Prognosis and Monitoring of VTE

Crit Care Nurs Q
Vol. 40, No. 3, pp. 288–300

Copyright c 2017 Wolters Kluwer Health, Inc. All rights reserved.
Prognosis and Monitoring

of VTE
Mouhib Naddour, MD; Mehboob Kalani, MD; Yousef Hattab, MD;
Viral Gandhi, MD; Anil C. Singh, MD, MPH, FCCP; Omer Bajwa, MD
Venous thromboembolism (VTE) can present in a variety of different clinical settings and in a
diverse, comorbid patient population, both of which will guide the clinician toward the appropri-
ate therapeutic response. Patients who present with pulmonary embolism are at risk for hemody-
namic instability, recurrence of VTE, cardiac comorbidities, and increased risk of overall mortality.
Prognostication models have been clinically validated for risk stratification and prediction of mor-
tality. Similar to pulmonary embolism, patients with deep vein thrombosis carry a higher risk of
VTE recurrence and cardiac comorbidities. Consequently, VTE can be treated by a variety of meth-
ods such as anticoagulants or inferior vena cava filters, which bear their own risks and benefits. It
is imperative that clinicians monitor patients for complications from VTE and the chosen therapy.
Key words: monitoring, prognosis, thromboembolism, venous thrombosis
V ENOUS THROMBOEMBOLISM (VTE)

can present in a variety of different clini-
cal settings and in a diverse, comorbid patient
Patients with pulmonary embolism (PE)
will require close monitoring, as they carry
a high risk of catastrophic outcomes.1 In the
population, both of which will guide the first 7 days from the initial event, patients
clinician toward the appropriate therapeutic carry a high risk for hemodynamic collapse
response. The presentation of the VTE and and, in the ensuing weeks, patients are at risk
patient history will determine the prognostic for VTE recurrence and pleuritis from evolv-
index of the patient. Consequently, the prog- ing pulmonary infarcts.1-4 Risk stratification
nosis of VTE is highly variable and should be models have been developed to help the clin-
considered in every patient so that appropri- ician predict early-stage mortality risk so that
ate follow-up care can be maintained. Outpa- patients can be appropriately managed.5,6
tient risk stratification and continued labora- Months after the initial event, the risk of early-
tory tests may be required at regular intervals, stage complications decreases; although pa-
depending on the chosen therapy when patients may develop comorbid conditions such
tients are discharged from an inpatient as chronic thromboembolic pulmonary hy-
setting. pertension (CTEPH) or recurrent VTE.2,3,7 In
addition, patients will have a higher rate of
all-cause mortality compared with the general
Author Affiliations: Division of Pulmonary and population.8-10 Therefore, close monitoring is
Critical Care Medicine and Department of Medicine, of paramount importance in the outpatient
Allegheny General Hospital, Pittsburgh,
Pennsylvania.
setting to prevent and treat possible compli-
cations.
The authors have disclosed that they have no signif-
icant relationships with, or financial interest in, any
Patients with deep vein thrombosis (DVT)
commercial companies pertaining to this article. are at risk for multiple complications, which
Correspondence: Mouhib Naddour, MD, Division of
also requires close observation by the clin-
Pulmonary and Critical Care Medicine, Allegheny Gen- ician. After the initial event, DVT can have
eral Hospital, 320 East North Ave, Pittsburgh, PA 15212 further clot extension or embolization, lead-
(mnaddou1@wpahs.org).
ing to a PE. DVT can also independently in-
DOI: 10.1097/CNQ.0000000000000167 crease the risk of recurrent VTE events.11-13
288
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Prognosis and Monitoring of VTE 289
Patients may also develop other comorbid Although 64% of these deaths were due
conditions such as postthrombotic syndrome to noncardiovascular events, the other 31%
or CTEPH.7,14 Therefore, although patients were due to non-PE-related cardiovascular
with DVT may not present with unstable vi- events.10 Therefore, patients who endure the
tal signs, they can develop an increased risk initial PE event have an increased risk of mor-
of VTE complications. tality because of other causes.
The treatment of VTE usually involves PE-related prognoses are divided into early-
long-term anticoagulation, with the goal and late-stage outcomes, with early stage de-
of preventing further clot propagation or fined as less than 3 months from the initial
developing new thrombi. On the one hand, PE event and late stage defined as greater
inadequate dosing or failure to comply with than 3 months. In the first 3 months, patients
treatment can lead to the above-mentioned carry a high risk for acute complications,
complications. On the other hand, antico- whereas after the 3-month period, they are
agulation places patients at a higher risk of at risk for long-term complications leading to
bleeding, so the clinician should assess for comorbidity.
conditions that may increase the half-life
of the medication. Unlike unfractionated EARLY STAGE: SHOCK
heparin, rivaroxaban, and apixaban, warfarin
requires outpatient management to follow The highest risk for a catastrophic event
the international normalized ratio (INR). is during the initial 7 days; mortality during
The ideal INR is 2 to 3, and dose adjustment this period is usually related to recurrent PE
may be required depending on patients’ and shock. Shock may be the initial presenta-
laboratory tests. In addition, patients taking tion or possibly an early complication and is
warfarin will also require adherence to a the most common cause of death in the first
strict diet because certain foods can alter 7 days, being associated with a 30% to 50%
the metabolism of the drug. Finally, those mortality risk.1 This necessitates that the clin-
who received inferior vena cava (IVC) filter ician prudently monitor the patient and ap-
should be reassessed for the resolution of propriately react in those circumstances by
anticoagulation risk to ensure they are started utilizing systemic thrombolysis or catheter-
on the appropriate anticoagulant. directed intervention.
Prognostic models have been developed
PULMONARY EMBOLISM PROGNOSIS to aid the clinician in determining the 30-day
mortality, thereby facilitating the decision of
PE is a commonly seen condition that whether to manage patients in an outpatient
accounts for 50 000 to 200 000 deaths ev- setting or recognize patients who require
ery year. Approximately 95% of PE-related inpatient treatment and vigilant monitoring.
deaths occur before diagnosis or treatment. Of the multiple prognostic models devel-
Untreated PE bears an overall mortality of oped to predict outcomes for acute PE, the
30%, compared with 10% in populations pulmonary embolism severity index (PESI)
treated with anticoagulation.8,9 Over the last and the simplified PESI (sPESI) are the most
10 years, mortality related to PE has been commonly recognized. Tables 1 and 2 outline
decreasing from 17% to 10%.15 This is likely the variables associated with the prognostic
due to the advent of improved diagnostic models.
technology and the prognostication of pa- The PESI score was initially proposed by
tients and treatment options, especially for Aujesky et al5 in 2005 for the risk stratifi-
those who are clinically unstable. However, cation of patients depending on their clini-
patients who have had a PE have a cumula- cal presentation. Before this score, risk fac-
tive 5-year mortality rate of 32%, of which tors for poorer outcomes were established,
only 5% of the deaths were related to PE. but not placed in a scoring system. Since
290 CRITICAL CARE NURSING QUARTERLY/JULY–SEPTEMBER 2017
Table 1. Pulmonary Embolism Severity Index its introduction, PESI has been validated by
Scorea studies, and is commonly used in the clinical
setting.16,17 The PESI score adds the patient’s
Clinical Feature Points age to the points assigned by the following
10 variables: male sex, history of malignancy,
Age X (ie, 75) heart failure, chronic lung disease, pulse 100
Male gender 10
or more beats per minute, systolic blood pres-
History of malignancy 30
Heart failure 10
sure less than 100 mm Hg, respiratory rate 30
Chronic lung disease 10 or more breaths per minute, temperature less
Pulse ≥110/min 20 than 36◦ C (96.8◦ F), altered mental status, and
Systolic blood pressure 30 arterial oxygen saturation of less than 90%.
<100 mm Hg The points are added and the total score cate-
Respiratory rate 20 gorizes the patient according to risk classes:
≥30/min Class I: less than 66 points
Temperature <36◦ C 20 Class II: 66 to 85 points
Altered mental status 60 Class III: 86 to 105 points
Arterial oxygen 20 Class IV: 106 to 125 points
saturation <90%
Class V: more than 125 points
Risk Class Total Points Patients in class I or II are considered to be
Low risk low risk, with a 30-day mortality rate of ap-
Class I <66 proximately 1% and 2% to 4%, respectively.5
Class II 66-85 These patients can be triaged and managed
High risk as outpatient, because they have a relatively
Class III 86-105 low risk of mortality and are clinically sta-
Class IV 106-125 ble. Patients who are identified as class III
Class V >125 to class V are labeled high risk, with 30-day
mortality risks of 3% to 7%, 4% to 11%, and
5
a
From Aujesky et al. 10% to 25%, respectively.5 Therefore, patients
with a PESI score of more than 86 points
Table 2. Simplified Pulmonary Embolism are usually admitted for anticoagulation and
Severity Index Scorea closer monitoring. The PESI score acknowl-
edges the patient’s vitals in its scoring sys-
Clinical Feature Points tem, and therefore it is not uncommon for pa-
tients with very high PESI scores to undergo
Age >80 y 1 thrombolytic therapy and receive intensive
History of malignancy 1 care unit-level care.
Chronic 1 Although the PESI score provides accurate
cardiopulmonary information and risk stratification, its calcu-
disease lation can be cumbersome in a busy clini-
Pulse ≥110/min 1 cal setting. Therefore, the sPESI was derived
Systolic blood pressure 1
from the original PESI score and introduced
<100 mm Hg
Arterial oxygen 1
by Jiménez et al6 in 2010 to establish a sim-
saturation <90% pler scoring system for patient classification
as low risk or high risk. The sPESI and PESI
Risk Class Total Points scoring systems predict similar 30-day mor-
Low risk 0 tality rates and therefore have been clini-
High risk >1 cally validated. The sPESI assigns one point
for the following 6 variables: age >80, his-
6
a
From Jiménez et al. tory of malignancy, chronic cardiopulmonary
disease, heart rate of 110 or more beats EARLY STAGE: RECURRENCE

per minute, systolic blood pressure less than
100 mm Hg, and arterial oxygen saturation VTE recurrence after a PE has been defined
of less than 90%.6 If the patient is given a by Heit et al22 as the “venous thrombosis of a
score of 0, he or she is categorized as low risk site that was either previously uninvolved or
and can be managed in the outpatient setting. had interval documentation of incident DVT
However, patients who have a score of 1 or or PE resolution.” In addition, one should also
more, are determined to be high risk, should consider the propagation of previously diag-
be monitored carefully, and are likely to be ad- nosed thrombus as a recurrent event. The risk
mitted for inpatient anticoagulation and mon- of a recurrent event is 5% to 7% during the
itoring. Patients who are categorized as high initial 3 months and increases to 20% to 25%
risk by the sPESI should undergo PESI scoring after 5 years.2,3 Recurrence depends heavily
to more accurately determine their class, and on the absence or presence of risk factors
establish a more definitive mortality risk. that can vary significantly between patient
Although the prognostic model give clin- populations.
icians excellent insight into the predicted Table 3 shows the clinical features and
mortality of patients with acute PE, it does laboratory markers associated with increased
not show the entire picture. Other clinical risk of VTE recurrence. Patients with unpro-
indictors such as right ventricle (RV) dysfunc- voked thrombosis (ie, those without risk fac-
tion, elevated troponin, and elevated brain tors such as recent surgery, travel, or trauma)
natriuretic peptide have been associated have a very high risk of recurrence, approach-
with increased mortality. RV dysfunction ing 25% 5 years after the initial event.23 Fur-
seen on CT scans or echocardiograms has thermore, the presence of persistent clini-
been associated with a 2-fold increase in cal risks such as malignancy, antiphospho-
mortality. The risk is greater if these patients lipid syndrome, and genomic mutations also
have concurrent symptomatic RV dysfunc- carry an annual risk of 15% of recurrence.24
tion leading to hemodynamic collapse.18 Therefore, it is common practice for these
The decision over whether to initiate sys- patient populations to continue on antico-
temic thrombolytic therapy or proceed with agulation for prolonged periods or even
catheter-directed intervention in patients indefinitely.
with asymptomatic RV dysfunction remains Gender independently increases the risk of
debatable.19 Further studies are still required recurrence, because males are approximately
to determine definitive guidelines. 2 to 4 times more likely to have a recurrence
Elevated cardiac biomarkers such as than females.5,6 However, during pregnancy
brain natriuretic peptide and troponin have and during the puerperium period, females
been associated with an increased risk of have a 4-fold to 20-fold increase in VTE
mortality.20 Furthermore, patients who have events, respectively.25 After pregnancy they
normal cardiac biomarkers in setting of acute carry a lower risk of recurrent events, but
PE usually proceed with a benign clinical in subsequent pregnancies their risk in-
course.21 creases. Therefore, clinicians can consider
Although multiple prognostic indicators anticoagulation on pregnant females who
are available, the clinician should always treat have had VTE events during their previous
patients according to their presentation and pregnancies.26 Oral contraceptives increase
clinical needs. Even though one may be able the risk of initial VTE event, although data
to predict the 30-day mortality, the manage- on recurrence risk is still conflicting.2 In
ment of the patient in the acute setting is of their practice, clinicians tend to err on the
utmost importance. After recovering from the side of caution, advising females who had a
initial event, patients are still at risk for fur- VTE on oral contraceptives to discontinue
ther complications, such as recurrent VTE. them to prevent further events. This usually
Table 3. Clinical Features and Laboratory Markers Associated With Increased Risk of Recurrent
VTEa
Patient Related Thrombus Related
Malignancy Unprovoked thrombosis

Male sex Residual vein thrombosis
Pregnancy PE or proximal DVT
Continued oral contraceptive use Postthrombotic syndrome
IVC filter >2 thrombotic events
High concentrations of factor VII or
IX
Factor V Leiden
High D-dimer
Abbreviations: DVT, deep vein thrombosis; IVC, inferior vena cava; PE, pulmonary embolism; VTE, venous thromboem-
bolism.
a
From Palareti2 and Kyrle et al.3
entails stopping any form of contraception for recurrence. Genetic mutations indepen-
that involves hormone therapy. dently increase the risk of recurrent VTE if
Patients with DVT can be re-evaluated with these patients are not started on appropriate
lower extremity ultrasound to monitor for anticoagulant after the initial VTE event.30,31
thrombus regression. Although the criteria Studies have shown that those with factor
for thrombus regression vary, the persistence VIII concentrations above the 90th percentile
of the thrombus is an independent marker of normal have a 6-fold greater risk of re-
for recurrent VTE, and may be an opti- current event.32 Elevated factor IX level in-
mal tool to determine appropriate length of creases the risk of recurrent events, and en-
anticoagulation.27,28 Further studies are still hances the risk when both factors VIII and IX
required to establish definitive guidelines. are elevated.33 Although these markers pro-
Those who cannot receive anticoagulation vide academic interest, they have low clini-
are usually treated with an IVC filter, but cal relevance. These markers have a high vari-
this intervention also carries risk of recurrent ability between assays and laboratories, and
VTE. Patients with IVC filters reduce the risk are too costly to implement in normal clini-
of recurrent PE, but increase the risk of re- cal practice.2,34 A marker that is commonly
current DVT. There is, approximately, a 25% checked in the clinical setting is factor V
risk of recurrent DVT in the first 5 years.29 Leiden mutation. Patients who are homozy-
Although DVTs do not cause unstable vitals, gous for this mutation have an increased risk
they increase the risk of hospitalization for for initial VTE and have a high risk of recur-
appropriate treatment, and thereby increase rence by approximately 3-fold compared with
risk of hospital acquired processes. Further- those without the mutation. Patients who are
more, thrombi formation at the IVC filter site heterozygous for the mutation also bear a risk
occurs in 10% of patients, which carries a risk of VTE event and recurrence, but not as high
of embolization and possible PE.29 Although as their homozygous counterparts.35 Patients
IVC filters reduce the risk of PE, they do not with these mutations are commonly placed
eliminate it entirely. on indefinite anticoagulation after a throm-
Genetic mutations involving the coagula- botic event, and therefore detection of these
tion factors are another cause of unprovoked mutations is of great importance.36
VTE events. As mentioned earlier, unpro- Because of their high negative predictive
voked VTE events carry an independent risk value, D-dimers are usually examined for
patients with suspected PE. Studies have new clots. However, surgical intervention is
shown that those with initial unpro- required for definitive treatment.
voked VTE and D-dimer concentration Aside from CTEPH, PE also increases the
less than 250 ng/mL had a 60% lower risk of other cardiovascular events. Patients
incidence of recurrent events compared have a 60% higher risk of developing atrial
with those with concentrations more than fibrillation than those without a VTE event.7
250 ng/mL.37 Furthermore, patients with This is thought to be due to increasing mus-
low D-dimer levels after appropriate dis- cular strain on the heart, leading to dila-
continuation of anticoagulation had lower tion and the subsequent development of an
risk of recurrence. Conversely, those with atrial arrhythmia. Patients who develop atrial
high D-dimer levels after completion of fibrillation are at risk of thrombus forma-
anticoagulation therapy had a 5-fold increase tion in the heart, which carries a risk for
in recurrence.38 It is postulated that checking embolization.42 Therefore, these patients are
D-dimer levels after treatment can guide the usually subjected to lifelong anticoagulation,
optimum length of anticoagulation; how- which places them at a higher bleeding risk.
ever, studies are still required to definitively Clinicians should therefore closely monitor
establish this practice.38,39 patients with recent PE for cardiovascular
signs and symptoms to indicate cardiovascu-
LATE STAGE lar complications.
PE may also independently place patients
Late-stage complications are events oc- at a higher risk of recurrent thrombus. One
curring 3 months after an initial PE diag- study found that, after discontinuation of an-
nosis. Patients with PE have an increased ticoagulation, patients with symptomatic PE
5-year mortality approaching 32%, and have had a 17% higher risk of developing recurrent
been reported to increase mortality for up events.43 Subsequent studies have not con-
to 30 years.10,40 The cause of mortality in cluded similar outcomes, and therefore this
40% of these patients is due to cardiovascu- remains a topic of controversy. However, clin-
lar events.10 Therefore, considering that the icians should recognize that a potential risk
cause of mortality was usually not related to might exist and continue to be vigilant for
PE, this patient population has a higher risk recurrence, especially in the setting of addi-
of developing future comorbidities causing tional risk factors.
early mortality. With this in mind, close clin-
ical surveillance is required to prevent and DEEP VEIN THROMBOSIS PROGNOSIS
treat development of complications.
CTEPH is the development of pulmonary Lower extremity DVTs can be divided into
artery pressure of more than 25 mm Hg at 2 categories: proximal and distal. A proxi-
rest or more than 30 mm Hg during exercise mal lower extremity DVT is a thrombus lo-
because of pulmonary embolism. CTEPH is cated in the popliteal, femoral, or iliac veins.
an uncommon though serious complication All cases of proximal DVTs are treated with
of PE, with a high mortality if untreated. The anticoagulant therapy, if no contraindication
incidence of CTEPH is 1% at 6 months, 3% to anticoagulation exists. Distal lower ex-
at 1 year, and 4% at 2 years.7 Patients who tremity DVT is a thrombus below the knee,
have untreated CTEPH are in danger of devel- involving the veins in the calf except the
oping progressive dyspnea related to worsen- popliteal vein. Most cases of distal DVT are
ing right heart failure. Those who have pul- subject to anticoagulation, as it carries a
monary artery pressure more than 30 mm Hg risk of thrombus propagation and emboliza-
carry a poorer prognosis.41 Medical treatment tion. However, patients with isolated distal
is usually initialed with anticoagulation to pre- DVT may not require such therapy, as they
vent clot progression and the formation of have a very low risk of complications.44 The
distinction between the locations of DVTs is increased risk with proximal DVT. As men-
important to recognize, as proximal DVTs are tioned earlier in the article, VTE increases the
prone to greater complication rates than their risk of development of CTEPH.
distal counterparts. Proximal DVTs carry a Postthrombotic syndrome (PTS) is a com-
higher risk of embolization, to cause acute mon occurrence that affects a significant
PE, and have a higher mortality risk than dis- portion of the patients with acute DVT. PTS
tal DVTs.11 is the development of signs and symptoms
Although mortality estimates in patients of chronic venous stasis after an acute DVT
with proximal DVT treated with observa- event. Patients with PTS develop signs and
tion over anticoagulation are not known, the symptoms such as edema, skin pigmentation,
treatment of acute DVT derived significant and possibly venous ulceration. From the
reduction in recurrence rate, and thereby initial DVT event, the incidence of PTS
improved mortality.12 Subsequently, patients increases over time from 49% after the first
with DVTs have been treated with antico- year to 55% after the second year, and to
agulation, which has improved recurrence 56% after 6 years.14 Most patients start to
risk. The risk of recurrent VTE decreases af- develop signs and symptoms within 2 years
ter the completion of anticoagulation, but of the initial event. The occurrence of PTS
patients remain at increased risk for fatal is thought to be due to increasing venous
VTE regardless.13 Therefore, most patients hypertension from thrombotic obstruction,
with DVT are treated with anticoagulation, al- resulting in valvular incompetence. Common
though there is a subset that may not require risk factors for developing PTS are female
such therapy. gender, obesity, a history of proximal DVT,
Patients who develop isolated DVT in and varicose veins. Elderly populations may
the sinusoidal veins draining the gastroc- have a lower risk of developing PTS.47 To
nemius or soleus muscle may not require minimize the development of PTS, antico-
anticoagulation. Studies have shown that agulation must be initiated and maintained
the patients with isolated distal DVT treated in a timely manner. Studies have shown that
with anticoagulation had the same risk of PTS occurs more frequently in patients who
proximal progression than those who were do not maintain adequate anticoagulation
treated without anticoagulation.44-46 There- during treatment of initial DVT.48 PTS causes
fore, this patient population carries a lower significant discomfort and disfigurement to
risk of disease progression and recurrence. patients. Therefore, it is important to initiate
Considering that anticoagulation under these anticoagulation promptly after diagnosis, if
circumstances places the patient at increased indicated, and to educate patients on the
risk of bleeding, it may be more prudent to importance of adherence to anticoagulation.
monitor progression of DVT than subjecting
patients to anticoagulation. MONITORING PATIENTS ON
When considering whether or not to start ANTICOAGULATION
a patient on anticoagulation, it is crucial to
ensure that benefits of this therapy outweigh Options for initial anticoagulation include
the risks. The rationale of anticoagulation is subcutaneous unfractionated heparin, low-
to improve and to avoid early and late com- molecular-weight heparin (LMWH), subcuta-
plications. Early complications include DVT neous fondaparinux, and oral factor Xa in-
clot propagation to proximal veins, emboliza- hibitors such as rivaroxaban or apixaban.
tion leading to PE, and major bleeding be- Warfarin is not given as the initial antico-
cause of anticoagulation. Late complications agulant because of delay in reaching thera-
involve thrombus recurrence, CTEPH, and peutic INR and the risk of hypercoaguable
postthrombotic syndrome. DVTs carry simi- state during the first few days of treatment.
lar risks of recurrence as PE, as well as an Therefore, warfarin is commonly transitioned
with heparin before it is given as the sole an- ficacy while balancing the risk-benefit ratio
ticoagulant. Clinicians should recognize the for patients requiring anticoagulation.51 Once
risks and benefits of each anticoagulant ac- the INR is in therapeutic range, monitoring is
cording to their patient and initiate treatment required every 2 to 4 weeks, depending upon
accordingly. clinician preference, to appropriately adjust
Maintenance and close monitoring of pa- dosages. Dose adjustments are frequently re-
tients on anticoagulation are extremely im- quired because of increasing age and drug
portant. Clinicians should periodically evalu- and food interactions. Tables 4 and 5 show
ate patients to ensure therapeutic efficacy to some of the common drugs and foods that the
prevent recurrence of VTE, assess the risk or patient should be educated to avoid. Further-
presence of bleeding, determine whether the more, clinicians should seek out information
patient may be developing conditions that af- regarding adherence to the prescribed diet
fect the half-life of the anticoagulant therapy and drugs.
(ie, acute kidney injury, pregnancy, cirrhosis, Drugs can increase the risk of bleeding by
and changes in weight), and assess the side ef- directly interrupting vitamin K metabolism,
fects of the medication. Clinicians should ad- disrupting intestinal flora leading to decrease
vise all patients on anticoagulation to select vitamin K production, decreasing metabolism
their activities prudently and avoid situations of warfarin by inhibiting hepatic CYP2C9, or
that may result in trauma or falls. by increasing risk of bleeding independently
LMWH and fondaparinux do not require leading to a synergistic effect. Reduced effi-
regular laboratory monitoring. However, clin- cacy of warfarin can be due to inducing hep-
icians can use antifactor Xa levels for dosage atic CYP2C9 (which causes increased war-
adjustment in patients who are obese, preg- farin metabolism) or supplementing vitamin
nant, or have poor renal function, and to de- K directly. Clinicians should check patients’
termine therapeutic anticoagulation if clini- medications meticulously to ensure that an in-
cally indicated.49 Clinicians should vigilantly teraction does not exist. At times, drug-drug
assess renal function, as these medications interactions cannot be avoided, and in these
are renally excreted. An increase in plasma scenarios the clinician should adjust the dose
creatinine, or a decrease in glomerular filtra- of warfarin and monitor vigilantly.
tion rate, will lead to longer half-lives of these Food-related interactions are largely due
medications. Doses should be adjusted to pre- to the consumption of vegetables high in
vent an increased risk of bleeding. Should the vitamin K, which in turn causes a decrease
patients have bleeding on these medications, in INR. Generally, green leafy vegetables have
they should seek supportive care in an in- a higher vitamin K content, and patients are
patient setting. Protamine sulfate is clinically advised to avoid such vegetables. However,
available for reversal of LMWH if the patient is there are other vegetables that are high in
actively bleeding or requires an emergent in- vitamin K that are listed in Table 5. Patients
vasive procedure.50 However, these medica- should be thoroughly educated about the dif-
tions are usually metabolized, rapidly provid- ferent vegetables to avoid, so that subthera-
ing relief from the bleeding event within 24 peutic INR does not result.
to 48 hours. Warfarin and LMWH have excellent thera-
Warfarin is a commonly used medication peutic anticoagulation effects and carry rela-
for VTE, as it has been available since 1948 tively low bleeding risks. Studies have shown
and clinicians are widely comfortable using that rates of major bleeding and fatal ma-
this medication. Warfarin requires outpatient jor bleeding on warfarin and LMWH were
monitoring of the prothrombin time (PT) ra- 1.6% and 0.2%, respectively, during the first
tio, expressed as INR. The optimal INR range 3 months of treatment.13 Although LMWH
is 2 to 3 (target of 2.5) and, as studies have has a lower risk of bleeding, it requires sub-
shown, this INR target has the greatest ef- cutaneous administration and tends to be an
Table 4. Common Drugs That Interact With Warfarin and Their Pathophysiologya
Pathophysiology of Interaction
Increased risk of bleeding

Acetominophen Interrupts vitamin K metabolism
Penicillins (except nafcillin and Disrupt intestinal flora, leading to
dicloxacillin) decreased production of vitamin K
Cephalosporins
Doxycycline
Fluoroquinolones
Macrolides
Metronidazole
Trimethoprim-sulfamethoxazole
Azole antifungals Inhibit hepatic CYP2C9, and therefore
Amiodarone decrease metabolism of warfarin
Gemfibrozil
Statins
Selective serotonin reuptake inhibitors
Aspirin Increase risk of bleeding independent to
Clopidogrel INR
Ticlopidine
NSAIDs
Reduced efficacy of anticoagulation
Dicloxacillin Stimulate hepatic CYP2C9, therefore
Nafcillin increase metabolism of warfarin
Rifampin
Antiepileptics (carbamazepine,
phenobarbital, phenytoin)
Cholestyramine
Ritonavir
Vitamin K Replete vitamin K
Abbreviations: INR, international normalized ratio; NSAID, nonsteroidal anti-inflammatory drug.

a
From Greenblatt and von Moltke52 and Holbrook et al.51
Table 5. Foods with High Vitamin K Content, expensive medication. Therefore, in clinical
Causing Decrease in INRa practice, warfarin is used more commonly
than LMWH. Consequently, a clinical scoring
Food Name mechanism has been created to predict the
bleeding risk when the patient is on warfarin.
Asparagus Collard greens Table 6 shows the HAS-BLED score for assess-
Beans Kale
ing bleeding risk for patients on warfarin.
Beet Lettuce
Brussels sprouts Okra
The HAS-BLED score examines patients’
Cabbage Peas clinical risk factors and classifies in an appro-
Carrots Spinach priate risk category. HAS-BLED is an acronym
Cauliflower Turnip for risk factors which include: Hyperten-
Coleslaw sion, Abnormal liver or renal function, Stroke,
Bleeding history or predisposition, Labile
Abbreviation: INR, international normalized ratio. INR, Age more than 65, and Drugs/alcohol
a
From US Department of Agriculture, Agricultural Re- use. The limitation of the HAS-BLED score
search Service.53 is that those with more than 6 risk factors
Table 6. HAS-BLED Score for Bleeding Risk imately 1% to 2%. When these medications
Assessment for Patients Receiving Warfarina initially came to market, studies had shown
the factor Xa inhibitors bear the same rate of
Risk Factor Score VTE recurrence, although they had a lower
rate of bleeding compared with conventional
Hypertension 1 therapy (heparin with warfarin).55 Retrospec-
Abnormal liver/renal 1 each
tive studies conducted since then have shown
function
similar rates of recurrence and bleeding.56
Stroke 1
Bleeding history or 1 Considering that these medications have sim-
predisposition ilar outcomes, clinicians can decide which
Labile INR 1 therapy to initiate on patients. Clinically, a
Age >65 1 large percentage of patients are still started
Drugs/alcohol use 1 each on warfarin given that clinicians have greater
experience with the medications and rever-
Major Bleeding Events Total Score
(% Patients) sal agents are readily available in the inpatient
setting. Andexanet is a newly developed re-
0.9 0 versal agents for factor Xa inhibitors; how-
3.4 1
ever, it is yet to be made widely available.57,58
4.1 2
5.8 3
8.9 4 MONITORING IVC FILTERS
9.1 5
Unknown 6 IVC filters are usually employed in patients
who have contraindications to start or con-
Abbreviation: INR, international normalized ratio. tinue anticoagulation. IVC filters are used to
a
From Palareti.2
prevent the progression of DVTs to PEs in the
setting of this contraindication to anticoagu-
were rare, and therefore the bleeding risk, lation. However, IVC filters can increase the
though not precisely known, is assumed to risk of recurrent DVTs by approximately 25%
be more than 10%. Although readily avail- in the first 5 years.29 This is likely due to per-
able, this clinical tool has only been validated sistently high risk of recurrence that was not
for atrial fibrillation.54 However, one can still mitigated by anticoagulant therapy. In addi-
use this score to recognize the risk of bleed- tion, IVC filters can be a nidus for clot for-
ing a patient may have and manage therapy mation, as it is a foreign body and carries a
accordingly. coagulable property. Studies have shown that
Recently, new anticoagulants have come thrombi can form at the IVC filter site in 10%
into clinical practice that are commonly of patients, thus placing patients at a potential
known as novel oral anticoagulants. These risk for developing PE.29,59 Therefore, IVC fil-
medications, which include rivaroxaban and ters reduce, but not preclude, patients from
apixaban, target clotting factor Xa. As is the having a PE event. Estimates indicate that
case with LMWH and fondaparinux, labora- 5% of patients with IVC filter may develop
tory monitoring is not required. These med- a PE.60 Consequently, clinicians must closely
ications have a relatively short half-life and re- monitor these patients for VTE recurrence,
quire daily dosing. However, clinicians should as it is a relatively common event. Finally,
continue to monitor renal function, as the kid- clinicians should continue to evaluate the rel-
neys metabolize these medications. Patients ative or absolute contraindication of antico-
who develop acute kidney injury may require agulation. If the risk of anticoagulant therapy
dose adjustment or cessation of medication. has improved or resolved, clinicians should
Studies have shown that the rate of major consider starting patients on anticoagulation
bleeding with factor Xa inhibitors is approx- to prevent further VTE complications.
CONCLUSION however, it places patients at a higher bleed-

ing risk. Furthermore, clinicians are obliged
VTE events are common occurrences and to continue to monitor changes in lifestyle
clinicians are advised to monitor patients or metabolic status to ensure that anticoag-
closely after the initial event. Patients who ulation does not deviate from therapeutic
have a PE are at a high risk of cardiogenic levels. Those patients who are treated with
shock and fatal recurrence during the first IVC filters should be evaluated for restarting
3 months. In later stages, patients with a anticoagulation once the risk of bleeding has
history of PE are at an increased risk for improved.
developing cardiovascular comorbidities and It is imperative that clinicians recognize the
are also at an increased risk of overall mor- overall prognosis of patients with VTE, and
tality. Although patients with DVT usually continue to evaluate patients for risks and
present with stable vitals, soon after the complications. In an era where significant em-
initial event they are at risk of thrombus phasis is given on preventative medicine and
extension, embolization to develop PE, clinicians have easy access to diagnostic tests,
and recurrence. Similar to the PE patient one can detect these events in their early
population, patients with DVT are at a higher stages and intervene appropriately. What con-
risk of developing cardiovascular complica- tinues to remain most important is keeping
tions. The risk of these clinical outcomes a keen eye on our patients and preventing
can be decreased with anticoagulation; avertable complications.
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Prognosis and Monitoring of VTE

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Prognosis and Monitoring of VTE

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Crit Care Nurs Q

Vol. 40, No. 3, pp. 288–300

Prognosis and Monitoring

V ENOUS THROMBOEMBOLISM (VTE)

disease, heart rate of 110 or more beats EARLY STAGE: RECURRENCE

Patient Related Thrombus Related

Malignancy Unprovoked thrombosis

Increased risk of bleeding

Abbreviations: INR, international normalized ratio; NSAID, nonsteroidal anti-inflammatory drug.

CONCLUSION however, it places patients at a higher bleed-

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