Factor XII-independent activation of factor XI in plasma: effects of sulfatides on tissue factor-induced coagulation

Factor XI (FXI) may be activated in a purified system by thrombin and by autoactivation in the presence of negatively charged substances such as dextran sulfate or sulfatides. The current studies were performed to determine if these processes occur during the coagulation of plasma. FXII--deficient plasma was supplemented with 125I-FXI and clot formation was induced with tissue factor and/or sulfatides. Cleavage of FXI was studied by standard polyacrylamide gel electrophoresis and autoradiography. Activated FXI (FXIa) was detected after 20 minutes of incubation with sulfatides alone and this process was markedly accelerated by the addition of tissue factor (TF). The enhancing effect of TF was blocked by hirudin, which indicated thrombin involvement in FXI activation. The contribution of FXIa to FIX activation in this system was studied using a 3H-FIX activation peptide release assay. Sulfatides increased FIX activation about twofold in plasma induced to clot with TF but had no effect if the plasma was immunodepleted of FXI. FIX activation was also increased in plasma induced to clot with FXa if sulfatides were present. The enhanced generation of FIXa was dependent on FXI and was blocked by hirudin. Some activation was seen in the reactions with sulfatides and hirudin and is likely solely caused by FXI autoactivation. The data indicate that during the coagulation of plasma in the presence of sulfatides, FXI is activated by a mechanism that is thrombin dependent and does not require FXII.     

How to obtain excellent response rates when surveying physicians

This paper outlines ways to maximize response rates to surveysby summarizing the most relevant literature to date and demonstratinghow these techniques have resulted in consistently high ratesof return in family practice research. We describe the methodologyused in recent surveys of physicians conducted by the Centrefor Studies in Family Medicine through its Thames Valley FamilyPractice Research Unit, located in London, Ontario, Canada andfunded by the Ontario Ministry of Health and Long-Term Care.The identification and implementation of these techniques tomaximize response rates is critical, as primary health careresearchers often rely on information gathered through questionnairesto study physicians' practice profiles, experiences and attitudes.Four separate and distinct mailed surveys of physicians usinga modified Dillman approach were conducted from 2001 to 2004.The sampling strategies, topics, types of questions and responseformats of these surveys varied. The first survey did not useany incentives or recorded delivery/registered mail and receiveda response rate of 48%. In sharp contrast, the other three surveysobtained responses rates of 76%, 74%, 74%, respectively, achievedthrough the use of gift certificates and recorded delivery/registeredmail. Sending a survey by recorded delivery/registered mailtends to result in the survey package being given priority inthe physicians' incoming mail at the practice. Gift certificatespartially compensate physicians for time spent completing thesurvey and recognition of the time required is appreciated.The response rates achieved provide strong evidence to supportthe use of monetary incentives and recorded delivery/registeredmail (along with the Dillman approach) in survey research. Itis anticipated that this evidence will be used by other researchersto justify requests for funding to cover the costs associatedwith incentives and recorded delivery/registered mail. We recommendthe use of these strategies to maximize response rates and improvethe quality of this type of primary health care research. Keywords. Response rates, surveys, physicians.