C W Francis

University of Rochester, Rochester, New York, United States

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Publications (267)2018.53 Total impact

  • P. T. Onundarson · C. W. Francis · O. S. Indridason

    No preview · Article · Dec 2015
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    ABSTRACT: Background: Transfusion of ABO non-identical platelets has been associated with fatal haemolytic reactions, increased red cell transfusion needs and other adverse effects, but the practice of ABO matching in platelet transfusion is controversial. Immune complexes can be formed from the anti-A and/or anti-B antibodies and ABO soluble antigen(s) present in donor and recipient plasma after ABO non-identical transfusions. We hypothesized that these immune complexes affect recipient red cell structural integrity, platelet function and haemostasis. Study design and methods: Haemolysis, platelet function and haemostatic function were assessed before and after incubation of recipient red cells, platelets and whole blood with normal saline controls, ABO-identical plasma controls or in vitro-generated ABO-immune complexes. Results: ABO-immune complexes caused significantly increased haemolysis (P < 0·001), inhibition of platelet function (P = 0·001) and disruption of clot formation kinetics (P < 0·005) in both group A and O recipient samples. Conclusions: Substantial changes in platelet function, red cell integrity and haemostasis occur after in vitro exposure to immune complexes. These in vitro findings may explain, in part, previously observed associations of ABO non-identical platelet transfusions with adverse effects including increased red cell transfusion needs, organ failure and mortality.
    Full-text · Article · Nov 2015 · Vox Sanguinis
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    ABSTRACT: Background Rapid fluctuations in factor VII during warfarin anticoagulation change the international normalised ratio (INR) but contribute little to the antithrombotic effect. We aimed to assess non-inferiority of anticoagulation stabilisation with a warfarin monitoring method affected only by factors II and X (Fiix-prothrombin time [Fiix-PT]) compared with standard PT-INR monitoring that includes factor VII measurement as well. Methods The Fiix trial was a single centre, double-blind, prospective, non-inferiority, randomised controlled clinical trial. Ambulatory adults on warfarin with an INR target of 2-3 managed by an anticoagulation dosing service using software-assisted dosing at the National University Hospital of Iceland, Reykjavik, Iceland, were eligible for inclusion in this study. We excluded patients undergoing electroconversion and nursing home residents. Patients were randomly assigned (1: 1) to either the Fiix-PT monitoring group or the PT monitoring group by block randomisation. A blinded research INR (R-INR) based on results of the respective test was reported to the dosing staff. Participants were contacted by a study nurse at 4-week intervals to elicit information about thromboembolism or bleeding otherwise unknown to the anticoagulation management centre. The primary efficacy outcome was a composite of objectively diagnosed non-fatal and fatal arterial or venous thromboembolism, including myocardial infarction and transient ischaemic attacks, assessed in all eligible patients who were randomised (intention-to-monitor population). The safety endpoint was major bleeding or other clinically relevant bleeding, assessed in the per-protocol population. We assumed a 3% annual thromboembolism incidence and a non-inferiority margin of 2.5%. This trial is registered with ClinicalTrials.gov, number NCT01565239. Findings Between March 1, 2012, and Feb 28, 2014, we enrolled 1156 patients. 573 patients were assigned to Fiix-PT and 575 to PT-INR monitoring after exclusion of four patients from each group for various reasons. Median follow-up was 1.7 years (IQR 1.1-1.9). During days 1-720, ten (1.2% per patient year) thromboembolic events occurred in the Fiix-PT group versus 19 (2.3% per patient year) in the PT group (relative risk [RR] 0.52, 95% CI 0.25-1.13; p(non-inferiority) < 0.0001). Major bleeding occurred in 17 of 571 patients in the Fiix group (2.2% per patient year) versus 20 of 573 patients in the PT group (2.5% per patient year; RR 0.85, 0.45-1.61; p(non-inferiority) = 0.0034). Anticoagulation stability was improved with Fiix-PT monitoring as manifested by fewer tests, fewer dose adjustments, increased time in range and less INR variability than reported with standard PT monitoring. Interpretation Monitoring of warfarin with Fiix-PT improved anticoagulation and dosing stability and was clinically non-inferior to PT monitoring. Results from this trial suggest that during vitamin K antagonist treatment INR monitoring could be replaced by Fiix-PT and that this would lead to at least a non-inferior clinical outcome compared with monitoring with PT-INR.
    Full-text · Article · May 2015
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    ABSTRACT: Cardiac-related clinical practice guidelines have become an integral part of the practice of cardiology. Unfortunately, these guidelines are often long, complex, and difficult for practicing cardiologists to use. Guidelines should be condensed and their format upgraded, so that the key messages are easier to comprehend and can be applied more readily by those involved in patient care. After presenting the historical background and describing the guideline structure, we make several recommendations to make clinical practice guidelines more user-friendly for clinical cardiologists. Our most important recommendations are that the clinical cardiology guidelines should focus exclusively on (1) class I recommendations with established benefits that are supported by randomized clinical trials and (2) class III recommendations for diagnostic or therapeutic approaches in which quality studies show no benefit or possible harm. Class II recommendations are not evidence based but reflect expert opinions related to published clinical studies, with potential for personal bias by members of the guideline committee. Class II recommendations should be published separately as "Expert Consensus Statements" or "Task Force Committee Opinions," so that both majority and minority expert opinions can be presented in a less dogmatic form than the way these recommendations currently appear in clinical practice guidelines. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Mar 2015 · The American Journal of Cardiology
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    ABSTRACT: Background Venous thromboembolism (VTE) treatment in patients with cancer has a high rate of recurrence and bleeding complications. Guidelines recommend low molecular weight heparin (LMWH) for at least 3-6 months and possibly indefinitely for patients with active malignancy. There are, however, few data supporting LMWH treatment beyond 6 months. The primary aim of the DALTECAN study (NCT00942968) was to determine the safety of dalteparin between 6 and 12 months in cancer-associated VTE.Methods Patients with active cancer and newly diagnosed VTE were enrolled in a prospective, multicenter study and received subcutaneous dalteparin for 12 months. The rates of bleeding and recurrent VTE were evaluated at months 1, 2-6, and 7-12.FindingsOf 334 patients enrolled, 185 and 109 completed 6 and 12 months of therapy. 49.1% had deep vein thrombosis (DVT); 38.9% had pulmonary embolism (PE); and 12.0% had both on presentation. The overall frequency of major bleeding was 10.2% (34/334). Major bleeding occurred in 3.6% (12/334) in the first month, and 1.1% (14/1237) and 0.7% (8/1086) per patient-month during months 2-6 and 7-12, respectively. Recurrent VTE occurred in 11.1% (37/334); the incidence rate was 5.7% (19/334) for month 1, 3.4% (10/296) during months 2-6, and 4.1% (8/194) during months 7-12. 116 patients died, four due to recurrent VTE and two due to bleeding.InterpretationMajor bleeding was less frequent during dalteparin therapy beyond 6 months. The risk of developing major bleeding complications or VTE recurrence was greatest in the first month of therapy and lower over the subsequent 11 months.This article is protected by copyright. All rights reserved.
    No preview · Article · Mar 2015 · Journal of Thrombosis and Haemostasis
  • Alok A. Khorana · Deborah Rubens · Charles W. Francis
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    ABSTRACT: Background The utility of screening for venous thromboembolism (VTE) in cancer patients is unknown. We evaluated this in a prospective cohort study of cancer patients initiating a new chemotherapy regimen and deemed high-risk (score ≥ 3) based on a validated Risk Score. Methods Patients were evaluated with baseline and Q4 (± 1) week serial ultrasonography for up to 16 weeks; additionally, computed tomography scans for restaging were also evaluated for VTE. Results The study population comprised 35 patients. Pancreatic and gastro-esophageal cancers were the most common diagnoses. Of these, 8 (23%) developed a VTE. This included 5 patients with DVT alone (14%), 1 patient with PE alone (3%) and 2 (6%) with both. Ultrasound examinations identified asymptomatic DVT in 9.3% of patients at baseline; 0% at weeks 4 and 8 and 5.6% at week 12. Restaging CT scans identified asymptomatic PE in one patient at week 6 and in one patient at week 9 with subsequent DVT at week 10. Conclusions Screening for asymptomatic VTE has not been previously used as a clinical strategy in ambulatory cancer patients. We report that one-tenth of patients at baseline had occult DVT and in this high-risk population, screening at baseline may be of value.
    No preview · Article · Sep 2014 · Thrombosis Research
  • Gregory C. Connolly · Richard P. Phipps · Charles W. Francis
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    ABSTRACT: Platelets have a newly appreciated and important role in many cancer related processes including tumor growth and metastases, angiogenesis, and promotion of a hypercoagulable state. Cancer patients commonly experience venous thromboembolism (VTE), a leading cause of mortality and a source of considerable morbidity and cost. The role of platelets in arterial thrombosis is well-established, but emerging evidence supports the concept that platelets are also involved in initiation of VTE. This is particularly true in cancer-associated thrombosis as extensive new evidence shows that thrombocytosis and platelet activation are predictive biomarkers of VTE. The role of therapeutic anti-platelet agents has been proven effective at preventing VTE in non-cancer patients, and there is early data suggesting benefit in cancer patients as well. This review summarizes platelet-related predictive biomarkers of cancer-associated thrombosis, platelet mediated mechanisms for VTE promotion in cancer patients, and antiplatelet agents in prevention of VTE.
    No preview · Article · Jun 2014 · Seminars in Oncology
  • Gregory C Connolly · Charles W Francis
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    ABSTRACT: Cancer-associated thrombosis accounts for almost one-fifth of all cases of venous thromboembolism (VTE) and is a leading cause of death, morbidity, delays in care, and increased costs. Our understanding of risk factors for cancer-associated thrombosis has expanded in recent years, and investigators have begun to use biomarkers and clinical prediction models to identify those cancer patients at greatest risk for VTE. The Khorana Risk Model, which is based on easily obtained biomarkers and clinical factors, has now been validated in several studies. Recent clinical trials of prophylaxis and treatment of VTE in cancer patients are reviewed here. In addition, consensus guidelines and expert opinion regarding management of VTE in specific challenging situations are presented.
    No preview · Article · Dec 2013 · Hematology
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    ABSTRACT: PURPOSE Using the previously described clinical risk score for venous thromboembolism (VTE) (Khorana et a, Blood 2008) to identify high risk patients, this study evaluates the utility of screening for thrombosis in a prospective cohort of initially asymptomatic cancer patients initiating outpatient chemotherapy. METHOD AND MATERIALS Asymptomatic cancer patients initiating a new chemotherapy regimen & found to be high-risk for VTE based on a predictive risk model (score ≥3) were enrolled on an ongoing prospective cohort study with informed consent. Patients were evaluated with a baseline & an every 4 (± 1) week serial US study for up to 16 weeks. Additionally, CT scans obtained for restaging purposes were also evaluated for VTE. RESULTS Of the 35 high-risk patients enrolled, 8 (23%) were found to have VTE, 5 patients w/ DVT alone (14%), 1 w/ PE alone (3%) & 2 (6%) w/ both. 32 patients underwent a baseline US & 3 asymptomatic DVTs were identified (9%), w/ 1 patient also having an asymptomatic PE detected on staging CT. Subsequent US were performed in 23 patients at week 4 (0DVT), 21 patients at week 8 (0DVT) &18 patients at week 12 (1 DVT, 6%). An additional 2 patients developed symptomatic DVT between screens. Restaging CT scans identified an asymptomatic PE in a patient at week 6 & an asymptomatic PE in a patient at week 9. Of the patients w/ isolated DVT, 2 had isolated unilateral calf clot, 2 had unilateral calf & thigh clot, &1 had unilateral upper extremity clot. CONCLUSION In this prospective observational study, 23% of cancer outpatients deemed high-risk for VTE developed clot at a rate much higher than found in both normal & acutely ill hospitalized populations (0.5 & 6% respectively). This study confirms the validity of the previously described risk score developed by Khorana et al & makes this model highly predictive of identifying patients at risk for VTE. In addition, these findings suggest that screening US for asymptomatic clot should be considered in high-risk patients based on this risk score. This study highlights the importance of VTE screening in the calf, w/ 50% of patients w/ VTE having calf clot & 25% having isolated unilateral calf clot, indicating that this region should be included in the assessment of DVT. CLINICAL RELEVANCE/APPLICATION Screening ultrasonography for asymptomatic thrombosis should be considered in high-risk patients based on this risk score with the goal of reducing the morbidity and mortality assocated with VTE.
    No preview · Conference Paper · Dec 2013
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    ABSTRACT: Stored red blood cells (RBCs) release hemoglobin (Hb) that leads to oxidative damage, which may contribute to thrombosis in susceptible transfusion recipients. Oxidative stress stimulates the generation of a new class of lipid mediators called F2 -isoprostanes (F2 -IsoPs) and isofurans (IsoFs) that influence cellular behavior. This study investigated RBC-derived F2 -IsoPs and IsoFs during storage and their influence on human platelets (PLTs). F2 -IsoP and IsoF levels in RBC supernatants were measured by mass spectrometry during storage and after washing. The effects of stored supernatants, cell-free Hb, or a key F2 -IsoP, 8-iso-prostaglandin F2α (PGF2α ), on PLT function were examined in vitro. F2 -IsoPs, IsoFs, and Hb accumulated in stored RBC supernatants. Prestorage leukoreduction reduced supernatant F2 -IsoPs and IsoFs levels, which increased again over storage time. Stored RBC supernatants and 8-iso-PGF2α induced PLT activation marker CD62P (P-selectin) expression and prothrombotic thromboxane A2 release. Cell-free Hb did not alter PLT mediator release, but did inhibit PLT spreading. Poststorage RBC washing reduced F2 -IsoP and IsoF levels up to 24 hours. F2 -IsoPs and IsoFs are produced by stored RBCs and induce adverse effects on PLT function in vitro, supporting a potential novel role for bioactive lipids in adverse transfusion outcomes. F2 -IsoP and IsoF levels could be useful biomarkers for determining the suitability of blood components for transfusion. A novel finding is that cell-free Hb inhibits PLT spreading and could adversely influence wound healing. Poststorage RBC washing minimizes harmful lipid mediators, and its use could potentially reduce transfusion complications.
    No preview · Article · Nov 2013 · Transfusion
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    ABSTRACT: It is unclear what proportion of VTE events in lung cancer patients are incidentally discovered and whether incidental events affect mortality. We conducted a retrospective cohort study of lung cancer patients seen at the University of Rochester between January 1, 2006 and December 31, 2008 with the goal of quantifying and characterizing VTE events. Multiple clinical variables and mortality outcomes were compared using Kaplan-Meier survival analysis and multivariate Cox proportional hazards. The study population consisted of 207 subjects with lung cancer. The median age was 66 years and 55% were female (n = 115). Thirty-one patients (14.9%) experienced at least 1 VTE event with 32.2% (10/31) of these incidentally discovered. Incidental events comprised 29.4% (n = 5) of pulmonary embolisms, 11.1% (n = 2) of deep vein thrombosis, and 100% (n = 3) of visceral events. The median survival for patients with incidental VTE was 23.4 months (95% confidence interval [CI], 4.8-32.1) compared with 45.8 months (95% CI, 34.1-56.8) in patients without VTE (HR 2.4; 95% CI, 1.2-4.9; P = .01), but in a subgroup analysis of stage IV patients overall survival was not significantly different (HR, 0.94; P = .33). Patients with clinically suspected VTE had the lowest median survival at 13.1 months (95% CI, 6.4-18.9) which was significantly lower than patients without VTE (HR, 2.7; 95% CI, 1.6-4.5; P = .002), but not significantly different from patients with incidental VTE (HR, 1.2; 95% CI, 0.4-2.0; P = .7). In multivariate analysis, occurrence of VTE (HR, 2.3; 95% CI, 1.3-3.8; P = .002) was significantly associated with mortality when adjusting for age, stage, and histology. One-third of VTE events in lung cancer patients are incidentally discovered and VTE has negative clinical effect in lung cancer patients.
    No preview · Article · Jul 2013 · Clinical Lung Cancer
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    Full-text · Dataset · Jul 2013
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    ABSTRACT: Purpose: To provide current recommendations about the prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer. Methods: PubMed and the Cochrane Library were searched for randomized controlled trials, systematic reviews, meta-analyses, and clinical practice guidelines from November 2012 through July 2014. An update committee reviewed the identified abstracts. Results: Of the 53 publications identified and reviewed, none prompted a change in the 2013 recommendations. Recommendations: Most hospitalized patients with active cancer require thromboprophylaxis throughout hospitalization. Routine thromboprophylaxis is not recommended for patients with cancer in the outpatient setting. It may be considered for selected high-risk patients. Patients with multiple myeloma receiving antiangiogenesis agents with chemotherapy and/or dexamethasone should receive prophylaxis with either low-molecular weight heparin (LMWH) or low-dose aspirin. Patients undergoing major surgery should receive prophylaxis starting before surgery and continuing for at least 7 to 10 days. Extending prophylaxis up to 4 weeks should be considered in those undergoing major abdominal or pelvic surgery with high-risk features. LMWH is recommended for the initial 5 to 10 days of treatment for deep vein thrombosis and pulmonary embolism as well as for long-term secondary prophylaxis (at least 6 months). Use of novel oral anticoagulants is not currently recommended for patients with malignancy and VTE because of limited data in patients with cancer. Anticoagulation should not be used to extend survival of patients with cancer in the absence of other indications. Patients with cancer should be periodically assessed for VTE risk. Oncology professionals should educate patients about the signs and symptoms of VTE.
    Full-text · Article · May 2013 · Journal of Clinical Oncology
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    ABSTRACT: An increasing number of academic senior physicians are approaching their potential retirement in good health with accumulated clinical and research experience that can be a valuable asset to an academic institution. Considering the need to let the next generation ascend to leadership roles, when and how should a medical career be brought to a close? We explore the roles for academic medical faculty as they move into their senior years and approach various retirement options. The individual and institutional considerations require a frank dialogue among the interested parties to optimize the benefits while minimizing the risks for both. In the United States there is no fixed age for retirement as there is in Europe, but European physicians are initiating changes. What is certain is that careful planning, innovative thinking, and the incorporation of new patterns of medical practice are all part of this complex transition and timing of senior academic physicians into retirement.
    No preview · Article · May 2013 · Progress in cardiovascular diseases
  • Article: Response.
    Yngve Falck-Ytter · Clive Kearon · Elie Akl · Charles Francis

    No preview · Article · Mar 2013 · Chest
  • Yngve Falck-Ytter · Clive Kearon · Elie Akl · Charles Francis

    No preview · Article · Mar 2013 · Chest
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    ABSTRACT: Dr. Cohen presents a passionate critique of the 9(th) edition of the American College of Chest Physician Guidelines on Antithrombotic Therapy (AT9), and in particular on its methodologist authors. We believe this attack is misguided and appreciate the opportunity to respond to Dr. Cohen. Dr. Cohen objects to the use of the term patient-important. © 2013 International Society on Thrombosis and Haemostasis.
    Full-text · Article · Feb 2013 · Journal of Thrombosis and Haemostasis
  • Charles W Francis
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    ABSTRACT: Venous thromboembolism (VTE) is a serious risk after major orthopedic surgery (MOS) including total knee replacement, total hip replacement and hip fracture surgery. This risk can be reduced with several pharmacologic and mechanical prophylactic approaches, and the choice among them depends on their ability to reduce VTE with an acceptable increase in adverse events, especially major bleeding complications. Improvements in medical and surgical care have led to a progressive decrease in the risk of VTE after MOS with an estimated baseline risk with contemporary practice of approximately 4.3 % up to day 39 after surgery. Low-molecular-weight heparin is the most thoroughly studied thromboprophylactic agent following MOS and demonstrates good effectiveness with an acceptable rate of bleeding complications. Warfarin, rivaroxaban, dabigatran, and apixaban have all been studied in large trials in comparison with low-molecular-weight heparin and also show an acceptable benefit: risk ratio. Mechanical approaches including graduated compression stockings, intermittent pneumatic compression and venous foot pump also offer protection against VTE, but there is less evidence is available regarding their effectiveness and risks. Combination therapy consisting of an antithrombotic agent and mechanical device is probably more effective than either alone. The appropriate use of thromboprophylaxis after MOS results in reduced VTE with acceptable bleeding risks.
    No preview · Article · Feb 2013 · Journal of Thrombosis and Thrombolysis

  • No preview · Article · Jul 2012 · Chest
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    ABSTRACT: BACKGROUND: ABO-mismatched platelets (PLTs) are commonly transfused despite reported complications. We hypothesized that because PLTs possess A and B antigens on their surface, ABO-mismatched transfused or recipient PLTs could become activated and/or dysfunctional after exposure to anti-A or -B in the transfused or recipient plasma. We present here in vitro modeling data on the functional effects of exposure of PLTs to ABO antibodies. STUDY DESIGN AND METHODS: PLT functions of normal PLTs of all ABO types were assessed before and after incubation with normal saline, ABO-identical plasma samples, or O plasma samples with varying titers of anti-A and anti-B (anti-A/B). Assays used for this assessment include PLT aggregation, clot kinetics, thrombin generation, PLT cytoskeletal function, and mediator release. RESULTS: Exposure of antigen-bearing PLTs to O plasma with moderate to high titers of anti-A/B significantly inhibits aggregation, prolongs PFA-100 epinephrine closure time, disrupts clot formation kinetics, accelerates thrombin generation, reduces total thrombin production, alters PLT cytoskeletal function, and influences proinflammatory and prothrombotic mediator release. CONCLUSIONS: Our findings demonstrate a wide range of effects that anti-A/B have on PLT function, clot formation, thrombin generation, PLT cytoskeletal function, and mediator release. These data provide potential explanations for clinical observations of increased red blood cell utilization in trauma and surgical patients receiving ABO-nonidentical blood products. Impaired hemostasis caused by anti-A/B interacting with A and B antigens on PLTs, soluble proteins, and perhaps even endothelial cells is a potential contributing factor to hemorrhage in patients receiving larger volumes of ABO-nonidentical transfusions.
    Full-text · Article · May 2012 · Transfusion

Publication Stats

13k Citations
2,018.53 Total Impact Points


  • 1983-2015
    • University of Rochester
      • • James P. Wilmot Cancer Center
      • • Division of Hematology/Oncology
      • • Division of Hospital Medicine
      • • Division of General Medicine
      • • Department of Medicine
      • • School of Medicine and Dentistry
      • • Division of Cardiology
      Rochester, New York, United States
  • 2008-2010
    • Duke University
      Durham, North Carolina, United States
  • 2009
    • Duke University Medical Center
      • Duke Comprehensive Cancer Center
      Durham, North Carolina, United States
  • 1980-2009
    • University Center Rochester
      • • Department of Medicine
      • • Department of Environmental Medicine
      Rochester, Minnesota, United States
  • 2004
    • Southwest Foundation For Biomedical Research
      San Antonio, Texas, United States
    • Michiana Hematology Oncology
      Indiana, Pennsylvania, United States
  • 2001-2003
    • Rochester General Hospital
      • Infectious Disease Unit
      Rochester, New York, United States
  • 2000
    • Swarthmore College
      • Department of Engineering
      Swarthmore, Pennsylvania, United States
  • 1992
    • Eastern Virginia Medical School
      Norfolk, Virginia, United States
  • 1989
    • Cleveland Clinic
      Cleveland, Ohio, United States
  • 1986
    • Stony Brook University
      • Department of Pathology
      스토니브룩, New York, United States
  • 1984
    • Columbia University
      New York, New York, United States