Ali, Zain

Ashfaq, Ammar

Lashari, MD, Bilal

Saeed, Rehan

Ullah, Waqas

English

Jefferson Digital Commons

Thomas Jefferson University Jefferson Digital Commons Abington Jefferson Health Papers Abington Jefferson Health 10-1-2020 Acute COVID-19 induced fulminant systemic vascular thrombosis: A novel entity. Zain Ali Abington Jefferson Health, PA, United States Waqas Ullah Abington Jefferson Health, PA, United States Rehan Saeed Abington Jefferson Health, PA, United States Ammar Ashfaq Abington Jefferson Health, PA, United States Bilal Lashari, MD Abington Jefferson Health, PA, United States Follow this and additional works at: https://jdc.jefferson.edu/abingtonfp  Part of the Cardiology Commons Let us know how access to this document benefits you Recommended Citation Ali, Zain; Ullah, Waqas; Saeed, Rehan; Ashfaq, Ammar; and Lashari, MD, Bilal, "Acute COVID-19 induced fulminant systemic vascular thrombosis: A novel entity." (2020). Abington Jefferson Health Papers. Paper 33. https://jdc.jefferson.edu/abingtonfp/33 This Article is brought to you for free and open access by the Jefferson Digital Commons. The Jefferson Digital Commons is a service of Thomas Jefferson University's Center for Teaching and Learning (CTL). The Commons is a showcase for Jefferson books and journals, peer-reviewed scholarly publications, unique historical collections from the University archives, and teaching tools. The Jefferson Digital Commons allows researchers and interested readers anywhere in the world to learn about and keep up to date with Jefferson scholarship. This article has been accepted for inclusion in Abington Jefferson Health Papers by an authorized administrator of the Jefferson Digital Commons. For more information, please contact: JeffersonDigitalCommons@jefferson.edu. CorrespondenceAcute COVID-19 induced fulminant systemicvascular thrombosis: A novel entityTo the editor,Coronavirus disease 2019 (COVID-19) has been implicated inthe etiology of deep venous thrombosis, stroke and pulmonaryembolism [1–3]. Here, we invoke a new variant of coagulopathy,acute COVID-19 induced fulminant systemic vascular thrombosis(ACoFSVT) characterized by a rapid, widespread, massive periph-eral arteriovenous coagulopathy.A 74-year-old male with a past medical history of Diabetes Mel-litus (DM) presented with lethargy and hypoxia since one dayprior. Additional history was limited, given his altered mentalstatus.In the emergency department (ED), he was febrile (39.1 celsius),tachycardic and tachypneic (respiratory rate 40 breaths per min-ute). His blood pressure was 75/50 mmHg. Arterial oxygen satura-tion was 44% requiring emergent intubation and mechanicalventilation. Electrocardiogram (EKG) demonstrated sinus tachy-cardia and a chest X-ray revealed bilateral interstitial infiltrates.He received vigorous intravenous fluid resuscitation followed byinotropic support with norepinephrine infusion. Given concernsfor sepsis, broad-spectrum antibiotics were also initiated.Initial laboratory investigation revealed prerenal azotemia(blood urea nitrogen 121 mEq/L, creatinine 3.59 mg/dl), hyperna-tremia (154 mEq/L), hyperkalemia (6.4 mEq/dL), and rhabdomyol-ysis Creatine Kinase (4673 U/L). His serum d-dimer level, C-reactive protein (CRP), and lactate dehydrogenase (LDH) were ele-vated at 69,000 ng/mL, 199 mg/dL and 910U/L, respectively (Fig. 1).The following day, a real-time polymerase chain reaction for sev-ere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)returned positive. He was initially treated with hydroxychloro-quine but this was later discontinued due to QT prolongationand short bursts of nonsustained ventricular tachycardia. Inter-leukin-6 (IL-6) inhibitors could not be utilized given his raisedaminotransferase levels (450 IU/L), alanine aminotransferase(540 IU/L) and thrombocytopenia. The latter also precluded usfrom starting empiric therapeutic anticoagulation.On day-2, he developed bilateral lower extremity edema,prompting venous imaging of the lower extremities. Doppler ultra-sound (DUS) revealed widespread occlusive thrombosis in theright femoral and bilateral popliteal veins. DUS of the upperextremities also revealed occlusive thrombi in the right cephalicand left basilic vein. He was immediately started on therapeuticintravenous unfractionated heparin.Two days later, he developed skin mottling and discoloration onthe bilateral lower extremities and peripheral pulses could not beelicited. An arterial DUS of the lower extremities demonstratedmassive occlusive thrombi in the bilateral common femoral, pro-funda femoris, superficial femoral, posterior tibial, peroneal andposterior tibial arteries. (Fig. 2) Given the extensive clot burden,anticoagulant was switched to argatroban, fearing heparin failureand considering the remote possibility of Heparin-induced throm-bocytopenia. An extensive hypercoagulability workup comprisingheparin-induced thrombocytopenia antibody testing, lupus antico-agulant (DRVVT), anticardiolipin antibody and beta-2-glycoproteinwere negative. The rapidly progressing ischemia on anticoagulants,and bilateral lower extremities involvement was concerning fornon-viable limbs.After introspection with hematology, vascular surgery, and thefamily, it was decided that he would be a poor candidate for bothfor catheter-directed thrombolysis or vascular bypass surgery. Sur-gical intervention with emergent bilateral femoral endarterectomyfollowed by thrombectomy were attempted, however he eventu-ally needed above knee lower extremity amputations. The hospitalcourse was further complicated by persistent fevers, rhabdomyol-ysis, diffuse coagulopathy and a urinary tract infection in conjunc-tion with COVID-19. Given his clinical deterioration, his familyeventually opted to proceed with comfort directed care and trans-fer to a hospice facility.The novel COVID-19 is a generation-defining global pandemic;the scale, scope and pace of which is unprecedented. The statisticsto date are staggering. As of April 30, 2020, more than 3millionconfirmed cases from over 180 countries and more than 233,000deaths had been documented worldwide. The estimated case bur-den in the US alone is expected to be 2–3 million. Given this, themounting toll of COVID-19 related systemic and vascular compli-cations requiring critical interventions could be daunting.SARS-CoV-2 infection can elicit an intense inflammatoryresponse by recruiting multiple cytokines and chemokines (IL-6,tumor necrosis factors), leading not only to direct endothelialinjury but also to diffuse vascular inflammation. The Endothelialdysfunction seems to be mediated via viral infection of theendothelial cell. Also the impaired systemic microcirculatory func-tioning, vasoconstriction, stasis of blood flow during immobiliza-tion, changes in circulating prothrombotic factors during activeinfection may all potentiate this procoagulant state [2,4]. COVID-19 induced hypoxia, immobilization and reactive thrombocytosis,can also precipitate multivessel thrombosis [5]. Contemporarystudies have shown that the degree of thrombosis may correlatewith titers of coagulation biomarkers. Elevated levels of d-dimerhave been shown to directly correlate with higher SequentialOrgan Failure Assessment (SOFA) scores and worse clinical out-comes [6]. A multivariable regression has also shown increasedodds of poor prognostic factors associated with d-dimer levelgreater than 1 lg/mL (1842, 264–12855; p = 00033) [4].In our case, irrespective of the endothelial injury, the collisionof COVID-19 induced direct vascular thrombosis, inherent to thedisease-specific hypercoagulable state, and possible vasculopathy,due to long-standing diabetes triggered vascular occlusion. Thehttps://doi.org/10.1016/j.ijcha.2020.1006202352-9067/ 2020 The Authors. Published by Elsevier B.V.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).IJC Heart & Vasculature 30 (2020) 100620Contents lists available at ScienceDirectIJC Heart & Vasculaturejournal homepage: www.journals .e lsevier .com/i jc -heart -and-vasculatureFig. 1. In-hospital course, vitals and lab findings (yellow indicates on presser support, highlighted areas are abnormal values, MV: Mechanical Ventilation, NC: NasalCannula). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)Fig. 2. (A) Left common femoral and (B) profunda femoris artery with a large occluding thrombus in the lumen and negative biphasic flow on Doppler ultrasound. (C)Biphasic flow waveform demonstrating absence of blood flow below proximal part of the femoral artery.2 Correspondence / IJC Heart & Vasculature 30 (2020) 100620rise in d-dimer levels tracked with inflammatory biomarkers (CRP),reflecting both coagulopathy and vascular inflammation, a causefor acute COVID-19 related fulminant systemic vascular thrombo-sis (ACoFSVT). While a constellation of multiple mechanismsincited ACoFSVT, the resulting rhabdomyolysis, electrolyte distur-bance and kidney failure further complicated the clinical course ofour patient.Although pathologically unproven, the dramatic cratering clin-ical trajectory of our patient despite being on therapeutic heparinalso suggests that ACoFSVT severely disrupts normal homeostaticmechanisms, exhausting anticoagulant factors and leading tounopposed clotting pathway activation. This, especially in the set-ting of possible pre-existing endothelial dysfunction due to DM,precipitated widespread thrombosis [6]. One can also argue thatlack of definitive treatment for COVID-19 and possible delay inthe administration of heparin infusion due to thrombocytopeniaon presentation might have contributed to the development ofACoFSVT. Regardless, it is imperative to identify early clinical riskfactors such as baseline medical conditions that predispose to vas-culopathy, significant elevated inflammatory markers and in par-ticular high levels of d-dimer, and adopt an individualizedapproach to initiation of early therapeutic anticoagulation in thesepatients.While remarkable efforts to unravel further management ofacute COVID-19 related thrombotic complications are ongoing,we advocate for early recognition and timely anticoagulation inpatients with high-risk features suggestive of ACoFSVT.Declaration of Competing InterestThe authors declare that they have no known competing finan-cial interests or personal relationships that could have appearedto influence the work reported in this paper.Appendix A. Supplementary materialSupplementary data to this article can be found online athttps://doi.org/10.1016/j.ijcha.2020.100620.References[1] F.A. Klok, M.J. Kruip, N.J. van der Meer, M.S. Arbous, D.A. Gommers, K.M. Kant, F.H. Kaptein, J. van Paassen, M.A. Stals, M.V. Huisman, H. Endeman, Incidence ofthrombotic complications in critically ill ICU patients with COVID-19,Thrombosis Res. (2020).[2] W. Ullah, R. Saeed, U. Sarwar, R. Patel, D.L. Fischman, COVID-19 complicated byacute pulmonary embolism and right-sided heart failure, JACC: Case Rep.(2020).[3] J.F. Llitjos, M. Leclerc, C. Chochois, J.M. Monsallier, M. Ramakers, M. Auvray, K.Merouani, High incidence of venous thromboembolic events in anticoagulatedsevere COVID-19 patients, J. Thromb. Haemost. (2020), https://doi.org/10.1111/jth.14869.[4] Z. Varga, A.J. Flammer, P. Steiger, M. Haberecker, R. Andermatt, A.S. Zinkernagel,M.R. Mehra, R.A. Schuepbach, F. Ruschitzka, H. Moch, Endothelial cell infectionand endotheliitis in COVID-19, The Lancet.[5] H. Mei, Y. Hu, Characteristics, causes, diagnosis and treatment of coagulationdysfunction in patients with COVID-19, Zhonghua xue ye xue za zhi= Zhonghuaxueyexue zazhi 41 (2020) E002.[6] F. Zhou, T. Yu, R. Du, G. Fan, Y. Liu, Z. Liu, J. Xiang, Y. Wang, B. Song, X. Gu, L.Guan, Clinical course and risk factors for mortality of adult inpatients withCOVID-19 in Wuhan, China: a retrospective cohort study, The Lancet (2020).Zain AliWaqas Ullah⇑Rehan SaeedAmmar AshfaqBilal LashariAbington Jefferson Health, PA, USA⇑ Corresponding author at: 1200 Old York Road, Abington, PA, USA.E-mail address: waqasullah.dr@gmail.com (W. Ullah).Received 10 May 2020Received in revised form 23 July 2020Accepted 10 August 2020Available online 14 August 2020Correspondence / IJC Heart & Vasculature 30 (2020) 100620 3

Acute COVID-19 induced fulminant systemic vascular thrombosis: A novel entity.

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Acute COVID-19 induced fulminant systemic vascular thrombosis: A novel entity.

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