Guidance for the evaluation and treatment of hereditary and acquired thrombophilia

Thrombophilias are hereditary and/or acquired conditions that predispose patients to thrombosis. Testing for thrombophilia is commonly performed in patients with venous thrombosis and their relatives; however such testing usually does not provide information that impacts management and may result in harm. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance for thrombophilia testing in five clinical situations: following 1) provoked venous thromboembolism, 2) unprovoked venous thromboembolism; 3) in relatives of patients with thrombosis, 4) in female relatives of patients with thrombosis considering estrogen use; and 5) in female relatives of patients with thrombosis who are considering pregnancy. Additionally, guidance is provided regarding the timing of thrombophilia testing. The role of thrombophilia testing in arterial thrombosis and for evaluation of recurrent pregnancy loss is not addressed. Statements are based on existing guidelines and consensus expert opinion where guidelines are lacking. We recommend that thrombophilia testing not be performed in most situations. When performed, it should be used in a highly selective manner, and only in circumstances where the information obtained will influence a decision important to the patient, and outweigh the potential risks of testing. Testing should not be performed during acute thrombosis or during the initial (3-month) period of anticoagulation

Infection and venous thromboembolism in patients undergoing colorectal surgery: what is the relationship?

BACKGROUND: There is evidence demonstrating an association between infection and venous thromboembolism. We recently identified this association in the postoperative setting; however, the temporal relationship between infection and venous thromboembolism is not well defined OBJECTIVE: We sought to determine the temporal relationship between venous thromboembolism and postoperative infectious complications in patients undergoing colorectal surgery. DESIGN, SETTING, AND PATIENTS: A retrospective cohort analysis was performed using data for patients undergoing colorectal surgery in the National Surgical Quality Improvement Project 2010 database. MAIN OUTCOME MEASURES: The primary outcome measures were the rate and timing of venous thromboembolism and postoperative infection among patients undergoing colorectal surgery during 30 postoperative days. RESULTS: Of 39,831 patients who underwent colorectal surgery, the overall rate of venous thromboembolism was 2.4% (n = 948); 729 (1.8%) patients were diagnosed with deep vein thrombosis, and 307 (0.77%) patients were diagnosed with pulmonary embolism. Eighty-eight (0.22%) patients were reported as developing both deep vein thrombosis and pulmonary embolism. Following colorectal surgery, the development of a urinary tract infection, pneumonia, organ space surgical site infection, or deep surgical site infection was associated with a significantly increased risk for venous thromboembolism. The majority (52%-85%) of venous thromboembolisms in this population occurred the same day or a median of 3.5 to 8 days following the diagnosis of infection. The approximate relative risk for developing any venous thromboembolism increased each day following the development of each type of infection (range, 0.40%-1.0%) in comparison with patients not developing an infection. LIMITATIONS: We are unable to account for differences in data collection, prophylaxis, and venous thromboembolism surveillance between hospitals in the database. Additionally, there is limited patient follow-up. CONCLUSIONS: These findings of a temporal association between infection and venous thromboembolism suggest a potential early indicator for using certain postoperative infectious complications as clinical warning signs that a patient is more likely to develop venous thromboembolism. Further studies into best practices for prevention are warranted

Narrow genetic base in forest restoration with holm oak (Quercus ilex L.) in Sicily

In order to empirically assess the effect of actual seed sampling strategy on genetic diversity of holm oak (Quercus ilex) forestations in Sicily, we have analysed the genetic composition of two seedling lots (nursery stock and plantation) and their known natural seed origin stand by means of six nuclear microsatellite loci. Significant reduction in genetic diversity and significant difference in genetic composition of the seedling lots compared to the seed origin stand were detected. The female and the total effective number of parents were quantified by means of maternity assignment of seedlings and temporal changes in allele frequencies. Extremely low effective maternity numbers were estimated (Nfe $\approx$ 2-4) and estimates accounting for both seed and pollen donors gave also low values (Ne $\approx$ 35-50). These values can be explained by an inappropriate forestry seed harvest strategy limited to a small number of spatially close trees

When are breast cancer patients at highest risk of venous thromboembolism: a cohort study using English healthcare data

Breast cancer patients are at increased risk of VTE, particularly in the peri-diagnosis period. However, no previous epidemiological studies have investigated the relative impact of breast cancer treatments in a time-dependent manner. We aimed to determine the impact of breast cancer stage, biology and treatment on the absolute and relative risks of VTE, using several recently linked data sources from England. Our cohort comprised 13,202 breast cancer patients from the Clinical Practice Research Datalink (linked to Hospital Episode Statistics and Cancer Registry data), diagnosed between 1997 and 2006 with follow-up continuing to the end of 2010. Cox regression analysis was performed to determine which demographic, treatment-related and biological factors independently affected VTE risk. Women had an annual VTE incidence of 6% whilst receiving chemotherapy which was 10.8-fold higher (95% CI, 8.2 to 14.4; absolute risk (AR) =59.6 per 1000 person-years) than women who did not receive chemotherapy. Following surgery the risk was significantly raised in the first month (HR=2.2; 95% CI 1.4 to 3.4; AR=23.5; reference group, no surgery), but it was not raised subsequent to this. Risk of VTE was noticeably higher in the 3-months following initiation of Tamoxifen compared with the risk before therapy (HR=5.5; 95% CI 2.3 to 12.7; AR=24.1), however commencement of aromatase inhibitors was not associated with VTE (HR=0.8; 95% CI 0.5 to 1.4; AR=28.3). In conclusion, women receiving chemotherapy for breast cancer have a clinically important risk of VTE, whilst an increased risk of VTE immediately following endocrine therapy is restricted to Tamoxifen

System Dynamics to Model the Unintended Consequences of Denying Payment for Venous Thromboembolism after Total Knee Arthroplasty

Background: The Hospital Acquired Condition Strategy (HACS) denies payment for venous thromboembolism (VTE) after total knee arthroplasty (TKA). The intention is to reduce complications and associated costs, while improving the quality of care by mandating VTE prophylaxis. We applied a system dynamics model to estimate the impact of HACS on VTE rates, and potential unintended consequences such as increased rates of bleeding and infection and decreased access for patients who might benefit from TKA. Methods and Findings: The system dynamics model uses a series of patient stocks including the number needing TKA, deemed ineligible, receiving TKA, and harmed due to surgical complication. The flow of patients between stocks is determined by a series of causal elements such as rates of exclusion, surgery and complications. The number of patients harmed due to VTE, bleeding or exclusion were modeled by year by comparing patient stocks that results in scenarios with and without HACS. The percentage of TKA patients experiencing VTE decreased approximately 3-fold with HACS. This decrease in VTE was offset by an increased rate of bleeding and infection. Moreover, results from the model suggest HACS could exclude 1.5% or half a million patients who might benefit from knee replacement through 2020. Conclusion: System dynamics modeling indicates HACS will have the intended consequence of reducing VTE rates. However, an unintended consequence of the policy might be increased potential harm resulting from over administration of prophylaxis, as well as exclusion of a large population of patients who might benefit from TKA

The treatment of polycythaemia vera: an update in the JAK2 era

The clinical course of polycythaemia vera is marked by a high incidence of thrombotic complications, which represent the main cause of morbidity and mortality. Major predictors of vascular events are increasing age and previous thrombosis. Myelosuppressive drugs can reduce the rate of thrombosis, but there is concern that their use raises the risk of transformation into acute leukaemia. To tackle this dilemma, a risk-oriented management strategy is recommended. Low-risk patients should be treated with phlebotomy and low-dose aspirin. Cytotoxic therapy is indicated in high-risk patients, with the drug of choice being hydroxyurea because its leukaemogenicity is low. The recent discovery of JAK2 V617F mutation in the vast majority of polycythaemia vera patients opens new avenues for the treatment of this disease. Novel therapeutic options theoretically devoid of leukaemic risk, such as alpha-interferon and imatinib, affect JAK2 expression in some patients. Nevertheless, these drugs require further clinical experience and, for the time being, should be reserved for selected cases

Accessible High-Throughput Virtual Screening Molecular Docking Software for Students and Educators

We survey low cost high-throughput virtual screening (HTVS) computer programs for instructors who wish to demonstrate molecular docking in their courses. Since HTVS programs are a useful adjunct to the time consuming and expensive wet bench experiments necessary to discover new drug therapies, the topic of molecular docking is core to the instruction of biochemistry and molecular biology. The availability of HTVS programs coupled with decreasing costs and advances in computer hardware have made computational approaches to drug discovery possible at institutional and non-profit budgets. This paper focuses on HTVS programs with graphical user interfaces (GUIs) that use either DOCK or AutoDock for the prediction of DockoMatic, PyRx, DockingServer, and MOLA since their utility has been proven by the research community, they are free or affordable, and the programs operate on a range of computer platforms