Low Molecular Weight Heparin Treatment Research Articles

Effect and safety of tirofiban in the treatment of acute coronary syndromes

Objective To analyze the clinical efficacy and safety of tirofiban in the treatment of acute coronary syndrom.Methods 80 cases with acute coronary syndrome , were randomly divided into the observation group and control group ,two groups were given aspirin ,grey,low molecular weight heparin treatment ,the observation group was given based on the class for tirofiban intravenous injection , the control group was given a placebo , the clinical effect were compared between two groups .Results In the observation group ,30 d end point event rate of 15.00%,significantly lower than that of the control group 30.00%（χ2 =4.56,P〈0.05）;The observation group was administered 3 d after the electrocardiogram showed the degree of ST-T segment depression in lead and ischemia were （0.30 ±0.43）mm,（2.1 ±2.5）,was significantly better than that of the control group （0.67 ±0.73） mm,（3.4 ± 2.5）（t =5.12,3.56,all P 〈0.05）.Conclusion Aspirin,clopidogrel,heparin combined voith tirofiban can effectively improve the clinical symptoms of patients with myocardial ischemia , and can reduce the incidence of adverse events,which is worthy of clinical application . Key words: Tirofiban; Coronary artery disease; Treatment Outcome

Low molecular weight heparin (LMWH) and low-dose aspirin treatment in patients with pre-existing high-risk conditions improves pregnancy outcomes when such pregnancies are complicated in addition by unexplained low maternal serum PAPP-A (LPAPP-A).

Low molecular weight heparin (LMWH) and low-dose aspirin treatment in patients with pre-existing high-risk conditions improves pregnancy outcomes when such pregnancies are complicated in addition by unexplained low maternal serum PAPP-A (LPAPP-A).

Prothrombotic Disorders in a Cohort of 25 Patients Undergoing Transplantation: Investigation and Management Implications

BackgroundMany patients referred for intestinal transplantation have a history of thrombosis. We undertook an analysis of transplanted patients to describe the history and frequency of thrombosis, clinical course, and management strategies used. ResultsTwenty-five patients underwent transplantation of intestine containing blocks between 2007 and 2012; 20 of 25 are still alive. Five of 25 patients were transplanted with history of portomesenteric thrombosis, 6 of 25 had experienced loss of venous access due to thrombosis, and 6 of 25 had history of mesenteric ischemia. Pretransplantation, 16 of 25 patients were anticoagulated. Thrombophilia screens identified 3 of 16 patients who were JAK2 positive, 1 of 25 who had antithrombin deficiency, and 1 of 25 who had a factor V Leiden heterozygote. Post-transplantation, of all 16 patients who were anticoagulated pretransplantation and continued postoperatively, 1 of 16 infarcted their small bowel graft and 4 of 16 developed a further venous thrombosis despite anticoagulation. Of the 9 without a previous history of thrombosis, 1 had a pulmonary embolus more than a decade after transplantation and another had an upper limb deep vein thrombosis associated with a line. Both were then anticoagulated. Seven of 25 are not anticoagulated, although they are administered antiplatelet prophylaxis. Postoperative bleeding complications of anticoagulation occurred in 3 patients. After a subarachnoid hemorrhage in 1 of those 3 patients, anticoagulation was stopped. The other 2 patients bled during ileal biopsy, and both remain on low molecular weight heparin treatment. ConclusionThose with identifiable thrombophilic tendency and a history of venous or arterial thrombosis are considered to be at high risk for recurrent thrombosis. Those without such a history could be considered low risk. Our practice is to anticoagulate all high-risk individuals before and after transplantation and offer antiplatelet prophylaxis to low-risk patients as the risk of anticoagulation probably outweighs the risk of thrombosis for them. Early input from hematologists is vital in the management of high-risk patients, particularly those who thrombose when anticoagulated.

Low molecular weight heparin treatment and impact of inherited thrombophilia type in pregnancies with previous adverse outcome

Objective: To assess the impact of low molecular weight heparin (LMWH) treatment in 50 pregnancies of women with inherited thrombophilia and adverse pregnancy outcome (APO) in previous untreated pregnancies. The impact of “Conventional” (FVL, PT, AT, PC, PS) and “Novel” (MTHFR, PAI-1, ACE) thrombophilias on APO was investigated.Methods: The primary outcomes (PO) were: early and late pregnancy loss (EPL, LPL), preterm birth (PTB) or term birth (TB) compared to the last untreated pregnancies of the same women. Secondary outcomes (SO) were APO in LMWH treated and last untreated pregnancies ended with birth. PO and SO were compared in relation to the thrombophilia type.Results: LMWH decreased EPL and LPL rate and improved TB rate compared with last untreated pregnancies (p < 0.001). There were less PTB (p = 0.019) and no cases of intrauterine fetal death (IUFD) (p = 0.0019) in LWMH-treated pregnancies. The division to Conventional and Novel thrombophilias showed: (a) difference between pregnancy losses and birth rate (p = 0.0069) and (b) no difference in the prevalence of APO in untreated pregnancies ended with birth.Conclusions: LMWH treatment improves pregnancy outcome in women with inherited thrombophilia and APO in previous pregnancies. Novel thrombophilias have the equal impact on the pregnancy outcome compared to the Conventional thrombophilias.

Intensified chemotherapy and simultaneous treatment with heparin in outpatients with pancreatic cancer – the CONKO 004 pilot trial

BackgroundAdvanced pancreatic cancer (APC), beside its high mortality, causes the highest rates of venous thromboembolic events (VTE). Enoxaparin, a low molecular weight heparin (LMWH), is effective in prevention and treatment of VTE. Some small studies indicated that this benefit might extend to patients with cancer and probably prolong survival due to independent mechanisms. We initiated this safety investigation to get feasibility information on intensified chemotherapy combined with LMWH in outpatients with APC treated in 1st line.MethodsThe trial was a prospective, open-label, single center investigation in outpatients with inoperable pancreatic cancer who were treated with intensified first-line chemotherapy along with concomitant application of subcutaneous LMWH. The combined chemotherapy consisted of gemcitabine 1 g/m2 (30 min), 5-FU 750 mg/m2 (24 h), folinic acid 200 mg/m2 (30 min), and Cisplatin 30 mg/m2 (90 min) on day 1 and 8; q3w for the first 12 weeks (GFFC) followed by gemcitabine alone in patients without cancer progression. The simultaneous application of prophylactic enoxaparin started on day 1 of chemotherapy with a fixed dose of 40 mg daily. Statistical analyses were performed using R 3.01 with software package CMPRSK and SPSS software v19.0.ResultsThe investigation was stopped after recruitment of 19 patients. At this time 15 patients had completed the required 12 weeks of treatment. Based on 71 cycles of GFFC + enoxaparin (median 4/pt [range: 2–4]) and 108 cycles of single-agent gemcitabine + enoxaparin (median 4/pt [range: 0–18]) the cumulative frequency of NCI-CTC toxicities grade 3/4 was below 10%. One case (5%) of a symptomatic non-lethal thromboembolic event was observed while receiving LMWH treatment. No severe bleeding event as defined in the protocol has been observed. The median overall survival was 10.05 [95% CI: 8.67-18.14] months.ConclusionsThe addition of enoxaparin to GFFC chemotherapy is feasible, safe and does not appear to affect the efficacy or the toxicity profile of the chemotherapy regimen in patients with advanced pancreatic adenocarcinoma. Based on these findings we have initiated the randomized CONKO-004 trial to examine whether enoxaparin reduces the incidence of thromboembolic events or increases overall outcome.Trial registrationClinical Trials NCT01945879.

Development and evaluation of PEGylated Enoxaparin: A novel approach for enhanced anti-Xa activity

Enoxaparin (ENX) is one of the most widely prescribed low molecular weight heparin inprophylaxis and treatment of venous thromboembolism. In this study, Enoxaparin–PEG conjugate (P-ENX) was synthesized from Enoxaparin and polyethylene glycol (PEG) and evaluated for its potential for extended duration of action. The esterification of the carboxyl groups of the drug moiety with the hydroxyl groups of mPEG-2000 was done by employing carbodiimide coupling chemistry. P-ENX conjugate was purified by dialysis and characterized by Fourier transform infrared spectroscopy (FTIR), Proton-Nuclear magnetic resonance (1H NMR) and matrix-assisted laser desorption/ionization (MALDI) mass analysis techniques. FTIR analysis revealed frequency of the carbonyl group in accord with ester linkage formation between the drug and the PEG moiety. 1H NMR of the conjugate showed significant change in the chemical shift further indicative of ENX and PEG chemical interaction. In MALDI spectra, small peaks at 12,907 and 16,137 m/z confirmed the probability of conjugation of ENX and PEG. P-ENX exhibited considerable enhancement in anti-Xa activity (by three-folds) in comparison to free ENX. Further, an increase in AUC (over four-folds) was observed in P-ENX. Thus, PEGylation of ENX is a novel approach for extended and enhanced activity of ENX with a potential for decreased dosing frequency.

PS-060 Use of venous thromboprophylaxis in critical illness in a traumatic intensive care unit (ICU)

BackgroundVenous thromboembolism (VTE) is a common and potentially lethal complication from hospitalisation. Critically ill patients have multiple risk factors for VTE such as prolonged immobility, use of central venous catheters,...

A vertebral artery dissection with basilar artery occlusion in a child.

This paper presents the case report of an 11-year-old boy with an acute dissection with thrombosis of the left vertebral artery and thrombosis of the basilar artery. The patient was treated with acute systemic thrombolysis, followed by intra-arterial thrombolysis, without any clinical improvement, showing left hemiplegia, bilateral clonus, hyperreflexia, and impaired consciousness. MRI indicated persistent thrombosis of the arteria basilaris with edema and ischemia of the right brainstem. Heparinization for 72 hours, followed by a two-week LMWH treatment and subsequent oral warfarin therapy, resulted in a lasting improvement of the symptoms. Vertebral artery dissection after minor trauma is rare in children. While acute basilar artery occlusion as a complication is even more infrequent, it is potentially fatal, which means that prompt diagnosis and treatment are imperative. The lack of class I recommendation guidelines for children regarding treatment of vertebral artery dissection and basilar artery occlusion means that initial and follow-up management both require a multidisciplinary approach to coordinate emergency, critical care, interventional radiology, and child neurology services.

Risk factors for recurrent events in subjects with superficial vein thrombosis in the randomized clinical trial SteFlux (Superficial Thromboembolism Fluxum)

To evaluate risk factors for recurrent events in patients enrolled in the SteFlux (Superficial Thromboembolism Fluxum) clinical trial which compared different doses and duration of low molecular weight heparin (parnaparin) for superficial vein thrombosis (SVT). Outpatients with acute SVT of at least 4 cm in length of the internal or external saphenous veins or their collaterals were randomized in a double blind fashion to receive either parnaparin 8500 UI aXa od for ten days followed by placebo for 20 days or 8500 UI aXa od for ten days followed by 6400 UI aXa od for 20 days or 4250 UI aXa od for 30 days. Outcomes were the composite of symptomatic and asymptomatic deep vein thrombosis, pulmonary embolism and SVT recurrence or extension in the first 30+/-3 days with a 60+/-3 day follow-up. 98 outcomes (14.7%) were recorded during 93 days among 664 patients (M/F: 246/418, mean age 65). After correction for treatment, outcomes during 33 days were associated with previous venous thromboembolism (VTE) and/or SVT and/or family history of VTE (odds ratio-OR: 2.5; 95% confidence interval - CI: 1.4-4.8; p=0.003). After stopping LMWH treatment, only the absence of varicose veins (OR: 2.5; 95% CI 1.3-5.0; p=0.004) and previous VTE and/or SVT and/or family history of VTE (OR: 1.9; 95% CI:1.0-3.7; p=0.048) were significantly associated with outcomes. SVT patients with these factors may deserve a higher intensity and/or longer anticoagulant treatment.

Pharmacological anti-thrombotic prophylaxis after elective caesarean delivery in thrombophilia unscreened women: should maternal age have a role in decision making?

In obstetrical practice, the best prevention strategy for pregnant women aged >35 years without known thrombosis risk factors who underwent elective caesarean delivery (CD) is controversial. We performed an observational-longitudinal cohort study on pregnant women aged >35 years who delivered at term by elective caesarean section after a physiological single pregnancy to evaluate the role of maternal age in the decision-making process of whether or not to perform low-molecular-weight heparin (LMWH) prophylaxis during the post-partum period after elective CD in healthy women with unknown inherited thrombophilia status. During the 6 post-partum weeks, we followed two groups: GROUP-A (349 women treated for 7 days with low-molecular-weight heparin) and GROUP-B (180 women not treated with LMWH treatment). The outcomes were as follows: onset of thromboembolic events during the post-partum period; non-obstetrical-linked maternal haemorrhage; blood transfusion; re-laparotomy; detection of a surgical site haematoma; length of hospitalisation; and treatment suspension because of decreased platelet count. Except for the parity number, the two groups were homogeneous with regard to general features. In both the groups, we reported no cases of thromboembolic events during the follow-up period. Maternal haemorrhage requiring transfusion occurred in 16 women in GROUP-A and none in GROUP-B. Among the GROUP-A women, 11 demonstrated a surgical site haematoma and 4 required re-laparotomy. No cases of treatment suspension were reported. Pneumatic compression stockings represent a better, low cost and safe way to prevent post-partum venous thromboembolic episodes after elective caesarean section in an unscreened population. Pharmacological prophylaxis after elective caesarean section should be performed only in case of clear and known adjunctive risk factors, independent of maternal age.

Edoxaban For Long-Term Treatment Of Venous Thromboembolism In Cancer Patients

Edoxaban For Long-Term Treatment Of Venous Thromboembolism In Cancer Patients

Exclusive Low-Molecular-Weight Heparin as Bridging Anticoagulant After Mechanical Valve Replacement

Unfractionated heparin has been the standard anticoagulant used immediately after mechanical heart valve replacement (MHVR). The purpose of this study was to assess a postoperative anticoagulation protocol with low-molecular-weight heparin (LMWH) immediately after MHVR without the use of unfractionated heparin or anti-factor Xa monitoring. We performed a prospective, single-center, observational study of 1,063 consecutive patients undergoing elective MHVR with postoperative LMWH anticoagulation treatment. The exclusion criteria were as follows: renal failure, intraaortic balloon counterpulsation, critical perioperative state, or a recent neurologic event. The postoperative anticoagulation protocol used subcutaneous enoxaparin as a bridging anticoagulant treatment beginning on the first postoperative day and continuing until vitamin K antagonist treatment was fully effective. Patients were followed for 6 weeks. The primary endpoints were the incidence of thromboembolic or major bleeding events. Eleven (1%) thromboembolic events occurred. Ten of these events were transient or permanent strokes. Major bleeding events occurred in 44 patients (4.1%), 7 of which were observed before the enoxaparin treatment period. At the time of discharge, 570 patients (53.6%) were no longer receiving LMWH treatment due to achieving the target international normalized ratio. The mean length of hospital stay was 8.5 ± 2.9 days. There were no deaths during the 6-week follow-up period. In our highly selected population, after MHVR, postoperative anticoagulation using LMWH is associated with a low rate of thromboembolic and major bleeding events. This large observational study demonstrates that the use of LMWH as an anticoagulant is effective and safe after MHVR.

Impact of chronic kidney disease on the risk of clinical outcomes in patients with cancer‐associated venous thromboembolism during anticoagulant treatment

Information on recurrent venous thromboembolic events (VTEs) and major bleeding risks during anticoagulant treatment in patients with cancer-associated VTEs and chronic kidney disease (CKD) is scarce, although it is of relevance in establishing better tailored management strategies in these patients. We compared risks of recurrent VTEs and major bleeds in cancer-associated VTE patients with and without CKD. A total of 1684 patients diagnosed with a cancer-associated VTE between 2001 and 2011 were followed for 180days after VTE diagnosis. Patients were treated mainly with low-molecular-weight heparin (LMWH) or vitamin-K antagonists (VKA). Primary outcomes were recurrent VTE and major bleeding. Secondary outcome was fatal bleeding. Recurrent VTEs occurred in 15.9/100 patient years (py) in patients without CKD (eGFR>60mL min(-1) ), 19.5/100py in those with CKD stage 3A (eGFR 45-60mL min(-1) ), 14.9/100py in those with CKD 3B (eGFR 30-45mL min(-1) ), and 6.8/100py in patients with CKD 4-5 (eGFR<30mL min(-1) ). Major bleeding occurred in 11.4/100 py in patients without CKD, 18.5/100 py in those with CKD stage 3A, 16.0/100 py in those with CKD 3B, and 40.8/100 py in patients with CKD 4-5. Fatal bleeding occurred in 1.1/100 py, 3.4/100 py, 6.3/100 py and 15.7/100 py, respectively. These increased bleeding risks in CKD patients were mainly observed in those on LMWH treatment, not VKA. The risk of major bleeding was increased in CKD patients with VTE and cancer, and was most prominent in those treated with LMWH and an eGFR<30mL min(-1) . These results indicate that LMWH should be used with caution in this specific population.

Heparin‐Induced Thrombocytopenia: Pathophysiology, Diagnosis, and Treatment Monitoring

ABSTRACT Clinical Development Phases I‐III Regulatory, Quality, Manufacturing Heparin‐induced thrombocytopenia (HIT) without or with thrombosis (HIT‐T) constitutes an acquired immune prothrombotic state, occurring in patients under unfractionated heparin or rarely low molecular weight heparin treatment. Heparin binding to secreted platelet factor‐4 (PF4) generates PF4 neo‐epitopes, against which polyclonal IgG‐antibodies are produced. IgG‐Hep/PF4 complexes bind on specific platelet, monocyte and endothelial cell Fcγ surface receptors, causing platelet consumption (thrombocytopenia), cell activation, release of prothrombotic tissue factor‐bearing microparticles and thrombin generation. Mild to moderate thrombocytopenia and venous or arterial thrombosis are the two hallmarks of HIT. “4T” scoring‐system predicts HIT‐probability, while diagnosis is further confirmed via specific laboratory assays, which reveal either the presence of IgG antibodies against Hep/PF4 complex (immunological assays), or whether patient's serum can activate donor platelets in the presence of heparin (functional assays). HIT‐treatment imposes immediate heparin cessation and initial parenteral anticoagulation with alternative anticoagulants, such as direct thrombin inhibitors (DTIs: lepirudin, argatroban, bivalirudin, desirudin) or indirect FXa inhibitors (IXaIs: danaparoid, fondaparinux). Monitoring of DTIs and IXaIs (via activated partial thromboplastin time or modern assays such as hemoclot thrombin inhibitor and anti‐Xa activity, respectively) is essential especially in patients with renal or hepatic failure or in patients with HIT‐related consumptive coagulopathy, in order to avoid serious bleeding events or anticoagulant underdosing. Vitamin K antagonists, which are contraindicated during acute phase, are permitted only after platelet count has substantially recovered and must be continued for at least 30 days and 3 months in isolated HIT and HIT‐T, respectively, with target international normalized ratio (INR) between 2.0 and 3.0.

Low molecular weight heparin relieves experimental colitis in mice by downregulating IL-1β and inhibiting syndecan-1 shedding in the intestinal mucosa.

Low molecular weight heparin (LMWH) exhibits anti-inflammatory properties, but its effect on inflammation in colitis remains unclear. This study aimed to evaluate the therapeutic effects of LMWH on dextran sulfate sodium (DSS)-induced colitis in mice, in which acute colitis progresses to chronic colitis, and to explore the potential mechanism involved in this process. C57BL/6 mice were randomly divided into control, DSS, and DSS plus LMWH groups (n = 18). Disease activity was scored by a disease activity index (DAI). Histological changes were evaluated by hematoxylin and eosin (HE) staining. The mRNA levels of syndecan-1, interleukin (IL)-1β, and IL-10 were determined by quantitative reverse transcription polymerase chain reaction. Protein expression of syndecan-1 was detected by immunohistochemistry. The serum syndecan-1 level was examined by a dot immunobinding assay. LMWH ameliorated the disease activity of colitis induced by DSS administration in mice. Colon destruction with the appearance of crypt damage, goblet cell loss, and a larger ulcer was found on day 12 after DSS administration, which was greatly relieved by the treatment of LMWH. LMWH upregulated syndecan-1 expression in the intestinal mucosa and reduced the serum syndecan-1 level on days 12 and 20 after DSS administration (P<0.05 vs. DSS group). In addition, LMWH significantly decreased the expression of both IL-1β and IL-10 mRNA on days 12 and 20 (P<0.05 vs. DSS group). LMWH has therapeutic effects on colitis by downregulating inflammatory cytokines and inhibiting syndecan-1 shedding in the intestinal mucosa.

Low molecular weight heparin for prevention of microvascular occlusion in digital replantation

The success of digital replantation is highly dependent on the patency of the repaired vessels after microvascular anastomosis. Antithrombotic agents are frequently used for preventing vascular occlusion. Low molecular weight heparin (LMWH) has been reported to be as effective as unfractionated heparin (UFH) in peripheral vascular surgery, but with fewer adverse effects. Its benefit in microvascular surgery such as digital replantation is unclear. To assess whether subcutaneous LMWH treatment improves the salvage rate of the digits in patients with digital replantation after traumatic amputation. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (October 2012), CENTRAL (2012, Issue 10) and trials databases. In addition, the authors searched PubMed, CNKI (China National Knowledge Infrastructure) and CEPS (Chinese Electronic Periodical Services), and sought additional trials from reference lists of relevant publications. We selected randomised or quasi-randomised controlled trials of LMWH in patients who received digital replantation. Two review authors independently extracted data and assessed the risk of bias of the included trials. Disagreements were resolved by discussion. Two randomised trials involving 114 patients with at least 122 replanted digits met the inclusion criteria and were included. Both trials compared the efficacy and safety of LMWH with UFH. We found no trials comparing LMWH with placebo or other anticoagulants. The data from the two included studies were insufficient for meta-analysis. The overall success rate of replantation did not differ between the LMWH and UFH groups, 92.3% versus 89.2% in one trial (risk ratio (RR) 1.03; 95% confidence interval (CI) 0.87 to 1.22) and 94.3% versus 94.15% in the other trial (RR 1.00; 95% CI 0.89 to 1.13). The incidence of both postoperative arterial and venous insufficiency were reported in one trial and did not significantly differ between the LMWH and UFH groups (RR 1.08; 95% CI 0.16 to 7.10 and RR 0.81; 95% CI 0.20 to 3.27, respectively). Direct and indirect causes of microvascular insufficiency were not reported in the trials. Different methods were used to monitor the adverse effects related to anticoagulation in the two trials. Bleeding tendency was monitored for the LMWH and UFH groups in one trial and was reported by the incidence of wound haemorrhage (11.5% versus 17.9%; RR 0.65; 95% CI 0.17 to 2.44), ecchymoses (3.8% versus 10.7%; RR 0.36; 95% CI 0.04 to 3.24), haematuria (3.8% versus 7.1%; RR 0.54; 95% CI 0.05 to 5.59), nasal bleeding (0% versus 7.1%; RR 0.21; 95% CI 0.01 to 4.28), gingival bleeding (0% versus 10.7%; RR 0.15, 95% CI 0.01 to 2.83) and faecal occult blood (0% versus 3.6%; RR 0.36; 95% CI 0.02 to 8.42). The bleeding tendency was increased in the UFH group but this was not statistically significant. This trial also monitored coagulability changes using parameters such as antithrombin activity, factor Xa activity, bleeding time, clotting time and activated partial thromboplastin time (aPTT). No comparison was made between the LMWH and UFH groups but all data consistently showed that coagulability was reduced more in the UFH group than in the LMWH group. The other trial reported a postoperative decrease in platelet count in the UFH group (preoperative 278.4 ± 18.7 x 10(9)/L, postoperative 194.3 ± 26.5 x 10(9)/L; P < 0.05) but not in the LMWH group (preoperative 260.8 ± 32.5 x 10(9)/L, postoperative 252.4 ± 29.1 x 10(9)/L; P > 0.05). Current limited evidence based on two small-scaled low-to-medium quality randomised trials found no differences in the success rate of replantation between LMWH and UFH, but a lower risk of postoperative bleeding and hypocoagulability after the use of LMWH. Further well-designed and adequately powered clinical trials are warranted.

The risk of venous thromboembolism in older patients with advanced stages of Parkinson’s disease

We are reporting in this letter the prevalence of patients who were admitted in our Hospital with advanced forms of Parkinsonism or PD and discharged with diagnosis of venous thromboembolism (VTE). Advanced stages of Parkinson’s disease (PD), defined according to the modified Hoehn and Yahr (HY still able to walk or stand unassisted; 5.0: Wheelchair bound or bedridden unless aided), are associated with many comorbidities in older hospitalized patients. Reduced mobility in PD is a hypothesized causal factor of the higher rates of poor outcomes observed in these patients. Reduced mobility is frequently associated with venous thromboembolism (VTE), delirium, inappropriate use of neuroleptics, falls, fractures, pneumonia, and other severe diseases [2]. The association between reduced mobility related to advanced stages of PD and the risk of VTE is not surprising. There is recent evidence that acutely ill patients with ‘‘reduced mobility’’ (defined as requiring total bed rest or being sedentary without bathroom privileges) are candidates to long-term use of low molecular weight heparin such as enoxaparin to reduce the risk of VTE. This treatment is strongly recommended despite the increased risk of major bleeding events observed in this age group [3]. Approximately 50–75 % of patients with VTE have a readily identifiable risk factor, either transient or permanent, whereas the remaining episodes are classified as unprovoked. The incidence of first-time VTE rises exponentially with age. However, whether the prevalence and the relative weight of major risk factors differ between elderly and younger patients is still unclear [4]. We performed an observational study on patients, aged 65 and older, who were admitted from January 2010 to October 2011 to the Geriatric Unit of University Hospital of Parma. The total number of subjects was 124 (87 men and 37 women). Sixty-six patients in the year 2010 and 58 in the year 2011 (from January to October) were admitted with diagnosis of Parkinsonism (ICD-9: code 332.1 and 332.2) (6.0 % of the total amount of patients admitted to our unit in this period of time). All these patients presented a H&Y stage of 4 or 5. Mean age ± SD of the patients was 80 ± 12 years. Nine patients (20.9 %) were affected by VTE (ICD-9: code 451.19, 451.81, 453.2, 451.0). None of these patients was on low molecular weight heparin or other treatments aimed to preventing VTE. COMMENT: In a relatively small sample of hospitalized patients, patients with advanced stages of Parkinsonism and ‘‘reduced mobility’’ were not routinely under any treatment for the prevention of VTE. Our findings are in accordance with recent Registry study [5], showing that the risk of VTE in the elderly, F. Lauretani (&) A. Giordano A. Nardelli Department of Geriatric Rehabilitation, Geriatric Unit and Laboratory of Movement Analysis, University Hospital of Parma, Via Gramsci 14, 43126 Parma, Italy e-mail: flauretani@ao.pr.it

Vascular Complications After Orthotopic Liver Transplantation in Estonia

The aim of this study was to analyse vascular complications (VC) accompanying the introduction in Estonia of orthotopic liver transplantation (OLT) for treatment of end-stage liver disease. We present the incidence and treatment of VC occurring among our first 23 OLT in 22 patients. The 11 female and 11 male patients were aged 12 to 67 years. Their diagnoses were cholestatic disease (n = 8); hepatitis C virus (HCV) cirrhosis (n = 6); tumor (n = 3); Budd-Chiari syndrome (n = 2); autoimmune hepatitis (n = 1); cystic fibrosis (n = 1); or fulminant hepatic failure (n = 1). Only end-to-end vascular reconstructions were used in OLT. The patients' 1-year post-OLT survival rate was 86%. VC were confirmed using computed tomography (CT) or magnetic resonance imaging (MRI). In cases of VC, we started a 1-week course of subcutaneous anticoagulant therapy with low–molecular weight heparin (LMWH) immediately followed by permanent oral treatment. The incidence of VC was 14% (n = 3). There was no hepatic artery thrombosis. One patient developed hepatic venous thrombosis at 3 weeks after retransplantation. She was treated successfully with immediate LMWH followed by a permanent oral anticoagulation. Two patients experienced portal vein complications: 1 with pre-OLT portal vein thrombosis developed right intrahepatic portal vein thrombosis at 5 weeks after OLT requiring portal thrombectomy. He was treated successfully with immediate LMWH followed by permanent oral anticoagulation. The other subject displayed left intrahepatic portal vein thrombosis at 1 week after OLT. Despite immediate LMWH treatment followed by a permanent oral anticoagulation, he required left lobe necrectomy and Roux-Y choledochojejunostomy for recovery. The survival and recovery of all studied patients with VC allow us to recommend immediate subcutaneous anticoagulant therapy for post-OLT portal or hepatic venous thrombosis.

Low molecular weight heparin prevents CLP-induced acute lung injury in rats by anti-inflammatory coagulation.

The aim of our study was to observe the influence of low molecular Weight heparin (LMWH) on systemic inflammation, including high mobility group box 1 protein (HMGB1) and protective effect on acute lung injury induced by cecal ligation and puncture(CLP). Discuss the mechanism of this effect. 144 male SD rats were randomly divided into sham operation group (A), normal treatment group (B), the LMWH treatment group (C), n=48.Group A received a sham operation and the other groups were underwent CLP operation. Groups A and B accepted intraperitoneal injection (i.p.) of normal saline (NS) at a dose of 2.0 ml/kg and ceftriaxone (30 mg/kg), Group C were intraperitoneal injection additional LMWH (150 U/kg) except saline and ceftriaxone. Observe points were made at 3, 6, 12, 18, 24, 48 h, the rats were anesthetized and killed, mortality, lungs wet/dry ratio and Pathology change were determined. HMGB-1 mRNA, protein of lung tissues was calculated by RT-PCR and Western blot. TNF-α and IL-6 of blood plasma calculated by ELSIA. There was significantly different in each index between A and B group (p<0.05).Compared with CLP group, there was a significant decrease in the lung injury, the mortality, HMGB1 mRNA and protein expression on lung tissues (p<0.05). LMWH can decreases cytokine, HMGB1 levels of lung tissue during CLP-induced inflammation. As a result, LMWH ameliorated lung pathology and reduces mortality in CLP-induced systemic inflammation in a rat model. This effect may be mediated through the inhibition of axis of inflammation and coagulation.

Low-Molecular-Weight Heparin Use with Thrombolysis: Is it Effective and Safe? Ten Years' Clinical Experience

Background: There is no data on the use of subcutaneous low-molecular-weight heparin (SC LMWH) in cases that require thrombolysis. Objective: Having used SC LMWH with thrombolytics for more than 10 years, we aimed to review our data, share our experiences and find out whether the use of SC LMWH with thrombolytics had been effective and safe. Method: This is a retrospective cohort study. Patients who were diagnosed as acute pulmonary embolism (PE) and received either SC LMWH treatment or SC LMWH with thrombolytics in our hospital (a tertiary hospital) between 2000 and 2010 were included in the study. For both treatments, the rates of mortality and complications were calculated. Results: A total of 392 patients, 210 female (53.5%) and 182 male (46.5%) with an average age of 60 years, ±16 SD, with acute PE, were included in the study. Of these patients, 107 (27.2%) were massive and 285 (72.8%) were nonmassive and were administered SC LMWH plus thrombolytics and only SC LMWH, respectively. The mortality rate was 16.8% (18 of 107) in patients who were massive and 3.5% (10 of 285) for those who were nonmassive (p < 0.001). Major hemorrhage occurred in 3.7% (n = 4) and 0.7% (n = 2) and minor hemorrhage in 12.1% (n = 13) and in 3.8% (n = 11) of the cases who received SC LMWH plus thrombolytics and SC LMWH, respectively. Conclusion: SC LMWH use with thrombolytics seems to be feasible and safe. Prospective, large, randomized control trials are still required in order to confirm these results.