Comparison of efficacy of nadroparin and fondaparinux sodium for prevention of deep vein thromboembolism in lower extremities after total hip arthroplasty and total knee arthroplasty: a retrospective study of 592 patients.

OBJECTIVES: To compare the efficacy of nadroparin and fondaparinux sodium for prevention of deep vein thromboembolism (DVT) in lower extremities after total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: A total of 592 patients were enrolled in the study. Clinical data of patients who underwent total hip arthroplasty (THA) and total knee arthroplasty (TKA) in our hospital from December 2021 to September 2022 were retrospectively collected, which mainly included patients' general information, surgery-related information, and DVT-related information. The patients were categorized into the nadroparin group(n = 278) and the fondaparinux sodium group(n = 314) according to the types of anticoagulants used. Anticoagulant therapy began 12-24 h after operation and continued until discharge. DVT prevalence between two groups was compared. The Statistical Package for Social Sciences (SPSS) software version 25 (SPSS, Armonk, NY, USA) was used for statistical analysis. RESULTS: The prevalence of DVT in the nadroparin group and the fondaparinux sodium group was 8.3% (23/278) and 15.0% (47/314), respectively(p = 0.012). Statistical analysis showed that nadroparin group showed a lower prevalence of thrombosis than fondaparinux group (OR = 1.952, P = 0.012). Subgroup analyses showed that nadroparin group had a lower prevalence of DVT than fondaparinux group in some special patients groups such as female patients (OR = 2.258, P = 0.007), patients who are 65-79 years old (OR = 2.796, P = 0.004), patients with hypertension (OR = 2.237, P = 0.042), patients who underwent TKA (OR = 2.091, P = 0.011), and patients who underwent combined spinal-epidural anesthesia (OR = 2.490, P = 0.003) (P < 0.05). CONCLUSION: Nadroparin may have an advantage over fondaparinux sodium in preventing DVT in lower extremities after THA and TKA.

Bleeding complications of thromboprophylaxis with dabigatran, nadroparin or rivaroxaban for 6 weeks after total knee arthroplasty surgery: a randomised pilot study.

OBJECTIVES: For the non-vitamin-K oral anticoagulants, data on bleeding when used for 42 days as thromboprophylaxis after total knee arthroplasty (TKA) are scarce. This pilot study assessed feasibility of a multicentre randomised clinical trial to evaluate major and clinically relevant non-major bleeding during 42-day use of dabigatran, nadroparin and rivaroxaban after TKA. PATIENTS AND METHODS: In 70 weeks, between July 2012 and November 2013, 198 TKA patients were screened for eligibility in the Martini Hospital (Groningen, the Netherlands). Patients were randomly assigned to dabigatran (n=45), nadroparin (n=45) or rivaroxaban (n=48). The primary outcome was the combined endpoint of major bleeding and clinically relevant non-major bleeding. Secondary endpoints of this study were the occurrence of clinical venous thromboembolism (VTE) (pulmonary embolism or deep venous thrombosis), compliance, duration of hospital stay, rehospitalisation, adverse events and Knee Injury and Osteoarthritis Outcome Score (KOOS). RESULTS: The primary outcome was observed in 33.3% (95% CI 20.0% to 49.0%), 24.4% (95% CI 12.9% to 39.5%) and 27.1% (95% CI 15.3% to 41.8%) of patients who received dabigatran, nadroparin or rivaroxaban, respectively (p=0.67). Major bleeding was found in two patients who received nadroparin (p=0.21). Clinically relevant non-major bleeding was observed in 33.3% (95% CI 20.0% to 49.0%), 22.2% (95% CI 11.2% to 37.1%) and 27.1% (95% CI 15.3% to 41.8%) for dabigatran, nadroparin and rivaroxaban, respectively (p=0.51). Wound haematoma was the most observed bleeding event. VTE was found in one patient who received dabigatran (p=0.65). The presurgery and postsurgery KOOS qQuestionnaires were available for 32 (71%), 35 (77%) and 35 (73%) patients for dabigatran, nadroparin and rivaroxaban, respectively. KOOS was highly variable, and no significant difference between treatment groups in mean improvement was observed. CONCLUSIONS: A multicentre clinical trial may be feasible. However, investments will be substantial. No differences in major and clinically relevant non-major bleeding events were found between dabigatran, nadroparin and rivaroxaban during 42 days after TKA. KOOS may not be suitable to detect functional loss due to bleeding. TRIAL REGISTRATION NUMBER: NCT01431456.

[Celiac crisis in patients with celiac disease. Case report].

Celiac crisis (CC) is a rare life-threatening course of celiac disease, observed mainly in children. In adults, CK can be the first manifestation of the disease and, very rarely, a relapse that occurs in patients who do not follow the gluten-free diet (AGD). Triggers can be stress, surgery, childbirth, etc. A clinical observation of CC developed in a 49-year-old patient with previously established latent celiac disease with subtotal villous atrophy, stage Marsh III C is presented. The patient did not comply with AHD. After severe angina, she developed anorexia, diarrhea, emaciation, coagulopathy, bilateral pulmonary embolism, infarction pneumonia, and enterogenic sepsis. As a result of intensive therapy with prednisolone, Fraxiparine, antibiotics, fresh frozen plasma and strict adherence to hypertension, remission of the disease was achieved.

Thromboembolic and bleeding complications in patients with oesophageal cancer.

BACKGROUND: In patients who undergo curative treatment for oesophageal cancer, risk estimates of venous thromboembolism (VTE), arterial thromboembolism and bleeding are needed to guide decisions about thromboprophylaxis. METHODS: This was a single-centre, retrospective cohort study of patients with stage I-III oesophageal cancer who received neoadjuvant chemoradiation followed by oesophagectomy. The outcomes VTE, arterial thromboembolism, major bleeding, clinically relevant non-major bleeding and mortality were analysed for four consecutive cancer treatment stages (from diagnosis to neoadjuvant chemoradiotherapy, during neoadjuvant treatment, 30-day postoperative period, and up to 6 months after postoperative period). RESULTS: Some 511 patients were included. The 2-year survival rate was 67·3 (95 per cent c.i. 63·2 to 71·7) per cent. During the 2-year follow-up, 50 patients (9·8 per cent) developed VTE, 20 (3·9 per cent) arterial thromboembolism, 21 (4·1 per cent) major bleeding and 30 (5·9 per cent) clinically relevant non-major bleeding. The risk of these events was substantial at all treatment stages. Despite 30-day postoperative thromboprophylaxis, 17 patients (3·3 per cent) developed VTE after surgery. Patients with VTE had worse survival (time-varying hazard ratio 1·81, 95 per cent c.i. 1·25 to 2·64). Most bleeding events occurred around the time of medical intervention, and approximately one-half during concomitant use of prophylactic or therapeutic anticoagulation. CONCLUSION: Patients with oesophageal cancer undergoing neoadjuvant chemoradiotherapy and surgery are at substantial risk of thromboembolic and bleeding events throughout all stages of treatment. Survival is worse in patients with thromboembolic events during follow-up.

ANTECEDENTES: Para tomar decisiones en cuanto a la profilaxis tromboembólica, es preciso estimar el riesgo de tromboembolismo venoso (venous thromboembolism, VTE), de tromboembolismo arterial y de hemorragia en pacientes a los que se vaya a realizar un tratamiento curativo para el cáncer de esófago. MÉTODOS: Se realizó un estudio de cohortes retrospectivo de un solo centro, de pacientes con cáncer de esófago en estadios I-III que fueron tratados con quimiorradioterapia neoadyuvante y esofagectomía. Se analizaron, en cuatro momentos del tratamiento (desde el momento del diagnóstico hasta la quimiorradioterapia neoadyuvante, durante el tratamiento neoadyuvante, en los 30 días del período postoperatorio y a los 6 meses de la cirugía) las siguientes variables: VTE, tromboembolismo arterial, hemorragia grave, hemorragia no grave clínicamente relevante y mortalidad. RESULTADOS: Se incluyeron 511 pacientes. La supervivencia a los 2 años fue del 67,3% (ic. del 95%, 63,2-71,7). Durante el seguimiento de 2 años, 50 pacientes desarrollaron un VTE (9,8%), 20 un tromboembolismo arterial (3,9%), 21 hemorragias graves (4,1%) y 30 hemorragias no graves clínicamente relevantes (5,9%). El riesgo de estos accidentes fue notable en todas las etapas del tratamiento. A pesar de la profilaxis tromboembólica posquirúrgica, a los 30 días, 17 pacientes (3,3%) desarrollaron un VTE después de la operación. Los pacientes con VTE tuvieron una supervivencia menor (cociente de riesgos instantáneos, hazard ratio en función del tiempo 1,81; i.c. del 95%, 1,25-2,64). La mayoría de los accidentes hemorrágicos ocurrieron en el contexto de una intervención médica y el 48% durante el uso concomitante de anticoagulación profiláctica o terapéutica. CONCLUSIÓN: Los pacientes con cáncer de esófago tratados con quimiorradioterapia neoadyuvante y cirugía tienen un riesgo sustancial de sufrir accidentes tromboembólicos y hemorrágicos en todas las fases del tratamiento. La supervivencia es peor en aquellos pacientes que presentan accidentes tromboembólicos durante el seguimiento.

Nadroparin Plus Compression Stockings versus Nadroparin Alone for Prevention of Venous Thromboembolism in Cerebellopontine Angle Tumour Excisions: A Cohort Study.

BACKGROUND: Both compression stockings and low molecular weight heparin (LMWH) are used for the prevention of post-operative venous thromboembolism (VTE) in cerebellopontine angle (CPA) tumour excisions. OBJECTIVE: In an attempt to optimise the prophylactic treatment in these patients, we compared LMWH (nadroparin) plus compression stockings to nadroparin as single therapy. METHODS: Patients undergoing CPA tumour excision in the period between January 2014 and November 2015 received nadroparin as a single therapy. Patients treated since November 2015 received, in addition to this therapy, peri-operative compression stockings as VTE prophylaxis due to a change in protocol. VTE was defined as symptomatic deep vein thrombosis or pulmonary embolism and was confirmed via radiological imaging or autopsy. RESULTS: A total of 146 consecutive patients were reviewed. Treatment groups were comparable with respect to demographics and risk factors. Six of the 60 patients (10.0%; 95% confidence interval [CI] 3.8-20.5) receiving nadroparin single therapy developed symptomatic VTE. One out of 86 patients (1.2%; 95% CI 0-6.3) treated with combination therapy developed VTE (p = 0.019) with a risk difference of 8.8% (95% CI 1.43-19.0). In comparison to combination therapy, nadroparin single therapy showed a relative risk of 8.6 (95% CI 1.1-69.6). CONCLUSION: Adding compression stockings to peri-operative nadroparin, as a prophylactic strategy for thromboembolic complications in patients undergoing surgical intervention for CPA tumours, was associated with a significant reduction in the occurrence of VTE.

Low molecular weight heparin (nadroparin) improves placental permeability in rats with gestational diabetes mellitus via reduction of tight junction factors.

Placental structural abnormalities and dysfunction in those with gestational diabetes mellitus (GDM) can lead to increased placental permeability, which is in turn related to a poorer maternal and fetal prognosis. The present study sought to assess whether increased placental permeability in rats with GDM was accompanied by alterations in tight junction (TJ) factors and to evaluate the impact of low molecular weight heparin (LMWH) on these factors. The present study was conducted using pregnant female rats that were randomized into control, GDM and GDM + LMWH groups. Diabetes was induced via intraperitoneal administration of streptozotocin to rats in the GDM and GDM + LMWH groups, whereas rats in the GDM + LMWH group received daily subcutaneous LMWH starting on day 5 of pregnancy. On gestational day 16, all rats were sacrificed and Evans Blue (EB) assay was used to gauge vascular permeability based on EB dye leakage. Transmission electron microscopy was further used to assess TJ structures, and the TJ proteins zonular occludens­1 (ZO­1) and occludin (OCLN) were assessed using immunohistochemistry and western blotting. Blood samples were obtained from the abdominal aorta for ELISA measurements of advanced glycation end products (AGEs) concentrations, and placental receptor for AGEs (RAGE) and vascular endothelial growth factor (VEGF) expression was assessed using reverse transcription­quantitative PCR. In addition, western blotting was used to measure placental NF­κB. Compared with in the control group, EB leakage was markedly increased in GDM group rats; this was associated with reduced ZO­1 and OCLN expression. Conversely, LMWH attenuated this increase in placental permeability in rats with GDM and also mediated a partial recovery of ZO­1 and OCLN expression. Blood glucose and serum AGEs concentrations did not differ between the GDM and GDM + LMWH groups. Furthermore, LMWH treatment resulted in decreases in RAGE and VEGF mRNA expression levels, which were upregulated in the GDM group, whereas it had the opposite effect on the expression of NF­κB. In conclusion, GDM was associated with increased placental permeability and this may be linked with changes in TJs. LMWH intervention mediated protection against this GDM­associated shift in placental permeability via the RAGE/NF­κB pathway.

Randomised phase 3 study of adjuvant chemotherapy with or without nadroparin in patients with completely resected non-small-cell lung cancer: the NVALT-8 study.

BACKGROUND: Retrospective studies suggest that low molecular weight heparin may delay the development of metastasis in patients with resected NSCLC. METHODS: Multicentre phase 3 study with patients with completely resected NSCLC who were randomised after surgery to receive chemotherapy with or without nadroparin. The main exclusion criteria were R1/2 and wedge/segmental resection. FDG-PET was required. The primary endpoint was recurrence-free survival (RFS). RESULTS: Among 235 registered patients, 202 were randomised (nadroparin: n = 100; control n = 102). Slow accrual enabled a decrease in the number of patients needed from 600 to 202, providing 80% power to compare RFS with 94 events (α = 0.05; 2-sided). There were no differences in bleeding events between the two groups. The median RFS was 65.2 months (95% CI, 36-NA) in the nadroparin arm and 37.7 months (95% CI, 22.7-NA) in the control arm (HR 0.77 (95% CI, 0.53-1.13, P = 0.19). FDG-PET SUVmax ≥10 predicted a greater likelihood of recurrence in the first year (HR 0.48, 95% CI 0.22-0.9, P = 0.05). CONCLUSIONS: Adjuvant nadroparin did not improve RFS in patients with resected NSCLC. In this study, a high SUVmax predicted a greater likelihood of recurrence in the first year. CLINICAL TRIAL REGISTRATION: Netherlands Trial registry: NTR1250/1217.

Outcomes following pancreatic surgery using three different thromboprophylaxis regimens.

BACKGROUND: Postpancreatectomy haemorrhage (PPH) and venous thromboembolism (VTE) are serious complications following pancreatic surgery. The aim was to assess the timing, occurrence and predictors of PPH and VTE. METHODS: Elective pancreatic resections undertaken in a single university hospital between November 2013 and September 2017 were assessed. Three intervals were reviewed, each with a different routine regimen of nadroparin: 2850 units once daily (single dose) administered in hospital only, or 5700 units once daily (double dose) or 2850 units twice daily (split dose) administered in hospital and continued for 6 weeks after surgery. Clinically relevant PPH (CR-PPH) was classified according to International Study Group of Pancreatic Surgery criteria. VTE was defined according to a number of key diagnostic criteria within 6 weeks of surgery. Cox regression analyses were performed to test the hypotheses that the double-dose group would experience more PPH than the other two groups, the single-dose group would experience more VTE than the other two groups, and the split-dose group would experience the fewest adverse events (PPH or VTE). RESULTS: In total, 240 patients were included, 80 per group. The double-dose group experienced significantly more CR-PPH (hazard ratio (HR) 2·14, 95 per cent c.i. 1·16 to 3·94; P = 0·015). More relaparotomies due to CR-PPH were performed in the double-dose group (16 versus 3·8 per cent; P = 0·002). The single-dose group did not experience more VTE (HR 1·41, 0·43 to 4·62; P = 0·570). The split dose was not associated with fewer adverse events (HR 0·77, 0·41 to 1·46; P = 0·422). Double-dose low molecular weight heparin (LMWH), high BMI and pancreatic fistula were independent predictors of CR-PPH. CONCLUSION: A double dose of LMWH prophylaxis continued for 6 weeks after pancreatic resection was associated with a twofold higher rate of CR-PPH, resulting in four times more relaparotomies. Patients receiving a single daily dose of LMWH in hospital only did not experience a higher rate of VTE.

A New Protocol for Venous Thromboembolism Prophylaxis in Bariatric Surgery.

BACKGROUND: Morbidly obese patients are at high risk for developing venous thromboembolism (VTE). The aim of this study was to evaluate the effect of a new VTE prophylaxis protocol (low dosage, low-molecular-weight heparin [LMWH]) with a pneumatic compression device (PCD) in patients undergoing bariatric surgery. MATERIALS AND METHODS: Between November 2015 and December 2017, 368 patients underwent surgery due to obesity. The patients received 0.2 ml of nadroparin (Fraxiparine, GlaxoSmithKline) 12 h before the operation. A PCD (Kendall SCD Compression System) was applied to the patient during the operation and left on the patient during the subsequent 24 h. Nadroparin 0.4 ml was started subcutaneously after the PCD was removed from the patient and the same dosage of nadroparin was given daily for 15 days following the bariatric operation. Ambulation within 2 h of surgery was encouraged and was performed frequently. RESULTS: A total of 368 patients underwent laparoscopic bariatric surgery. The median age was 34.1 years (range, 18-61), the median weight was 128 kg (range, 90-182), and the median body mass index (BMI) was 47.2 kg/m2 (range, 36-72). No thrombotic events were observed postoperatively or at the 1-, 3-, and 6-month follow-up visits. Four bleedings occurred requiring transfusions. None of these patients required a re-laparotomy for hemorrhage control. The mortality rate was 0% at 30 and 90 days and during the hospitalization. CONCLUSION: Low dosage LMWH with PCD is very effective for VTE prophylaxis in bariatric surgery.

The Effect of Obesity on Anti-Xa Concentrations in Bariatric Patients.

BACKGROUND: Morbidly obese patients are at increased risk to develop venous thromboembolism (VTE), especially after bariatric surgery. Adequate postoperative thrombosis prophylaxis is of utmost importance. It is assumed that morbidly obese patients need higher doses of low molecular weight heparin (LMWH) compared to normal-weight patients; however, current guidelines based on relative efficacy in obese populations are lacking. OBJECTIVES: First, we will evaluate the relationship between body weight descriptors and anti-Xa activity prospectively. Second, we will determine the dose-linearity of LMWH in morbidly obese patients. SETTING: This study was performed in a general hospital specialized in bariatric surgery. METHODS: Patients were scheduled for a Roux-en-Y gastric bypass with a total bodyweight (TBW) of ≥ 140 kg. Patients (n = 50, 64% female) received a daily postoperative dose of 5700 IU of nadroparin for 4 weeks. Anti-Xa activity was determined 4 h after the last nadroparin administration. To determine the dose linearity, anti-Xa was determined following a preoperative dose of 2850 IU nadroparin in another 50 patients (52%). RESULTS: TBW of the complete group was 148.5 ± 12.6 kg. Mean anti-Xa activity following 5700 IU nadroparin was 0.19 ± 0.07 IU/mL. Of all patients, 32% had anti-Xa levels below the prophylactic range. Anti-Xa activity inversely correlated with TBW (correlation coefficient - 0.410) and lean body weight (LBW; correlation coefficient - 0.447); 67% of patients with a LBW ≥ 80 kg had insufficient anti-Xa activity concentrations. No VTE events occurred. CONCLUSIONS: In morbidly obese patients, a postoperative dose of 5700 IU of nadroparin resulted in subprophylactic exposure in a significant proportion of patients. Especially in patients with LBW ≥ 80 kg, a higher dose may potentially be required to reach adequate prophylactic anti-Xa levels.

Association between protein C levels and mortality in patients with advanced prostate, lung and pancreatic cancer.

INTRODUCTION: Procoagulant factors promote cancer progression and metastasis. Protein C is involved in hemostasis, inflammation and signal transduction, and has a protective effect on the endothelial barrier. In mice, administration of activated protein C reduced experimental metastasis. We assessed the association between protein C and mortality in patients with three types of cancer. METHODS: The study population consisted of patients with advanced prostate, non-small cell lung or pancreatic cancer, who participated in the INPACT trial (NCT00312013). The trial evaluated the addition of nadroparin to chemotherapy in patients with advanced malignancy. Patients were divided into tertiles based on protein C at baseline. The association between protein C levels and mortality was evaluated with Cox proportional hazard models. RESULTS: We analysed 477 patients (protein C tertiles: <97, 97-121 and ≥121%). Mean age was 65±9years; 390 (82%) were male; 191 patients (40%) had prostate cancer, 161 (34%) had lung cancer, and 125 (26%) pancreatic cancer. During a median follow-up of 10.4months, 291 patients (61%) died. Median protein C level was 107% (IQR 92-129). In the lowest tertile, 75 patients per 100 patient-years died, as compared to 60 and 54 in the middle and high tertile, respectively. Lower levels of protein C were associated with increased mortality (in tertiles: HR for trend 1.18, 95%CI 1.02-1.36, adjusted for age, sex and nadroparin use; as a continuous variable: HR 1.004, 95%CI 1.00-1.008, p=0.07). CONCLUSION: Protein C seems inversely associated with mortality in patients with advanced prostate, lung and pancreatic cancer. Further research should validate protein C as a biomarker for mortality, and explore the effects of protein C on progression of cancer.

[Prevention of thrombohemorrhagic postoperative complications in patients with benign prostatic hyperplasia].

AIM: To improve the results of surgical treatment of benign prostatic hyperplasia. MATERIALS AND METHODS: The study investigated the effectiveness of a comprehensive preoperative preparation of patients with benign prostatic hyperplasia. The clinical efficacy of traditional methods of preoperative preparation (compression bandaging of the lower extremities during surgery and in the postoperative period and Fraxiparine at a prophylactic dose) was compared with the same preoperative protocol used in combination with intravenous laser blood irradiation. The explored parameters included changes in clinical and laboratory coagulation indices and prostatic blood flow measured by Doppler sonography. The real time visualization was used to assess the effect of intravenous laser irradiation of blood on the morphofunctional state of platelets. CONCLUSION: The study findings showed a high effectiveness of intravenous laser blood irradiation in preoperative preparation of patients with benign prostatic hyperplasia. It was found to reduce the incidence of thrombotic events by 6% and hemorrhagic complications by 4.9% (p<0.05).

Anticoagulant therapy for symptomatic calf deep vein thrombosis (CACTUS): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The efficacy and safety of anticoagulant treatment is not established for patients with acute symptomatic deep vein thrombosis (DVT) of the calf. We aimed to assess whether therapeutic anticoagulation is superior to placebo in patients with symptomatic calf DVT. METHODS: In this randomised, double-blind, placebo-controlled trial, we enrolled low-risk outpatients (without active cancer or previous venous thromboembolic disease) with a first acute symptomatic DVT in the calf from 23 university medical centres or community medical clinics in Canada, France, and Switzerland. We randomly assigned (1:1) patients to receive either the low-molecular-weight heparin nadroparin (171 UI/kg, subcutaneously, once a day) or placebo (saline 0·9%, subcutaneously, once a day) for 6 weeks (42 days). Central randomisation was done using a computer-generated randomisation list, stratified by study centre. Random allocation sequences of variable block size were centrally determined by an independent research clinical centre. Study staff, patients, and outcome assessors (central adjudication committee) were masked to group assignment. Numbered boxes of active drug or placebo were provided to pharmacies in identical packaging. All patients were prescribed compression stockings and followed up for 90 days. The primary efficacy outcome was a composite measure of extension of calf DVT to proximal veins, contralateral proximal DVT, and symptomatic pulmonary embolism at day 42 in the modified intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding at day 42. The trial was registered with ClinicalTrials.gov, number NCT00421538. FINDINGS: Between Feb 1, 2008, and Nov 30, 2014, we screened 746 patients, enrolling 259 patients (50% of the prespecified sample size), before the trial steering committee terminated the trial because of expiry of study drug and slow recruitment. The intention-to-treat analysis population comprised 122 patients in the nadroparin group and 130 in the placebo group. There was no significant difference between the groups in the composite primary outcome, which occurred in four patients (3%) in the nadroparin group and in seven (5%) in the placebo group (risk difference -2·1%, 95% CI -7·8 to 3·5; p=0·54). Bleeding occurred in five patients (4%) in the nadroparin group and no patients in the placebo group (risk difference 4·1, 95% CI 0·4 to 9·2; p=0·0255). In the nadroparin group one patient died from metastatic pancreatic cancer and one patient was diagnosed with heparin-induced thrombocytopenia type 2. INTERPRETATION: Nadroparin was not superior to placebo in reducing the risk of proximal extension or venous thromboembolic events in low-risk outpatients with symptomatic calf DVT, but did increase the risk of bleeding. Avoidance of systematic anticoagulation for calf DVT could have a substantial impact on individual patients and from a public health perspective. FUNDING: Swiss National Science Foundation, the Programme Hospitalier de Recherche Clinique in France, and the Canadian Institutes of Health Research.

Antithrombotic prophylaxis in a patient with nephrotic syndrome and congenital protein S deficiency.

BACKGROUND: Nephrotic syndrome confers an acquired prothrombotic phenotype due to the urinary loss of anticoagulant proteins.Patients with reactivation of nephrotic syndrome may develop thrombosis. CASE PRESENTATION: We report the case of a life-threatening cerebral venous thrombosis in a 13 year-old boy affected by a relapse of nephrotic syndrome during a P. aeruginosa otitis/mastoiditis. Due to the worsening general conditions and the severe neurological impairment, a course of systemic thrombolysis was successfully administered, followed by anticoagulant therapy. In the present case severe inherited thrombophilia (inherited dysfunctional protein S deficiency) was identified as an important additional risk factors for thrombosis. CONCLUSIONS: A careful evalutaion of risk factos for thrombosi during reactivation of nephrotic syndrome include measurement of plasma anticaogulant proteins. When low, antithrombotic prophylaxis with heparin should be considered to prevent thrombotic episodes.

Microvascular effects of the low molecular weight heparins in a colorectal xenograft model: an intravital microscopy study.

BACKGROUND: Low molecular weight heparins (LMWHs) are the cornerstone of the prevention of thromboembolic events in surgical patients. Recent clinical data suggest that LMWHs might improve survival of cancer patients, independent of their anticoagulant effect. The anti-cancer mechanism of LMWHs is incompletely understood, but may include effects on tumor angiogenesis. We assessed the effects of LMWHs on tumor angiogenesis and microcirculation in a mouse colorectal xenograft model using in vivo microscopy in window chambers. METHODS: HT29 human colorectal cancers were implanted in dorsal skinfold window chambers in athymic mice. Animals (n = 8 per group) were treated with 200 IU of nadroparin, enoxaparin, or saline for 8 d. Repeated intravital fluorescence microscopy was performed to calculate functional microcirculatory parameters as follows: number (N) and length (L) of microvessels, vascular area fraction (AF), and red blood cell velocity. Microvessel density, microvessel fractal dimension, and pericyte coverage were assessed histologically. RESULTS: Active angiogenesis was observed in control animals, resulting in a significant increase in N, L, and AF. In nadroparin- and enoxaparin-treated animals, however, AF did not change significantly over time and N and L remained significantly lower than untreated animals on day 7. Compared with control animals, nadroparin- and enoxaparin-treated animals showed a significantly lower microvessel density, but a higher pericyte coverage index, indicating a more mature microvessel network. CONCLUSIONS: The LMWHs nadroparin and enoxaparin inhibit tumor angiogenesis and result in microvessel normalization in this in vivo observed colorectal xenograft model.

Low molecular weight heparin improves healing of chronic venous ulcers especially in the elderly.

Venous ulcers are common, especially in the elderly, accounting for more than 50% of all lower extremity ulcers with important socioeconomic problems. Improving extracellular matrix functioning, by heparin administration, seems to be a way to support wound healing. A total of 284 patients with venous ulcers were recruited in a 4-year period. All patients were subjected to the most appropriate treatment after considering their preference (compression therapy followed or not by vein surgery). Patients were randomised into two groups of 142 persons in each (group A and group B as cases and controls, respectively). Patients of group A, in addition to the basic treatment as described earlier, received administration of nadroparin 2850 IU/0.3 ml through subcutaneous injection once a day for 12 months, whereas group B patients received basic treatment alone. Healing was assessed by means of direct ulcer tracing with computerised planimetry. Group A showed a healing rate of 83·80% at 12 months, whereas that of group B was 60·56%. Results by age group surprisingly showed that the group of older patients took the most advantage from long-term treatment with low molecular weight heparin; this group also had lowest recurrence rate.

Pulmonary embolism after abdominal flap breast reconstruction: prediction and prevention.

BACKGROUND: Symptomatic pulmonary embolism constitutes a significant risk following abdominal flap breast reconstruction. Reported rates vary from 0 to 6 percent. The authors assessed risk factors associated with symptomatic pulmonary embolism and constructed a prediction model to identify high-risk patients. METHODS: Patients undergoing deep inferior epigastric perforator or transverse rectus abdominis musculocutaneous flap breast reconstructions at two academic centers from January of 2005 through January of 2011 were included. Thromboprophylaxis measures included early ambulation, low-molecular-weight heparin, elastic stockings, A-V Impulse System foot pumps, and pneumatic stockings. Risk factors for symptomatic pulmonary embolism were analyzed and weights were assigned to these risk factors. Sensitivity and specificity were maximized using receiver operating characteristic curves. RESULTS: Of 430 consecutive patients, symptomatic pulmonary embolism occurred in 17 cases (4.0 percent). Two independent predictors for symptomatic pulmonary embolism were found, body mass index higher than 25, additionally higher than 28, and the BRCA gene mutation. Operation duration and bilaterality of reconstructions were dependent on the BRCA mutation and both indirect predictors for symptomatic pulmonary embolism. Optimization of sensitivity and specificity resulted in a prediction model. No significant differences in efficacy were found between the different thromboprophylaxis measures. CONCLUSIONS: The rate of symptomatic pulmonary embolism was 4.0 percent, despite standard thromboprophylaxis. Body mass index and BRCA were significant predictors for symptomatic pulmonary embolism. The authors integrated these factors into a prediction model, which provides a useful tool for identification of high-risk patients. This latter category may benefit from a more aggressive thromboprophylaxis approach. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.