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Serum total thyroxine, triiodothyronine, and thyrotropin response to thyrotropin- releasing hormone (TRH-TSH test) were measured in 126 consecutive patients admitted with atrial flbrillation: 33 patients with an acute arterial limb embolism (Group I), 31 patients with an acute embolic stroke (Group II), and 62 patients without any arterial occlusion (Group III). A blunted TRH-TSH test, suggestive of thyrotoxicosis, was found in 5 patients in Group I, 8 patients in Group 11, and 2 patients in Group IU. The diagnosis of hyperthyroidism was confirmed in 8 patients (by repeated TRH-TSH test and scintigraphy): 4 patients in Group I (12.1%) and 4 patients in Group II (12.9%). All of them had a nonvalvular atrial fibrillation. Thyrotoxicosis should not be recognized in 6 of them if TRH-TSH test was not performed, because peripheral hormone levels were normal. Five of these 8 patients with thyrotoxicosis had reversion to sinus rhythm after treatment with carbimazole, either spontaneously or after cardioversion. This outcome prevented prolongation of anticoagulant therapy for an indefinite time. [ABSTRACT FROM AUTHOR]

In patients, advanced cirrhosis only regresses partially once the etiological agent is withdrawn. Animal models for advanced cirrhosis regression are missing. Lifestyle interventions (LIs) have been shown to improve steatosis, inflammation, fibrosis, and portal pressure (PP) in liver disease. We aimed at characterizing cirrhosis regression after etiological agent removal in experimental models of advanced cirrhosis and to study the impact of different LI on it. Advanced cirrhosis was induced in rats either by carbon tetrachloride (CCl 4 ) or by thioacetamide (TAA) administration. Systemic and hepatic hemodynamics, liver fibrosis, hepatic stellate cell (HSC) activation, hepatic macrophage infiltration, and metabolic profile were evaluated after 48 h, 4 wk or 8 wk of etiological agent removal. The impact of LI consisting in caloric restriction (CR) or moderate endurance exercise (MEE) during the 8-wk regression process was analyzed. The effect of MEE was also evaluated in early cirrhotic and in healthy rats. A significant reduction in portal pressure (PP), liver fibrosis, and HSC activation was observed during regression. However, these parameters remained above those in healthy animals. During regression, animals markedly worsened their metabolic profile. CR although preventing those metabolic disturbances did not further reduce PP, hepatic fibrosis, or HSC activation. MEE also prevented metabolic disturbances, without enhancing, but even attenuating the reduction of PP, hepatic fibrosis, and HSC activation achieved by regression. MEE also worsened hepatic fibrosis in early-TAA cirrhosis and in healthy rats. NEW & NOTEWORTHY We have developed two advanced cirrhosis regression experimental models with persistent relevant fibrosis and portal hypertension and an associated deteriorated metabolism that mimic what happens in patients. LI, despite improving metabolism, did not enhance the regression process in our cirrhotic models. CR did not further reduce PP, hepatic fibrosis, or HSC activation. MEE exhibited a profibrogenic effect in the liver blunting cirrhosis regression. One of the potential explanations of this worsening could be ammonia accumulation.

Chronic liver diseases are multifactorial and the need to develop effective therapies is high. Recent studies have shown the potential of ameliorating liver disease progression through protection of the liver endothelium. Polyamine spermidine (SPD) is a caloric restriction mimetic with autophagy-enhancing properties capable of prolonging lifespan and with a proven beneficial effect in cardiovascular disease in mice and humans. We evaluated the use of dietary supplementation with SPD in two models of liver disease (CCl 4 and CDAAH diet). We analyzed the effect of SPD on endothelial dysfunction in vitro and in vivo. C57BL/6J mice were supplemented with SPD in the drinking water prior and concomitantly with CCl 4 and CDAAH treatments. Endothelial autophagy deficient (Atg7endo) mice were also evaluated. Liver tissue was used to evaluate the impact of SPD prophylaxis on liver damage, endothelial dysfunction, oxidative stress, mitochondrial status, inflammation and liver fibrosis. SPD improved the endothelial response to oxidative injury in vitro and improved the liver endothelial phenotype and protected against liver injury in vivo. SPD reduced the overall liver oxidative stress and improved mitochondrial fitness. The absence of benefits in the Atg7endo mice suggests an autophagy-dependent effect of SPD. This study suggests SPD diet supplementation in early phases of disease protects the liver endothelium from oxidative stress and may be an attractive approach to modify the chronic liver disease course and halt fibrosis progression.

Background and Aims: Porto-sinusoidal vascular disease (PSVD) is a rare disease that requires excluding cirrhosis and other causes of portal hypertension for its diagnosis because it lacks a specific diagnostical test. Although it has been occasionally associated with autoimmune diseases, the pathophysiology of PSVD remains unknown. The aim of this study was to evaluate the potential role of autoimmunity in the pathophysiology and diagnosis of PSVD., Methods: Thirty-seven consecutive patients with PSVD and 39 with cirrhosis matched by gender, signs of portal hypertension and liver function were included (training set). By using Indirect Immunofluorescence, ELISA and slot-blot methods data 22 autoantibodies were identified in patients with PSVD and cirrhosis. Presence of anti-endothelial cells antibodies (AECA) was assayed by a cell-based ELISA. Thirty-one PSVD, 40 cirrhosis patients, 15 patients with splenomegaly associated with haematological disease and 14 healthy donors were included in a validation set., Findings: The proportion of patients with at least one positive antibody was statistically significantly higher in patients with PSVD compared with cirrhosis (92% vs 56%; P < .01). Specifically, AECA were significantly more frequent in PSVD than in cirrhosis (38% vs 15%; P = .013). Results were confirmed in the validation set. In the overall population, presence of AECA had a 63% positive predictive value for diagnosing PSVD and a 71% negative predictive value, with a specificity of 94% when the 1/16 level is used as cut-off. AECA positive serum samples react with a 68-72 kDa protein of human liver endothelial sinusoidal cells., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Liver fibrosis is a common feature of sustained liver injury and represents a major public health problem worldwide. Fibrosis is an active research field and discoveries in the last years have contributed to the development of new antifibrotic drugs, although none of them have been approved yet. Liver sinusoidal endothelial cells (LSEC) are highly specialized endothelial cells localized at the interface between the blood and other liver cell types. They lack a basement membrane and display open channels (fenestrae), making them exceptionally permeable. LSEC are the first cells affected by any kind of liver injury orchestrating the liver response to damage. LSEC govern the regenerative process initiation, but aberrant LSEC activation in chronic liver injury induces fibrosis. LSEC are also main players in fibrosis resolution. They maintain liver homeostasis and keep hepatic stellate cell and Kupffer cell quiescence. After sustained hepatic injury, they lose their phenotype and protective properties, promoting angiogenesis and vasoconstriction and contributing to inflammation and fibrosis. Therefore, improving LSEC phenotype is a promising strategy to prevent liver injury progression and complications. This review focuses on changes occurring in LSEC after liver injury and their consequences on fibrosis progression, liver regeneration, and resolution. Finally, a synopsis of the available strategies for LSEC-specific targeting is provided.

Background & Aims: Cirrhosis and its clinical consequences can be aggravated by bacterial infections, ultimately leading to the development of acute on chronic liver failure (ACLF), characterized by acute decompensation, organ failure, and high mortality within 28 days. Little is known about cellular and molecular mechanisms of ACLF in patients with cirrhosis, so no therapeutic options are available. We developed a sepsis-associated preclinical model of ACLF to facilitate studies of pathogenesis and evaluate the protective effects of simvastatin., Methods: Male Wistar rats inhaled CCl 4 until they developed cirrhosis (at 10 weeks) or cirrhosis with ascites (at 15-16 weeks). Male Sprague-Dawley rats received bile-duct ligation for 28 days or intraperitoneal thioacetamide for 10 weeks to induce cirrhosis. After induction of cirrhosis, some rats received a single injection of lipopolysaccharide (LPS) to induce ACLF; some were given simvastatin or vehicle (control) 4 hours or 24 hours before induction of ACLF. We collected data on changes in hepatic and systemic hemodynamics, hepatic microvascular phenotype and function, and survival times. Liver tissues and plasma were collected and analyzed by immunoblots, quantitative polymerase chain reaction, immuno(fluoro)histochemistry and immunoassays., Results: Administration of LPS aggravated portal hypertension in rats with cirrhosis by increasing the severity of intrahepatic microvascular dysfunction, exacerbating hepatic inflammation, increasing oxidative stress, and recruiting hepatic stellate cells and neutrophils. Rats with cirrhosis given LPS had significantly shorter survival times than rats with cirrhosis given the control. Simvastatin prevented most of ACLF-derived complications and increased survival times. Simvastatin appeared to increase hepatic sinusoidal function and reduce portal hypertension and markers of inflammation and oxidation. The drug significantly reduced levels of transaminases, total bilirubin, and ammonia, as well as LPS-mediated activation of hepatic stellate cells in liver tissues of rats with cirrhosis., Conclusions: In studies of rats with cirrhosis, we found administration of LPS to promote development of ACLF, aggravating the complications of chronic liver disease and decreasing survival times. Simvastatin reduced LPS-induced inflammation and liver damage in rats with ACLF, supporting its use in treatment of patients with advanced chronic liver disease., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: In cirrhosis, activated hepatic stellate cells (HSC) play a major role in increasing intrahepatic vascular resistance and developing portal hypertension. We have shown that cirrhotic livers have increased reactive oxygen species (ROS), and that antioxidant therapy decreases portal pressure. Considering that mitochondria produce many of these ROS, our aim was to assess the effects of the oral mitochondria-targeted antioxidant mitoquinone on hepatic oxidative stress, HSC phenotype, liver fibrosis and portal hypertension., Methods: Ex vivo: Hepatic stellate cells phenotype was analysed in human precision-cut liver slices in response to mitoquinone or vehicle. In vitro: Mitochondrial oxidative stress was analysed in different cell type of livers from control and cirrhotic rats. HSC phenotype, proliferation and viability were assessed in LX2, and in primary human and rat HSC treated with mitoquinone or vehicle. In vivo: CCl 4 - and thioacetamide-cirrhotic rats were treated with mitoquinone (5 mg/kg/day) or the vehicle compound, DecylTPP, for 2 weeks, followed by measurement of oxidative stress, systemic and hepatic haemodynamic, liver fibrosis, HSC phenotype and liver inflammation., Results: Mitoquinone deactivated human and rat HSC, decreased their proliferation but with no effects on viability. In CCl 4 -cirrhotic rats, mitoquinone decreased hepatic oxidative stress, improved HSC phenotype, reduced intrahepatic vascular resistance and diminished liver fibrosis. These effects were associated with a significant reduction in portal pressure without changes in arterial pressure. These results were further confirmed in the thioacetamide-cirrhotic model., Conclusion: We propose mitochondria-targeted antioxidants as a novel treatment approach against portal hypertension and cirrhosis., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In cirrhosis, increased intrahepatic vascular resistance (IHVR) is the primary factor for portal hypertension (PH) development. Hepatic stellate cells (HSCs) play a major role increasing IHVR because, when activated, they are contractile and promote fibrogenesis. Protease-activated receptors (PARs) can activate HSCs through thrombin and factor Xa, which are known PAR agonists, and cause microthrombosis in liver microcirculation. This study investigates the effects of the oral anticoagulant, rivaroxaban (RVXB), a direct antifactor Xa, on HSC phenotype, liver fibrosis (LF), liver microthrombosis, and PH in cirrhotic rats. Hepatic and systemic hemodynamic, nitric oxide (NO) bioavailability, LF, HSC activation, and microthrombosis were evaluated in CCl 4 and thioacetamide-cirrhotic rats treated with RVXB (20 mg/kg/day) or its vehicle for 2 weeks. RVXB significantly decreased portal pressure (PP) in both models of cirrhosis without changes in portal blood flow, suggesting a reduction in IHVR. RVXB reduced oxidative stress, improved NO bioavailability, and ameliorated endothelial dysfunction. Rivaroxaban deactivated HSC, with decreased alpha-smooth muscle actin and mRNA expression of other HSC activation markers. Despite this marked improvement in HSC phenotype, no significant changes in LF were identified. RVXB markedly reduced fibrin deposition, suggesting reduced intrahepatic microthrombosis., Conclusion: RVXB decreases PP in two rat models of cirrhosis. This effect is mostly associated with decreased IHVR, enhanced NO bioavailability, HSC deactivation, and reduced intrahepatic microthrombosis. Our findings suggest that RVXB deserves further evaluation as a potential treatment for cirrhotic PH. (Hepatology 2017;65:2031-2044)., (© 2017 by the American Association for the Study of Liver Diseases.)

Background & Aims: Increased hepatic vascular resistance due to fibrosis and elevated hepatic vascular tone is the primary factor in the development of portal hypertension. Heparin may decrease fibrosis by inhibiting intrahepatic microthrombosis and thrombin-mediated hepatic stellate cell activation. In addition, heparin enhances eNOS activity, which may reduce hepatic vascular tone. Our study aimed at evaluating the effects of acute, short-, long-term and preventive enoxaparin administration on hepatic and systemic hemodynamics, liver fibrosis and nitric oxide availability in cirrhotic rats., Methods: Enoxaparin (1.8 mg/kg subcutaneously), or its vehicle, was administered to CCl4-cirrhotic rats 24h and 1h before the study (acute), daily for 1 week (short-term) or daily for 3 weeks (long-term) and to thioacetamide-cirrhotic rats daily for 3 weeks with/without thioacetamide (preventive/long-term, respectively). Mean arterial pressure, portal pressure, portal blood flow, hepatic vascular resistance and molecular/cellular mechanisms were evaluated., Results: No significant changes in hemodynamic parameters were observed in acute administration. However, one-week, three-week and preventive treatments significantly decreased portal pressure mainly due to a decrease in hepatic vascular resistance without significant changes in mean arterial pressure. These findings were associated with significant reductions in liver fibrosis, hepatic stellate cell activation, and desmin expression. Moreover, a reduction in fibrin deposition was observed in enoxaparin-treated rats, suggesting reduced intrahepatic microthrombosis., Conclusion: Enoxaparin reduces portal pressure in cirrhotic rats by improving the structural component of increased liver resistance. These findings describe the potentially beneficial effects of enoxaparin beyond the treatment/prevention of portal vein thrombosis in cirrhosis, which deserve further investigation., (Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Increased hepatic vascular resistance is the primary factor in the development of portal hypertension. Metformin ameliorates vascular cells function in several vascular beds. Our study was aimed at evaluating the effects, and the underlying mechanisms, of metformin on hepatic and systemic hemodynamics in cirrhotic rats and its possible interaction with the effects of propranolol (Prop), the current standard treatment for portal hypertension. CCl4-cirrhotic rats received by gavage metformin 300 mg/kg or its vehicle once a day for 1 wk, before mean arterial pressure (MAP), portal pressure (PP), portal blood flow (PBF), hepatic vascular resistance, and putative molecular/cellular mechanisms were measured. In a subgroup of cirrhotic rats, the hemodynamic response to acute Prop (5 mg/kg iv) was assessed. Effects of metformin ± Prop on PP and MAP were validated in common bile duct ligated-cirrhotic rats. Metformin-treated CCl4-cirrhotic rats had lower PP and hepatic vascular resistance than vehicle-treated rats, without significant changes in MAP or PBF. Metformin caused a significant reduction in liver fibrosis (Sirius red), hepatic stellate cell activation (α-smooth muscle actin, platelet-derived growth factor receptor β polypeptide, transforming growth factor-βR1, and Rho kinase), hepatic inflammation (CD68 and CD163), superoxide (dihydroethidium staining), and nitric oxide scavenging (protein nitrotyrosination). Prop, by decreasing PBF, further reduced PP. Similar findings were observed in common bile duct ligated-cirrhotic rats. Metformin administration reduces PP by decreasing the structural and functional components of the elevated hepatic resistance of cirrhosis. This effect is additive to that of Prop. The potential impact of this pharmacological combination, otherwise commonly used in patients with cirrhosis and diabetes, needs clinical evaluation., (Copyright © 2015 the American Physiological Society.)

In a previous study we tried to assess the clinical usefulness of platelet count (PlC) to confirm whether postoperative pulmonary embolism could be suspected early. Unexpectedly, the 19 patients who subsequently developed pulmonary embolism had significantly lower mean PlC levels even before surgery. In an attempt to discover whether the preoperative PlC levels were associated with a different incidence of postoperative blood loss, we decided to retrospectively study the relationship between preoperative PlC levels and the consequences of blood loss. There were 459 consecutive patients undergoing hip surgery. After excluding 5 patients who died during the first 3 postoperative days, and 16 patients who bled from a definitive anatomic site, there were 438 patients. Blood loss was considered to be excessive when two or more of the following conditions were present: (1) total transfusion requirements exceeding 1,000 ml whole blood or 2 units of packed red cells; (2) a drop in hemoglobin level of 5 g/dl or more, and (3) a hemoglobin level below 8 g/dl at any moment during the first 8 postoperative days. Blood loss was considered to be excessive in 91 patients. Preoperative PlC levels were significantly lower in these patients as compared to patients without the condition (204 +/- 52 vs. 236 +/- 79 x 10(9) liter-1; p = 0.0002). When patients were classified according to the quartiles of preoperative PlC, the odds ratio of developing excessive blood loss was 0.69 (95% CI: 0.38-1.26) in patients in the second quartile; 0.57 (95% CI: 0.30-1.06) in the third quartile, and 0.27 (95% CI: 0.13-0.57) in patients in the highest quartile. After adjusting for age, sex, type of surgery and type of prophylaxis, the preoperative PlC levels maintained a statistically significant inverse correlation with postoperative blood loss.

Pulmonary embolism (PE) is a serious complication following hip surgery. Trials of antiplatelet thromboprophylaxis indicated a substantial reduction in PE rate, and we prospectively studied the effect of a combination of low-dose heparin and two different antiplatelets. Furthermore, our experience in previous studies suggested that platelet count (PC) levels could be useful to reliably suspect PE at a very early stage, and we prospectively tried to confirm our previous findings. Ours is a prospective study in 459 consecutive patients operated on because of hip fracture (265) or elective hip replacement (194), aimed to determine: 1) whether the benefits of antiplatelets plus heparin on PE outweigh the risks; 2) to assess the clinical usefulness of PC monitoring in these patients, so as to confirm whether PE could be recognized early. It was a prospective, randomized, double-blind study. All patients received unfractioned heparin (7500 IU sc twice daily, starting 2 h before operation). In addition, they received aspirin (200 mg thrice daily, with meals), Triflusal (300 mg thrice daily, with meals), or placebo. Real time B-mode ultrasonography (US) was performed on all patients on the 8-9th day after surgery. Venography was performed in patients with normal US, if clinical symptoms suggested venous thrombosis. Twelve out of the 459 patients (2.6%) had to discontinue prophylaxis, because of major bleeding (6 patients), or gastric intolerance (6 patients). There were no significant differences between groups in either deep vein thrombosis (26 patients (18%) with aspirin, 18 (12%) with Triflusal, 26 (17%) with placebo), or PE development (7 patients (5%) with aspirin, 3 (2%) with Triflusal, 8 (5%) taking placebo).(ABSTRACT TRUNCATED AT 250 WORDS)

We performed a prospective study in 86 consecutive patients with central vein catheter-related deep venous thrombosis (DVT) of the upper extremity, to evaluate the prevalence of pulmonary embolism (PE), and to identify clinical variables that would increase the likelihood of developing PE in an individual patient. Since upper-extremity DVT was established, all patients received intravenous heparin therapy. Then, a ventilation-perfusion lung scan was obtained within 24 h of DVT diagnosis, whether respiratory symptoms were present or not. Six points of clinical information were recorded on entering in the study, and then compared with the scintigraphic findings: age, sex, the underlying disease, the catheter material, the character of the infusate, and the duration of cannulation. Thirteen patients were considered to have PE. Sixty-six patients were finally classified as having a normal lung scan, and 7 patients were excluded from the study (because of indeterminate lung scan 6; because of femoropopliteal thrombosis simultaneously present 1). Two out of the 13 patients with PE subsequently died because of recurrent, massive embolism, despite adequate heparin therapy. PE was more commonly present in patients with polyvinyle chloride or polyethylene catheters (10/38, 26%) as compared to patients with either polyurethane or siliconized catheters (3/41, 7%; p < 0.05, Chi-Square test; Odds Ratio = 4.52, 95% CI 1.01-23.07). We conclude that PE is not a rare event in these patients, and it may be life-threatening even despite adequate heparin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

We have prospectively studied a large series of patients with acute venous thromboembolism, trying to correlate pulmonary embolism (PE) recurrences to a number of clinical variables, and platelet count behavior. A baseline lung scan was obtained initially in every patient. Repeated chest X-ray and lung scans were obtained routinely 8 days after heparin onset. The primary trial endpoint was confirmed, clinically apparent recurrent PE; in addition, laboratory evidence of subclinical PE at the repeat scan was also considered. PE recurrences were found in 26/180 patients, and 3 out of these patients died because of massive, recurrent PE. No significant differences were found in age and sex distribution, or in the degree of deep vein thrombosis proximity between patients who did or did not develop recurrences. There were, however, differences between groups in platelet count: No differences were found in baseline counts, but mean values were significantly lower by the 8th day when recurrences had appeared (229 +/- 86 x 10(9) liters-1 versus 314 +/- 129 x 10(9) liters-1; p < 0.005). The sensitivity, specificity, positive predictive value and negative predictive value for platelet count decrease were 52, 71, 21 and 91%, respectively. Thus, platelet count cannot be reliably used for individual cases, but our findings add to the pathophysiological picture of the disease.

We have previously reported that patients with deep vein thrombosis (DVT) and scintigraphic evidence of pulmonary embolism (PE) had a fall in platelet count, as compared with their levels before thrombosis had developed. Otherwise, no changes were found in DVT patients without embolism. We recently conducted a prospective study with a larger series of patients and studied platelet count behavior in 189 consecutive patients with acute venous thromboembolism (VTE) in whom a baseline blood cell count was available (obtained before thromboembolism developed). We found no significant differences in baseline platelet counts between groups. However, at the time of VTE diagnosis the analysis of variance demonstrated that mean platelet count was significantly higher in patients without embolism as compared with PE patients (p less than 0.001). On the other hand, no differences were found between patients with silent PE and those with clinically obvious PE. When patients with postoperative VTE and those with nonpostoperative VTE were analyzed separately, mean platelet count increased only in postoperative DVT patients without embolism (p less than 0.001). In the absence of a previous intervention, DVT did not produce any change in platelet count, while PE significantly reduced platelet number (p less than 0.008). In DVT patients without respiratory symptoms of embolism, we suggest that a lung scan should be performed when platelet count is lower than baseline value. For patients with a higher count, the probability of finding PE is very low, and scintigraphy is not cost-effective.

The thrombogenicity presented in different types of endovenous catheters and their anomalies are the cause of the development of pulmonary thromboembolism (PTE) in some patients, secondary to deep venous thrombosis (DVT) of the upper limbs. Presentation of a study made on the incidence of PTE in patients with prior history of DVT of the upper limbs. Of the 30 cases of DVT of the upper limbs studied, 20 were directly attributed to catheters. 18 were attached to a central catheter and the other 2 one or two peripheral catheters. 0,32% of DVT of the upper limbs secondary to a central catheter was calculated. Five of the 20 DVT patients (25%) had symptomatic or sub-clinical DVT. Emphasis was placed on the importance of DVT and its intrinsically serious nature and the need for studies on this condition, since it is possible for the patient not to develop the complete symptoms of DVT at the onset, which led to death in one patient. We recommend the establishing of strict norms with regard to the indications for inserting the central catheter and the choice of the correct material, aseptic and non-traumatic insertion, radiological control (essential) of the position of the catheter and its tip, establishing of a protocol for the correct maintenance and a device for controlling thrombotic complications in upper limbs, to ensure rapid treatment and a rapid check of the possibility of DVT by pulmonary gammagraphy during the first 24-48 hours.

We prospectively evaluated the prevalence of pulmonary embolism (PE) in 30 consecutive patients with proved deep venous thrombosis (DVT) of the upper extremity. Ten patients (seven male and three female; mean age, 43 years) had primary DVT, and 20 patients (14 male and six female; mean age, 52 years) had catheter-related DVT. Ventilation-perfusion lung scans were routinely performed at the time of hospital admission to all but one patient (one patient was critically ill, and he died four days after DVT diagnosis because of massive PE). Lung scan findings were normal in nine of ten patients with primary DVT, and they were indetermine in the remaining patient. By contrast, perfusion defects were considered highly suggestive of PE in four patients with catheter-related DVT; two patients had indeterminate lung scans, and 13 patients had normal scans. We conclude that PE is not a rare complication in upper extremity DVT, and that patients with catheter-related DVT seem to be at a higher risk.

In a randomized, blind study, both the antithrombotic efficacy (reduction of thrombus weight) and potency (anti-Xa activity) of several commercially available low-molecular-weight heparins (LMWHs) were compared with those of unfractioned heparin (UFH) and placebo. Three different thrombogenic challenges were used: venous thrombosis was induced by direct endothelial damage in 60 New Zealand rabbits (group I), intracarotid injection of bovine thrombin in an additional series of 60 rabbits (group II), or after inferior-vena-cava ligature in 60 Wistar rats (group III). The drugs were administered subcutaneously 2 h before surgery in a blind fashion. The doses recommended for clinical practice were used (adjusted by body weight), except in group II animals, in whom doses were doubled. No differences were found between UFH and most LMWHs in terms of reduction of thrombus weight in group I animals. But UFH showed a weaker antithrombotic efficacy in the other two models. Similarly, one of the LMWHs used (Clexane) proved to be not as effective as the remainder. However, only clinical studies will provide enough information to verify these differences. Additionally, our findings confirm that the antithrombotic efficacy of a given drug differs according to the stimulus used to induce venous thrombosis.