Therapeutic Low Molecular Weight Heparin Research Articles

Catheter Ablation of Atrial Fibrillation in Patients at Low Thrombo‐Embolic Risk: Efficacy and Safety of a Simplified Periprocedural Anticoagulation Strategy

To prevent thrombo-embolic (TE) events during ablation of atrial fibrillation (AF), warfarin is recommended in all patients irrespective of baseline TE risk. We evaluated the efficacy and safety of a simplified periprocedural anticoagulation strategy of aspirin (ASA) and low molecular weight heparin (LMWH) in patients at low TE risk. We collected data from 214 low TE risk patients (CHADS2 score ≤1 and no warfarin at baseline) undergoing pulmonary vein isolation. After discontinuation of ASA, periprocedural antithrombotic therapy consisted of therapeutic subcutaneous LMWH injections (nadroparin 1 mL/kg once daily) from 10 days before until 10 days after the procedure, followed by ASA in all patients. At the time of procedure, transesophageal echocardiography (TEE) was not performed on a routine basis. During the procedure, unfractionated heparin was administered to achieve an ACT between 350 and 400 seconds. Data on TE events (stroke or transient ischemic attack), cardiac tamponade/perforation, and major vascular access complications within 3 months after the procedure were collected. Mean CHADS2 was 0.3 ± 0.5. TEE was performed in 3% of patients. No periprocedural TE events occurred. No cardiac tamponade/perforation was observed. Major vascular access complications occurred in 3 patients (1.4%). No permanent injury was observed (0%). In selected low TE risk patients undergoing ablation for AF, a short period of periprocedural therapeutic anticoagulation with LMWH together with aspirin is an effective and safe strategy to prevent TE events. If confirmed in a randomized trial, this approach might simplify periprocedural antithrombotic management in ablation of selected AF patients.

The effects of location and low-molecular-weight heparin administration on deep vein thrombosis outcomes in trauma patients

Deep vein thrombosis (DVT) is common after trauma. Pulmonary embolism (PE) is a feared complication of DVT. Standard doses of low-molecular-weight heparin (LMWH) are commonly used to prevent and treat DVT and PE. There is variable bioavailability of LMWH with standard therapy. The traditional concept that below-knee DVT is associated with a lower risk of subsequent PE may result in less aggressive therapy. The purposes of this study were to assess the rates of PE in above-knee versus below-knee DVT and longitudinally evaluate outcomes of DVT treated with LMWH therapy. This was a retrospective review of patients at a university Level I trauma center during the years 2005 through 2010. Patients diagnosed with lower-extremity DVT were included in this study. Patients were classified by location of lower-extremity DVT and type of LMWH therapy received. All high-risk trauma patients were evaluated with weekly duplex Doppler ultrasonography. All duplex studies were reviewed for DVT resolution or improvement. Symptomatic patients were evaluated with computed tomographic angiography to rule out PE. Demographics, total length of hospital stay, length of intensive care unit stay, and Injury Severity Score (ISS) were collected. Three-hundred eight trauma patients with lower-extremity DVT were included. More patients developed below-knee DVT (65.6%) compared with above-knee DVT (34.4%). Increased length of hospital stay, intensive care unit stay, and higher ISS were noted in patients with above-knee DVT. More patients had below-knee DVT in the prophylactic dosing group. With LMWH therapy, three PEs occurred in patients in the prophylactic dosing group with below-knee DVT, and no PEs occurred in the therapeutic treatment group. The incidence of PE between patients with below-knee DVT compared with above-knee DVT overall was not different (3.3% and 4.7%, p = 0.59). To assess DVT outcomes, 157 of the 308 patients had serial duplex studies following diagnosis of lower-extremity DVT. The number of patients receiving either therapeutic or prophylactic LMWH was similar (51% and 49%). There was no difference in rates of resolution or improvement between LMWH dosing groups or location of DVT. In screened trauma patients, below-knee DVT is more common than above-knee DVT. There was no difference in the incidence of PE between groups. Standard prophylactic and therapeutic dosing of LMWH does not affect the rates of resolution or improvement of lower-extremity DVT. Rates of resolution and improvement of DVT is not dependent of location of lower-extremity DVT. Therapeutic study, level IV; epidemiologic study, level III.

Half-dose enoxaparin vs. full-dose enoxaparin for postoperative bridging therapy in patients after cardiac surgery: Which dose regimen should be preferred?

Patients who require oral anticoagulation (OAC) after cardiac surgery due to an increased risk for thromboembolic events should receive bridging therapy with heparin until the INR is in a therapeutic range. For this purpose, unfractionated heparin (UFH) or low molecular weight heparin (LMWH) can be used. Recently published studies have demonstrated the safety and efficiency of therapeutic dose LMWH as bridging anticoagulant in cardiac surgery. The present study compares a full-therapeutic dose regimen with a half-therapeutic dose regimen of LMWH looking for safety and efficiency. This study represents a retrospective, single-center cohort study. In a period of 19 months all patients in whom a postoperative bridging therapy after cardiac surgery was necessary (atrial fibrillation, mechanical heart valve replacement, tricuspid valve repair, intracardiac patch implantation, excision of intracardiac tumors) were selected. In the first part of the study, patients received full-dose (FD = 1 mg/kg bodyweight twice daily) LMWH (Enoxaparin). Analogously, patients in the second part of the study were treated with half-dose (HD = 0.5 mg/kg bodyweight twice daily) LMWH. In case of renal insufficiency (GFR <30 ml/min) the dose was adjusted to one daily application. The duration of follow-up was the patients' entire stay in hospital. Main outcome parameters were bleeding, thromboembolic events, and death. The first dose of LMWH was given on the morning of the first postoperative day, considered that the bleeding risk was acceptable. OAC (Phenprocoumon) was started on the evening of the first postoperative day. Altogether 402 out of 3133 patients met the inclusion criteria (201 patients in each group). Despite a reduced renal function in the HD-group (p = 0.002) both groups were well matched. Mortality was significantly higher in the HD-group than in the FD-group (5.5% vs. 0.5%, p = 0.003) but not related to the anticoagulation regimen. We observed more bleeding events in the FD-group (11 vs. 5, p = 0.126) but vice versa more thromboembolic events in the HD-group (9 vs. 5, p = 0.277). In the HD-group postoperative dialysis was required more often (29 vs. 12, p = 0.011) and there was a higher incidence of patients who were psychic disorientated (42 vs. 26, p = 0.033). The hospital stay was longer in the FD-group (FD: 15.1 ± 9.3 days, HD 12.5 ± 8.1 days, p = 0.003). This study shows that a bridging therapy with LMWH is feasible and safe no matter which dose-regimen is used. The differences observed seem not to be related to the anticoagulation. The decision of using a full-dose or half-dose LMWH bridging regimen should be determined by the individual risk of the patient and the general bleeding risk of the procedure.

Low molecular weight heparin inhibits plasma thrombin generation via direct targeting of factor IXa: contribution of the serpin‐independent mechanism

Although heparin possesses multiple mechanisms of action, enhanced factor Xa inhibition by antithrombin is accepted as the predominant therapeutic mechanism. The contribution of FIXa inhibition to heparin activity in human plasma remains incompletely defined. To determine the relevance of FIXa as a therapeutic target for heparins, particularly serpin-independent inhibition of intrinsic tenase (FIXa-FVIIIa) activity. Thrombin generation was detected by fluorogenic substrate cleavage. The inhibitory potencies (EC(50) s) of low molecular weight heparin (LMWH), super-sulfated LMWH (ssLMWH), fondaparinux and unfractionated heparin (UFH) were determined by plotting concentration vs. relative velocity index (ratio ± heparin). Inhibition was compared under FIX-dependent and FIX-independent conditions (0.2 or 4 pm tissue factor [TF], respectively) in normal plasma, and in mock-depleted or antithrombin/FIX-depleted plasma supplemented with recombinant FIX. UFH and fondaparinux demonstrated similar potency under FIX-dependent and FIX-independent conditions, whereas LMWH (2.9-fold) and ssLMWH (5.1-fold) demonstrated increased potency with limiting TF. UFH (62-fold) and fondaparinux (42-fold) demonstrated markedly increased EC(50) values in antithrombin-depleted plasma, whereas LMWH (9.4-fold) and ssLMWH (two-fold) were less affected, with an EC(50) within the therapeutic range for LMWH. The molecular target for LMWH/ssLMWH was confirmed by supplementing FIX/antithrombin-depleted plasma with 90 nm recombinant FIX possessing mutations in the heparin-binding exosite. Mutated FIX demonstrated resistance to inhibition of thrombin generation by LMWH and ssLMWH that paralleled the effect of these mutations on intrinsic tenase inhibition. Therapeutic LMWH concentrations inhibit plasma thrombin generation via antithrombin-independent interaction with the FIXa heparin-binding exosite.

Thalidomide thromboprophylaxis in multiple myeloma: A review of current evidence

Currently multiple antithrombotic agents are used for thalidomide thromboprophylaxis in multiple myeloma patients. Agents used include low-dose aspirin, fixed low-dose and therapeutic warfarin and prophylactic low molecular weight heparin. To evaluate the evidence for the efficacy and safety of aspirin, warfarin and low molecular weight heparin thromboprophylaxis in multiple myeloma patients on thalidomide a literature search was conducted in May and June 2011. Databases searched included the Cochrane Database of Systemic Reviews and the Database of Abstracts of Reviews of Effects, Evidence Based Medicine Reviews and Ovid MEDLINE. The search was restricted to English language articles and limited to articles published from 2005 to 2011. Most studies consisted of small prospective cohort studies not originally designed to assess thromboprophylaxis as an outcome. A single comparative randomized trial, several retrospective review articles, two meta-analyses and two clinical practice guidelines were also identified. Current evidence fails to demonstrate a clear advantage of any particular thromboprophylaxis strategy. Results from the only prospective comparative randomized trial found no significant differences among aspirin, warfarin and low molecular weight heparin. More studies are required that consider not only efficacy and safety, but also costs, lifestyle burden and patient preference.

Coumadin-induced skin necrosis in a 64 year-old female despite LMWH bridging therapy

SummaryBackground:Coumadin is the standard oral anticoagulant used in a variety of clinical conditions. Coumadin inhibits the vitamin-K dependent gamma-carboxylation of coagulation factors II, VII, IX, X and the anticoagulant proteins C and S. Rarely, skin necrosis occurs when the resultant initial procoagulant state in the first few days of starting coumadin leads to thrombosis and formation of blood clots tin the dermal capillaries. This in turn causes skin necrosis due to interruption in blood supply to the skin.Case Report:We are presenting the case of a 64 year-old female admitted for acute respiratory distress secondary to newly-diagnosed pulmonary embolism. The patient was started on therapeutic doses of low molecular weight heparin (LMWH) and coumadin. After 5 days of treatment, the patient started complaining of pain and numbness in both upper extremities. Overnight, this rapidly progressed to manifest hemorrhagic bullae with necrotic areas. This was immediately recognized as coumadin-induced skin necrosis. Coumadin was stopped immediately. Vitamin K was administered and local wound care was provided. Therapeutic LMWH was continued. The skin lesions began to show improvement after 3 days.Conclusions:In coumadin-induced skin necrosis, the patient initially presents with pain and erythema, followed by petechial lesions which progress to become purpuric. Hemorrhagic bullae with necrosis and eschar formation may soon develop. Once it is suspected, coumadin should be stopped and the patient should be given Vitamin K and FFP to reverse the effects of coumadin.

The HAS-BLED score predicts bleedings during bridging of chronic oral anticoagulation

Patients who receive long-term oral anticoagulant (OAC) therapy often require interruption of OAC for an elective invasive procedure. Current guidelines allow bridging therapy with either unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Apart from the risk of embolism, bleeding is an important complication in this setting and the optimal perioperative management of such patients is still under discussion. The aims of this prospective, observational, multicentre registry of patients treated by cardiologists were: 1) to evaluate current practice of perioperative management of OAC in a large outpatient cohort, 2) to document embolic and haemorrhagic events, and 3) to identify risk factors predicting adverse events. In the years 2009 and 2010, 1,000 invasive procedures (cardiac catheterisation n=533, pacemaker implantation n = 128, surgery n = 194, other n = 145) were performed in patients with OAC. Sixty- one (6.1%) of those patients did not receive bridging therapy during interruption of OAC, 937 (93.7%) patients were treated with LMWH, two patients (0.2%) received UFH. In 22 patients (2.2%) LMWHs were given in prophylactic dose, 727 patients (72.7%) were treated with halved therapeutic (i.e. weight-adapted) LMWH doses and 188 (18.8%) received full therapeutic LMWH doses. Four thromboembolic complications were observed during 30 days of follow-up (two retinal embolisms, one stroke, one myocardial infarction; 0.4%). One major bleeding (0.1%) and 35 clinically relevant bleedings (3.5%) occurred. Rehospitalisation after bleedings was necessary in 20 patients. Independent predictors for bleedings were history of mechanical heart valve replacement (MVR) (p=0.0002) and the HAS-BLED score (<0.0001), with a cut off value ≥ 3 being the most predictive variable for haemorrhage (hazard ratio 11.8, 95% confidence interval 5.6-24.9, p<0.0001). A total of 527 patients with atrial fibrillation and a CHADS₂ score ≤ 2 received halved therapeutic or full therapeutic dosages of LMWH despite a low embolic risk, whereas 49 of the patients with heart valve replacement (51%) did not receive dosages of bridging therapy as recommended in guidelines. In conclusion, in this registry of patients treated by cardiologists, 94% of patients who required interruption of OAC before invasive procedures received LMWH as a bridging therapy, of whom 73% were treated with halved therapeutic LMWH-dosages. Guideline recommendations were followed in only 31% of cases. Importantly, 69% of patients with AF were over-treated while 51% of patients with heart valve replacement were under-treated with LMWHs. A HASB-BLED score ≥ 3 was highly predictive of bleeding events.

Guidelines on oral anticoagulation with warfarin – fourth edition

Guidelines on oral anticoagulation with warfarin – fourth edition

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

Maternal Complications and Pregnancy Outcome in Women With Mechanical Prosthetic Heart Valves Treated With Enoxaparin

Obstetric Anesthesia Digest 30(4):p 223-224, December 2010. | DOI: 10.1097/01.aoa.0000389599.26353.cd

Changes in the USP Heparin Monograph and Implications for Clinicians

Changes in the USP Heparin Monograph and Implications for Clinicians

Use of therapeutic dose low molecular weight heparin during pregnancy in women with mechanical heart valves

Management of anticoagulation in women with mechanical heart valves (MHV) is one of the most challenging issues faced by obstetric physicians who manage pregnant women with cardiac problems. The already high risk of valve thrombosis is increased further during pregnancy because of the prothrombotic changes of pregnancy. The safest option for the mother, to reduce the risk of valve thrombosis leading to valve failure or systemic thromboembolism, is to remain on oral anticoagulants such as warfarin. However, warfarin crosses the placenta with a 5–6% risk of warfarin embryopathy if taken between six and nine weeks gestation.1 In addition, warfarin anticoagulates the fetus and there is a high rate of late fetal loss, up to 40% in some studies,2 which further increases women's reluctance to continue taking this form of anticoagulation. Heparin, which does not cross the placenta, is an effective alternative to warfarin for treatment and prevention of venous thrombosis during pregnancy, but there are concerns relating to its efficacy as an anticoagulant in women with MHV. Subcutaneous unfractionated heparin, even when given in high and monitored doses, is associated with an unacceptably high rate of maternal thrombosis. The more predicable anticoagulant effect of low molecular weight heparin (LMWH) makes it is an attractive agent for use in this clinical situation but there are limited data relating to its safety and efficacy. In 2004, Oran and co-workers3 reviewed published case reports and case series of LMWH use in pregnant women with MHV. The overall rate of thromboembolic complications in 81 pregnancies was 11.1% but four of these events were reported in single case studies. Monitoring of anti-Xa levels was not carried out in all centres and women received LMWH for variable periods during pregnancy. Such discrepancies make it difficult to extrapolate these data to other situations.

Maternal Complications and Pregnancy Outcome in Women With Mechanical Prosthetic Heart Valves Treated With Enoxaparin

Anticoagulation therapy is recommended throughout pregnancy for women with mechanical heart valves, to reduce the risk of thromboembolic complications. Although warfarin is the preferred therapeutic agent for such patients when not pregnant, warfarin is teratogenic; during pregnancy, unfractionated or low molecular weight heparin (LMWH) may be considered because it is safer for the fetus, although it is not clear that it provides adequate anticoagulation. A large number of studies have reported a wide variation (3.9%–22%) in the percentage of thrombotic complications reported in pregnant women with mechanical heart valves managed with LMWH (enoxaparin), although most studies were small. When analysis was limited to studies including 5 or more pregnancies, a rate of 6.9% was reported. This retrospective single center study investigated the rate of maternal thrombotic and hemorrhagic complications and other maternal and fetal outcomes in 31 women with mechanical heart valves who were treated with therapeutic dose LMWH (enoxaparin) during pregnancy. Between 1997 and 2008, data were extracted from the medical records of these women and analyzed for the maternal primary endpoints of thromboembolism and hemorrhagic complications. Secondary maternal and fetal outcomes that were analyzed included miscarriage, stillbirth, neonatal or infant death, live birth, small for gestational age, warfarin embryopathy, and warfarin-associated fetal loss. Most patients received therapeutic dose enoxaparin (1 mg/kg BID) and aspirin 100 to 150 mg q day until planned delivery. A total of 47 pregnancies were evaluated in 31 subjects. Thirty-four (72.3%) were managed with enoxaparin as the primary anticoagulant and the remaining 13 (27.7%) received warfarin as the main anticoagulant, with enoxaparin used between 6 and 12 weeks of gestation and/or peridelivery. Thromboembolic complications occurred in 7 (14.9%) pregnancies; of these, 5 (10.6%) were directly related to enoxaparin therapy. Poor compliance with enoxaparin was a major factor in 3 of these events and failure to achieve therapeutic target anti-Xa levels was a major contributing factor in the other 2 cases. The other 2 thrombotic complications occurred because the patients electively stopped taking their anticoagulant (warfarin). Antenatal bleeding occurred in 17% (8/47) of the pregnancies; 5 of the 8 bleeds were associated with enoxaparin, and the other 3 occurred during treatment with intravenous unfractionated heparin. Primary or secondary postnatal hemorrhage complicated 32% (15/47) of the pregnancies; 6 were due to enoxaparin, one occurred on unfractionated heparin, one on unfractionated heparin and warfarin, and one on warfarin alone. Among the 35 pregnancies continued beyond 20 weeks of gestation, 96% (22/23) of the women taking mainly enoxaparin had a surviving infant compared with 75% (9/12) of those taking primarily warfarin (P = 0.11). There were 4 perinatal deaths; 3 due to warfarin. These findings suggest to the investigators that administration of therapeutic dose enoxaparin in combination with low-dose aspirin to pregnant women with mechanical heart valves can achieve a low risk of valve thrombosis and a high rate of infant survival, provided that there is close clinical follow-up and high compliance.

Using low molecular weight heparin in special patient populations

Clinical trials evaluating low molecular weight heparin (LMWH) for the prevention and treatment of venous thromboembolism and acute coronary syndromes have led to their regulatory approval for these indications in the general population. However, certain patient populations have been excluded from these landmark clinical trials, including patients with renal insufficiency, obese patients and pregnant women. In these special populations, data on safety and efficacy is limited and typically based on pharmacokinetic studies often performed in healthy subjects, or small cohort studies which are generally not powered to evaluate clinical outcomes such as bleeding or recurrent thrombosis. Because LMWH is mainly cleared renally, patients with severe renal insufficiency are at risk of LMWH accumulation and increased bleeding risks. In obese patients, there is concern regarding possible overdosing of therapeutic dose LMWH, since LMWH does not distribute in fat tissue. There are also concerns about possible underdosing of prophylactic dose LMWH in obese individuals using the standard fixed doses, particularly in the extremely obese individuals undergoing bariatric surgery. Last, pregnancy poses challenges with regards to the safety of LMWH during pregnancy and use of LMWH around delivery. This review summarizes the existing data in these special populations and proposes general recommendations for practice.

Bridging of Chronic Oral Anticoagulation with Enoxaparin in Patients with Atrial Fibrillation: Results from the Prospective BRAVE Registry

Current American College of Chest Physicians (ACCP) guidelines on the perioperative management of oral anticoagulation (OAC) suggest bridging therapy with therapeutic doses of low-molecular-weight heparin (LMWH) in patients with atrial fibrillation (AF) if at high or moderate thromboembolic (TE) risk, and with reduced doses in patients with low TE risk. Our objective was to assess the efficacy and safety of bridging OAC with enoxaparin in AF patients. These are the results of an open, prospective monocenter register. Hospitalized and ambulatory patients with AF requiring bridging therapy at high or moderate TE risk and normal renal function were treated with therapeutic LMWH doses; all other patients received reduced doses. A total of 703 patients were enrolled, of whom 358 (50.9%) were at moderate-to-high and 345 (49.1%) at low TE risk. Renal impairment was detected in 308 patients (43.8%). One hundred ninety patients (27.1%) were treated with therapeutic LMWH doses and 513 (72.9%) with reduced doses. No TE events were observed during the follow-up period (0%; 95% confidence interval [CI] 0.0-0.52). Three major bleeds (0.4%; 0.1-1.2) and 60 minor bleeds were noted (8.9%; 6.6-10.9). Age and total LMWH doses were risk factors for bleeding in the multivariate analysis. The study, under conditions of everyday clinical care, supports a predefined bridging regimen based on the individual patient's TE risk and renal function. Patients with low TE risk or with impaired renal function can be bridged effectively and safely with reduced LMWH doses.

Perkutane endoskopische Gastrostomie

BackgroundPercutaneous endoscopic gastrostomy (PEG) has been classified to date as a high-risk procedure (ASGE guidelines). Coagulopathies, thrombocyte aggregation inhibitors (Aspirin, clopidogrel etc.) and phenprocoumone or warfarin are considered to be contraindications. The study examined for the first time the risk factors in patients with and without concurrent anticoagulation.MethodsBetween 2001 and 2007 PEGs were placed in 450 patients with neurological diseases at the University Hospital for General and Visceral Surgery in Freiburg and studied prospectively during hospitalization. The patients were divided into 3 groups: group 1 controls (n=50, no anticoagulation), group 2 low-molecular-weight heparin (LMWH) prophylaxis (n=152) and group 3 therapeutic anticoagulation (unfractionated heparin, phenprocoumone, therapeutic LMWH, aspirin, clopidorel and combinations, n=248). Univariate analyses were performed to determine risk factors for the occurrence of infection, bleeding and peritonitis. The p-values (p), odds ratios (OR) and 95% confidence intervals (CI) are given.ResultsThe average hospitalization time was 27.4 days (range 1–268 days) and hospital mortality was 6%. There were no cases of death due to the PEG. Complications included peristomal infections (n=30, 6.6%) and peritonitis (n=6, 1.3%). Post-PEG bleeding did not occur either with or without anticoagulation. The investigated risk factors showed no statistically significant values with respect to prognosis for these complications. Multivariate testing could not be carried out due to the low number of complications. ConclusionComplications of PEG placement with the method used here are rare. An increased risk of bleeding during therapeutic anticoagulation was not observed. In our opinion the present data indicate that PEG placement can be carried out in selected patients with increased risk of thromboembolism without discontinuation of anticoagulation.

Dose escalation of low molecular weight heparin to manage recurrent venous thromboembolic events despite systemic anticoagulation in cancer patients.

Cancer patients with venous thromboembolism (VTE) are at high risk of recurrent VTE despite standard anticoagulation. To date, very little published literature is available to guide the treatment of cancer patients with recurrent VTE. To evaluate the benefit and risk of low molecular weight heparin (LMWH) dose escalation in cancer patients with recurrent VTE. This was a retrospective cohort study of consecutive cancer outpatients referred for management of a symptomatic, recurrent VTE while receiving an anticoagulant. Confirmed episodes of recurrent VTE were treated with either dose escalation of LMWH in patients already anticoagulated with LMWH, or initiation of therapeutic dose LMWH in patients who were taking a vitamin K antagonist (VKA). All patients were followed for a minimum of 3 months after the index recurrent VTE unless they died during this period. Seventy cancer patients with a recurrent VTE despite ongoing anticoagulation were included. At the time of the recurrence, 67% of patients were receiving LMWH, and 33% were receiving a VKA. A total of six patients [8.6%; 95% confidence interval (CI) 4.0-17.5%] had a second recurrent VTE during the 3-month follow-up period, at an event rate of 9.9 per 100 patient-years (95% CI 2.0-17.8%). Three patients (4.3%; 95% CI 1.5-11.9%), or 4.8 per 100 patient-years (95% CI 0.0-10.3%) of follow-up, had bleeding complications. The median time between the index recurrent VTE to death was 11.4 months (range, 0-83.9 months). Cancer patients with recurrent VTE have a short median survival. Escalating the dose of LMWH can be effective for treating cases that are resistant to standard, weight-adjusted doses of LMWH or a VKA.

Post Discharge Prophylactic Anticoagulation in Gastric Bypass Patient—How Safe?

It is becoming an increasingly common practice to discharge gastric bypass (GBP) patients on prophylactic anticoagulation. This is because pulmonary embolism (PE) is a common cause of mortality postoperatively. This study was undertaken to: (1) determine the incidence of major bleeding in GBP patients discharged on prophylactic low molecular weight heparin (LMWH)-enoxaparin and, (2) correlate the bleeding risk to the dose used. Retrospective chart review of all open GBP operation from June 2004 to August 2005. One hundred and twenty seven patients were sent home on LMWH for 2 weeks. Body mass index (BMI) > or =50 kg/m(2) with chronic venous stasis and/or obstructive sleep apnea, previous history of PE or deep vein thrombosis (DVT) or BMI > or =60 kg/m(2). The study group was divided into two subgroups: 40 mg twice daily (bid) and 60 mg bid LMWH. Statistical analysis was done with the chi-square. The primary outcome measure was major bleeding; defined as bleeding during the period of LMWH use associated with symptomatic decrease in hematocrit (HCT), necessitating stopping LMWH administration before the end of the study period (2 weeks), bleeding-related readmission, blood transfusion, or intervention. Excluded were patients on warfarin or treated with therapeutic LMWH. The groups were similarly matched for age, body mass index, and risk factors. No episode of major bleeding after discharge occurred in either group. The use of low molecular weight heparin for prophylactic anticoagulation after open gastric bypass is not associated with risk of major bleeding.

Pharmacokinetics, efficacy, and safety of LMWHs in venous thrombosis and stroke in neonates, infants and children

Since the early nineties it has been shown that low molecular weight heparin (LMWH) has significant advantages over unfractionated heparin and oral anticoagulants for both the treatment and the prevention of thrombosis, not only in adults, but also in children. The present review was based on an 'EMBASE', 'Medline' and 'PubMed' search including literature published in any language since 1980 on LMWH in neonates, infants and children. It included paediatric pharmacokinetic studies, the use of LMWH in children with venous thrombosis, LMWH administration in paediatric patients with ischaemic stroke, and its use in order to prevent symptomatic thromboembolism in children at risk. An increasing rate of off-label use of LMWH in children has been reported, showing that LMWHs offer important benefits to children with symptomatic thromboembolic events and poor venous access. Two well-conducted pharmacokinetic studies in this age group showed that neonates and younger infants require higher LMWH doses than older children to achieve the targeted anti-Xa levels, due to an increased extra vascular clearance. Recurrent symptomatic thromboses under LMWH occur in approximately 4% of children treated for venous thrombosis, and in 7% of children treated for stroke; major bleed was documented in 3% of children with therapeutic target LMWH anti-Xa levels, whereas minor bleeding was reported in approximately 23% of children receiving either therapeutic or prophylactic doses, respectively. Further randomized controlled trials are recommended to evaluate the optimum duration and application for different LMWH indications in children.

Free tissue transfer and deep vein thrombosis

Reconstruction of the post-oncologic defect of the lower limb frequently requires free tissue transfer and these often extensive bone and soft tissue resections can occasionally be compounded by the presence of a deep venous thrombosis (DVT). We describe two patients in whom free tissue transfer was attempted, following extensive resection of a sarcoma in the thigh. Both patients had been diagnosed with DVT prior to surgery and received therapeutic low molecular weight heparin preoperatively. In the first patient, flap failure occurred due to venous congestion initially resulting from poor flow in the reconstructed femoral vein and then thrombosis and failure of the vascular reconstruction. In the second patient the superficial venous system was used for successful microvascular anastomosis leading to survival of the flap. Therefore, patients undergoing lower extremity free tissue transfer who are at high risk of DVT, or when there is a clinical suspicion of DVT, thorough preoperative assessment of the deep and superficial venous system is warranted for reconstruction planning.