Nello studio vengono analizzati i fattori di rischio in pazienti con infezione da COVID 19 e trombosi venosa profond

Arici V.

Bozzani A.

Bruno R.

Mojoli F.

Ragni F.

Rumi E.

Sterpetti A. V.

Tavazzi G.

English

Archivio della ricerca- Università di Roma La Sapienza

LetterAcute deep vein thrombosis in COVID 19hospitalized patients. Risk factors andclinical outcomesCOVID19 infects cells binding to the angiotensin-converting enzyme 2 receptor. The type 2 transmem-brane serine protease facilitates viral infection bycleaving ACE2 and activating the COVID19 structuralprotein which determines its high virulence.1 The viru-lence is increased by the action of COVID19 on theimmune system with severe lymphopenia. In laterstages of infection, epithelial-endothelial barrier integ-rity is compromised. Dysfunctional alveolar-capillaryoxygen transmission and impaired oxygen diffusioncapacity are characteristic features of COVID-19. Insevere COVID-19, activation of coagulation and con-sumption of clotting factors occur. Patients who devel-op acute deep vein thrombosis during COVID19infection are in a critical condition, in which deepvein thrombosis represents the iceberg of a generalhemostatic derangement.1–3 The aim of our study wasto analyze the risk factors and clinical outcomes ofCOVID19 patients who developed deep vein thrombo-sis during hospitalization in the acute phase of the out-break in our region (Lombardia-Italy). From March1th to April 28th, 942 COVID19 patients with severesymptoms were admitted to our hospital. Patients whodeveloped deep vein thrombosis before admission werenot included into the study. Patients with probableimmune deficiency (history of tumor diagnosis, previ-ous organ transplant) were not include into thestudy. Thirty-two patients developed clinical evidenceof deep vein thrombosis during hospitalization (mean393 hours after admission) and they were prospectivelyevaluated. Nine patients died in a condition of multipleorgan failure, 23 patients survived and left the hospitalin good general conditions. At 1month follow-up noneof the 23 patients complained of major symptoms.Table 1 shows the clinical characteristics and the labo-ratory parameters at admission, at diagnosis and 5 daysafter full anticoagulation and aggressive anti-inflammatory therapy of the patients. All patientswere in critical conditions. Treatment included sup-portive management of acute hypoxic respiratoryfailure and of hemodynamic instability, antibiotic ther-apy, correction of the fluid–electrolyte and metabolicunbalances. All patients received prophylaxis withLMWH and anti-inflammatory therapy. At the timeof diagnosis full anticoagulation was started and thedosage of anti-inflammatory therapy was increased.All patients had significant alterations of hemostaticand inflammatory parameters at admission. In univar-iate analysis advanced age (70 years of age or more)and associated specific comorbidities (CAD, diabetes,renal failure) were significant clinical risk factors formortality (p< 0.0001). High levels of D-Dimers(15.000 or more), Fibrinogen, LDH, and CK were sig-nificant risk factors for mortality (p< 0.0001).However, aggressive therapy allowed a 72% survival,including also for patients in critical clinical conditionsand with high risk parameters. The most important riskfactors were reduced or no change of several laboratoryparameters after therapy, including increased CRPvalues after initial treatment, high levels of D-Dimersand Fibrinogen after full anticoagulation and aggres-sive anti-inflammatory therapy, persistence of highlevels of LDH and CK in all stages of therapy(p< 0.001). The persistence of altered laboratoryparameters despite aggressive therapy was more evi-dent in patients 70 years of age or older, with associateddiabetes and/or renal failure, who might have hadreduced immunologic defenses. The analysis of time-related changes in our study supports the theory thatCOVID19 infection is mainly related to hemostaticchanges in patients with probable immune deficiency.These hemostatic changes may trigger an inflammatorystorm which aggravate the hemostatic changes in avicious circle. There is a high risk group for mortality,characterized by persistence of laboratory changesdespite optimal standard therapy, in whom additionaltherapy should be taken into consideration. Ongoingtrials are testing antiviral therapies, immune modula-tors, and anticoagulants. Monoclonal antibodiesand hyperimmune globulin may provide additionalstrategies. Randomized trial of 103 patients withPhlebology0(0) 1–3! The Author(s) 2020Article reuse guidelines:sagepub.com/journals-permissionsDOI: 10.1177/0268355520958598journals.sagepub.com/home/phlTable1.Mortalityinhospitalizedcovid19patientswithdeepveinthrombosis.ClinicalcharacteristicsandlaboratoryvaluesMortality(9patients)Nomortality(23patients)Sex(M/F)8/116/7Age(mean;range)71.2(62–83)58.8(30–94)P<0.05Comorbidities(mean)2.3(1–4)1.1(0–3)Smoking4/910/23Arterialhypertension8/910/23Coronaryarterydisease4/92/23Diabetes4/90/23Renalfailure2/90/23OxygentherapyHighFlow04Noninvasivemechanicalventilation47Invasivemechanicalventilation512LocalizationthrombosisProximalLowerLimb57DistalLowerLimb210UpperLimb26Evidencepulmonaryembolism44Paduascore(mean;range)3.6(3–4)3.2(3–4)Laboratoryparameters(mean;range)AdmissionDiagnosisAftertherapy(5days)AdmissionDiagnosisAftertherapy(5days)Platelet222(154–289)242(139–324)243(94–529)255(63–526)272(112–669)281(114–775)Fibrinogen599(367–700)423(122–687)573(158–750)450(219–775)397(172–717)379(198–724)P<0.0001PT72.2(51–83)57.6(37–74)60(40–65)74.8(49–93)75.7(36–118)70(40–75)aPTT22(21–28)25(20–34)28(19–42)26(20–48)25(20–43)24(1.55)D-Dimer(x103)13.9(17.1–35)25.3(10.8–35)14.3(4.3–35)6.7(0.5–35)14.4(1–35)4.9(3.2–18.5)P<0.0001Antithrombin82(60–117)75(71–82)70(53–80)76(51–117)78(46–110)80(64–100)LDH597(370–1203)482(276–778)1296(229–3760)474(229–1313)437(250–876)303(168–548)P<0.0001CreatininKinase241(67–669)362(15–2264)215(15–821)282(50–1481)124(15–842)82(15–197)P<0.0001CRP16.4(7.3–27.0)26.3(1.4–98)15.9(1.5–28)19.2(1–40)16.4(0.1–4.6)5.8(0.1–22.5)WBC8.9(6.0–14.7)10.4(1.4–21.3)10.9(2.1–29.0)10.6(3.7–18)10.2(3.0–15)Neutrophyls70(65–80)59(60–75)74(65–80)55(55–70)Lymphocytes0.6(0.3–1.1)0.5(0.2–0.9)0.7(0.2–1.8)1.2(0.5–1.8)0.98(0.4–2.1)1.2(0.3–2.2)CRP:C-reactiveprotein(mg/dL)Platelet(x103/mcL);PT:prothrombintime(%);aPTT:activatethromboplastintime(%);D-Dimers(mcg/L);Antothrombin(%);LDH:lactatedehydrogenase(mU/mL);CreatinKinase(mU/mL);WBCWhiteBloodCount(x103/mcL);Neutrophyls(%ofWBC);lymphocyes(x103/mcL).2 Phlebology 0(0)COVID-19, convalescent plasma did not shorten timeto recovery.4,5Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest withrespect to the research, authorship, and/or publication of thisarticle.FundingThe author(s) received no financial support for the research,authorship, and/or publication of this article.Ethical approvalAll procedures performed in studies involving human partic-ipants were in accordance with the ethical standards of theinstitutional and/or national research committee and with the1964 Helsinki declaration and its later amendments or com-parable ethical standards. The Institutional Review Board(IRB) approval has been obtained.GuarantorFR.ContributorshipAB, GT, VA and AVS researched literature and conceivedthe study. ER, FM, RB and FR was involved in protocoldevelopment, gaining ethical approval, patient recruitmentand data analysis. AB, GT, VA and AVS wrote the firstdraft of the manuscript. All authors reviewed and editedthe manuscript and approved the final version of themanuscript.AcknowledgementsNone.ORCID iDAntonio Bozzani https://orcid.org/0000-0003-3274-6248References1. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, et al.Pathophysiology, transmission, diagnosis, and treatmentof coronavirus disease 2019 (COVID-19): a review.JAMA 2020; 324: 782.2. W€olfel R, Corman VM, Guggemos W, et al. Virologicalassessment of hospitalized patients with COVID-2019.Nature 2020; 581: 465–469.3. Richardson S, Hirsch JS, Narasimhan M, et al.;the Northwell COVID-19 Research Consortium. TheNorthwell COVID-19 research consortium. presentingcharacteristics, comorbidities, and outcomes among 5700patients hospitalized with COVID-19 in the New York cityarea. JAMA 2020; 323: 2052–2059.4. Wang C, Li W, Drabek D, et al. A human monoclonalantibody blocking SARS-CoV-2 infection. Nat Commun2020; 11: 2251.5. Brouwer PJM, Caniels TG, van der Straten K, et al.Potent neutralizing antibodies from COVID-19 patientsdefine multiple targets of vulnerability. Science 2020;369: 643–650.Antonio Bozzani1 , Guido Tavazzi2,3, Vittorio Arici1,Antonio V Sterpetti4, Elisa Rumi5,6Francesco Mojoli2,3, Raffaele Bruno3,7, Franco Ragni11Vascular and Endovascular Surgery Unit, FondazioneIRCCS Policlinico San Matteo, Pavia, Italy2Anesthesiology and Intensive Care Unit, FondazioneIRCCS Policlinico San Matteo, Pavia, Italy3Department of Medical, Surgical, Diagnostic andPediatric Science, University of Pavia, Pavia, Italy4Department of Surgery, University of Rome Sapienza,Rome, Italy5Hematology Unit, Fondazione IRCCS Policlinico SanMatteo, Pavia, Italy6Department of Molecular Medicine, University ofPavia, Pavia, Italy7Infectious Diseases Unit, Fondazione IRCCSPoliclinico San Matteo, Pavia, ItalyCorresponding author:Antonio Bozzani, P.le Golgi 19, 27100 Pavia, Italy.Email: a.bozzani@smatteo.pv.itBozzani et al. 3

Acute deep vein thrombosis in COVID 19 hospitalized patients. Risk factors and clinical outcomes

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Acute deep vein thrombosis in COVID 19 hospitalized patients. Risk factors and clinical outcomes

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