Advantages of Anticoagulant Therapy

Anticoagulant therapy remains the mainstay of

medical therapy for deep venous thrombosis (DVT)
because it is noninvasive, it treats most patients
(approximately 90%) with no immediate
demonstrable physical sequelae of DVT, it has a
low risk of complications, and its outcome data
demonstrate an improvement in morbidity and
mortality. Meta-analyses of randomized trials of
unfractionated heparin (UFH) and low-molecular-
weight heparin (LMWH) showed that they were
similar, with risk of recurrent DVT of 4%, a risk of
pulmonary embolism (PE) of 2%, and a risk of
major bleeding of 3%.[1, 2]

Initial Heparin Therapy
Initial anticoagulation therapy traditionally
involves continuous IV heparin until adequate
systemic anticoagulation is achieved. Rapid
anticoagulation is essential within the first 24 hours
of diagnosis, reducing the incidence of recurrent
venous thrombosis during the first 3 months from
25% to 5%.[3, 4]

Continuous IV heparin for therapy initiation has
been increasingly replaced by single or twice-daily
subcutaneous injections of low-molecular-weight
heparin (LMWH). LMWH antithrombotic effects
correlate with body weight and permit fixed dosing
without laboratory monitoring; it also allows for
outpatient treatment of uncomplicated deep venous
thrombosis (DVT).[5, 6, 7] However, IV heparin
remains the treatment of choice for those with end-
stage renal failure.

The current guidelines recommend short-term
anticoagulation with LMWH subcutaneously (SC)
(Grade 1A), unfractionated heparin (UFH) IV
(Grade 1A), fixed-dose UFH SC (Grade 1A), or
fondaparinux SC (Grade 1A). Initial treatment with
LMWH, UFH, or fondaparinux should continue for
at least 5 days and until the international
normalized ratio (INR) is 2 or higher for 24 hours
(Grade 1C). A vitamin K antagonist such as
warfarin should be initiated together with LMWH,
UFH, or fondaparinux on the first treatment day
(Grade 1A).[8]

Long-term Anticoagulation
Long-term anticoagulation is necessary to prevent
Avantajele de tratament anticoagulant
Tratament anticoagulant rmne de temelie a
tratamentului medical pentru tromboza venoasa
profunda ( TVP ), deoarece este neinvaziv , ea
trateaza mai multi pacienti ( aproximativ 90 % ) ,
fr sechele fizice demonstrabil imediat a TVP ,
ea are un risc redus de complicatii , iar datele
rezultate demonstreze o imbunatatire a morbiditii
i mortalitii . Meta-analize a studiilor clinice
randomizate de heparina nefractionata ( HNF ) i
heparina cu greutate moleculara mica (HGMM ) au
artat c acestea au fost similare , cu riscul de TVP
recurente de 4 % , un risc de embolie pulmonara (
PE ) de 2 % , iar un risc de hemoragie majora de 3
% [ 1 , 2 ] .

Terapie iniial Heparina
Terapie iniial anticoagulant implic n mod
tradiional cu heparin iv continu pn
anticoagulant sistemic adecvat este obinut .
Anticoagulant Rapid este esenial n primele 24 de
ore de la diagnostic , reducnd incidena trombozei
venoase recurente n primele 3 luni de la 25 % la 5
% [ 3 , 4 ] .

Heparina iv continu pentru Iniierea tratamentului
a fost tot mai mult nlocuit cu injecii unice sau de
doua ori pe zi subcutanate de heparina cu greutate
moleculara mica ( HGMM ) . HGMM efecte
antitrombotice se coreleaza cu greutatea corpului i
permite fix de dozare, fr monitorizarea de
laborator , permite , de asemenea, pentru
tratamentul ambulatoriu al trombozei necomplicate
venoasa profunda ( TVP ) [ 5 , 6 , 7 ] Cu toate
acestea , heparina IV rmne tratamentul de alegere
pentru cei cu sfritul . insuficiena renal n stadiu
.

Orientrile actuale recomanda tratament
anticoagulant pe termen scurt, cu HGMM
subcutanat ( SC ) ( gradul 1A ) , heparina
nefracionat ( HNF ) IV ( gradul 1A ) , cu doza
fixa HNF SC ( gradul 1A ) , sau fondaparinux SC (
gradul 1A ) . Tratamentul initial cu HGMM , HNF ,
sau fondaparinux trebuie s continue pentru cel
puin 5 zile i pn la raportul internaional
normalizat ( INR ) este de 2 sau mai mare de 24 de
ore ( grad 1C ) . Un antagonist al vitaminei K , cum
ar fi warfarina ar trebui s fie iniiat mpreun cu
HGMM , HNF , sau fondaparinux n prima zi de
tratament ( gradul 1A ) . [ 8 ]
the high frequency of recurrent venous thrombosis
or thromboembolic events. Interruption of
anticoagulation within the first 12 weeks of therapy
resulted in a 25% incidence of recurrent
thrombosis.[5] Oral vitamin K antagonists
(warfarin) remain the preferred approach for long-
term treatment, which allows for single-dosing oral
therapy that can be continued on an outpatient
basis.

Warfarin interrupts the production of vitamin K
dependent coagulation factor production by the
liver. The effect is delayed by 72 hours until the
existing circulating coagulation factors are cleared
or used. The initial effect creates a hypercoagulable
state because vitamin Kdependent anticoagulants
(protein C and S) are cleared first from the body
while vitamin Kdependent procoagulants continue
to circulate. During this period, heparin
anticoagulation is important to prevent worsening
thrombosis. An international normalized ratio
(INR) maintenance at 2-3 is recommended; higher
ratios do not improve effectiveness, and lower
ratios do not reduce bleeding complications.[9, 7]

The duration of therapy with warfarin has been
evaluated by multiple prospective, randomized
clinical trials.[5, 10, 11] Duration of therapy varies
depending on patient risk factors and presumed
etiology. A first-episode venous thrombosis or
thrombotic event due to a transient reversible risk
factor should be treated for at least 3 months.
Interruption of therapy prior to 12 weeks results in
an 8% absolute increase in recurrent thrombosis
within the following 12 months. Treatment for the
entire 3 months results in an annual recurrent deep
venous thrombosis (DVT) incidence of 3%.

For patients with first-episode idiopathic venous
thrombosis, treatment length should be 6-12
months.[5] However, the benefit of anticoagulation
is lost after stopping treatment at 1 year, prompting
many physicians to continue treatment
indefinitely.[12] The decision to continue
anticoagulation should be tailored to each patient,
taking into consideration bleeding risk and patient
preference, with treatment reassessment at periodic
intervals.

For patients with a first-episode venous thrombosis
and documented antiphospholipid antibodies or 2

Anticoagulant pe termen lung
Anticoagulant pe termen lung este necesar pentru
a preveni de nalt frecven de tromboza venoasa
recurenta sau evenimente tromboembolice .
ntreruperea anticoagulant in primele 12 saptamani
de tratament a dus la o inciden de 25 % din
trombozei recurente . [ 5 ] antagoniti orale de
vitamina K ( warfarina ), rmne abordarea
adecvat pentru tratamentul pe termen lung , care
permite pentru dozare - un singur tratament pe cale
orala , care poate fi continuat pe o baza in
ambulatoriu .

Warfarin ntrerupeproducia de vitamina K -
dependent coagulare producerea factorului deficat .
Efectul este amnat cu 72 de ore, pn cnd
factorii de coagulare circulaie existente sunt
eliminate sau utilizate . Efectul iniial creeaz o
stare de hipercoagulabilitate , deoarece vitamina
anticoagulante K - dependente ( proteina C i S )
sunt eliminate n primul rnd din organism n timp
ce vitamina K procoagulante - dependente continu
s circule . n aceast perioad , anticoagulant cu
heparin, este important pentru a preveni tromboza
agravarea . Este recomandat un raport normalizat (
INR ) meninerea internaional la 2-3 , raporturi
mai mari , nu a mbunti eficiena , i raporturi
mai mici nu reduce complicatii hemoragice [ 9 , 7 ]
.

Durata tratamentului cu warfarina a fost evaluat
de ctre mai multe studii clinice prospective ,
randomizate . [ 5 , 10 , 11 ] Durata tratamentului
variaz n funcie de factorii de risc pacientului i
etiologia prezumat. Un tromboza venoasa primul
episod sau eveniment trombotic din cauza unui
factor de risc reversibil tranzitorie ar trebui s fie
tratate pentru cel puin 3 luni . ntreruperea
tratamentului nainte de 12 sptmni duce la o
crestere absoluta 8 % n trombozei recurente n
urmtoarele 12 luni . Tratamentul pentru ntregul 3
luni duce la o recurente trombozei venoase
profunde ( TVP ), incidenta anuala de 3 % .

Pentru pacientii cu primul episod tromboza venoasa
profunda idiopatica , durata tratamentului trebuie s
fie de 6-12 luni . [ 5 ] Cu toate acestea , beneficiul
de anticoagulant este pierdut dup ntreruperea
tratamentului puin 1 an , fapt care ia determinat
multi medici pentru a continua tratamentul pe
or more thrombophilic conditions (combined factor
V Leiden and prothrombin 20210A gene
mutations), at least 12 months of treatment is
indicated. Six to 12 months of initial therapy is
indicated in those patients with any one of the
following: deficiencies of antithrombin, protein C,
or protein S; factor V Leiden; prothrombin
20210A; hyperhomocysteinemia; or high factor
VIII levels (>90th percentile). Indefinite therapy is
also considered in both of these patient
populations.[5]

Limitations of Anticoagulation
Anticoagulation does have its limitations. Although
it inhibits propagation, it does not remove the
thrombus, and a variable risk of clinically
significant bleeding is observed. In 2-4% of
patients, deep venous thrombosis (DVT) progresses
to symptomatic pulmonary embolism (PE) despite
anticoagulation. In the setting of a PE, 8% of
patients have recurrences despite anticoagulation,
30-45% of which are fatal. Although
anticoagulation markedly reduces the risk of PE
and extension of the DVT, it does not reduce the
incidence of postthrombotic syndrome (PTS),
which requires expedited removal of the existing
thrombus without damaging the underlying venous
valves.

The main adverse effects of heparin therapy
include bleeding and thrombocytopenia.
Approximately 2% of patients experience major
bleeding within the first 3 months of therapy and 1-
3% thereafter per year.[13] The estimated fatality
rate for each episode of major bleeding is 13%.[13]
The development of thrombocytopenia must alert
clinicians to the diagnosis of heparin-induced
thrombocytopenia (HIT), which can occur in up to
3% of patients treated with heparin for more than 4
days. Two types exist: the most common form is a
self-limiting nonimmune mediated
thrombocytopenia that resolves with cessation of
therapy; the less common immune-mediated
thrombocytopenia has potentially catastrophic
thromboembolic complications.

Anticoagulation for Calf Vein DVT
Treatment of isolated calf vein deep venous
thrombosis (DVT) is best individualized, taking
into account local preferences, patient reliability,
the availability of follow-up care, and an
termen nelimitat . [ 12 ] Decizia pentru a continua
anticoagulant trebuie s fie adaptate pentru fiecare
pacient , lund n considerare riscul de hemoragie
i preferina pacientului , cu reevaluare tratament la
intervale periodice .

Pentru pacientii cu tromboza venoasa primul episod
i anticorpi antifosfolipidici documentate sau 2 sau
mai multe condiii trombofilice ( combinat factor V
Leiden si protrombinei 20210A mutatii genetice ) ,
cel puin 12 luni de tratament este indicat . Sase
pana la 12 luni de terapie initiala este indicat la
pacientii cu oricare dintre urmtoarele : deficiene
de antitrombin , protein C , sau proteina S , factor
V Leiden ; protrombinei 20210A ,
hiperhomocisteinemie , sau un nivel ridicat de
factor VIII ( > percentila 90 ) . Terapia cu durat
nedeterminat este , de asemenea, luate n
considerare n ambele grupe de pacienti . [ 5 ]

Limitri de anticoagulare
Anticoagulant are limitele sale . Dei a inhiba
propagare , aceasta nu elimin trombusului , i un
risc variabil hemoragiilor semnificative clinic se
observ . n 2-4 % din pacienti , tromboza venoasa
profunda ( TVP ) progreseaza la embolism
pulmonar simptomatic ( PE ) , n ciuda
anticoagulant . n stabilirea unei PE , 8 % dintre
pacienti au recurente in ciuda anticoagulant , din
care 30-45 % sunt fatale . Dei anticoagulant
reduce semnificativ riscul de PE i extindere a TVP
, aceasta nu reduce incidenta sindromului
posttrombotic ( PTS ) , care prevede eliminarea de
urgen a trombului existente, fr a deteriora
valvele venoase subiacente.

Principalele efecte adverse ale terapiei cu heparin
includ sngerare i trombocitopenie . Aproximativ
2 % dintre pacienii cu sngerri majore n primele
3 luni de tratament i de 1-3% , ulterior, pe an . [ 13
] Rata de fatalitate estimat pentru fiecare episod de
hemoragie majora este de 13 % . [ 13 ] Dezvoltarea
de trombocitopenie trebuie s alerteze medici la
diagnosticul de trombocitopenie indusa de heparina
( HIT ) , care pot aprea la pn la 3 % dintre
pacientii tratati cu heparina pentru mai mult de 4
zile. Exist dou tipuri : cea mai comuna forma este
o auto- limitare trombocitopenie mediat non-
imune , care rezolv cu ntreruperea tratamentului
,mai puin frecvente trombocitopenie mediat imun
are complicaii tromboembolice potenial
assessment of ongoing risk factors. Despite the
lower (but not 0) risk of pulmonary embolism (PE)
and mortality associated with calf vein DVT,
current guidelines recommend short-term
anticoagulation for 3 months in symptomatic
patients, albeit with a relatively low Grade 2B
recommendation. Asymptomatic patients with
isolated calf vein DVT do not require
anticoagulation, and surveillance ultrasound studies
over 10-14 days to detect proximal extension is
recommended instead. At certain centers, patients
with isolated calf vein DVT are treated with full
anticoagulant therapy.


With the introduction of low-molecular-weight
heparin (LMWH) or fondaparinux, selected
patients qualify for outpatient treatment only if
adequate home care and close medical follow-up
can be arranged. As discussed, subcutaneous
unfractionated heparin (UFH) may be substituted
for LMWH or fondaparinux if insurance issues are
a limiting factor. Outpatient therapy with UFH
carries a higher risk of heparin-induced
thrombocytopenia and remains a second-line drug.

While the patient is initiating therapy with
warfarin, the prothrombin time (PT) or
international normalized ratio (INR) must be
monitored closely (daily or alternate days) until the
target is achieved, then weekly for several weeks.
When the patient is stable, monitor monthly.
Inability to monitor INR precludes outpatient
treatment of DVT.

Patients with suspected or diagnosed isolated calf
vein DVT may be discharged safely on a
nonsteroidal anti-inflammatory drug (NSAID) or
aspirin, with close follow-up care and repeat
diagnostic studies (ie, ultrasonography) in 7 days to
evaluate for proximal extension. Patients with
suspected DVT but with negative initial
noninvasive study results need to be reassessed by
their primary care provider within 7 days. Patients
with ongoing risk factors need to be reevaluated at
1 week to detect proximal extension because of the
limited accuracy of noninvasive tests for calf vein
DVT.
catastrofale .

Anticoagulant pentru Calf TVP Vein
Tratamentul venoase tromboz venoas profund
viel izolat ( TVP ) este cel mai bine individualizat ,
innd cont de preferinele locale , fiabilitate
pacientului , disponibilitatea de ingrijire follow - up
, i o evaluare a factorilor de risc n curs de
desfurare . n ciuda risc mai mic ( dar nu 0 ) de
embolie pulmonara ( PE ) si a mortalitatii asociate
cu TVP vena viel , orientarile actuale recomanda
tratament anticoagulant pe termen scurt, timp de 3
luni la pacientii simptomatici , dei cu o
recomandare relativ sczut 2B Grad . Pacientii
asimptomatici cu izolat TVP vena viel nu necesit
tratament anticoagulant , iar studiile de ultrasunete
de supraveghere de peste 10-14 de zile pentru a
detecta extensia proximal este recomandat n
schimb . n anumite centre , pacienii cu izolate
TVP venelor gambei sunt tratate cu terapia
complet anticoagulant .

Odat cu introducerea de heparina cu greutate
molecular mic ( HGMM ) sau fondaparinux ,
pacientii selectati beneficia de tratament in
ambulatoriu numai n cazul n ngrijire la domiciliu
adecvat i aproape medical follow - up pot fi
aranjate . Aa cum sa discutat , heparina
nefractionata subcutanat ( HNF ) poate fi nlocuit
cu masa moleculara mica sau fondaparinux n cazul
n care probleme legate de asigurare este un factor
de limitare . Tratamentul ambulatoriu , cu UFH
implica un risc mai mare de trombocitopenie
indus de heparin i rmne un medicament de
linia a doua .

n timp ce pacientul este iniierea tratamentului cu
warfarin , timpul de protrombin ( TP ) sau a
raportului internaional normalizat ( INR ) trebuie
monitorizat cu atenie ( zile de zi cu zi sau
alternativ ), pn cnd obiectivul este atins , apoi
sptmnal timp de mai multe sptmni . Atunci
cndpacientul este stabil , monitoriza lunar .
Incapacitatea de a monitoriza INR exclude
tratamentul ambulatoriu de TVP .

Pacientii cu TVP suspectate sau diagnosticate vena
viel izolat pot fi evacuate n condiii de siguran
pe un medicament antiinflamatoare nesteroidiene (
AINS ) sau aspirina , cu follow - up de ingrijire si
repeta aproape studiile de diagnostic ( de exemplu ,
ecografie ) 7 zile pentru a evalua pentru extindere
proximal . Pacientii cu suspiciune de TVP , dar cu
rezultate negative initiale de studiu neinvaziv
trebuie s fie reevaluate de ctre furnizorul lor de
ingrijire medicala primara termen de 7 zile .
Pacienii cu factori de risc n curs de desfurare
trebuie s fie reevaluat la data de 1 sptmn
pentru a detecta extinderea proximala , din cauza
preciziei limitat de teste neinvazive pentru TVP
vena viel .