Injection Of Low Molecular Weight Heparin Research Articles

Patient Compliance with Extended Low Molecular Weight Heparin Injections following Hip and Knee Arthroplasty

The use of extended duration thromboprophylaxis following hip and knee arthroplasty is becoming widespread. The aim of our study was to determine patient compliance with extended duration thromboprophylaxis using low molecular weight (LMWH) injections following hip and knee arthroplasty. 42 consecutive patients undergoing hip and knee arthroplasty were prospectively contacted during their fifth post operative week. A fully anonymised questionnaire was completed by each patient. All patients responded. One was excluded having been prescribed warfarin for pre existing atrial fibrillation. Twenty nine (71%) patients were discharged with the intention of self administering LMWH injections. Eight (20%) and four (9%) patients were discharged with the intention of administration by a relative or district nurse respectively. No patient required the person administering the injections to be changed after discharge from hospital. 90% (n=37) of patients reported not missing any doses. 10% (n=2) of patients missed one dose and 10% (n=2) missed two doses. Patient compliance with extended duration thromboprophylaxis using LMWH injections is extremely high. Oral thromboprophylaxis may be useful in the minority of patients requiring daily visits by a nurse to administer injections.

In Vivo Neutralization of Unfractionated Heparin and Low-Molecular-Weight Heparin by a Novel Salicylamide Derivative

Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are widely used anticoagulants for surgical and interventional use. Currently, the anticoagulant and bleeding effects of heparin are neutralized by protamine sulfate. There are several problems associated with the use of protamine sulfate, including allergic reactions, cardiovascular effects, heparin rebound, and incomplete neutralization of LMWHs. The objective of this investigation is to characterize the effectiveness of a novel salicylamide-derived heparin antagonist, PMX 60056, in neutralizing the antithrombotic and bleeding effects of UFH and LMWHs. Animals were first anticoagulated using an intravenous injection of UFH or LMWH followed by protamine sulfate or PMX 60056. Established animal models of hemorrhage (rat-tail transection) and thrombosis (jugular vein clamping) were then performed. Blood samples were collected for ex vivo analysis using activated partial thromboplastin time (aPTT), anti-Xa, and anti-IIa assays. We demonstrate that PMX 60056 neutralized the antithrombotic, anticoagulant, and bleeding effects of heparins as effectively as protamine sulfate and may be slightly more efficacious against LMWHs. These results suggest that PMX 60056 may provide an improved approach for the neutralization of UFH and LMWHs.

The reason of low molecular weight heparin injection site bruising and to investigate the injection method

Objective To analyze the reason of low molecular weight heparin injection site bruising and to investigate the injection method. Methods A total of 120 cases treated by subcutaneous injection of low molecular weight heparin calcium were received two kinds of injection technique: injection technique A was the new improved injection method ( Detaining air bubble skill combined with translation abdomen fold method used 30 s injection duration) and injection technique B was the routine method. The injected sites of method A was the left side of abdomen, the injection duration was 30 s, and 618 injections were executed; while the injection sites of method B was the right side of the abdomen, the injection duration was 10 s, and 617 injections were executed. Self comparison was done to analyze the local reactivity condition and pain degree of the two injection methods. Results There were significant differences in injection site bruising incidence rate (73.9% vs 37.2% ), hemorrhagic petechia average diameter (P＜0.01) and the degree of pain ( P ＜ 0. 05 ) between method A and method B. Conclusions Injection technique A could obviously reduce the rate of injection site hemorrhage and pain in low molecular weight heparin calcium injection. Key words: Low molecular weight heparin; Hemorrhage; Injection technique

Comparison of therapeutic efficacy between fondaparinux and low molecular weight heparin for patients with acute coronary syndrome

To compare the efficacy and safety of fondaparinux with that of low molecular weight heparin (LMWH) in the treatment of acute coronary syndrome (ACS). One hundred and five patients with ACS admitted from November 2009 to August 2010 were randomly divided into two groups. They were all treated with nitrates, β-blockers, angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), statins, clopidogrel, enteric-coated aspirin and other basic drugs. On the basis of the above treatment, the fondaparinux group patients (n=50) received hypodermic injection of fondaparinux 2.5 mg, once a day, and the LMWH group patients (n=55) received hypodermic injection of LMWH 0.4 ml, twice a day, the therapeutic course being 3-8 days in both groups. The therapeutic efficacy, the cardiovascular event and bleeding incidences during 7 days and 30 days of the treatment were observed. There was no significant difference between the fondaparinux group and LMWH group in the total effective rate (96.0% vs. 92.7%,P>0.05), also no significant differences were found between the two groups in cardiovascular events (death, acute myocardial infarction and recurrence of myocardial infarction) during 7 days and 30 days (7 days : 4.0% vs. 7.3%, 30 days: 8.0% vs. 10.9%, both P>0.05). There was no major bleeding incident, and the incidence of minor bleeding in fondaparinux group was obviously lower than that in LMWH group (2.0% vs. 32.7%, P<0.01). The efficacy of fondaparinux in the treatment of ACS is not inferior to that of LMWH, and adverse events during and after its administration were significantly lower than those in LMWH group, so that fondaparinux treatment for ACS is safe and can be highly recommended.

Patient Compliance with Extended Low Molecular Weight Heparin Injections Following Hip and Knee Arthroplasty

Abstr A ct . The use of extended duration thromboprophylaxis following hip and knee arthroplasty is becoming widespread. The aim of our study was to determine patient compliance with extended duration thromboprophylaxis using low molecular weight (LMWH) injections following hip and knee arthroplasty. 42 consecutive patients undergoing hip and knee arthroplasty were prospectively contacted during their fifth post operative week. A fully anonymised questionnaire was completed by each patient. All patients responded. One was excluded having been prescribed warfarin for pre existing atrial fibrillation. Twenty nine (71%) patients were discharged with the intention of self administering LMWH injections. Eight (20%) and four (9%) patients were discharged with the intention of administration by a relative or district nurse respectively. No patient required the person administering the injections to be changed after discharge from hospital. 90% (n=37) of patients reported not missing any doses. 10% (n=2) of patients missed one dose and 10% (n=2) missed two doses. Patient compliance with extended duration thromboprophylaxis using LMWH injections is extremely high. Oral thromboprophylaxis may be useful in the minority of patients requiring daily visits by a nurse to administer injections.

Patient Preferences for an Oral Anticoagulant after Major Orthopedic Surgery

Since 2008, the availability of the oral direct thrombin inhibitor dabigatran etexilate provides a further therapeutic alternative to injectable low-molecular-weight heparin (LMWH) for thromboprophylaxis following hip or knee replacement surgery. The intention of this study is to analyze patient preferences for this new oral thromboprophylaxis agent. Face-to-face interviews were conducted with 73 doctors and nurses in 12 German hospitals, 195 current hip and knee replacement patients in six German rehabilitation hospitals, and 202 former thromboprophylaxis patients. Qualitative questions were complemented by a full-profile ranking-based conjoint analysis regarding alternative thromboprophylaxis regimens. Nearly 100% of the interviewed medical staff viewed the daily subcutaneous LMWH injection as a source of inconvenience for patients. However, both current and former patients perceived their discomfort to be much less intense. In contrast, the conjoint estimates of preferences showed that older and male patients in particular understated their levels of discomfort in a face-to-face interview situation and had a strong preference for oral anticoagulation. Patients in Germany appear to have a positive preference for oral thromboprophylaxis after major orthopedic surgery.

The effect of low-molecular-weight heparin on rat tendon healing

We investigated the effect of low-molecular-weight heparin (LMWH) on the healing of tendons. Forty-five adult Wistar rats weighing 300 g were randomized into three groups equal in number. All the rats underwent full-thickness surgical incision of the Achilles tendon followed by primary repair. After the operation, two groups received daily subcutaneous LMWH injections (nadroparin calcium) for four weeks at high or low doses (group I, 6 mg/kg, 170 IU AXa; group II, 3 mg/kg, 85 IU AXa). Group III remained untreated as the control group. Histologically, the specimens were examined under light and electron microscopy with regard to the amount of fibrillar collagen synthesis, mitochondrial degeneration, and the composition of the extracellular matrix collagen. Biomechanically, maximum load to failure and correspondent elongation of the tendons were measured. Compared to the control group, histologically, both LMWH-treated groups exhibited increased number of fibroblasts, increased fibrillar collagen formation in the extracellular matrix, and higher counts of granular endoplasmic reticula in cytoplasmic contents of fibroblasts as well as decreased mitochondrial vacuolization and degeneration. Biomechanical assessments showed that tendons in group I had significantly higher maximum load to failure and elongation values than group II and III (31 N vs. 24.6 N and 23.1 N; 25 mm vs. 19.6 mm and 17.3 mm, respectively; p<0.05). Groups II and III did not differ significantly in this respect (p>0.05). Daily administration of single dose LMWH improves tendon healing through increasing the number of fibroblasts and fibrillar collagen synthesis and decreasing mitochondrial degeneration.

Low-Molecular-Weight Heparin versus Compression Stockings for Thromboprophylaxis after Knee Arthroscopy

Knee arthroscopy, the most common orthopedic operation worldwide, carries a definite risk for deep venous thrombosis; however, postsurgical thromboprophylaxis is not routinely recommended. To evaluate whether low-molecular-weight heparin (LMWH) better prevents deep venous thrombosis and does not cause more complications than graduated compression stockings in adults having knee arthroscopy. Assessor-blind, randomized, controlled trial. The Department of Knee Surgery, Abano Terme Clinic, Abano Terme (knee surgery, random assignment, and bleeding event survey), and the Unit of Angiology, University Hospital of Padua, Padua (efficacy outcomes evaluation, follow-up, data management, and analysis), Italy. 1761 consecutive patients undergoing knee arthroscopy between March 2002 and January 2006. Patients were randomly assigned to wear full-length graduated compression stocking for 7 days (660 patients) or to receive a once-daily subcutaneous injection of LMWH (nadroparin, 3800 anti-Xa IU) for 7 days (657 patients) or 14 days (444 patients). The data and safety monitoring board prematurely stopped the 14-day heparin group after the second interim analysis. Combined incidence of asymptomatic proximal deep venous thrombosis, symptomatic venous thromboembolism, and all-cause mortality (primary efficacy end point) and combined incidence of major and clinically relevant bleeding events (primary safety end point). All patients had bilateral whole-leg ultrasonography at the end of the allocated prophylactic regimen or earlier if indicated. All patients with normal findings were followed for 3 months, and none was lost to follow-up. The 3-month cumulative incidence of asymptomatic proximal deep venous thrombosis, symptomatic venous thromboembolism, and all-cause mortality was 3.2% (21 of 660 patients) in the stockings group, 0.9% (6 of 657 patients) in the 7-day LMWH group (absolute difference, 2.3 percentage points [95% CI, 0.7 to 4.0 percentage points]; P = 0.005), and 0.9% (4 of 444 patients) in the prematurely stopped 14-day LMWH group. The cumulative incidence of major or clinically relevant bleeding events was 0.3% (2 of 660 patients) in the stockings group, 0.9% (6 of 657 patients) in the 7-day LMWH group (absolute difference, -0.6 percentage point [CI, -1.5 to 0.2 percentage points]), and 0.5% (2 of 444 patients) in the 14-day LMWH group. The study was not double-blind or double-dummy. Almost half of the events making up the composite outcome measure were distal deep venous thromboses. Stockings were used instead of placebo because of local prophylaxis policies. In patients undergoing knee arthroscopy, prophylactic LMWH for 1 week reduced a composite end point of asymptomatic proximal deep venous thrombosis, symptomatic venous thromboembolism, and all-cause mortality more than did graduated compression stockings.

Cardioverter-defibrillator lead-related thrombus treated with prolonged anticoagulation in patient with prothrombotic disorder

Following an accidental finding of a large atrial lead-related thrombus in a 33-year-old woman with suspected prothrombotic disorder, a conservative treatment with low molecular weight heparin injections and close transthoracic and transesophageal echocardiographic monitoring was used. It led to a complete resolution of the thrombus in 4 weeks without the need for a high-risk operation in this patient.

Platelet activation in clinical haemodialysis: LMWH as a major contributor to bio-incompatibility?

The sum of undesirable side effects, occurring during haemodialysis (HD), is called bio-incompatibility. Concerning platelets, both an increase in the expression of the cell surface marker P-selectin (CD62p) and release of the intracellular granule product platelet factor 4 (PF4) have been described. However, as PF4 is also abundantly present on endothelium-bound proteoglycans, it is questionable whether the HD-induced increase is exclusively attributable to release from platelets. With respect to the cause of HD-induced bio-incompatibility, interest has been focused mainly on the extracorporeal circuit (ECC), especially the dialyser, whereas only little attention has been paid to other parts of the ECC and the mode of anticoagulation applied. To address the cause and origin of platelet activation and PF4 release during clinical HD, two complementary clinical studies were performed. In study I, the relative influence of the various parts of the ECC was evaluated by measuring the expression of CD62p, platelet aggregation and levels of PF4 and serotonin at various sampling points. In study II, low-molecular-weight heparin (LMWH) was administered 10 min before the actual start of HD, in order to separate the effects from LMWH and the ECC on platelet activation. In study I, CD62p expression increased across the entire length of the ECC, including the roller pump and dialyser (median at t(5) from 26% to 43%, P = 0.008; median at t(30) from 28% to 48%, P = 0.007). Increments in PF4 and aggregation of platelets were relatively modest. Platelet serotonin content, which was below reference values in healthy controls, and plasma serotonin concentration, which was above reference values, did not change. In study II, PF4 levels increased markedly after the injection of LMWH (from 12 IU/ml at t(-10) to 75 IU/ml at t(0), P = 0.018), whereas CD62p expression remained stable until the start of HD. Platelet activation, as measured by the up-regulation of CD62p, is an early process, occurring not only within the dialyser, but across the entire length of the ECC. As CD62p remained unaltered after the administration of LMWH 10 min before the actual start of HD, this kind of activation is independent of LMWH. Considering PF4 however, a sharp increment was observed after the administration of LMWH and before the start of HD. This finding suggests that the PF4 release observed early in clinical HD is largely independent from the ECC, and is probably the result of LMWH-induced detachment from the endothelium. As the platelet serotonin content was relatively reduced and the plasma serotonin levels were elevated, platelets from chronic HD patients might be depleted due to chronic repetitive activation. Based on these data, it appears first, that PF4 is an inferior marker of platelet activation in clinical HD and second, that LMWH is a major contributor to HD-induced bio-incompatibility.

Agents to Control Bleeding Show Promise

Every year, thousands of patients develop deep vein thrombosis (DVT) and are at risk of pulmonary embolism after undergoing surgeries, particularly orthopedic procedures in the hips and legs. Although low-molecular-weight heparin is considered the standard therapy for DVT and other forms of venous thromboembolism, it is far from an ideal anticoagulant. Its drawbacks include the need for daily injections, adverse interactions with many types of drugs, and a wide variation in patient response. Researchers have therefore continued to search for alternative therapies. A phase 2 randomized, open-label trial funded by Sanofi-Aventis assessed the potential of idraparinux for preventing DVT and pulmonary embolism. This anticoagulant, which targets a molecule in the coagulation cascade, can be taken less often than low-molecular-weight heparin. In the study,2904patientswithaprevious DVT episode were randomized to receive idraparinuxbysubcutaneous injectiononceaweekorstandardtreatment, including daily injections of lowmolecular-weightheparin.After3months of therapy, idraparinux proved to be as effectiveas thestandardtreatment inpreventing venous clot recurrence (2.9% vs 3.0% recurrence respectively). Severe bleeding, apotential adverseeffectof anticoagulants,occurredin4.5%ofpatients taking idraparinux and in 7.0% of those receiving standard therapy.

Effect of Subconjunctivally Injected, Liposome-Bound, Low-Molecular-Weight Heparin on the Absorption Rate of Subconjunctival Hemorrhage in Rabbits

To investigate the effect of subconjunctival injection of liposome-bound, low-molecular-weight heparin (LMWH) on the absorption rate of subconjunctival hemorrhages. Subconjunctival hemorrhages were induced in both eyes of 30 rabbits by the subconjunctival injection of 0.1 mL of autologous blood from auricular marginal veins. After 8 hours, randomized subconjunctival injections of one of three materials were made: 5 IU/mL liposome-bound LMWH (0.1 mL) in 18 eyes (group A), only liposomes (0.1 mL) in 14 eyes (group B), the free form of LMWH (5 IU/mL, 0.1 mL) in 14 eyes (group C), or no injection in 14 eyes (group D). Subconjunctival hemorrhages were photographed with a digital camera at 8, 24, 48, 72, 96, and 120 hours after induction of subconjunctival hemorrhages, sized with an image analyzer, and compared between groups. Subconjunctival hemorrhages were absorbed faster in group A (liposome-bound LMWH injected) than in with group B (liposome injected). Comparison of groups A and C (free LMWH injected) showed statistical differences in the absorption rates at 96 and 120 hours except at 24, 48, and 72 hours. The mean elapsed time for the complete resorption of subconjunctival hemorrhages was shortest in group A among four groups, whereas group B and the control showed no significant differences. The ocular and systemic absorption of LMWH were significantly lower after injection of the liposome-bound than the free form. The subconjunctival injection of liposome-bound LMWH appears to enhance subconjunctival hemorrhage absorption in rabbits.

Regional Anesthesia for a Parturient with Venous Sinus Thrombosis and Placental Abruption Undergoing Fractional Heparin Therapy

THE increased incidence of thrombosis and hypercoagu-lability during pregnancy are well recognized and require anticoagulation for symptomatic sequelae. The following case illustrates our perioperative treatment of a patient with vaginal bleeding while undergoing treatment for a transverse sinus thrombosis.

Low-Molecular-Weight Heparin in Patients With Advanced Cancer: A Phase 3 Clinical Trial

To prospectively assess whether low-molecular-weight heparin (LMWH) provides a survival benefit in patients with advanced cancer. Between December 1998 and June 2001, we performed a randomized controlled study of patients with advanced cancer. Initially, the study was double blinded and placebo controlled, with the patients receiving daily injections of 5000 U of LMWH or saline. However, because of low accrual midway through the study, the placebo injection arm was eliminated, and the study became open labeled, with patients receiving either LMWH injections plus standard clinical care or standard clinical care alone. The primary study end point was overall survival. Of 141 patients randomized to this clinical trial, 3 dropped out, leaving 138 patients. The median survival time was 10.5 months (95% confidence interval, 7.6-12.2 months) for the combined standard care and placebo groups. The median survival time for the combined LMWH arms was 7.3 months (95% confidence interval, 4.8-12.2 months). These median survival times were not significantly different (log-rank P = .46). The median survival times for the blinded and unblinded LMWH groups were 6.2 months and 9.0 months, respectively. The median survival times were 10.3 months for the blinded placebo arm and 10.5 months for the standard care arm. The rate of severe or life-threatening venous thromboembolism was 6% in the LMWH arms and 7% in the control arms. The rate of severe or life-threatening bleeding was 3% in the LMWH arms and 7% in the control arms.

Preparation and evaluation of oral solid heparin using emulsifier and adsorbent for in vitro and in vivo studies

Oral anticoagulant therapy with heparin has been challenged by formulating heparin in oral solid preparation. As heparin, low molecular weight heparin (LMWH) was used. LMWH was dispersed with a surfactant used for the self-microemulsifying drug delivery system (SMEDDS), PEG-8 caprylic/capric glycerides (Labrasol), and the mixture was solidified with three kinds of adsorbents, microporous calcium silicate (Florite™ RE), magnesium alminometa silicate (Neusilin™ US 2) and silicon dioxide (Sylysia™ 320). The in vitro release study showed that the T50%s were 3.2 ± 0.1 min for Sylysia 320, 4.6 ± 0.2 min for Florite RE, 13.7 ± 0.1 min for Neusilin US 2. The in vivo rat absorption study showed that Florite RE system had the highest C max, 0.42 ± 0.01 IU/mL and AUC, 0.59 ± 0.06 IU h/mL, where plasma LMWH levels were measured as anti-Xa activity. Other preparations had the C max and AUC, 0.12 ± 0.01 IU/mL and 0.15 ± 0.02 IU h/mL for Neusilin US 2 and 0.25 ± 0.02 IU/mL and 0.40 ± 0.03 IU h/mL for Sylysia 320, respectively. The bioavailability (BA) of LMWH from the microporous calcium silicate preparation, Florite RE, was 18.8% in rats by comparing the AUC obtained after i.v. injection of LMWH, 40 IU/kg to another group of rats. Florite RE system was evaluated in dogs after oral administration in an enteric capsule made of Eudragit S100 at the LMWH dose of 200 IU/kg. High plasma anti-Xa activity levels were obtained, i.e., the C max was 0.48 ± 0.11 IU/mL and AUC was 1.64 ± 0.32 IU h/mL. These results suggest that adsorbent system is useful as an oral solid delivery system of poorly absorbable drugs such as LMWH.

The Safety of Low-Molecular-Weight Heparin Therapy During Labor

For some years, low-molecular-weight heparin (LMWH) has been widely used to prevent thromboembolic complications in pregnancies at risk. Its safety has been well established in previous studies. This study was designed to determine the safety of discontinuing LMWH for 12 to 24 hours before vaginal delivery or an invasive procedure. Hemorrhagic and other complications were surveyed in 284 women given enoxaparin during pregnancy and in 16,132 others not given this treatment. Enoxaparin was self-administered by subcutaneous injection, as a preventive measure (0.5–1 mg/kg daily) in 84% of women, and therapeutically (1.5–2 mg/kg daily) in the remaining 16%. Postpartum hemorrhage was defined as an estimated loss of more than 500 mL of blood after vaginal delivery, more than 1000 mL after cesarean section, or a drop of at least 2 gram% of hemoglobin or 10% in hematocrit 24 to 72 hours after giving birth. The duration of treatment averaged 251 days and included at least 6 postpartum weeks. Nearly one fourth of treated women had previously experienced thromboembolism. The treated and untreated women were similar in age and pregestational body mass index. Postpartum hemorrhage was rare in both groups, occurring in 2.1% of treated women and 1.9% of those not treated. Three of 6 hemorrhages in LMWH-treated women were ascribed to uterine atony after prolonged labor with oxytocin. Four of the 6 treated women with postpartum hemorrhage had their last treatment more than 24 hours earlier. In only one case did the dose of enoxaparin exceed 0.5 mg/kg daily. Just over three fourths of treated women had an epidural catheter placed. The last injection of LMWH generally was given 12 to 24 hours before delivery, cesarean section, or catheter placement. No spinal hematomas were diagnosed. Discontinuing LMWH 12 to 24 hours or longer before vaginal or section delivery did not influence the 5-minute Apgar score, umbilical arterial blood pH, or admission to neonatal intensive care. None of the infants born to LMWH-treated mothers had hemorrhagic complications. LMWH in the form of enoxaparin may be safely discontinued 12 hours before labor is induced whether vaginal or operative delivery is carried out. It also appears that epidural anesthesia is safe if 12 or more hours have elapsed since the last dose of enoxaparin.

Heparin and Low-Molecular-Weight Heparin: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy

This article about unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) is part of the Seventh American College of Chest Physicians Conference on Antithrombotic and Thrombolytic Therapy: Evidence-Based Guidelines. UFH is a heterogeneous mixture of glycosaminoglycans that bind to antithrombin via a pentasaccharide, catalyzing the inactivation of thrombin and other clotting factors. UFH also binds endothelial cells, platelet factor 4, and platelets, leading to rather unpredictable pharmacokinetic and pharmacodynamic properties. Variability in activated partial thromboplastin time (aPTT) reagents necessitates site-specific validation of the aPTT therapeutic range in order to properly monitor UFH therapy. Lack of validation has been an oversight in many clinical trials comparing UFH to LMWH. In patients with apparent heparin resistance, anti-factor Xa monitoring may be superior to measurement of aPTT. LMWHs lack the nonspecific binding affinities of UFH, and, as a result, LMWH preparations have more predictable pharmacokinetic and pharmacodynamic properties. LMWHs have replaced UFH for most clinical indications for the following reasons: (1) these properties allow LMWHs to be administered subcutaneously, once daily without laboratory monitoring; and (2) the evidence from clinical trials that LMWH is as least as effective as and is safer than UFH. Several clinical issues regarding the use of LMWHs remain unanswered. These relate to the need for monitoring with an anti-factor Xa assay in patients with severe obesity or renal insufficiency. The therapeutic range for anti-factor Xa activity depends on the dosing interval. Anti-factor Xa monitoring is prudent when administering weight-based doses of LMWH to patients who weigh > 150 kg. It has been determined that UFH infusion is preferable to LMWH injection in patients with creatinine clearance of < 25 mL/min, until further data on therapeutic dosing of LMWHs in renal failure have been published. However, when administered in low doses prophylactically, LMWH is safe for therapy in patients with renal failure. Protamine may help to reverse bleeding related to LWMH, although anti-factor Xa activity is not fully normalized by protamine. The synthetic pentasaccharide fondaparinux is a promising new antithrombotic agent for the prevention and treatment of venous thromboembolism.

Assessment of recombinant factor VIIa as an antidote for bleeding induced in the rabbit by low molecular weight heparin

While protamine sulfate reverses the anticoagulant effect of standard heparin, there currently is no effective antidote for low molecular weight heparin (LMWH)-induced bleeding. Recently, recombinant activated factor VII (rFVIIa) was approved by the FDA for use in hemophilia patients with factor (F)VIII or FIX inhibitors. However, this new pro-hemostatic agent has potential utility in other clinical scenarios. In this study, we utilized a well-characterized rabbit ear puncture model to test the efficacy of rFVIIa to reverse LMWH-induced prolonged bleeding. Animals were first treated with bolus intravenous LMWH (1800 anti-FXa U kg(-1)) which increased the primary bleeding time approximately fourfold and raised the plasma anti-FXa activity immediately and continuously throughout the 90-min experiment. In a randomized and blinded fashion, animals then received either rFVIIa (400 microg kg(-1)) or placebo by bolus intravenous injection, following which the ear puncture bleeding times were measured, along with blood levels of heparin (anti-FXa activity) and FVII. FVII activity increased 5.3-fold over baseline in treated animals, decreasing by only 24% over the full observation period. The rFVIIa-treated animals showed a slight decrease in bleeding time immediately after injection, but there was no statistically significant difference in bleeding after rFVIIa or placebo administration. In this study using a rabbit ear bleeding model, rFVIIa was not an effective antidote to LMWH-induced bleeding. However, the bolus injection of LMWH produced a very high blood anti-FXa level, which may have precluded rFVIIa effectiveness.

Recent Advances in Venous Thromboembolic Prophylaxis in Major Orthopedic Surgery: A Regional Perspective

Recent Advances in Venous Thromboembolic Prophylaxis in Major Orthopedic Surgery: A Regional Perspective

Subcutaneous Nodules at the Injection Site of Low–Molecular-Weight Heparin: A Mimic of Metastatic Disease at CT

To describe the appearance and prevalence of subcutaneous nodules in the anterior abdominal wall seen at CT in cancer patients receiving subcutaneous injections of low-molecular-weight heparin (LMWH). CT examinations were reviewed in 426 patients receiving subcutaneous abdominal wall injections of LMWH for the presence of nodules. Nodules were evaluated for contour, maximal diameter, CT attenuation, and presence of hazy changes or air in the surrounding fat. Fourteen (3%) of the 426 patients had nodules attributable to subcutaneous injections of LMWH. Findings included poorly defined borders (100%), adjacent hazy soft tissue changes (100%), adjacent air (57%), and a mean CT attenuation of -4.4 HU (range: -50-40 HU). Three (0.7%) of 426 patients had nodules caused by metastatic disease. One (33%) nodule had poorly defined borders, two (67%) had surrounding hazy changes, one (33%) had air in adjacent tissue, and there was a mean CT attenuation of 44 HU (range: 14-140 HU). One (0.2%) patient had a subcutaneous nodule of uncertain etiology. Patients receiving subcutaneous injections of LMWH may develop nodules at the injection sites. Such nodules can resemble metastatic tumor deposits at CT, and careful correlation with clinical history and growth trends of metastatic deposits elsewhere in the patient is needed to avoid misdiagnosis.