Si discute l'importanza di una analisi accurata nel definire il fattore di rischio di trasfusioni nella genesi della trombosi profonda delle vene degli arti inferior

Sterpetti, Antonio V.

English

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Acquisition, analysis, or interpretation of data: Benz, Taggart, Klug, Basson.Drafting of the manuscript:Dyke, Klug, Basson.Critical revision of the manuscript for important intellectual content: Benz,Taggart, Klug, Basson.Statistical analysis:Dyke, Benz, Klug, Basson.Administrative, technical, or material support: Basson.Supervision:Dyke, Basson.Conflict of Interest Disclosures:None reported.1. Aoyama R, Takano H, Suzuki K, et al. The impact of blood pressure variabilityon coronary plaque vulnerability in stable angina: an analysis using opticalcoherence tomography. Coron Artery Dis. 2017;28(3):225-231. doi:10.1097/MCA.00000000000004622. Chang TI, Reboussin DM, Chertow GM, et al; SPRINT Research Group*.Visit-to-visit office blood pressure variability and cardiovascular outcomes inSPRINT (Systolic Blood Pressure Intervention Trial).Hypertension. 2017;70(4):751-758. doi:10.1161/HYPERTENSIONAHA.117.097883. BassonMD, KlugMG, Hostetter JE, Wynne J. Visit-to-visit variability of bloodpressure is associated with hospitalization andmortality in an unselected adultpopulation [published online May 31, 2018]. Am J Hypertens.4. Chung PJ, Carter TI, Burack JH, Tam S, Alfonso A, Sugiyama G. Predicting therisk of death following coronary artery bypass graft made simple:a retrospective study using the American College of Surgeons National SurgicalQuality Improvement Program database. J Cardiothorac Surg. 2015;10:62.doi:10.1186/s13019-015-0269-y5. Shahian DM, O’Brien SM, Filardo G, et al; Society of Thoracic SurgeonsQuality Measurement Task Force. The Society of Thoracic Surgeons 2008cardiac surgery risk models: part 1–coronary artery bypass grafting surgery. AnnThorac Surg. 2009;88(1)(suppl):S2-S22. doi:10.1016/j.athoracsur.2009.05.0536. Grassi G, Bombelli M, Brambilla G, Trevano FQ, Dell’oro R, Mancia G. Totalcardiovascular risk, blood pressure variability and adrenergic overdrive inhypertension: evidence,mechanisms and clinical implications. Curr Hypertens Rep.2012;14(4):333-338. doi:10.1007/s11906-012-0273-8COMMENT&RESPONSEAvoidable Blood TransfusionsTo the Editor I readwithmuch interest the article byGoel et al,1titled, “Association of Perioperative Red Blood Cell Transfu-sions With Venous Thromboembolism in a North AmericanRegistry.” The authors should be congratulated for their ef-forts to findcauses forpostoperativedeepvein thrombosisand,eventually,pulmonaryembolism.Theyanalyzeddata fromtheAmerican College of Surgeons National Surgical Quality Im-provement Program registry regarding 750 937 patients whohad surgery in 525 hospitals over a 1-year period. They foundthat therewas ahigher incidenceof deepvein thrombosis andpulmonary embolism within 30 days from surgery in pa-tientswhohadreceivedperioperativebloodtransfusion.About6.3% of the patients received at least 1 blood transfusion. In aretrospective analysis, they found that blood transfusionwasan independent risk factor for thromboembolismanddeepveinthrombosis.I have concerns about their study. In the United States,training programs teach the importance of avoiding unneces-saryblood transfusions. It is almost adogma, and this is some-what testified by the low number of patients who receivedblood transfusions in their data (6.3%). It is very difficult tocomparepatients retrospectivelywithout anobjective assess-ment of their general conditions and without the possibilitytodeterminewhy thosepatients hadblood transfusions.Dataabout preoperative hematocrit level were not available. Goelet al1 performed retrospectivepropensity scorematching; thisanalysis presents many drawbacks when it is not possible todetermine all characteristics of the general status of the pa-tients.Unfortunately,propensity scorematching impliesmanyinadvertent selection biases.It is wise to accept the conclusions of Goel et al1 thatblood transfusions carry a significant risk, especially forother reasons than thromboembolism, like transmission ofHIV, hepatitis C, and other unknown, unpredictable diseases.Still, I have doubts about the appropriateness of the correla-tion between blood transfusions and deep vein thrombosis;I think that the final messages of the authors are of para-mount importance, and there is the need for clear guidelinesabout perioperative blood transfusions. Too often, surgeonsfeel much better if the patient’s hematocrit level is in anacceptable range. National guidelines can support the deci-sion in difficult clinical situations as well as support a legaldefense in times when all of us are obliged to do more thanrequired just to avoid future consequences.Antonio V. Sterpetti, MDAuthor Affiliation: Istituto Pietro Valdoni, University of Rome Sapienza,Rome, Italy.Corresponding Author: Antonio V. Sterpetti, MD, Istituto Pietro Valdoni,University of Rome Sapienza, Policlinico Umberto I, Viale del Policlinico, 00167Rome, Italy (antonio.sterpetti@uniroma1.it).Published Online:October 31, 2018. doi:10.1001/jamasurg.2018.3866Conflict of Interest Disclosures:None reported.1. Goel R, Patel EU, CushingMM, et al. Association of perioperative red bloodcell transfusions with venous thromboembolism in a North American registry.2018;153(9):826-833. doi:10.1001/jamasurg.2018.1565In Reply We thank Sterpetti for his response and close atten-tion to our study.1 We agree with the author’s assertion thatin the United States, there has been an immense focus on re-ducing unnecessary blood transfusions, supported by clini-cal practice guidelines and patient blood managementprograms.2 The effect of patient blood management initia-tives in the United States is evident by recent data showingnationwide decreases in red blood cell (RBC) and plasmatransfusions.3Our study aimed to evaluate the association of periopera-tive RBC transfusions with postoperative new-onset/progressivevenous thromboembolism(VTE).This studyques-tion stems frommultiple translational andclinical studies thathave suggested a relationship between transfused RBC andpathologic thrombosis.4,5 As outlined in our article, multiplemechanistic pathwayshavebeenhypothesized to explain thispotential association.6 Although Sterpetti questions the ap-propriateness of our study question, we see value in explor-ing a potential association that is both biologically plausibleand clinically relevant. It should be noted that this studywasnot intended to or designed to calculate causal effects.Weconductedasecondaryanalysisofdata fromtheAmeri-can College of Surgeons National Surgical Quality Improve-mentProgram,avalidatedandwidely recognizednational reg-istry for studying surgical outcomes. The registry includesparticipation from more than 500 academic and nonaca-demichospitals.While theprospectivedesignand largesamplesize of the registry make the data powerful, these data haveLetters94 JAMA Surgery January 2019 Volume 154, Number 1 (Reprinted) jamasurgery.com© 2018 American Medical Association. All rights reserved.Downloaded From: https://jamanetwork.com/ by a Universita Degli Studi di Roma La Sapienza User  on 04/29/2019limitations,aswestated in theDiscussionsectionof thearticle.1An inherent limitationofanyretrospectiveobservational studyis the inability to account for unmeasured (or unmeasurable)covariates, regardless of the statistical method used to ana-lyze the data (eg, multivariate regression or propensity scorematching). For instance, the specific preoperativehealth con-ditionsand indications forperioperativeRBC transfusionwereunknown.However, it is noteworthy that the associationwasobserved across a number of surgical subspecialties indepen-dent of several factors related to severity of illness. We hopefutureprospective studieswill account forpotential confound-ers that could not be examined in our analysis.As Sterpetti notes, the study did not provide data on pre-operative hematocrit levels. For patients with available data,mean (SD) preoperative hematocrit levelswere 39.8% (4.9) inthe group that did not receive any perioperative RBC transfu-sion and 33.4% (6.4) in the group that received at least 1 peri-operative RBC transfusion. Including preoperative hemato-crit levels as a continuous variable in the fully adjustedmodeldoes not affect the findings reported in the primary analysis;any perioperative RBC transfusion remains significantlyassociated with the development of postoperative VTE(adjusted odds ratio, 2.1; 95% CI, 2.0-2.3) in the overall studypopulation. Postoperative hematocrit levels are not availablein the registry.Ultimately, our retrospective study supports the hypoth-esis thatperioperativeRBCtransfusionsmaybeassociatedwithdevelopment of new or progressive VTE within 30 days ofsurgery. These data support the need for prospective studiesas VTE continues to be a public health problem.Ruchika Goel, MD, MPHEshan U. Patel, MPHAaron A. R. Tobian, MD, PhDAuthor Affiliations:Division of TransfusionMedicine, Department ofPathology, Johns Hopkins University, Baltimore, Maryland (Goel, Patel, Tobian);Simmons Cancer Institute, Southern Illinois University School of Medicine,Springfield (Goel).Corresponding Author: Aaron A. R. Tobian, MD, PhD, Division of TransfusionMedicine, Department of Pathology, Johns Hopkins University, 600 NWolfe St,Carnegie 437, Baltimore, MD 21287 (atobian1@jhmi.edu).Published Online:October 31, 2018. doi:10.1001/jamasurg.2018.3867Conflict of Interest Disclosures:None reported.1. Goel R, Patel EU, CushingMM, et al. Association of perioperative red bloodcell transfusions with venous thromboembolism in a North American registry.2018;153(9):826-833. doi:10.1001/jamasurg.2018.15652. Carson JL, Guyatt G, Heddle NM, et al. Clinical practice guidelines from theAABB: red blood cell transfusion thresholds and storage. JAMA. 2016;316(19):2025-2035. doi:10.1001/jama.2016.91853. Goel R, Chappidi MR, Patel EU, et al. Trends in red blood cell, plasma, andplatelet transfusions in the United States, 1993-2014. JAMA. 2018;319(8):825-827. doi:10.1001/jama.2017.201214. Byrnes JR,Wolberg AS. Red blood cells in thrombosis.Blood. 2017;130(16):1795-1799. doi:10.1182/blood-2017-03-7453495. Litvinov RI, Weisel JW. Role of red blood cells in haemostasis and thrombosis.ISBT Sci Ser. 2017;12(1):176-183. doi:10.1111/voxs.123316. Barr JD, Chauhan AK, Schaeffer GV, Hansen JK, Motto DG. Red blood cellsmediate the onset of thrombosis in the ferric chloride murine model. Blood.2013;121(18):3733-3741. doi:10.1182/blood-2012-11-468983Prehospital Advanced Life Supportfor Out-of-Hospital Cardiac Arrestin Blunt TraumaPatientsTo the EditorWe thank Fukuda et al1 for their study analyzingtheassociationofprehospital advanced life support (ALS)withtheoutcomesofout-of-hospital cardiacarrest.Theauthorscon-clude that ALS by physicians resulted in a higher 30-day sur-vival than ALS by emergency medical service (EMS) person-nel and basic life support (BLS).However, the implications of the study may be over-stated. First, given the retrospectivedesignof the study, therearemultiple confounding factors that the authorshavenot ac-counted for. Thesemainly includepatient demographic char-acteristics, like age and sex;modifiable predictors of survivaloutcomes, like body mass index; general health status as as-sessedby theAmericanSocietyofAnesthesiologists index;andcomorbidities present, as shown in Table 1.1 Importantly, theextent of blunt injury (assessed by the Injury Severity Scoreor Abbreviated Injury Scale score) and etiology of cardiac ar-restwerenot evaluated.Amajorpredictorof survivalwas timetoresponse,2whichwasstatisticallydifferentbetweenthevari-ous cohorts (Tables 1 and 3).1 When comparing between EMSand physicians, it is pertinent to match their expertise, sincephysicians, unlike EMS, may have differing experience andhence success in providing life support.3 Similarly, manypatientswhosurvive longenough to reach thehospital forALSby physicians fare better because of other above-mentionedfactors.In addition to the differing sample sizes between thevarious cohorts, the authors do not know how patients wereallocated to these cohorts. This introduces selection and allo-cation bias, especially since these are decisions guided byclinical findings. Similarly, patients often receive additionalinterventions, so using a composite end point such as 30-daysurvival is not necessarily a valid measure of the effective-ness of either ALS or BLS or who provides it. Instead, a moreimmediate assessment of ALS success as well as a compre-hensive assessment of complications during hospital stay isnecessary. Thus, while the study design improves the gener-alizability of the results, its decreases the internal validity ofthe conclusions.Nevertheless, we agree and emphasize that the promptprovisionofALSorBLSby trainedprofessionals is vital for op-timizingsurvival inout-of-hospital cardiacarrest.Furtherworkis required to determine if these results are observed inmatched cohorts and, if so, to subsequently incorporate thesefindings into treatment guidelines.Vikram Aakash Khanna, BScSwathikan Chidambaram, MBBS, BScEn Lin Goh, MBBS, BScAuthor Affiliations: School of Medicine, Imperial College London, London,United Kingdom.Corresponding Author: Swathikan Chidambaram, MBBS, BSc, School ofMedicine, Imperial College London, South Kensington Campus, Exhibition Road,London SW7 2AZ, United Kingdom (swathikan.chidambaram12@imperial.ac.uk).Published Online:November 7, 2018. doi:10.1001/jamasurg.2018.4291Conflict of Interest Disclosures:None reported.Lettersjamasurgery.com (Reprinted) JAMA Surgery January 2019 Volume 154, Number 1 95© 2018 American Medical Association. All rights reserved.Downloaded From: https://jamanetwork.com/ by a Universita Degli Studi di Roma La Sapienza User  on 04/29/2019

Avoidable blood transfusions

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Avoidable blood transfusions

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