Low Molecular Weight Heparin Therapy Research Articles

Orbital Hemorrhage and Compressive Optic Neuropathy in Patients With Midfacial Fractures Receiving Low-Molecular Weight Heparin Therapy

While the implementation of deep vein thrombosis (DVT) prophylaxis in the hospital setting is a major concern, the use of antithrombotic agents is fraught with a variety of hemorrhagic complications. Due to increasing reports of adverse reactions to unfractionated heparin (UFH), several manufacturers have initiated product recalls. As a result, the use of low-molecular weight heparins (LMWHs) such as enoxaparin has risen substantially. In this paper, 2 orbital hemorrhagic complications in patients receiving enoxaparin therapy will be presented. The incidence of DVT in the OMS patient, recent prophylactic strategies, and their effectiveness will be reviewed.

Clinical observation of heparin-induced thrombocytopenia

To explore the treatment of heparin-induced thrombocytopenia (HIT) in venous thromboembolism. A total of 202 patients with venous thromboembolism without anticoagulation contraindications were enrolled. All of them were treated with low molecular weight heparin (LMWH) and/or unfractionated heparin (UFH). The peripheral blood cells were examined regularly. HIT occurred in 6 patients. And argatroban was used to treat HIT. The overall incidence rate of HIT in this study was 2.97%. The time of occurrence of HIT was about Days 3 - 9 after using heparin. The platelet recovered to the basic level at Days 3 - 7 after withdrawing heparin and initiating argatroban. The count of platelet should be measured in the patients receiving regular LMWH and/or UFH therapy. And the above regimen should be discontinued timely when the platelet count declined progressively by over 50%. Argatroban was effective.

Preoperative blood donation program and postoperative Low Molecular Weight Heparine (LMWH) prophylaxis in patients undergoing radical prostatectomy

The need and timing of perioperative heparin prophylaxis is matter of debate. The aim of our work is to review the incidence of venous thromboembolism (VTE) after radical retro pubic prostatectomy (RRP) in patients undergoing preoperative blood donation, compressive stockings, haemodilution, surgical prevention of lymphocoele and postoperative low molecular weight heparin therapy as prophylaxis for thrombotic events. This is a retrospective analysis considering a series of 500 RRP performed between 1999 and 2006 by the same Surgeon (MG) at the Urological Unit, Desio, Hospital, Milan, Italy. All the patients were enrolled in an auto transfusion program and were subjected to autologous blood donation. Low molecular weight heparin (.04 ml of Calcic Nadroparin 3800 UI s.c. daily) was administrated within 24 hours following surgery until the 11th post-operative. Age, PSA, basal, preoperative and postoperative haemoglobin values were assessed in each patient. The incidence of venous thromboembolism was calculated taking into consideration occurrences of both pulmonary embolism and deep venous thrombosis. In this retrospective analysis we did not observe any major event including intra- or peri-operative deaths. There was one occurrence of pulmonary microembolism and one sural phlebitis that were treated with prolonged heparin and dicumarol therapy. Two significant haemorrhagic events occurred in the postoperative period requiring surgical revision. These data suggest that low weight heparin prophylaxis starting with 24 hours following radical prostatectomy, associated with preoperative blood donation, intra-operative haemodilution, compression stockings, surgical care to avoid lymphocoele and early mobilization in preventing venous thromboembolism.

Mobilização precoce na fase aguda da trombose venosa profunda de membros inferiores

O tratamento convencional da trombose venosa profunda na fase aguda consiste em restrição ao leito. Porém, estudos recentes contestam essa abordagem terapêutica, enfatizando que a mobilização precoce propicia resultados clínicos favoráveis. O objetivo deste estudo foi pesquisar em literatura científica, principalmente ensaios clínicos controlados, sobre a mobilização precoce de pacientes portadores de trombose venosa profunda de membros inferiores na fase aguda. Utilizou-se como estratégia de pesquisa o site PubMed para a busca de estudos relacionados à mobilização precoce, deambulação e trombose venosa profunda na fase aguda. Os artigos consultados abrangeram o período de 1992 a 2007. Em todos os estudos, a mobilização precoce esteve associada à heparina de baixo peso molecular e a terapia de compressão. Estudos avaliados nesta revisão têm demonstrado os benefícios na redução da dor e edema, com melhora da qualidade de vida, pela estratégia terapêutica de mobilização precoce em combinação com anticoagulação e compressão da perna na trombose venosa profunda, sem que ocorra maior risco de desfechos relevantes, como embolia pulmonar e morte.

Efficacy of Low- molecular- weight- heparin versus Vitamin K antagonists for long term treatment of cancer-associated venous thromboembolism in adults: A systematic review of randomized controlled trials

Background Patients with malignancy have a 4-fold increase in the risk of developing a venous thrombosis and a 3-fold increase in risk of bleeding. Both low-molecular-weight-heparin (LMWH) and vitamin K antagonists (VKA) have been used for treatment of cancer-associated thrombosis. However, the best anticoagulation approach remains a matter of debate. Objective In adult patients with cancer and an acute venous thromboembolic event we sought to determine the rates of recurrent venous thromboembolism (VTE) and major hemorrhage when treated with prolonged LMWH therapy compared to vitamin-K antagonists. Patients/Methods A systematic literature search strategy was used to identify potential trials on MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and Medline in-process using an OVID interface. Risk assessment of bias of randomized controlled trials (RCTs) was performed according to the Cochrane Collaboration-Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome measure was symptomatic VTE recurrence rate during the anticoagulation period. Relative risk (RR) was used as the primary measurement with 95% confidence intervals (CIs). Pooled measurements were calculated using random –effects and fixed-effects model. Results Five articles met our inclusion criteria. All compared LMWH and VKA for secondary prevention of VTE. The pooled RR of VTE recurrence was 0.53 (95% CI: 0.36-0.76; p = 0.007). The pooled RR of major bleeding was 0.98 (95% CI: 0.49-1.93, p = 0.95). Minor bleeding events and all cause mortality were similar between the 2 intervention arms. Conclusions The results of our review suggest that the long term use of LMWH after the acute first week of treatment is superior to VKAs for secondary prevention of venous thromboembolism in adult patients with cancer.

Low Molecular Weight Heparins as Extended Prophylaxis Against Recurrent Thrombosis in Cancer Patients

Cancer has been shown to be an independent risk factor for the development of venous thromboembolism (VTE; deep vein thrombosis and pulmonary embolism). Thromboprophylaxis reduces the incidence of VTE in patients with cancer; however, active cancer places patients at high risk for recurrent VTE, necessitating extended prophylactic regimens. Extended prophylaxis in patients with cancer can be problematic because of increased risk for bleeding. Oral anticoagulants, such as warfarin, have been the standard of care for extended prophylaxis, but maintaining a clinically effective level of anticoagulation can be difficult because of a wide range of drug interactions, a narrow therapeutic window, and an increased risk of bleeding complications, particularly in patients with cancer. Recent evidence indicates that long-term prophylaxis with low-molecular-weight heparins (LMWHs) is an effective and safe alternative to oral anticoagulation in patients with VTE and cancer, reducing the risk for recurrent VTE by up to 52%. LMWHs can also be seen as cost-effective for long-term prophylaxis, because higher drug acquisition costs are offset by the potential for reduced hospital stays, reduced need for coagulation monitoring, and fewer bleeding complications. Some studies suggest that LMWHs may also have direct antitumor effects and improve survival rates, most notably in patients with non-metastatic disease. Further clinical research is needed to evaluate the potential survival benefits of LMWH therapy in patients with cancer.

Successful Treatment of Catastrophic Antiphospholipid Antibody Syndrome (CAPS) Associated With Splenic Marginal-zone Lymphoma With Low-molecular Weight Heparin, Rituximab and Bendamustine

A 69-year-old woman with splenic marginal-zone lymphoma was admitted with progressive abdominal pain and splenomegaly as the suspected cause of pain. Rituximab treatment (375 mg/m) had been initiated on the day of admission. Abdominal computerized tomography revealed splenic infarction. Laboratory tests showed elevation of liver enzymes and creatinine, low platelet count, prolonged partial thromboplastin time, and lupus anticoagulant positivity. The diagnosis of catastrophic antiphospholipid antibody syndrome was made. Weight-adjusted low-molecular weight heparin therapy was initiated. Freedom from symptoms and normalization of liver enzymes and creatinine occurred within 4 weeks. Treatment was continued with 6 cycles of bendamustine monotherapy (90 mg/m) and heparin, leading to partial remission of lymphoma and lupus anticoagulant negativity. In case of multiorgan failure in patients suffering from lymphoma and showing features of disseminated intravascular coagulation, catastrophic antiphospholipid antibody syndrome should be considered. In our patient, rituximab followed by weight-adjusted low-molecular weight heparin and bendamustine therapy led to recovery.

A clinical trial of using antiplatelet therapy to prevent restenosis following peripheral artery angioplasty and stenting

To evaluate the clinical effect and restenosis rate of antiplatelet therapy following peripheral artery angioplasty and stenting. After successful placement of peripheral artery stents to 103 patients with peripheral arterial occlusive disease (PAOD) in were randomized assigned to 2 groups: antiplatelet therapy group receiving clopidogrel 75 mg plus aspirin 100 mg (n = 56) and control group (n = 47) receiving anticoagulation therapy low molecular weight heparin (LWMH) for 7 d plus long-term warfarin. The patients were followed up 1 day, and 1, 6, 12, and 18 months after the operation to undergo color Doppler ultrasonography, and examinations of blood routine, bleeding time, coagulation time, and ankle-brachial Index. The primary endpoint events included major bleeding rate, and composite rate of restenosis and reocclusion. The secondary endpoint events included cardiovascular events, death, and adverse drug reaction. There were no significant differences in the baseline data between these two groups. The thrombotic occlusion rate was 1.8% in the antiplatelet group and 0% in control group, and the restenosis rate was 14.3% in the antiplatelet group and 25.5% in control group (both P > 0.05). The bleeding complication rate of the antiplatelet group was 1.8%, significantly lower than that of the anticoagulation group (19.1%, P < 0.01). There were not significant differences in cardiovascular event rate and mortality 18 months after operation between these two groups. Antiplatelet therapy combined with clopidogrel plus aspirin is effective and safe in preventing restenosis following peripheral artery angioplasty and stenting.

A Clinical Perspective of Venous Thromboembolism

A large number of individuals develop venous thromboembolism (VTE) every year.1 Each patient’s episode of DVT or PE is, naturally, unique. To highlight a variety of aspects about VTE a compilation case is presented that is composed of clinical data and images from several real patients. ### History of Present Illness A 36-year-old woman presents to the Emergency Department with severe shortness of breath and moderately intense anterior chest pain, worse on deep inspiration, which had started suddenly that morning. She also reports a 6-wk history of mild shortness of breath, for which she had been seen 4 wk earlier by her primary care physician who diagnosed her with “asthma.” Bronchodilators and steroids were prescribed but led to no significant improvement in her symptoms. She also gives a history of mild left calf pain that had started about 2 months earlier without preceding trauma, immobilization, or surgery. Her primary care physician had seen her and prescribed Ibuprofen for a “pulled muscle.” However, in the 1 week before her present presentation her leg symptoms worsened, and she had increased diffuse leg pain and swelling and slightly bluish discoloration of the whole leg. Her past medical history is only significant for an appendectomy at age 16. She has never been pregnant. She is on no medications, except for an estrogen and progestin-containing oral contraceptive, started 10 months earlier. She does not smoke. There is no family history of venous thromboembolism, although the patient reports that her paternal grandmother had a “swollen leg for many years” until she died in her 70’s, but no further details are known of the patient. ### Physical Examination The patient’s weight is 86 kg and her height 165 cm, calculating to a body mass index (weight divided by [height in meters]2) of 31.6 kg/m2, ie, she has grade 1 obesity. Her …

“Sticky Platelet Syndrome”: In Vitro Response to Small Dose Aspirin Is Reflected in Clinical Benefit.

Introduction: “Sticky Platelet Syndrome” (SPS), a consistently demonstrable platelet aggregability to subthreshold concentrations of epinephrine and/or adenosine dinucleotide phosphate (ADP), is an autosomal dominant condition with thrombotic consequences (Mammen, 1984). Because published studies regarding SPS are few and platelet function testing unusual in thrombophilia evaluation, SPS may be an under-recognized contributor to arterial and venous thrombosis. The precise pathogenesis of SPS is undefined, but prior observations have suggested that small-dose aspirin may be useful in modulating increased aggregability and preventing recurrent thrombosis.Methods: Laboratory and clinical response to aspirin in patients with SPS was determined by retrospective review of a large university thrombophilia clinic database in which platelet function was a routine component of extensive thrombophilia testing. As previously reported, SPS was diagnosed by demonstration of aggregation amplitude of 50% or more with epinephrine and/or ADP concentrations 20-fold lower than routine activation thresholds on two separate occasions at least 2 weeks apart. Records of individuals exhibiting SPS prescribed antiplatelet therapy for whom follow-up laboratory and clinical data were available were analyzed for modulation of aggregation abnormality and clinical outcome. Laboratory response to anti-platelet therapy was defined as return of function to laboratory “normal” or “decreased” function on testing >2 weeks following initiation of therapy. Platelet function and clinical outcomes were followed for 6 months to 13 years.Results: Of 149 patients with treated SPS, 97 (65%) had one or more thrombotic events prior to presentation 42/149 (28%) despite warfarin or low molecular weight heparin therapy. Of 149, 53% had venous, 35% arterial, 5% both arterial and venous events; 7% had recurrent fetal loss. 52/149 (35%) were individuals evaluated for primary family relationship to an SPS patient. 25 (16.7%) patients had SPS as a solitary risk factor. 147/149 patients (98.6%) demonstrated reversal of hyperfunction, 108/147 (73%) with aspirin (81mg/day); all responders normalized with </= 325 mg aspirin daily and experienced no significant side-effects. Aspirin was used in 56% of patients as a sole anti-thrombotic agent, in 27% with anticoagulants (warfarin or a parenteral agent), in 10% with other anti-platelet agent(s), in 2% with anticoagulant and anti-platelet agent(s). 4% of patients received no aspirin because of allergy. Of those demonstrating response, 7 patients (4.8%) had a further thrombotic event. Of these, 2 patients received clopidogrel alone due to aspirin allergy and 5 patients received aspirin plus anticoagulants at “therapeutic” levels; all had multiple thrombotic risk factors.Conclusions: Aspirin, in minimal, inexpensive, well-tolerated doses, “normalized” in vitro platelet function in SPS patients and prevented thrombosis recurrence in most, many of whom had experienced rethrombosis on anticoagulants alone. Because undiagnosed platelet hyperfunction (identified in 1/3 of patients evaluated at a large urban university center: Faraz et al., 2007) may predispose to rethrombosis and classical anticoagulants alone do not abrogate thrombogenic potential in pateints with SPS, platelet function testing deserves a place in thrombophilia evaluation - and may be of greater utility than the currently performed “thrombophilia panels.”

Recurrent venous thromboembolism during coumarin therapy. Data from the computerised registry of patients with venous thromboembolism

Recurrent venous thromboembolism during coumarin therapy. Data from the computerised registry of patients with venous thromboembolism

The Effect of Postoperative Anticoagulation on Microvascular Thrombosis

Numerous protocols exist to prevent thrombosis after free-tissue transfer. Many surgeons advocate using aspirin or other antiplatelet agents, but little objective evidence supports this practice. This study evaluates the rate of microvascular thrombosis in patients undergoing free-tissue transfer treated with or without antiplatelet agents. All consecutive free flaps from 2002-2005 at a single center were reviewed using a prospectively maintained database. Patients were in 2 groups based on postoperative anticoagulation administration. In group 1, 325 mg of aspirin was administered daily for 5 days postoperatively. In group 2, patients were treated with 5000 units of low-molecular-weight heparin (LMWH) per day until ambulating. Patient demographics, procedure type, diagnosis, adjuvant treatment, and procedure type were recorded. Outcome variables included microvascular thrombosis, partial or total flap loss, hematoma, bleeding, deep venous thrombosis (DVT), pulmonary embolism, and death. Four hundred seventy patients underwent 505 microvascular free flaps to reconstruct oncologic defects. Two hundred sixty flaps (group A) received postoperative aspirin therapy; 245 flaps (group B) received LMWH therapy. Both groups were statistically similar in their composition. No statistically significant difference was noted between the 2 groups when comparing outcome variables including microvascular thrombosis, partial or total flap loss, hematoma, bleeding, DVT, pulmonary embolism, and death. Postoperative anticoagulation choice has no statistically significant effect on the incidence of free flap complications, including bleeding, thromboembolism, and flap loss. We conclude that aspirin or LMWH therapy demonstrates equivalent outcomes when used as single-agent postoperative anticoagulation in oncologic free flap reconstruction.

Effects of low molecular weight heparin on angiogenic factors in advanced cancer patients

21158 Background: The relationship between cancer and thrombosis is known for many years. Thrombosis can be associated with the biology and therapy of the disease in cancer patients. Low molecular weight heparin (LMWH) is shown to increase the duration of life in several types of cancer in clinical trials. Low molecular weight heparin is thought to be inhibiting with tumor growth and metastasis in several ways. In our study, we evaluate effects of LMWH therapy on angiogenic factors. Methods: Thirty-two advanced cancer patients who used prophylactic LMWH before chemotherapy. Median age was 64.5 years with range from 18 to 80. Sixteen healthy volunteers that are of same age and gender with study patients comprised the control group. VEGF, HGF, FGF, EGF, PDGF, ICAM, p-selectin, e-selectin levels were evaluated before and 7 days after LMWH therapy. Results: In baseline measurements HGF and ICAM levels were higher in treatment group compared the control group. But, levels of EGF and VEGF were not statistically significant higher in the treatment group compared to control group. After LMWH therapy, VEGF, FGF, PDGF, ICAM, e-selectin levels appeared to decrease and HGF, EGF, p-selectin levels appeared to increase but none of these changes were statistically significant. In a subset of seventeen patients with adenocarcinoma, levels of ICAM declined significantly after LMWH therapy this group. Before LMWH therapy; HGF was correlated with PDGF, VEGF, p-selectin, e-selectin; EGF was correlated with p-selectin; e-selectin was correlated with p- selectin. After therapy HGF was correlated with PDGF and EGF; PDGF was correlated with FGF and p-selectin; EGF was correlated with ICAM levels. Conclusions: In summary, with a short course of LMWH therapy a change in anjiogenic biomarkers was observed only in adenocarcinoma patients and this change was limited only to ICAM levels. The study focused on long term course was warranted. No significant financial relationships to disclose.

Assessing, preventing, and treating venous thromboembolism: Evidence-based approaches

The long-term complications of deep vein thrombosis (DVT), assessment of risk for venous thromboembolism (VTE) in medical and surgical patients, recommendations in evidence-based guidelines for VTE prophylaxis in surgical and medical patients and the treatment of VTE, and a new alternative for VTE prophylaxis and treatment are discussed. Pulmonary embolism (PE) is an acute complication of DVT, and recurrent DVT, post-thrombotic syndrome, and death are long-term complications of DVT. The need to assess VTE risk and provide VTE prophylaxis are well recognized in surgical patients. However, VTE prophylaxis is underutilized in medical patients despite the fact that DVT is common and guidelines for prophylaxis are available, partly because the condition often is asymptomatic in these patients. The risk for VTE increases as the number of risk factors increases, so the aggressiveness of VTE prophylaxis in medical and surgical patients increases as the risk of VTE increases. The most recent American College of Chest Physicians (ACCP) guidelines recommend low-dose unfractionated heparin or low-molecular-weight heparin (LMWH) for VTE prophylaxis in acutely ill medical patients. The treatment of VTE recommended by ACCP involves short-term LMWH or unfractionated heparin therapy plus long-term oral warfarin therapy. The pentasaccharide, factor Xa inhibitor, fondaparinux is a new alternative for VTE prophylaxis and treatment. Reducing LMWH doses for patients with severe renal impairment may offer a safety advantage. Fixed doses of LMWH are customarily used for VTE prophylaxis regardless of body weight or body mass index, but weight-based dosing with larger doses for obese patients may be more effective than fixed doses. Efforts to assess VTE risk and apply evidence-based guidelines for VTE prophylaxis and treatment in medical patients as well as surgical patients can improve patient care and outcomes. Findings from recent clinical research provide clinicians with clarification about the optimal prophylactic and treatment strategies, and future guidelines will reflect these findings.

Anticoagulant Effects of Low‐Molecular‐Weight Heparins in Healthy Cats

Background:Low‐molecular‐weight heparin (LMWH) has potential benefit in cats at risk for thromboembolic disease. However, LMWH pharmacokinetics has not been characterized in the cat. Drug effect with LMWH may be evaluated with analysis of factor Xa inhibition (anti‐Xa) or thromboelastography (TEG).Hypothesis:Administration of LMWH at previously recommended dosages and schedules to healthy cats will result in inhibition of factor Xa and hypocoagulable TEG.Animals:In vivo research with heparin was performed in 5 purpose‐bred cats.Methods:In a prospective study with randomized crossover design, heparin or placebo was administered. Treatments were unfractionated heparin (UFH), 250 IU/kg q6h; dalteparin, 100 IU/kg q12h; enoxaparin, 1 mg/kg q12h; or 0.9% saline, 0.25 mL/kg q6h. Each drug was administered for 5 consecutive days followed by a minimum washout of 14 days. Baseline and post‐treatment analyses included anti‐Xa, TEG, and prothrombin time/activated partial thromboplastin time.Results:Mean anti‐Xa activity 4 hours after enoxaparin (0.48 U/mL) approached the human therapeutic target (0.5–1.0 U/mL); however, mean trough anti‐Xa activity was below detection limits. Mean anti‐Xa activity 4 hours after dalteparin was lower, and only 1 cat attained therapeutic target at a single time point. Cats receiving UFH attained target anti‐Xa activity and changes in TEG at trough and 4 hours.Conclusions: Cats have rapid absorption and elimination kinetics with LMWH therapy. On the basis of pharmacokinetic modeling, cats will require higher dosages and more frequent administration of LMWH to achieve human therapeutic anti‐factor Xa activity of 0.5–1 U/mL. Peak anti‐Xa activity is predicted at 2 hours after administration of LMWH.

Long‐term Management of an Implantable Left Ventricular Assist Device Using Low Molecular Weight Heparin and Antiplatelet Therapy: A Possible Alternative to Oral Anticoagulants

Between January 2004 and December 2005, out of 14 patients with decompensated heart failure who were treated with an INCOR left ventricular assist device (Berlin Heart AG, Berlin, Germany), 10 patients were kept on a long-term regime of low molecular weight heparin (LMWH) and antiplatelet therapy. The treatment objective was bridge-to-transplantation. All patients received LMWH in therapeutic doses according to body weight, in combination with daily aspirin 160 mg, clopidogrel 75 mg, and three times dipyridamole 75 mg. Effectiveness of the low molecular weight regime was monitored through measurement of antifactor Xa activity (base and peak levels). Antiplatelet therapy was monitored through weekly platelet function tests. Within this group of 10 patients, six patients successfully received transplants and four patients died, the latest death after 405 days of INCOR support. Causes of death were sepsis, intestinal hemorrhage, acute right ventricular failure, and one major stroke. Long-term management of INCOR assist devices using a combination of LMWH and antiplatelet therapy is feasible. This treatment strategy can serve as an alternative to oral anticoagulants.

Rectus sheath hematoma complicating low‐molecular weight heparin therapy

Rectus sheath hematoma (RSH) is an uncommon but serious bleeding complication of anticoagulant therapy that has received little attention in the literature. Two cases of RSH among recent admissions to an inpatient medicine service and four archival cases were reviewed. All six patients were on low-molecular weight heparin (LMWH) therapy. Five of the six patients had a creatinine clearance of 40 ml/min or less, and five also had cough. Two patients with the most serious outcome were aged 90 and 92 years. RSH complicating LMWH therapy appears to constitute a clinical syndrome consisting of sudden onset of abdominal pain in the setting of renal insufficiency, advanced age and abdominal straining (e.g. cough). Risk of RSH may be reduced in patients receiving LMWH by assessing renal function, monitoring heparin levels (e.g. when the creatinine clearance is 40 ml/min or less) and adjusting the dose accordingly; by avoidance of abdominal strain (e.g. by treating cough); and by attention to technique when the abdominal wall is used as the injection site. Patients of advanced age may be at particular risk for RSH.

The low molecular weight heparin on rat pulmonary surfactant associated protein A of acute pulmonary embolism

To explore the effect of low molecular weight heparin (LMWH) on the changes of pulmonary surfactant associated protein A (SPA) of rats in acute pulmonary embolism. Male SD rats were injected with medical gelfoam microspheres via jugular vein to induce PE model. Rats were randomized into three groups: control group (n = 8), embolism for 2 weeks group (n = 8) and LMWH therapy group (n = 8); The LMWH therapy group were injected Nadroparin subcutaneously immediately after operation, 0.1 ml/10 kg, once every 12 h. Saline were injected into the control group instead of gelfoam granule solution without further procedure. All the rats were sacrificed at the time of 2 weeks. Pulmonary artery pressure were detected by right heart catheterization and artery blood gas were analyzed at the time of sacrifice. Lung tissue were sliced and dyed with HE to observe the embolism of pulmonary artery. Methods of RT-PCR and western blot were used to study the changes of SPA mRNA and SPA protein in lung tissue. In control group, embolism group and LMWH group, the pulmonary pressure were (14.2 +/- 4.1) mm Hg, (29.0 +/- 8.2) mm Hg, (25.50 +/- 2.74) mm Hg respectively (F3.01, P < 0.05); the artery oxygen blood pressure (PaO2) were (94.1 +/- 8.8) mm Hg, (73.4 +/- 14.3) mm Hg, (82.86 +/- 3.73) mm Hg respectively (F 1.31, P < 0.05); SPA mRNA in three groups were 1.43 +/- 0.51, 0.87 +/- 0.35, 1.07 +/- 0.20 respectively (F 2.87, P < 0.05); and SPA protein were 1.00 +/- 0.00, 0.52 +/- 0.32, 0.90 +/- 0.22 respectively (F 2.96, P < 0.05); Under microscope, lung tissue were seen congestion, edema, infiltration of inflammatory cells in embolism group, which were lessened in LMWH group. The lung SPA decrease significantly in acute pulmonary embolism, and LMWH can increase the SPA, which may be one of mechanisms of LMWH in treatment of pulmonary embolism.

Thrombin generation in mesalazine refractory ulcerative colitis and the influence of low molecular weight heparin

In ulcerative colitis (UC), a state of hypercoagulation has frequently been observed. Low molecular weight heparin (LMWH) has shown beneficial effects as an adjuvant treatment of steroid refractory UC in open trials. We assessed potential therapeutic effects of the LMWH reviparin in hospitalised patients with mesalazine refractory UC, as well as its influence on haemostasis factors. Twenty-nine patients with mild-to-moderately active UC were included in a double-blind placebo controlled trial. All patients had a flare-up of disease under mesalazine treatment. Reviparin (Clivarin) 3,436 IU anti-Xa/0.6 ml or placebo s.c. was added, and self-administered twice daily for 8 weeks. Patients were monitored for possible adverse events and changes in clinical symptoms. Endoscopical, histological, biochemical and haemostasis parameters were analysed. Tolerability and compliance were excellent and no serious adverse events occurred. No significant differences were observed on the clinical, endoscopical and histological outcome, as compared to placebo. A high intrinsic and extrinsic thrombin potential was found before LMWH therapy. However, the significant reduction in the thrombin generation by LMWH was not related to the reduction in disease activity. The LMWH reviparine reduces thrombin generation in patients with mild-to-moderately active, mesalazine refractory UC, but is not associated with a reduction in disease activity.

Preoperative low molecular weight heparin reduces heparin responsiveness during cardiac surgery

Cardiac surgery with cardiopulmonary bypass requires systemic anticoagulation, defined by an activated clotting time (ACT) of 400-480 sec. Patients with altered heparin responsiveness require disproportionately higher doses of heparin to achieve this target ACT. A common risk factor for heparin resistance is preoperative heparin therapy. Recently, therapy with low molecular weight heparin (LMWH) has become an acceptable substitute for prolonged heparin therapy. The current study examines the effect of preoperative LMWH therapy on subsequent heparin responsiveness during cardiac surgery. Records of patients undergoing cardiac surgery with cardiopulmonary bypass over a period of four months were reviewed. We identified patients who, during the week preceding surgery, had received prolonged (>24 hr) therapy with either sc LMWH (LMWH group) or continuous iv unfractionated heparin (Heparin group). A Control group consisted of patients who received neither heparin nor LMWH preoperatively. The heparin sensitivity index (calculated as the first change in ACT from baseline divided by the first intraoperative heparin dose, normalized to body weight), was compared among groups using ANOVA. One hundred and thirty-nine patients were included in the analysis. The heparin sensitivity index was 33-45% higher in the Control group (1.6+/-0.7 sec.IU-1.kg-1; P<0.0001) compared to the LMWH (1.2+/-0.4 sec.IU-1.kg-1) and Heparin (1.1+/-0.5 sec.IU-1.kg-1) groups. In a multivariable model, the use of preoperative LMWH remained a significant predictor of reduced intraoperative heparin responsiveness (P=0.002). Prolonged preoperative LMWH therapy, similar to the known effect of prolonged unfractionated heparin infusion, reduces subsequent intraoperative response to heparin.