.01, 95% confidence interval [CI]: 1.28-4.97). Among the subpopulation who filled at least 2 warfarin prescriptions, noncompliant patients (based on MPR) were also found to be more likely to have recurrent VTE events, compared with compliant patients (HR = 1.60, 95% CI: 1.18-2.16). Patients who discontinued warfarin were more likely to have recurrent VTE events compared with patients who did not discontinue on warfarin treatment (HR = 1.48, 95% CI: 1.09-2.01). Adherence to a year of therapy was low in patients at high risk of recurrent VTE, even though long-term therapy should be considered in this population. Noncompliance and discontinuation of warfarin treatment over a 1-year period was associated with a higher risk of recurrent VTE. Future research should investigate and differentiate between patient and provider discontinuation to develop strategies to improve compliance and persistence with appropriate anticoagulation therapy that may potentially reduce recurrent VTE.

Stroke prevention in atrial fibrillation—An Asian stroke perspective

Despite relatively lower prevalence of atrial fibrillation (AF) in Asians (~1%) than in Caucasians (~2%), Asia has a much higher overall disease burden because of its proportionally larger aged population. For example, on the basis of reported age-adjusted prevalence rates and projected population figures in China, there will be an estimated 5.2 million men and 3.1 million women with AF older than 60 years by year 2050. Stroke is a disabling complication of AF that is of increasing cause for concern in Asians patients. Implementing consensus expert recommendations for managing stroke risk in patients with AF can considerably reduce stroke rates. However, caution is necessary when aligning management of Asian patients with AF to that of their Caucasian counterparts. Current international guidelines and risk stratification tools for AF management are based on findings in predominantly Caucasian populations and may therefore have limited relevance, in certain respects, to Asian patients. Oral anticoagulants play an important role in preventing AF-related stroke. The vitamin K antagonist warfarin is recommended for reducing the risk of stroke and thromboembolism in high-risk patients with nonvalvular AF; however, warfarin interacts with many drugs and food ingredients, which may pose significant challenges in administration and monitoring among Asian patients. Further research is needed to inform specific guidance on the implications of different stroke and bleeding profiles in Asians vs Caucasians. Moreover, there is scope to improve physician perceptions and patient knowledge, as well as considering alternative new oral anticoagulants, for example, direct thrombin inhibitors or factor Xa inhibitors.

DVT PROPHYLAXIS

Objectives: To evaluate the effectiveness of LMWH prophylaxis for DVT in high risk patients after general surgery. Study design: Randomized controlled study. Setting: Surgical Unit-IV, District Head Quarters Hospital, Faisalabad. Period: From March 2009 to August 2009. Patients and Methods: Sixty patients in the LMWH group were given perioperative enoxaparin (Clexane) as prophylaxis while compression stockings were used in another control group comprised of 60 patients. At 5th postoperative day, Doppler study was performed to detect DVT in both groups. Categorical data were analyzed for significance using Chi square test through SPSS. Results: There were significant difference in age factor, history of DVT, Medical factor, surgical trauma factor and interpretation on the basis of points. However, there is non significant difference between LMWH group and control group for chemoprophylasis. Conclusions: LMWH administration is effective for the prevention of venous thromboembolism in high risk patients and its practice should be the standard of care in the practice of surgery.

New oral anticoagulants: just a new therapeutic option or a real breakthrough?

The number of anticoagulant agents currently available for clinical use is relatively limited. This is immediately clear when the number of the available anticoagulants is matched up to that of antimicrobial or the anti-inflammatory agents or the drugs used to treat arterial hypertension. Despite their reduced number, treatment with the available anticoagulant agents has been associated with an outstanding improvement of clinical care. Unfractionated heparin, several low-molecular weight heparins and fondaparinux reduce by more than 60% the rate of venous thromboembolism in patients undergoing major orthopedic or cancer surgery and in high-risk medical patients. Vitamin K antagonists reduce by more than 90% the risk of recurrence in patients with deep vein thrombosis or pulmonary embolism and by about 60% the risk of stroke in patients with atrial fibrillation. Bivalirudin, a parenteral thrombin inhibitor, has been shown to be effective and safe in patients with acute coronary syndromes who had a stent implanted. Given these achievements, it could be easy to assume that the currently available agents, if properly used, are able to meet most of the clinical needs in the antithrombotic therapy. However, the currently available agents have several limitations. Unfractionated or lowmolecular weight heparin, fondaparinux or bivalirudin require parenteral administration and are cumbersome to be used in the so-called ‘‘chronic indications’’, that is to say, those requiring a prolonged administration. The oral vitamin K antagonists are associated with a remarkable individual variability in the dose‐response and therefore require relatively frequent laboratory monitoring for dose adjustment. It makes clinical sense to anticipate that an oral agent at least as effective and safe as the vitamin K antagonists (but possibly more) to be given at fixed doses without laboratory monitoring would be a real breakthrough in the current clinical practice. Indeed, prophylaxis of postoperative thromboembolism in high-risk patients could be easily extended, long-term treatment of venous thromboembolism and prophylaxis of stroke in patients with atrial fibrillation could be made less cumbersome. In patients with atrial fibrillation treatment would be made available for that 50% of patients to whom anticoagulant treatment is denied for the impracticality of the vitamin K antagonists. In the last 10 years a number of new oral agents have entered the procedures of the clinical evaluation. The clinical development of most of these agents did not go beyond the phase II (dose-finding) studies, but some among the survivors of such a tremendous selection process reached or are about to reach the clinical use. The clinical development of an antithrombotic agent follows a secure pathway which a critical mind could also see as a sort of imagination-free stereotype. Indeed, almost all the new agents are first tested in the prevention of venous thromboembolism in major orthopedic surgery and, only after they have been shown to be effective and safe in this indication, are further evaluated in the treatment of venous thromboembolism and in the prevention of stroke in patients with atrial fibrillation. Prevention of venous thromboembolism in major orthopedic surgery is the preferred initial step for Phase II and Phase III studies as it is associated with a high and predictable event rate, a reliable measurability of the study outcome (deep vein thrombosis as assessed by venography) and a relatively careful assessment of agent-related bleeding. Once the clinical development has been completed, the

Review: compression plus pharmacological prophylaxis reduces VTE more than monotherapy in high-risk patients

S K Kakkos Dr S K Kakkos, Henry Ford Hospital, Detroit, MI, USA; kakkosstavros@gmail.com; s.kakkos@imperial.ac.uk How does intermittent pneumatic leg compression (IPC) plus pharmacological prophylaxis compare with either monotherapy for...

Combined Intermittent Pneumatic Leg Compression and Pharmacological Prophylaxis for Prevention of Venous Thrombo-Embolism in High-Risk Patients

It has been suggested that combined modalities (methods of treatment) are more effective than single modalities in preventing venous thrombo-embolism (defined as deep vein thrombosis and pulmonary embolism, or both) in high-risk patients. To assess the efficacy of intermittent pneumatic leg compression combined with pharmacological prophylaxis versus single modalities in preventing venous thrombo-embolism in high-risk patients. The Cochrane Peripheral Vascular Diseases (PVD) Group searched the reference lists of their Specialised Register (last searched 17 July 2007) and the Cochrane Central Register of Controlled Trials (CENTRAL) (last searched The Cochrane Library 2008, issue 3) for relevant articles to identify additional trials. Randomised controlled trials (RCTs) or controlled clinical trials (CCTs) of combined intermittent pneumatic leg compression and pharmacological interventions used to prevent venous thrombo-embolism in high-risk patients. Data extraction was undertaken independently by two review authors using data extraction sheets.

Treatment of Cancer-Associated Thrombosis: Distinguishing Among Antithrombotic Agents

The risk of cancer-associated thrombosis can be substantial, depending on tumor type, extent of cancer, and type of treatment. Unfractionated heparin and warfarin have been used in the prevention of cancer-associated thrombosis, but low-molecular-weight heparin (LMWH) is widely used for the prevention of venous thromboembolism in high-risk patients. Long-term management with warfarin is associated with close monitoring, an increased risk of drug interactions, and bleeding. LMWHs may offer an alternative outpatient treatment strategy for prophylactic treatment because of their simpler dosing, more predictable anticoagulant activity, and improved safety profile. Clinical trials examining the treatment of venous thromboembolism with LMWH in patients with cancer suggest a survival advantage for the treated groups. Subtle differences in the pharmacokinetics of available LMWHs exist, and each LMWH should be regarded as a distinct drug. Pharmacists should be aware of the US Food and Drug Administration-approved uses for each LMWH, dosing options, and the advantages and disadvantages of available delivery systems for various patient populations. Pharmacists can play a major role in educating patients and other health care professionals on risk factor recognition, patient risk stratification, and proper agent selection for prevention and treatment of cancer-associated thrombosis.

Prevention of Venous Thromboembolism in High-Risk Patients

The prevention of venous thromboembolism (VTE) in patients recovering from major trauma, spinal cord injury (SCI), or other critical illness is often challenging. These patient groups share a high risk for VTE, they often have at least a temporary high bleeding risk, and there are relatively few thromboprophylaxis trials specific to these populations. A systematic literature review has been conducted to summarize the risks and prevention of VTE in these three groups. It is concluded that routine thromboprophylaxis should be provided to major trauma, SCI and critical care patients based on an individual assessment of their thrombosis and bleeding risks. For patients at high risk for VTE, including those recovering from major trauma and SCI, prophylaxis with a low molecular weight heparin (LMWH) should commence as soon as hemostasis has been demonstrated. For critical care patients at lower thrombosis risk, either LMWH or low-dose heparin is recommended. For those with a very high risk of bleeding, mechanical prophylaxis should be instituted as early as possible and continued until pharmacologic prophylaxis can be initiated. The use of prophylactic inferior vena caval filters is strongly discouraged because their potential benefit has not been shown to outweigh the risks or substantial costs. Implementation of thromboprophylaxis in these patients requires a local commitment to this important patient safety priority as well as a highly functional delivery system, based on the use of pre-printed orders, computer prompts, regular audit and feedback, and ongoing quality improvement efforts.

Thromboembolism in children with acute lymphoblastic leukaemia treated on Dana‐Farber Cancer Institute protocols: effect of age and risk stratification of disease

Children with acute lymphoblastic leukaemia (ALL) are at increased risk for thromboembolism (TE). Identification of a susceptible population is crucial for effective thromboprophylaxis. However, the risk factors for ALL-associated TE are unclear. Concomitant asparaginase (ASP) and steroid therapy has been shown to increase the incidence of TE. Dana-Farber Cancer Institute (DFCI)-ALL protocols use a combination of ASP and steroids during the postinduction intensification phase when high-risk (HR) patients receive thrice the steroid-dose given to standard-risk (SR) patients. We studied prospectively assembled cohorts of children treated on two consecutive DFCI-ALL protocols to define the risk factors for symptomatic TE. Ten (11%) of 91 patients developed symptomatic TE; eight (seven HR) during intensification. Seven (44%) of 16 older patients (>/=10 years) compared with three of 75 (4%) younger patients developed TE (P < 0.0001). Nine of 35 (26%) HR and one of 56 (2%) SR patients developed TE (P = 0.0006). Gender, ALL-immunophenotype, steroid-type or ASP dosing schedule did not alter the risk but older age and HR-disease were factors predisposing to TE associated with DFCI-ALL protocols. Age-related risk may partly reflect the effect of ALL-risk stratification. Higher dose steroids combined with ASP may lead to an increased risk of TE in HR patients.

New anticoagulants for the prevention and treatment of venous thromboembolism

Anticoagulant therapy is effective at preventing the development of venous thromboembolism in high-risk patients, and reduces morbidity and mortality in individuals with established thromboembolic disease. Vitamin K antagonists and heparins are currently the most commonly used anticoagulant drugs, but they have practical limitations. Therefore, new antithrombotic agents with predictable dose-responses (thereby decreasing the need for monitoring without compromising efficacy or safety), ideally available in an oral formulation and with a rapidly reversible anticoagulant effect, are needed. New drugs fulfilling some of the above criteria have been developed and have proven to be effective agents for the treatment and prevention of venous thromboembolism.

Low Molecular Weight Heparin during Surgery in Parients on Long Term Oral Anticoagulant Treatment (OAT): A Prospective Observational Study.

The perioperative management of patients on long term OAT is an open issue. The problem is the prevention of both the thromboembolic (TE) and the hemorrhagic complications. The therapeutic options are: 1) discontinuation of OAT with an INR target <2.0 at the scheduled time and its resumption after surgery, 2) substitution of OAT with low molecular weight heparin (LMWH) in the perioperative period. We report on 477 consecutive patients who underwent elective surgery in 7 FCSA centers (November 2001 to August 2003). Major and minor surgery and other minor procedures were carried out in 68, 206 and 203 patients respectively; median age 72 years (25–97); 279 males, 198 females. The aim of the study was to evaluate the complications occurring during and within 2 months after surgery with the different modalities of prophylaxis. Indications for OAT./bold]Low and intermediate TE risk patients:secondary prophylaxis of venous thrombosis (VT) 75; non valvular atrial fibrillation (AF) 225; aortic mechanical or biological valves 58, dilatative myocardiopathy 8, valvulopathy 10; myocardial infarction 3; coronary artery by-pass graft 4; stroke 4.High TE risk patients: mitral mechanical valve, mechanical valves + AF or previous TE 53, AF + ≥2 other risk factors (arterial hypertension, dilatative myocardiopathy, previous TE, biological heart valve) 6; intracardiac thrombosis 1.Results: LMWH therapy: Nadroparin (Seleparina®) and enoxaparin (Clexane®) in 394 and 28 patients respectively. Comments. One patients with high thromboembolic risk died because of sudden cardiac arrest 13 days after a procedure. TE events (0.6%) occurred in 2 patients with mechanical aortic valve and valvulopathy respectively and treated with s.i.d dose. Incidence of major bleeding is higher in patients treated with LMWH b.i.d but it is in accordance with the data reported in the literature.Table ITherapyno OATLMWH (s.i.d.)LMWH (b.i.d.)Dose (U/kg)60.6 (±12.8)65.9 (±17.4)Patients-number5532993ComplicationsTE n (%)02 (0.6)0arterial02 (0.6)0venous000Bleeding n (%)09 (2.7)7 (7.5)major04 (1.2)3 (3.2)minor05 (1.5)4 (4.3)s.i.d.=single in die; b.i.d.= bis in die

Management of venous thromboembolism: past, present, and future.

Venous thromboembolism, including deep vein thrombosis and pulmonary embolism, represents a significant source of morbidity and mortality in the United States and worldwide. The pharmacologic management of venous thromboembolic disease has witnessed significant advances since oral anticoagulant and heparin therapies began to gain widespread use more than 50 years ago. Cumulative clinical experience gained from using these 2 classes of antithrombotic agents for the prevention and treatment of venous thromboembolism in high-risk patients pointed to a number of efficacy and safety limitations. This prompted further research and the eventual introduction, in the 1980s, of low-molecular-weight heparin(s) as a potentially superior therapeutic modality. Within the last decade the pace of development of newer classes of antithrombotic agents for venous thromboembolism prevention and treatment (as well as other indications) has accelerated. Among agents at late stages of investigation are ximelagatran (a direct thrombin inhibitor), nematode anticoagulant peptide c2 (a tissue factor VIIa inhibitor), and sodium N-[8(2-hydroxylbenzoyl)amino]caprylate (SNAC)/heparin (a heparin derivative). The most recently approved agents for venous thromboembolism indications include the heparinoid, danaparoid sodium, and the newly introduced selective factor Xa inhibitor, fondaparinux.

Antithrombotic drugs in vascular medicine: a historical perspective.

Many new antithrombotic and antiplatelet drugs have been developed that have markedly improved prophylaxis and treatment of thrombotic diseases. Clopidogrel, a potent new antiplatelet compound, is the first clinical alternative to aspirin for long-term oral treatment and prevention of arterial thrombosis. Another new, exciting category of antiplatelet compounds is the GPIIb/IIIa-antagonists, the first antiintegrins in clinical use and the most potent inhibitors of platelet aggregation. Low molecular weight heparins (LMWHs) are the quantitatively dominating group of new antithrombotics, which has replaced unfractionated heparin for the prophylaxis and treatment of venous thromboembolism. Current clinical evidence suggests that LMWHs might replace unfractionated heparin for the treatment and prophylaxis of atherothrombotic complications in acute coronary syndromes in the near future. Fondaparinux is the first synthetic pentasaccharide and a selective inhibitor of factor Xa with exciting clinical data; it could become an alternative LMWH for prophylaxis of arterial and venous thromboembolism in high-risk patients. The field of oral thrombin inhibitors is still dominated by the coumarins. However, much effort is being undertaken to develop new orally active drugs from which ximelagatran is currently the leading compound with a predicted better safety and efficacy profile. Alternatively, inhibitors of factor VIIa might be of interest as well. Open questions include, in particular, the possible individualization of drug therapy in dependence on the kind of disturbed platelet function or blood hypercoagulability, respectively.

5 Anticoagulants in pregnancy: fetal effects

Anticoagulants are used during pregnancy to prevent venous thrombo-embolism in highrisk patients, to prevent systemic embolism in patients with prosthetic heart valves or native valvular heart disease, and to treat patients with acute venous thrombo-embolism. Neither unfractionated nor low-molecular-weight heparin cross the placenta and both appear to be safe for the fetus. Oral anticoagulants do cross the placenta and they have been associated with the development of warfarin embryopathy, central nervous system anomalies, and fetal haemorrhage. The true incidence of these events is not known. Both heparin and oral anticoagulants can be safely administered to nursing mothers.

Thromboembolism in high risk patients undergoing bidirectional cavopulmonary anastomosis

Thromboembolism in high risk patients undergoing bidirectional cavopulmonary anastomosis

Patients at risk of venous thromboembolism—Clinical results with reviparin

Perioperative thromboembolism can be effectively prevented by low-dose heparin. However, its clinical benefit is limited, due to the risk of bleeding, the need for multiple daily doses, infrequent disorders of platelet function and other potential side effects. Low molecular weight heparin (LMWH) was developed with the aim that the antithrombotic efficacy of heparin could be maintained, while the risk of bleeding and other side effects would be reduced. Prior to recent studies, the anticipated clinical benefit of LMWH remained a controversial issue. We have reviewed the clinical pharmacology and the results of several prospective trials using reviparin a LMWH which has been compared with unfractionated heparin (UFH) and another LMWH. The efficacy and safety of reviparin was examined in the prevention of venous thromboembolism in high risk patients undergoing elective major abdominal and hip surgery. The results of these clinical trials show that reviparin is as effective as UFH in preventing venous thromboembolism whilst having a lower incidence of bleeding complications. Of major significance was the finding that a very low dose of reviparin, namely 1750 anti-Xa IU once daily, was found to be as effective as UFH in preventing deep vein thrombosis whilst having a significantly lower incidence of bleeding complications in patients undergoing major abdominal surgery. Reviparin has also been shown to be effective and safe as enoxaprin in patients undergoing elective hip surgery. Further clinical trials are required to test different dosage regimens as a thromboprophylactic agent in high risk patients. It is possible that reviparin and other LMWHs with similar pharmacological properties may have an important clinical benefit over earlier compounds. However, this needs to be assessed in large scale, double-blind, randomised clinical trials.