AMBULANTNO LEČENJE PLUĆNE
TROMBOEMBOLIJE - PREPORUKE
I NAŠA ISKUSTVA
OUTPATIENT TREATMENT OF PULMONARY
THROMBOEMBOLISM - RECOMMENDATIONS
AND OUR EXPERIENCES
Marija Laban1
Jelena Janković1, 2
Jasmina Opačić1
Marina Đikić3
1
Klinika za pulmologiju, Univerzitetski klinički centar Srbije, Beograd,
Srbija
2
Medicinski fakultet Univerziteta u Beogradu, Beograd, Srbija
3
Urgentni centar, Univerzitetski klinički centar Srbije, Beograd, Srbija
Korespondencija sa autorom:
Dr Jasmina Opačić
Klinika za pulmologiju, Univerzitetski klinički centar Srbije, Dr
Koste Todorovica 26, Beograd, Srbija
jasmina89.opacic@gmail.com
Sažetak
Dijagnoza plućne tromboembolije sve je češća u kliničkoj
praksi, zbog čega postoji potreba za ambulantnim
lečenjem. Odluka o tome zavisi od kliničke slike, faktora
rizika, rizika od krvarenja, komorbiditeta, laboratorijskih
parametara, adherence i socijalnog faktora. Pacijenti
koji ispunjavaju PESI I, PESI II i sPESI kriterijume niskog
rizika od smrtnosti, kao i pacijenti sa Hestia skorom
0, lečenje mogu započeti ambulantno. Iako se mogu
primeniti zajedno, niskomolekularni heparin i direktni
oralni antikoagulansi, niskomolekularni heparin i oralni
antagonisti vitamina K, zlatni standard je primena samo
novih, direktnih oralnih antikoagulanasa. Ambulantni
tretman traje najmanje tri meseca, a zavisi od više činilaca,
najpre od reverzibilnosti faktora rizika. Iako se lekari i dalje
retko odlučuju za započinjanje ambulantnog tretmana
plućne tromboembolije, ispitivanja ukazuju da je ovakav
način lečenja bezbedan, da smanjuje rizik od bolničkih
infekcija, troškove i omogućava bolji kvalitet života.
Ključne reči: plućna embolija, Hestia kriterijumi,
ambulantno lečenje, antikoagulansi
REVIJALNI RADOVI
Uvod
Plućna tromboembolija (Pulmonary Thromboembolism,
PTE) i tromboza dubokih vena (Deep vein thrombosis, DVT)
čine venski tromboembolizam (Venous thromboembolism,
VTE). U 70% slučajeva PTE je udružena sa dubokom ven-
skom trombozom. PTE je treća kardiovaskularna bolest po
učestalosti, nakon infarkta miokarda i moždanog udara1.
Prema različitim epidemiološkim studijama, godišnja stopa
incidence za PTE kreće se od 39 do 115 na 100.000 stanov-
nika, a podaci ukazuju i da postoji trend opadanja smrtnosti
od akutne PTE2. Nelečena akutna PTE ima stopu mortaliteta
do 30%, dok je stopa mortaliteta lečene PTE, nakon tri me-
seca, od 8-17%. Mortalitet hemodinamski stabilnih normo-
tenzivnih pacijenata je 2%. Plućna hipertenzija, kao kompli-
kacija mesec dana nakon akutne PTE, zaostaje kod čak 25%
bolesnika1.
Faktori rizika za VTE dele se na faktore velikog, srednjeg
i malog rizika. Faktori velikog rizika su prelomi kuka, kole-
na, velike hirurške intervencije i trauma; faktori srednjeg
rizika su centralni venski kateter, hemioterapija, maligniteti,
kardiorespiratorna slabost, trudnoća, porođaj, trombofilija,
hormonska terapija, in vitro fertilizacija; dok su faktori ma-
log rizika nepokretnost, gojaznost, DM (Diabetes Mellitus),
starije životno doba, venski varikoziteti.
Osnovni elementi dijagnostike su klinička prezentacija
uz anamnestičke podatke, procena pre-test verovatnoće za
PTE (revidirani Ženeva skor za utvrđivanje kliničke verovat-
noće da je u pitanju PTE), vrednost D-dimera i vizualizacione
dijagnostičke metode. PTE je stratifikovana prema riziku od
smrtnosti na osnovu indeksa težine PTE (Pulmonary Emboli-
sm Severity Index, PESI) i modifikovanog i pojednostavljenog
PESI (simplified Pulmonary Embolism Severity Index, sPESI)
skora na mali, srednji i visok rizik. Kandidati za ambulantni
tretman su bolesnici sa malim rizikom od smrtnosti od PTE,
prema PESI skoru. Očekivani procenat pacijenata sa potvr-
đenom PTE je oko 10% u kategoriji niske verovatnoće, 30%
u kategoriji intermedijarne verovatnoće i 65% u kategoriji
visoke verovatnoće3. Negativna prediktivna vrednost D-di-
mera je visoka, te normalne vrednosti D-dimera čine plućnu
tromboemboliju malo verovatnom, dok je pozitivna predi-
ktivna vrednost povišenog D-dimera niska, tako da njegovo
određivanje nije korisno za potvrdu dijagnoze PTE1. Plućna
Galenika Medical Journal, 2023; 2(8):61-66. 61
angiografija kompjuterizovanom tomografijom (Multi-dete-
ctor computed tomography pulmonary angiography, MDCT-
PA) je metod izbora za potvrdu plućne tromboembolije. Ona
omogućava vizualizaciju arterija pluća do subsegmentnog
nivoa. Ventilaciono-perfuziona (V/Q) scintigrafija može da
se primeni kod ambulantnih pacijenata sa niskom klinič-
kom verovatnoćom za PE i normalnim rentgenom grudnog
koša. Primenjiva je kod trudnica i pacijenata sa bubrežnom
slabošću. Ultrazvuk srca nije obavezan deo dijagnostičkog
postupka kod hemodinamski stabilnih pacijenata sa suspe-
ktnom PTE, dok je neophodan kod suspektne visoko rizične
PTE, kada se odsustvo znakova disfunkcije desne komore
praktično isključuje3. CDF (Color Doppler Scan, CDF) vena
ekstremiteta u 30-50% slučajeva pokazuje duboku vensku
trombozu kod pacijenata sa PTE.
Kod pacijenata sa visokom ili intermedijarnom kliničkom
verovatnoćom za PTE, antikoagulantna terapija uobičajeno
podrazumeva primenu niskomolekularnog heparina (Low
Molecular Weight Heparin, LMWH), supkutano, ili fondapa-
rinuksa, kao i nefrakcionisanog heparina, intravenski. Isti
antikoagulantni efekat sa najvišim nivoom dokaza postiže
se i primenom direktnih antikoagulantnih lekova (Direct
oral anticoagulants, DOAC)3. DOAC (apiksaban, dabigatran,
rivaroksaban) imaju prednost nad oralnim antagonistima
vitamina K (Vitamin K Antagonists, VKA), ali nisu preporučeni
kod pacijenata sa teškom bubrežnom slabošću, u trudnoći
i periodu dojenja, kao ni kod antifosfolipidnog sindroma3.
Iako sama PTE nije primarno plućna, već sistemska i kar-
diovaskularna bolest, godinama unazad to je jedna od naj-
češćih indikacija za hospitalizaciju na pulmološkim odeljenji-
ma. U evropskim zemljama prosečna dužina hospitalizacije
pacijenata primljenih zbog PTE je 7-14 dana4. U Sjedinjenim
Američkim Državama prosečno trajanje hospitalizacije zbog
PTE je 7 dana, a procenjuje se da je 25% ovih pacijenata
moglo biti lečeno kod kuće5. U literaturi, pod ambulantnim
lečenjem PTE podrazumevaju se ambulantni tretman, rani
otpust i kućno lečenje, mada nedostaje preciznija definicija.
Pod kućnim lečenjem podrazumeva se i otpuštanje nakon
24 h opservacije u odnosu na inicijalnu prezentaciju pacije-
nta, a rani otpust podrazumeva otpust nakon hospitalizaci-
je od 72 h6. Postoje mnoge prednosti vanbolničkog lečenja
pacijenata sa plućnom tromboembolijom. Ipak, odluka za
ambulantno uvođenje i potpuno ambulantno lečenje PTE u
praksi je retka, delikatna i prepušta se samo iskusnim spe-
cijalistima.
Preporuke za ambulantno lečenje PTE
Prema preporukama Britanskog torakalnog udruženja
(British Thoracic Society, BTS), na osnovu indeksa težine pluć-
ne tromboembolije, kandidati za ambulantno lečenje PTE
su bolesnici sa malim rizikom od 30-odnevne smrtnosti,
odnosno, klase PESI I i PESI II i oni sa simplifikovanim sPE-
SI skorom 07, 8. Pacijenata sa malim rizikom smrtnosti ima
oko 20%. Najveći broj bodova nose godine života, prisustvo
62 DOI: 10.5937/Galmed2308060L
karcinoma i hipotenzija, dok mentalni status, koji kao kate-
gorija može biti veoma delikatan ukoliko se procenjuje ge-
neralno, a ne kao deo kliničke slike PTE, sam nosi čak 60 bo-
dova (tabela 1). Prema pomenutom simplifikovanom skoru
sPESI, pacijenti sa kriterijumima koji nose bar 1 bod (stariji
od 80 godina, muški pol, sistolni pritisak ispod 100 mmHg,
SF preko 110/min, SpO2 ispod 90% ili hronična kardiorespi-
ratorna bolest) ne mogu da se leče ambulantno. Negativna
prediktivna vrednost sPESI skora za 30-odnevni mortalitet
je 100%.
Prema Hestia kriterijumima (tabela 2), koji se pored PESI
skora koriste u proceni za ambulantni tretman, ukoliko su
odgovori na svih 11 pitanja „NE”, pacijent se može lečiti
ambulantno. Ukoliko je bar jedan odgovor „DA”, tretman se
započinje u bolnici9. Negativna prediktivna vrednost Hestia
skora za 30-odnevni mortalitet je 99%. Hestia kriterijumi
uključuju trudnice i socijalni status, kao i insuficijenciju je-
tre i bubrega, dok PESI kriterijumi uključuju malignitete, pa
se u praksi mogu koristiti oba sistema bodovanja, jer pokri-
vaju različite oblasti. Socijalni status odnosi se na moguć-
nost adekvatne adherence za terapiju, mogućnost redovnih
kontrola i podobnost pacijenata za kućno lečenje. Zondag
je uporedio Hestia i sPESI kriterijume i predložio da se paci-
jenti koji su klasifikovani kao visokorizični prema sPESI sko-
ru, zbog starosti ili osnovne maligne ili kardiopulmonalne
bolesti, ukoliko se na njih primene i budu negativni Hestia
kriterijumi, mogu bezbedno lečiti ambulantno9, 10. Ukoliko
su PESI skor i Hestia kriterijumi dijametralno suprotni, od-
luka se donosi na osnovu dominantnih komorbiditeta. Uko-
liko bolesnici imaju 0 bodova i prema sPESI i prema Hestia
skoru, moguće je potpuno bezbedno započeti ambulantnu
antikoagulantnu terapiju, sa ili bez procene funkcije desne
komore (tabele 1 i 2)8. Oba skora imaju visoku osetljivost za
adekvatan odabir pacijenata sa PTE niskog rizika za rani ot-
pust i/ili kućno lečenje11.
Korišćenje PESI skora, prema istraživanju Aujeskog i sa-
radnika, potvrdilo je da ambulantni tretman nije inferioran
u smislu recidiva PTE, smrtnog ishoda, kao i velikih krvare-
nja 14 dana od početka lečenja12. Prema Kabrhelu i sarad-
nicima, odsustvo parametara kao što su sistolni pritisak <
90 mmHg, Sat O2 < 90%, koronarna bolest, srčana slabost,
stanje duboke venske tromboze i aktivni malignitet, daje
prednost ambulantnom lečenju pacijenata sa PTE13. Am-
bulantno se može lečiti velika grupa pacijenata sa PTE kao
posledicom hronične srčane insuficijencije i atrijalne fibrila-
cije, bez de novo tegoba, kao i bolesnici sa malignitetom, na
hemio, radio ili biološkoj terapiji kod kojih je PTE slučajno
verifikovana, najčešće u sklopu praćenja efekata terapije.
Ambulantno se mogu lečiti i svi pacijenti kod kojih je mogu-
će pravilno, uz kontrolu vrednosti anti Xa i krvne slike, ordi-
nirati niskomolekularni heparin. Pacijenti koji su kandidati
za ambulantni tretman mogu se kratkotrajno opservirati u
hitnim službama 24 h, a potom pustiti na kućno lečenje6, 8.
Za konačnu odluku uzima se: opšte stanje pacijenta, nalaz
MSCT pulmoangiografije i UZ srca, laboratorijski markeri
- troponin i NTpro BNP (čiji porast kod prethodno zdravih
Tabela 1. Originalni i pojednostavljeni indeks težine plućne tromboembolije (PESI i sPESI). SpO2 - saturacija hemoglobina kiseonikom
Kriterijum PESI sPESI

Životno doba Godine > 80 godina 1

Muški pol 10 1

Karcinom 30

Srčana slabost 10
Hronična kardiorespiratorna bolest 1
Hronična plućna bolest 10

Srčana frekvenca ≥ 110/min 20 1

Sistolni krvni pritisak < 100 mmHg 30 1

Respiracije ≥ 30/min 20

Temperatura < 36 C° 20

Izmenjen mentalni status 30

SpO2 < 90% 20 1

I ≤ 65 veoma nizak rizik (0-1,6%)

II ≤ 66-85 nizak rizik (1,7-3,5%)
0 nizak rizik (0-2,1%)
Rizik od ranog mortaliteta III ≤ 86-105 umeren rizik (3,2-7,1%)
≥ visok rizik (8,5-13,2%)
IV ≤ 106-125 nizak rizik (4-11,4%)
V ≥ 125 veoma visok rizik (10-24,5%)

Tabela 2. Hestia kriterijumi

Kriterijum DA / NE Lečenje

Da li je bolesnik hemodinamiski nestabilan? da / ne

Da li su tromboliza ili embolektomija neophodne? da / ne

Da li postoji aktivno krvarenje ili visok rizik od krvarenja? da / ne

Da li je potrebna oksigenoterapija duže od 24 h da bi se održala SpO2 > 90%? da / ne

Da li je PE dijagnostikovana tokom primene antikoagulantne terapije? da / ne

0 DA - vanbolničko
Da li postoji jak bol koji zahteva intravensku primenu analgetika > 24 h? da / ne
≥ 1 DA - bolničko
Da li postoje medicinski ili socijalni razlozi za lečenje u bolnici > 24 h? da / ne

Da li bolesnik ima klirens kreatinina < 30 mL/min? da / ne

Da li bolesnik ima tešku jetrenu disfunkciju? da / ne

Da li je bolesnica trudna? da / ne

Da li je bolesnik imao HIT? da / ne

I ≤ 65 veoma nizak rizik (0-1,6%)

II ≤ 66-85 nizak rizik (1,7-3,5%)
0 nizak rizik (0-2,1%)
Rizik od ranog mortaliteta III ≤ 86-105 umeren rizik (3,2-7,1%)
≥ visok rizik (8,5-13,2%)
IV ≤ 106-125 nizak rizik (4-11,4%)
V ≥ 125 veoma visok rizik (10-24,5%)

pacijenata ili stabilnih hroničara indikuje bolničko lečenje),
procena rizika od krvarenja ili recidiva, ali nažalost i finansij-
ska mogućnost pacijenta. D-dimer nije najvažniji marker na
osnovu kog se donosi odluka o načinu lečenja, dok negativ-
ne vrednosti NT proBNP i troponina dozvoljavaju bezbedan
ambulantni tretman14. Troponin se, prema istraživanjima,
smatra jednim od ključnih biomarkera kada je odluka o pri-
jemu u bolnicu u pitanju.
Rizici i kontraindikacije za
ambulantno lečenje PTE
Pri donošenju odluke o ambulantnom započinjanju le-
čenja najvažniji je adekvatan odabir pacijenata. Jedan od
najvećih problema ambulantne antikoagulacije je rizik od
krvarenja. Ambulantni tretman se ne može sprovoditi ako
kod pacijenta postoji bilo kakav oblik aktivnog ili skorijeg
krvarenja, npr. krvareći ulkus ili drugi oblici gastrointesti-
nalne hemoragije, hemoragijski CVI (Cerebrovascular Insult,
CVI), subarahnoidalno krvarenje, veće povrede, nedavne
operacije, maligna hipertenzija, vrednost trombocita8 ispod
75.
Za procenu rizika od krvarenja koristi se HASBLED skor
koji predstavlja akronim sastavljen od početnih slova naj-
važnijih faktora rizika: H - hipertenzija; A - abnormalna funk-
cija bubrega ili jetre; S - moždani udar (stroke); B - krvarenje
(bleeding); L - labilan INR; E - osobe starije od 65 godina (el-
derly); D - upotreba lekova (drugs) koji predisponiraju krva-
renje ili upotreba alkohola. Prema ovom skoru, broj bodova
≥ 3 označava visok rizik od major krvarenja15. Pacijenti sa
visokim rizikom od krvarenja trebalo bi da budu redovno
pregledani i kontrolisani nakon započinjanja antikoagulan-
tne terapije. Zašto o tome treba voditi računa, govori i pri-
mer da starost preko 65 godina, korišćenje antiagregacione

REVIJALNI RADOVI Galenika Medical Journal, 2023; 2(8):61-66. 63

terapije i sistolni pritisak preko 160 mmHg prema ovom
skoru, već nose tri boda, a u toj kategoriji je značajan broj
pacijenata. Za ambulantni tretman nisu pogodni pacijenti
sa bilo kakvom simptomatologijom koja može biti vezana
za kompleksniju PTE, kao što su: nesvestice, vrtoglavice,
izražena nelagodnost u grudima, kao ni pacijenti sa jakim
bolovima. Kontraindikacije su i insuficijencija desnog srca,
hronična bubrežna insuficijencija i insuficijencija jetre. Oni
pacijenti koji su na oralnoj antikoagulantnoj terapiji i razvi-
ju PTE kada je vrednost INR (International Normalized Ratio,
INR) > 2 moraju biti hospitalizovani8. Hospitalno uvođenje
antikoagulantne terapije je neophodno i kod trudnica, kao i
kod svih drugih koji su neadekvatno adherentni za terapiju.
Lečenje PTE
Lečenje PTE se može započeti na više načina. Mogu se
primeniti kombinacije niskomolekularnog heparina i dabi-
gatrana ili LMWH i edoksabana, a u našoj zemlji je još uvek
česta kombinacija LMWH i oralnih antagonista vitamina K8,
14, 16
. Drugi način je primena direktnih oralnih antikoagulana-
sa, apiksabana ili rivaroksabana, od samog početka14, 16. Svi
pomenuti modaliteti lečenja imaju nivo dokaza A. Primena
novih, direktnih antikoagulanasa (DOAC) smatra se zlatnim
standardnom u lečenju PTE, pre svega zbog mogućnosti
peroralne primene jedne doze leka, bez neophodnog labo-
ratorijskog praćenja17. Za sada ne postoje jasni dokazi koji
bi favorizovali određeni DOAC u odnosu na PESI ili Hestia
kriterijume. DOAC nisu indikovani u trudnoći i dojenju, kao
i kod antifosfolipidnog sindroma2. Prema preporukama, po-
djednako adekvatna je i alternativa oralnim antagonistima
vitamina K, inicijalno uz niskomolekularni heparin, najma-
nje pet dana istovremeno, dok se ne postigne INR između
2-318. Trajanje antikoagulantne terapije koja je uvedena am-
bulantno može da bude različito. Svi pacijenti sa PTE moraju
da primaju antikoagulantnu terapiju najmanje tri meseca.
Međutim, u mnogim situacijama se ne može na samom po-
četku odrediti dužina njenog trajanja19. Pacijenti sa velikim,
ali reverzibilnim faktorom rizika leče se tri meseca, dok se
rekurentna PTE, koja nije povezana sa reverzibilnim fakto-
rom rizika leči uvek duže od tri meseca, nekada i doživot-
no17.
Iako postoje jasne preporuke i kriterijumi na osnovu
kojih se može slobodno započeti ambulantno lečenje, to je
i dalje izazov u praktičnom sprovođenju. Kako su pacijenti
sa PTE veoma različiti i kompleksni, odluku o započinjanju
ambulantne terapije mora doneti iskusni specijalista. Spe-
cijalista koji je terapiju započeo, mora biti stalno dostupan
pacijentu, jer u našoj zemlji ima malo ambulanti za preven-
ciju tromboza i praćenje pacijenta najčešće obavlja izabrani
lekar u domu zdravlja.
64 DOI: 10.5937/Galmed2308060L
Naša iskustva
Nakon 16 meseci rada urgentne pulmološke ambulante
u Urgentnom centru, Univerzitetskog kliničkog centra Srbi-
je (UC UKCS), najčešća patologija sa kojom su se suočavali
pulmolozi, bila je plućna tromboembolija. Plućna trombo-
embolija često je zadesan nalaz, te se pulmolog poziva u
konsultaciju, a da sam nije tražio dijagnostiku u pravcu iste.
Nekada je verifikovani tromb u plućnim krvnim sudovima
praktično jedini patološki nalaz nakon opsežne dijagnostike
kod starijih osoba, pacijenata sa brojnim komorbiditetima
i terminalnim stanjima, kod traumatizovanih, teško pokret-
nih pacijenata sa neplućnim karcinomima, pa se zaključak
ostavlja pulmologu.
Kada se u UC odlučujemo za ambulantno započinjanje
lečenja PTE, strogo se pridržavamo preporuka Britanskog
torakalnog društva za ambulantno lečenje PTE iz 2018. godi-
ne7. Prednost urgentne pulmološke ambulante u UC je, što
je lekarima dostupna sva potrebna dijagnostika: biomarke-
ri- troponin, NT proBNP, D-dimer, krvna slika, INR, radiogra-
fija grudnog koša, MSCT pulmoangiografija, UZ srca, kon-
sultacije drugih specijalista, te se odluka o ambulantnom
započinjanju antikoagulantne terapije lakše donosi. Svako
ovakvo započinjanje lečenja zahteva detaljan razgovor sa
pacijentom i familijom u vezi sa prednostima i rizicima te-
rapije. Ukoliko se akcidentalno verifikuje subsegmentna
tromboembolija jedne grane, u odsustvu duboke venske
tromboze i jakih faktora rizika, ista se ne mora lečiti. Prema
našem iskustvu, najvažniju ulogu u proceni mogućnosti za
ambulantno lečenje imaju komorbiditeti, rizik od krvarenja
i socijalni momenat.
Po pitanju izbora i doziranja medikamenata za lečenje
PTE, u našoj službi najčešće se ambulantno savetuju apik-
saban i rivaroksaban, a odluka uglavnom zavisi od starosti
pacijenata, bubrežne funkcije i rizika od krvarenja. Prema
protokolu koga se pridržavamo, početna doza apiksabana
je 2 x 10 mg/dan prvih 7 dana, nakon 7 dana doza se sma-
njuje na 2 x 5 mg/dan, a ukoliko se lečenje nastavlja i posle
6 meseci, doza se dalje smanjuje na 2 x 2,5 mg/dan. Doza
rivaroksabana sa kojom se počinje ambulantno lečenje je
2 x 15 mg prve tri nedelje, a potom 20 mg/dan, a ukoliko
je potrebno nastaviti lečenje i nakon 6 meseci nastavlja se
dozom od 10 mg/dan. Pacijenti kod kojih je terapija zapo-
četa ambulantno, redovno i pažljivo se prate i niko do sada
nije hospitalizovan zbog loše komplijanse ili hemoragijskog
sindroma.
Zaključak
S obzirom na značajan broj predisponirajućih faktora, starenje populacije, porast broja
traumatizovanih i bolesnika sa malignitetom, nalaz plućnog tromboembolizma je sve češći. Mnogi
pacijenti su asimptomatski, neke tromboembolije su subsegmentne, jedan broj pacijenata ne
prihvata bolničko lečenje, zbog čega postoji neophodnost ambulantnog zbrinjavanja PTE. Prema
preporukama Britanskog torakalnog udruženja, na osnovu indeksa težine plućne tromboembolije,
kandidati za ambulantno lečenje su bolesnici sa malim rizikom od 30-odnevne smrtnosti, klase
PESI I i PESI II, bolesnici sa simplifikovanim skorom 0, kao i oni sa Hestia skorom 0. Oba skora su
jednostavna, pogodna za ambulantnu primenu i imaju visoku osetljivost za pravilan odabir pacijenata
sa PTE niskog rizika. Ambulantno lečenje podrazumeva i ambulantno uvođenje antikoagulantne
terapije i lečenje nakon kratke hospitalizacije, odnosno opservacije od 24 h. U proceni mogućnosti
vanbolničkog lečenja najvažniju ulogu imaju kliničko stanje bolesnika, rizik od krvarenja, pridružene
bolesti i komplijantnost za terapiju. Lečenje podrazumeva primenu više modaliteta, koji uključuju
i niskomolekularni heparin, dok se samostalno lečenje direktnim oralnim antikoagulansima, pre
svega apiksabanom ili rivaroksabanom, sprovodi sve češće. Ambulantni antikoagulantni tretman
je bezbedan, smanjuje mogućnost bolničkih infekcija i troškove hospitalizacije i omogućava bolji
kvalitet života, te ga treba razmotriti kod svih pacijenata koji ispunjavaju uslove. Ovakav način lečenja
zahteva posvećenost lekara i edukaciju pacijenata, kao i dogovor u vezi sa mogućnosti vanredne
kontrole, ukoliko je neophodno. U našoj zemlji i dalje se mali broj lekara odlučuje da na ovaj
način započne i vodi antikoagulantnu terapiju. Ipak, očekuje se da će rezultati aktuelnih i budućih
istraživanja učvrstiti razloge i preporuke za kućno lečenje i osloboditi lekare za širu primenu ove
komforne i isplative terapijske opcije.

Abstract
Due to more common diagnoses of pulmonary thromboembolism in clinical practice, it is necessary to initiate outpatient
treatments. Such a decision is based on the clinical picture, risk factors, risk of bleeding, comorbidities, laboratory
findings, adherence, and social factors. Patients meeting PESI I, PESI II, and sPESI criteria of low mortality risk, as well
as patients with a Hestia score 0, may start receiving outpatient treatment. Even though low-molecular-weight heparin
(LMWH) and direct oral anticoagulants can be administered together, as well as LMWH and oral vitamin K antagonists, the
gold standard is to use only new, direct oral anticoagulants. Outpatient treatment lasts at least 3 months, depending on
several factors, first of all on risk factors reversibility. Doctors still rarely decide to start outpatient treatment of pulmonary
thromboembolism, even though studies show that this kind of treatment is safe, that it reduces the number of unnecessary
hospital admissions and risk of infections, cuts the costs, and enables a better quality of life.

Keywords: pulmonary thromboembolism, Hestia score, outpatient treatment, anticoagulation therapy

pulmonary embolism of the European Society of Cardiology (ESC). 2019

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Konflikt interesa: Nema
Primljeno: 26. 09. 2023.
Prihvaćeno: 31. 10. 2023.
Onlajn: 01. 12. 2023.
 OUTPATIENT TREATMENT OF PULMONARY
THROMBOEMBOLISM - RECOMMENDATIONS
AND OUR EXPERIENCES
Marija Laban1
Jelena Janković1, 2
Jasmina Opačić1
Marina Đikić3
1
Pulmonology Clinic, University Clinical Center of Serbia, Belgrade, Serbia
2
Faculty of Medicine, University of Belgrade, Serbia
3
Emergency Center, University Clinical Center of Serbia, Belgrade, Serbia
Corresponding author:
Dr Jasmina Opačić
Klinika za pulmologiju, Univerzitetski klinički centar Srbije, Dr
Koste Todorovica 26, Beograd, Srbija
jasmina89.opacic@gmail.com
Abstract
Due to more common diagnoses of pulmonary
thromboembolism in clinical practice, it is necessary to
initiate outpatient treatments. Such a decision is based
on the clinical picture, risk factors, risk of bleeding,
comorbidities, laboratory findings, adherence, and social
factors. Patients meeting PESI I, PESI II, and sPESI criteria
of low mortality risk, as well as patients with a Hestia score
0, may start receiving outpatient treatment. Even though
low-molecular-weight heparin (LMWH) and direct oral
anticoagulants can be administered together, as well as
LMWH and oral vitamin K antagonists, the gold standard
is to use only new, direct oral anticoagulants. Outpatient
treatment lasts at least 3 months, depending on several
factors, first of all on risk factors reversibility. Doctors still
rarely decide to start outpatient treatment of pulmonary
thromboembolism, even though studies show that this
kind of treatment is safe, that it reduces the number of
unnecessary hospital admissions and risk of infections,
cuts the costs, and enables a better quality of life.
Keywords: pulmonary thromboembolism, Hestia score,
outpatient treatment, anticoagulation therapy
Introduction
Pulmonary Thromboembolism (PTE) and Deep Vein
Thrombosis (DVT) constitute Venous Thromboembolism
REVIEW PAPER
(VTE). In 70% of cases, PTE is associated with deep vein
thrombosis. PTE is the third most common cardiovascular
disease after myocardial infarction and stroke1. According
to various epidemiological studies, the annual incidence
rate for PTE ranges from 39 to 115 per 100,000 populati-
on, and data also indicate a trend of decreasing mortality
from acute PTE2. Untreated acute PTE has a mortality rate
of up to 30%, while the mortality rate for treated PTE after
three months ranges from 8-17%. The mortality rate for he-
modynamically stable normotensive patients is 2%. Pulmo-
nary hypertension, as a complication one month after acute
PTE, persists in as many as 25% of patients1.
Risk factors for VTE are categorized into high, modera-
te, and low-risk factors. High-risk factors include hip and
knee fractures, major surgeries, and trauma. Moderate-ri-
sk factors include central venous catheters, chemotherapy,
malignancies, cardiorespiratory weakness, pregnancy, chil-
dbirth, thrombophilia, hormone therapy, and in vitro fertili-
zation. Low-risk factors consist of immobility, obesity, dia-
betes mellitus (DM), advanced age, and venous varicosities.
The basic elements of diagnosis include the clinical pre-
sentation along with historical data, assessment of pre-test
probability for PTE (revised Geneva score for determining
the clinical likelihood of PTE), D-dimer levels, and visual dia-
gnostic methods. PTE is stratified based on the risk of mor-
tality using the Pulmonary Embolism Severity Index (PESI)
and the modified and simplified PESI (simplified Pulmonary
Embolism Severity Index, sPESI) scores into low, interme-
diate, and high-risk categories. Candidates for outpatient
treatment are patients with a low risk of PTE-related mor-
tality according to the PESI score. The expected percenta-
ge of patients with confirmed PTE is around 10% in the low
probability category, 30% in the intermediate probability
category, and 65% in the high probability category3. The
negative predictive value of D-dimer is high, meaning that
normal D-dimer levels make pulmonary thromboembolism
unlikely. On the other hand, the positive predictive value of
elevated D-dimer is low, making its determination not use-
ful for confirming the diagnosis of PTE1.
Multi-detector computed tomography pulmonary angi-
ography (MDCTPA) is the method of choice for confirming
pulmonary thromboembolism. It allows visualization of the
pulmonary arteries down to the subsegmental level. Ventila-
tion-perfusion (V/Q) scintigraphy can be used in outpatient
patients with low clinical probability for PE and a normal
chest X-ray. It is applicable in pregnant women and patients
with renal insufficiency. Echocardiography is not a man-
datory part of the diagnostic process in hemodynamically
Galenika Medical Journal, 2023; 2(8):53-58. 53
stable patients with suspected PTE, but it is essential in ca-
ses of highly suspected high-risk PTE, where the absence
of signs of right ventricular dysfunction practically rules out
PTE3. Color Doppler Scan (CDF) of the extremity veins shows
deep vein thrombosis in 30-50% of cases in patients with
PTE.
In patients with high or intermediate clinical probability
for PTE, anticoagulant therapy typically involves the use of
low molecular weight heparin (LMWH) administered sub-
cutaneously or fondaparinux, as well as unfractionated he-
parin administered intravenously. The same anticoagulant
effect with the highest level of evidence is achieved with the
use of direct oral anticoagulants (DOACs)3. DOACs (including
apixaban, dabigatran, and rivaroxaban) have an advantage
over vitamin K antagonists (VKAs), but they are not recom-
mended in patients with severe renal insufficiency, during
pregnancy and breastfeeding, or in cases of antiphospho-
lipid syndrome3.
Although PTE itself is not primarily a pulmonary but rat-
her a systemic and cardiovascular disease, it has been one
of the most common reasons for hospitalization in pulmo-
nary departments for years. In European countries, the ave-
rage length of hospitalization for patients admitted due to
PTE is 7-14 days4. In the United States, the average duration
of hospitalization for PTE is 7 days, and it is estimated that
25% of these patients could have been treated at home5. In
the literature, outpatient treatment of PTE includes ambu-
latory care, early discharge, and home treatment, although
a more precise definition is lacking. Home treatment also
involves discharge after 24 hours of observation relative to
the patient's initial presentation, and early discharge refers
to discharge after 72 hours of hospitalization6. There are
many advantages to outpatient treatment for patients with
pulmonary thromboembolism. However, the decision to in-
troduce outpatient care and fully treat PTE on an outpatient
basis in practice is rare, delicate, and is left to experienced
specialists.
Recommendations for outpatient
treatment of PTE
According to the recommendations of the British Thora-
cic Society (BTS), based on the Pulmonary Embolism Severity
Index (PESI), candidates for outpatient treatment of PTE are
patients with a low risk of 30-day mortality, specifically tho-
se in PESI classes I and II, and those with a simplified sPESI
score of 07, 8. Patients with a low risk of mortality constitute
about 20%. The highest number of points is attributed to
age, the presence of cancer, and hypotension, while mental
status, which can be a delicate category when assessed glo-
bally rather than as part of the clinical picture of PTE, carries
up to 60 points (Table 1). According to the mentioned simpli-
fied score sPESI, patients with criteria earning at least 1 po-
int (age over 80, male gender, systolic blood pressure below
100 mmHg, heart rate over 110/min, SpO2 below 90%, or
54 DOI: 10.5937/Galmed2308060L
chronic cardiorespiratory disease) cannot be treated on an
outpatient basis. The negative predictive value of the sPESI
score for 30-day mortality is 100%.
According to the Hestia criteria (Table 2), which are used
in conjunction with the PESI score for outpatient treatment
assessment, if the answer to all 11 questions is "NO," the
patient can be treated on an outpatient basis. If at least one
answer is "YES," treatment is initiated in the hospital. The
negative predictive value of the Hestia score for 30-day mor-
tality is 99%. Hestia criteria include pregnant women and
social status, as well as liver and kidney insufficiency, while
PESI criteria include malignancies. In practice, both scoring
systems can be used because they cover different areas. So-
cial status refers to the ability to adhere to therapy adequa-
tely, the possibility of regular check-ups, and the suitability
of patients for home treatment. Zondag compared Hestia
and sPESI criteria and suggested that patients classified as
high-risk according to the sPESI score, due to age or under-
lying malignant or cardiopulmonary disease, could be safely
treated on an outpatient basis if they also meet negative
Hestia criteria9, 10. If the PESI score and Hestia criteria are
diametrically opposite, the decision is made based on do-
minant comorbidities. If patients have 0 points according to
both the sPESI and Hestia scores, it is entirely safe to initiate
outpatient anticoagulant therapy, with or without an asse-
ssment of right ventricular function (Tables 1 and 2)8. Both
scores have high sensitivity for the appropriate selection of
patients with low-risk PTE for early discharge and/or home
treatment11.
The use of the PESI score, according to research by Auje-
sky and colleagues, confirmed that outpatient treatment is
not inferior in terms of recurrent PTE, mortality, and major
bleeding within 14 days from the start of treatment12. Accor-
ding to Kabrhel and colleagues, the absence of parameters
such as Sat O2 < 90 mmHg, oxygen saturation < 90%, co-
ronary artery disease, heart failure, deep vein thrombosis,
and active malignancy favors outpatient treatment of pa-
tients with PTE13. Outpatient treatment can be considered
for a large group of patients with PTE as a consequence of
chronic heart failure and atrial fibrillation without de novo
symptoms. Additionally, patients with malignancy undergo-
ing chemotherapy, radiotherapy, or biological therapy, whe-
re PTE is incidentally verified, often as part of monitoring
therapy effects, can be treated on an outpatient basis. All
patients for whom it is possible to properly administer low
molecular weight heparin with monitoring of anti-Xa levels
and blood counts can also be treated on an outpatient ba-
sis. Patients eligible for outpatient treatment can be briefly
observed in emergency departments for 24 hours and then
released for home treatment6, 8. The final decision is based
on several factors, including the patient's overall condition,
findings from MSCT pulmonary angiography and echocardi-
ography, laboratory markers such as troponin and NT-proB-
NP (whose elevation in previously healthy patients or stable
chronic patients indicate hospital treatment), assessment of
the risk of bleeding or recurrence, and unfortunately, the
Table 1. Original and simplified pulmonary thromboembolism severity index (PESI i sPESI). SpO2 - hemoglobin oxygen saturation
Criterion PESI sPESI

Life span Age > 80 years 1

Male gender 10 1

Carcinoma 30

Heart failure 10
Chronic cardiorespiratory disease
Chronic pulmonary disease 10

Heart rate ≥ 110/min 20 1

Systolic blood pressure < 100 mmHg 30 1

Respiration ≥ 30/min 20

Temperature < 36 C° 20

Altered mental status 30

SpO2 < 90% 20 1

I ≤ 65 very low risk (0-1.6%)

II ≤ 66-85 low risk (1.7-3.5%)
0 low risk (0-2.1%)
Early mortality risk III ≤ 86-105 moderate risk (3.2-7.1%)
≥ high risk (8.5-13.2%)
IV ≤ 106-125 low risk (4-11.4%)
V ≥ 125 very high risk (10-24.5%)

Table 2. Hestia criteria

Criterion YES/NO Treatment

Is the patient hemodynamically unstable? yes/no

Is thrombolysis or embolectomy necessary? yes/no

Is there active bleeding or high bleeding risk? yes/no

Is oxygen therapy required for more than 24 hours to maintain SpO2 > 90%? yes/no

Was PE diagnosed during anticoagulant therapy? yes/no

0 YES - out-of-hospital
Is there severe pain requiring intravenous analgesics > 24 h? yes/no
≥ 1 YES - hospital
Are there medical or social reasons for hospital treatment > 24 h? yes/no

Does the patient have creatinine clearance < 30 mL/min? yes/no

Does the patient have severe liver dysfunction? yes/no

Is the patient pregnant? yes/no

Did the patient have HIT? yes/no

I ≤ 65 very low risk (0-1.6%)

II ≤ 66-85 low risk (1.7-3.5%)
0 low risk (0-2.1%)
Early mortality risk III ≤ 86-105 modreate risk (3.2-7.1%)
≥ high risk (8.5-13.2%)
IV ≤ 106-125 low risk (4-11.4%)
V ≥ 125 very high risk (10-24.5%)

patient's financial capability. D-dimer is not the most criti-
cal marker for deciding on the treatment approach, while
negative values of NT-proBNP and troponin allow for safe
outpatient treatment14. According to research, troponin is
considered one of the key biomarkers when deciding on
hospital admission.
Risks and contraindications for
outpatient treatment of PTE
When deciding on the initiation of outpatient treatment,
the most crucial factor is the proper selection of patients.
One of the major challenges in outpatient anticoagulation
is the risk of bleeding. Outpatient treatment is not feasible if
the patient has any form of active or recent bleeding, such as
a bleeding ulcer or other forms of gastrointestinal hemorr-
hage, hemorrhagic stroke (Cerebrovascular Insult, CVI), su-
barachnoid hemorrhage, major injuries, recent surgeri-
es, malignant hypertension, or a platelet count8 below 75.
To assess the risk of bleeding, the HAS-BLED score is
used, which is an acronym composed of the initial letters
of the most important risk factors: H - hypertension; A - ab-
normal kidney or liver function; S - stroke; B - bleeding; L
- labile INR (International Normalized Ratio); E - elderly (age
over 65); D - drugs predisposing to bleeding or alcohol use.
According to this score, a total score of ≥ 3 indicates a high
risk of major bleeding15. Patients with a high risk of blee-
ding should be regularly monitored and supervised after
starting anticoagulant therapy. It is important to consider
these factors because, for example, in the HAS-BLED sco-
re, age over 65, the use of antiplatelet therapy, and systolic
blood pressure over 160 mmHg already contribute three
points, and a significant number of patients fall into this ca-
tegory. Patients with any symptoms potentially related to a
more complex PTE, such as fainting, dizziness, severe chest

REVIEW PAPER Galenika Medical Journal, 2023; 2(8):53-58. 55

discomfort, or those experiencing intense pain, are not su-
itable for outpatient treatment. Contraindications also inc-
lude right heart failure, chronic renal insufficiency, and liver
insufficiency. Patients on oral anticoagulant therapy who
develop PTE when the International Normalized Ratio (INR)
is > 2 must be hospitalized8. Hospital initiation of anticoa-
gulant therapy is necessary for pregnant women and for all
others who are inadequately adherent to therapy.
Treatment of PTE
Treatment of PTE can be initiated in several ways. Com-
binations of low molecular weight heparin (LMWH) and
dabigatran or LMWH and edoxaban can be applied. In our
country, the combination of LMWH and oral vitamin K anta-
gonists is still common8, 14, 16. Another approach is the use
of direct oral anticoagulants (DOACs) such as apixaban or
rivaroxaban right from the start14, 16. All these treatment mo-
dalities have Level A evidence. The use of new DOACs is con-
sidered the gold standard in PTE treatment, primarily due to
the possibility of oral administration without the need for la-
boratory monitoring17. There is currently no clear evidence
favoring a specific DOAC over PESI or Hestia criteria. DOACs
are not recommended in pregnancy and breastfeeding, as
well as in antiphospholipid syndrome2. According to recom-
mendations, an alternative to oral vitamin K antagonists is
equally adequate, initially with LMWH for at least five days
simultaneously until an INR between 2 and 3 is achieved18.
The duration of anticoagulant therapy introduced on an
outpatient basis may vary. All PTE patients must receive
anticoagulant therapy for at least three months. However,
in many situations, the duration of therapy cannot be de-
termined initially19. Patients with a large but reversible risk
factor are treated for three months, while recurrent PTE not
associated with a reversible risk factor is treated for a lon-
ger period, sometimes even a lifetime17.
Although there are clear recommendations and criteria
based on which outpatient treatment can be safely initiated,
it remains a challenge in practical implementation. As pa-
tients with PTE are very diverse and complex, the decision to
start outpatient therapy must be made by an experienced
specialist. The specialist who initiated the therapy must be
constantly available to the patient, as there are few antico-
agulation clinics in our country, and patient monitoring is
often carried out by the primary care physician in the health
center.
Our experiences
After 16 months of working in the emergency pulmono-
logy clinic at the Emergency Center, University Clinical Cen-
ter of Serbia (UC UKCS), the most common pathology that
pulmonologists faced, was pulmonary thromboembolism.
Pulmonary thromboembolism is often a coincidental fin-
ding, and a pulmonologist is called in consultation, without
56 DOI: 10.5937/Galmed2308060L
having asked for diagnostics in the direction of the same.
Sometimes a thrombus was verified in the pulmonary blood
vessels practically the only pathological finding after exten-
sive diagnostics in elderly people, patients with numerous
comorbidities and terminal conditions, in traumatized, diffi-
cult-to-move patients patients with non-lung cancers, so the
conclusion leaves the pulmonologist.
When deciding on outpatient initiation of PTE treatment
in the Urgent Care (UC), we strictly adhere to the recom-
mendations of the British Thoracic Society for outpatient
PTE treatment from 20187. The advantage of the urgent pul-
monary outpatient clinic in UC is that all necessary diagno-
stics are readily available to physicians: biomarkers such as
troponin, NT-proBNP, D-dimer, complete blood count, INR,
chest X-ray, MSCT pulmonary angiography, echocardiograp-
hy, consultations with other specialists, deciding to start
outpatient anticoagulant therapy easier. Each initiation of
treatment of this kind requires a detailed discussion with
the patient and family regarding the benefits and risks of
therapy. If a subsegmental embolism of a branch is acci-
dentally verified without deep vein thrombosis and strong
risk factors, it may not require treatment. According to our
experience, comorbidities, bleeding risk, and social consi-
derations play a crucial role in assessing the feasibility of
outpatient treatment.
Regarding the choice and dosage of medications for the
treatment of PTE in our department, apixaban and rivaroxa-
ban are most commonly recommended for outpatient use.
The decision typically depends on the patient's age, renal
function, and bleeding risk. According to the protocol we
follow, the initial dose of apixaban is 2 x 10 mg/day for the
first 7 days, then the dose is reduced to 2 x 5 mg/day after 7
days. If treatment continues beyond 6 months, the dose is
further reduced to 2 x 2.5 mg/day. The starting dose for out-
patient treatment with rivaroxaban is 2 x 15 mg for the first
three weeks, followed by 20 mg/day, and if treatment needs
to continue after 6 months, it is continued with a dose of
10 mg/day. Patients whose therapy is initiated on an out-
patient basis are regularly and carefully monitored, and so
far, no one has been hospitalized due to poor compliance or
bleeding syndrome.
Conclusion
Given the significant number of predisposing factors, aging populations, and an increase in
traumatized and cancer patients, the diagnosis of pulmonary thromboembolism (PTE) is becoming
more common. Many patients are asymptomatic, some thromboembolisms are subsegmental, and a
several patients do not accept hospital treatment, highlighting the need for outpatient management
of PTE. According to the recommendations of the British Thoracic Society, candidates for outpatient
treatment are patients with a low risk of 30-day mortality, PESI class I and II, patients with a
simplified score of 0, as well as those with a Hestia score of 0. Both scores are simple, suitable for
outpatient use, and have high sensitivity for the correct selection of low-risk PTE patients. Outpatient
treatment also involves initiating anticoagulant therapy on an outpatient basis and treating after
a short hospitalization or observation period of 24 hours. The assessment of outpatient treatment
possibilities is mainly influenced by the patient's clinical condition, bleeding risk, comorbidities, and
compliance with therapy. Treatment involves the use of various modalities, including low-molecular-
weight heparin, while standalone treatment with direct oral anticoagulants, especially apixaban
or rivaroxaban, is becoming more common. Outpatient anticoagulant treatment is safe, reduces
the risk of hospital-acquired infections and hospitalization costs, and improves the quality of life. It
should be considered for all patients who meet the criteria. This approach requires the dedication
of healthcare professionals and patient education, as well as an agreement on the possibility of
emergency control if necessary. In our country, only a small number of doctors currently choose to
initiate and manage anticoagulant therapy in this way. However, it is expected that the results of
current and future research will strengthen the reasons and recommendations for home treatment
and encourage wider adoption of this comfortable and cost-effective therapeutic option.

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58 DOI: 10.5937/Galmed2308060L