Prior thrombosis is a well-established risk factor for re-thrombosis in polycythemia vera and essential thrombocythemia but scarce data are available on the rate of re-thrombosis and the optimal ...strategy for prevention of recurrence.
We retrospectively estimated the rate of recurrence in a multicenter cohort of 494 patients (poly-cythemia vera/essential thrombocythemia 235/259) with previous arterial (67.6%) or venous thrombosis (31%) or both (1.4%). First thrombosis was cerebrovascular disease in 191 cases, acute coronary syndrome in 106, peripheral arterial thrombosis in 44, and venous thromboembolism in 160. Microcirculatory events were not computed.
Thrombosis recurred in 166 patients (33.6%), with an incidence of 7.6% patient-years. Sex, diagnosis (polycythemia vera or essential thrombocythemia), and presence of vascular risk factors did not predict recurrence, whereas age >60 years did (multivariable hazard ratio HR, 1.67; 95% confidence interval CI 1.19-2.32). Increased leukocyte count at the time of the first thrombosis was a risk factor for recurrence in patients <60 years old (HR 3.55; 95% CI 1.02-12.25). Cytoreduction halved the risk in the overall cohort (HR 0.53; 95% CI 0.38-0.73) and the combination with antiplatelet agents or oral anticoagulants was more effective than administration of single drugs. Significant prevention of rethrombosis was independently achieved in patients with venous thromboembolism by both oral anticoagulants (HR 0.32; 95% CI 0.15-0.64) and antiplatelet agents (HR 0.42; 95% CI 0.22-0.77), in those with acute coronary syndrome by cytoreduction (HR 0.30; 95% CI 0.13-0.68), and in those with cerebrovascular disease by antiplatelet agents (HR 0.33; 95% CI 0.16-0.66). The overall incidence of major bleeding was 0.9% patient-years and rose to 2.8% in patients receiving both antiplatelet and anti-vitamin K agents.
In patients with polycythemia vera and essential thrombocythemia, cytoreduction protects against recurrent thrombosis, particularly after acute coronary syndrome. The contemporary use of oral anticoagulants (after venous thromboembolism) or antiplatelet agents (after cerebrovascular disease or venous thromboembolism) further improves the protective effect. Such findings call for prospective studies aimed at investigating whether strategies tailored according to the type of first thrombosis could improve prevention of recurrences.
The optimal duration of treatment with vitamin K antagonists (VKA) after venous thromboembolism (VTE) in patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) is uncertain. To ...tackle this issue, we retrospectively studied 206 patients with MPN-related VTE (deep venous thrombosis of the legs and/or pulmonary embolism). After this index event, we recorded over 695 pt-years 45 recurrences, venous in 36 cases, with an incidence rate (IR) of 6.5 per 100 pt-years (95% confidence interval (CI): 4.9-8.6). One hundred fifty-five patients received VKA; the IR of recurrent thrombosis per 100 pt-years was 4.7 (95% CI: 2.8-7.3) on VKA and 8.9 (95% CI: 5.7-13.2) off VKA (P=0.03). In patients receiving VKA, the IR of recurrent thrombosis per 100 pt-years was 5.3 (95% CI: 3.2-8.4) among 108 patients on long-term VKA and 12.8 (95% CI: 7.3-20.7) after discontinuation among the 47 who ceased treatment (P=0.008), with a doubled risk of recurrence after stopping VKA (hazard ratio: 2.21, 95% CI: 1.19-5.30). The IR of major bleeding per 100 pt-years was 2.4 (95%: CI: 1.1-4.5) on VKA and 0.7 (95% CI: 0.08-2.5) off VKA (P=0.08). In conclusion, in MPN patients with VTE recurrent thrombosis is significantly reduced by VKA and caution should be adopted in discontinuation; however, the incidence of recurrence on treatment remains high, calling for clinical trials aimed to improve prophylaxis in this setting.
Abstract Obesity in renal transplantation has proven to affect both patient and graft survival. The scientific community seems to be split into 2 groups: one claims similar outcomes among obese and ...nonobese, showing only marginally increased postoperative complications; whereas the other group report a higher rate of complications, including graft loss and mortality. These results did not provide sufficient evidence to be applied in practice. In this study we analyzed the outcomes of obese recipients of renal transplant in our institution. One hundred fourteen renal transplantations were performed between January 1993 and December 2003. To estimate the impact of various degrees of obesity, the patients were allocated into 2 cohorts: Group A (body mass index BMI 30–34.9) and Group B (BMI 35 and greater). We analyzed patient and donor characteristics. Wound infection rates were similar in the 2 groups. The aggregate Group A and B patient survival rate was 95.6% at 1 year and 93% at 5 years. Graft survival rate was 93.9% at 1 year and 88% at 5 years. However, the analysis of the outcomes in the 2 groups with different degrees of obesity showed that the patient survival rate at 1 year in Group A was 98.9% (1 death) and 95.6% at 5 years (4 deaths). In Group B the patient survival rate at 1 year was 87.5% (3 deaths; P = .007) and at 5 years was 79.2% ( P = .006). Graft survival rate in Group A was 98.9% (1 graft loss) at 1 year and 94.5% (5 graft losses) at 5 years; in Group B the graft survival rate was 75% (6 graft loss) at 1 year and 63% (9 graft losses) at 5 years ( P < .0001 both at 1 and 5 years). The present study showed that overall obese recipient outcomes were as expected when evaluating the obese as a single group of recipients with a BMI >30. The overall patient and graft survival did not show particularly different results from already published studies claiming similar outcomes. However, this series showed different outcomes when we divided them into 2 groups by BMI. There was a remarkable difference between moderate obese (Group A) and morbid obese (Group B) recipients as regards patient and graft survival. It is possible that the excellent outcome in Group A may be the result of super-selection and stringent cardiovascular risk screening that is implemented for this category of potential recipients. Obese recipients with a BMI of >35 are a high-risk category. Because of the difference in the outcomes of the 2 groups, it does not seem reasonable to address obese recipients as a single group. We believe that obese patients should not be discriminated simply on the basis of the BMI. A strict evaluation should be performed before denying the opportunity to receive a renal transplant to these patients.
Cigarette smoking plays a major role in the development of atherosclerosis and is associated with increased morbidity and mortality for coronary heart disease, stroke and peripheral vascular disease. ...In spite of the abundance of epidemiological evidence that links cigarette smoking to vascular disease, the pathologic mechanisms for such interaction are not clear. The endothelium is a major target organ that undergoes activation when exposed to common vascular triggers, including hypertension, hypercholesterolemia, hyperglycaemia and smoking. Changes in endothelial function may lead to a dysfunctional vascular phenotype characterized by anomalous responses of the vascular tone, abnormal endothelial proliferation and prothrombotic activation. Several studies have demonstrated that smoking may alter endothelial function by a direct toxic effect and consequently trigger haemostatic activation and thrombosis. In this article we will review the evidence that loss of normal endothelial function may result in a loss of the balance of the haemostatic system and in changes of the platelet physiology that may be relevant for the pathogenic effect of smoking on the development of atherothrombosis.
Eur J Clin Invest 2011; 41 (6): 616–626
Background Cigarette smoking is associated with cardiovascular morbidity and mortality. Exposure to cigarette smoke can cause endothelial dysfunction with ...impaired endothelium‐dependent vasodilation and ‘endothelial activation’, which predispose to atherothrombosis. The effects of continued smoking and smoking cessation on the level of endothelial, platelet and clotting activation have not been described previously. Here, we prospectively monitored changes in circulating endothelial‐coagulative activation markers in smokers undertaking smoking cessation.
Method This 12‐month prospective study of 174 smokers with no commonly acquired atherothrombotic risk factors underwent an intensive smoking‐cessation programme investigating the effect of quitting on circulating levels of von Willebrand’s Factor Antigen (vWF:Ag), soluble Thrombomodulin (sTM), d‐Dimer (d‐D), prothrombin fragment F1 + 2 (F1 + 2), platelet factor‐4 (PF4) and β‐Thromboglobulin (β‐TG). Blood samples and study measures were collected and compared at baseline and at 2, 6 and 12 months after smoking cessation from quitters and relapsers’.
Results No significant differences in demographic or laboratory parameters at baseline were observed between the study groups. Significant changes in von Willebrand’s Factor activity were observed at 2 months after smoking cessation, with levels decreasing from 141·8% to 113·6%. Substantial modifications in d‐Dimer, prothrombin fragment F1 + 2, platelet factor‐4 and β‐thromboglobulin concentrations were observed only at 6 and 12 months after smoking cessation. Positive associations between baseline levels of these biomarkers and number of pack per years have been demonstrated.
Conclusions Chronic exposure to cigarette smoke sustains the activation of the endothelial‐coagulative system and abstinence may result in the improvement of several endothelial‐coagulative abnormalities in regular smokers. This may translate into an overall decline in cardiovascular risk.
The Authors report their experience with the routine use of surgical drainage in a large series of splenectomies.
Benefits and risks related to surgical drains have been always discussed, with some ...surgeons in favor of them and skeptic others considering not physiological their use. After splenectomy, their use is also largely debated, especially because of susceptibility of operated patients to infections.
Two thousand nine cases have been reviewed. Indications for splenectomy, performed either by open or laparoscopic approach, included idiopathic thrombocytopenic purpura in 137 patients (65,4%), splenic lymphoma in 36 (17,2%), hereditary spherocytosis in 15 (7,4%), β-thalassemia in 8 (3,7%), other diseases in 13 (6,1%).
"Active" or "passive" drains were placed in 80% and 20% of cases, respectively. Drains were removed 2-3 days after surgery in 90,2%, within 10 days in 4,3%, within 2 months in 0,4% of cases. In 2 cases a post-operative bleeding, detected through the drainage, required re-operation. One patient developed a subphrenic abscess, successfully treated by a percutaneous drainage. One case of pancreatic fistula was observed.
In Authors' experience, the use of drains after splenectomy does not affect the risk of subsequent infectious complications, independently on the type of the drainage system used. Early removal of drains in this series might have played an important role in the very low incidence of abdominal infections reported. The use of surgical drains after splenectomy might play an important role to early detect post-operative bleeding, as it happened in 2 cases of this series.
Hereditary spherocytosis is an inherited hemolytic anemia caused by a deficiency in erythrocyte membrane proteins. Removal of the spleen may reduce the intra-splenic hemolytic process of the disease ...and, therefore, may correct the anemia. Furthermore, it seems to decrease the levels of serum bilirubin, thus reducing the formation of gallbladder stones. Indications and timing of splenectomy, however, are still debated. Twelve patients with severe hereditary spherocytosis operated on with laparoscopic splenectomy were retrospectively reviewed. Median age at diagnosis was 13.8 years (range 8–25 years). Male to female ratio was 5/7. Indications for laparoscopic removal of the spleen included anemia unresponsive to iron supplementation in eight patients (66.6 %) with increase need for red cells transfusions, and jaundice with symptoms related to cholelitiasis in four patients (33.3 %). Laparoscopic splenectomy was associated in four cases to laparoscopic cholecystectomy. Mean operative time was 50 min (range 40–75 min) with no conversion to open surgery. Mean hospital stay ranged from 3 to 7 days. In a 16-month follow-up, no complications were recorded and a persistent correction of anemia was observed. With the advent of laparoscopic surgery, splenectomy has been performed by this mini-invasive approach in referral centers. Laparoscopic splenectomy is an effective technique, when performed in patients with hereditary spherocytosis. Low complication rate and persistent correction of the hematologic disorders can be expected after the laparoscopic splenectomy, provided that a proper technique is performed and an experienced surgical team is available.
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