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254 Chapter 24 Treatment algorithms for acute venous thromboembolism
https://t.me/med1917
Confirmed acute DVT
Iliofemoral DVT
Limb-threatening
Moderate-to-severe
symptoms?
No
Is ancoagulaon
contraindicated?
No
Prompt
Temporary IVC
ancoagulaon
Ancoagulaon
safe to iniate?
No
IVC filter kept and plan for
re-evaluaon is developed
DVT?
Yes
filter
Femoropopliteal DVT
Ancoagulaon
Yes
Early thrombus
removal
Yes
Prompt filter
removal and
ancoagulaon
Thrombosis
confined to calf
muscles or high
risk of bleeding
Serial ultrasound
(weekly for 2
weeks or with
worsening
symptoms)
Thrombus
extension?
Yes
Ancoagulaon
Isolated distal DVT
Severe
symptoms or
risk factors for
extension
Ancoagulaon
No
Ultrasound
imaging stopped
24.1 Management of conrmed DVT. Abbreviations: DVT: deep vein thrombosis; IVC: inferior vena cava.
Due to the high risk of bleeding associated with systemic
thrombolysis, catheter-directed thrombolysis (CDT) with
local thrombolytic agent infusion has been adopted,
though it is still debatable whether CDT can lower longterm risks of PTS.
19,28–32
Additionally, pharmacomechanical
devices have been gaining popularity, as it has been demonstrated that they can reduce procedure time and decrease
thrombolytic agent usage when compared to CDT, while
still providing comparable long-term physiologic and functional venous outcomes.
30,33,34
When compared to anticoagulation alone, thrombolysis carries additional risks. The most reported side effects
are increased rates of minor and major bleeding, including
intracranial hemorrhage.
19,35,36
As a result, current guidelines recommend intervention for select iliofemoral DVT
patients who are candidates for thrombolysis and for
whom the benets outweigh the risks.
17,18,22,25,26
The ACCP
CHEST and American Heart Association (AHA) guidelines recommend early thrombus removal for patients
with limb-threatening thrombus such as phlegmasia or
threatened venous gangrene.
17,25
The National Institute for
Health and Care Excellence (NICE) and SVS guidelines
provide very similar criteria for choosing which patients
to intervene on and include those with iliofemoral DVT
and (1) symptoms lasting less than 14 days, (2) good functional status, (3) a life expectancy of at least 1year, and
(4) a low risk of bleeding.
26
In addition to patients with
limb-threatening DVT, the SIR recommends intervention
for nonelderly (<65 years) patients with good pre-DVT
functional status and a nonthreatened limb but moderate-to-severe symptoms.
22
Both the SIR and the AHA
suggest intervention for patients who continue to exhibit
symptomatic or functional deterioration despite initial
anticoagulation.
22,25
The extent to which early thrombus removal can reduce
the incidence of PTS after iliofemoral DVTs is unclear.
However, studies have shown that it can improve venous
disease–specic quality of life, including being associated with lower PTS severity scores.
to open surgical venous thrombectomy, which is mostly
of historical value, other thrombus removal approaches
are currently available: pharmacomechanical thrombolysis (PMT), pharmacological thrombolysis (or CDT),
and mechanical thrombectomy (MT). The SVS and AHA
guidelines favor PMT over CDT when the expertise and
resources are available so as to reduce patients’ exposure
to thrombolytic agents.
18,25
Open surgical thrombectomy
had been traditionally reserved for patients for whom
thrombolytic agents are contraindicated
has been largely replaced by MT thrombectomy in current
practice.
New MT devices, which do not use any thrombolytic
agents, have recently been introduced as a less invasive
alternative to open surgical thrombectomy and thrombol-
19,20,24,37
In addition
18
; however, this
Early thrombus removal
https://t.me/med1917
indicated
Paent at high-risk for
iatrogenic PE?
24.4 Treatment of iliofemoral DVT 255
24
Yes
IVC filter placement
pharmacomechanical
Yes
Mechanical or
thrombectomy
Iliocaval compressive or
No
High bleeding risk?
No
Mechanical or
pharmacomechanical
thrombectomy, or catheter-
directed thrombolysis
IVUS
obstrucve lesion
uncovered?
24.2 Algorithm for early thrombus removal. Abbreviations: PE: pulmonary embolism; IVC: inferior vena cava; IVUS: intravascular
ultrasound.
ysis. Available options include rheolytic devices, aspiration
devices, and clot capture devices. Single-arm trials have
been established to assess the efcacy of these devices.
For example, the multicenter prospective single-arm data
from the ClotTriever Outcomes (CLOUT) registry aims to
assess the efcacy of the ClotTriever System,
BOLT trial aims to assess the Indigo Aspiration system.
Interim results from the CLOUT registry
rospective studies,
appearing to be a safe and effective option for patients
who have contraindications to thrombolysis. However,
since none of these studies included comparison arms,
robustevidence for MT devices remains to be determined,
Stent placement
ancoagulaon
38
while the
38
40,41
show promising results, with MT
, and a few ret-
Yes
followed by
39
No
Ancoagulaon
and the incorporation of those devices into guidelines has
yet to be established.
Due to the lack of randomized comparative trials,
the selection of a specic early-clot removal approach—
CDT, PMT, or MT—is individualized for each patient and
is based on the expert opinion of the treating physician.
Furthermore, the role of CDT following PMT and the
number of thrombolysis sessions, particularly for thrombi
resistant to single-stage PMT—whether or not a stent has
been placed—are still up for debate. Figures 24.1 and
24.2 depict the decision-making process for patients with
iliofemoral DVT and those who require early thrombus
removal, respectively.
256 Chapter 24 Treatment algorithms for acute venous thromboembolism
https://t.me/med1917
24.5 STENTING FOR DVT MANAGEMENT
Due to the lack of randomized trials comparing stenting
versus no-stenting groups, robust evidence for the use of
venous stents in the treatment of acute DVT remains lacking, and current practice is based primarily on retrospective
and cohort series studies. According to one meta-analysis of
studies, the use of stents for acute DVT improves not only
patency, rethrombosis, and PTS rates but also patients’ quality of life.
42
Although the results are promising, many of these
studies utilized arterial, rather than venous-specic, stents
and did not provide long-term data, limiting the applicability
of their ndings to routine clinical practice. While the ACCP
and the NICE
26
do not discuss the role of stenting following
17
thrombectomy/thrombolysis in their most recent guidelines,
the SVS, SIR, and AHA guidelines, on the other hand, recommend stent placement for obstructive iliac lesions revealed
by any thrombus removal strategy.
cally recommends the use of self-expanding stents.
were not recommended for femoral or popliteal lesions.
18,22,25
The SVS speci-
18
Stents
18
In
summary, while more studies are needed, the current body
of evidence supports the use of appropriately sized stents in
selected patients with iliofemoral or more proximal lesions,
and this has become the standard of practice.
Intravascular imaging, particularly intravascular ultrasound (IVUS), has become the standard of care for deep
venous intraprocedural imaging, as it improves the visualization of thrombotic, nonthrombotic, and compressive
lesions and allows for more accurate selection of appropriate-sized stents.
43
In the Venogram vs IVUS for Diagnosing Iliac Vein Obstruction (VIDIO) trial, which was
designed to compare the sensitivity of IVUS and multiplanar venography, IVUS was found to have superior
sensitivity for detecting iliofemoral obstructive lesions.
44
In this 100-patient trial, IVUS detected stenotic lesions
in 30% more patients than venography did. Furthermore, investigators revised the treatment plan in 57% of
patients following IVUS, with 72% of those cases being
revised because venography had failed to detect a significant lesion.
44
Similarly, in a systematic review of studies
that compared imaging modalities for the evaluation of
chronic iliofemoral venous obstruction, IVUS was found
to have diagnostic superiority over other three-dimensional contrast imaging modalities, including multiplanar
venography.
45
Arecent study looked at the role of IVUS
in stent selection and found that when compared to multiplanar venography usealone, adjunctive IVUS use was
associated with different stent dimensions and landing
segment selection, and this was protective against 30-day
and 2-year stent reintervention rates.
46
The use of IVUS
for stent sizing, placement, and ensuring stent apposition
has become the standard of care for iliofemoral DVT.
24.6 INFERIOR VENA CAVA FILTERS
FOR DVT MANAGEMENT
According to several recent guidelines, temporary IVC lters
can be used in patients with iliofemoral DVTs who have contraindications to anticoagulation and for whom PE clinical
risk factors—such as DVT extent,thrombotic risk factors, and
the anticipated duration of the risk of bleeding—are assessed
to weigh the risks versus benets of lter placement.
Additionally, the guidelines agree that lter placement should
only be considered for patients who experience recurrent
VTE while receiving therapeutic anticoagulation if the anticoagulation regimen and compliance have been optimized
and all plausible causes of anticoagulation failure have been
investigated. Once the lter has been implanted, a routine lter surveillance strategy and a plan for lter removal should
be established, as prompt removal is recommended once
anticoagulation can be safely commenced.
The role of lter placement to prevent iatrogenic PE
25,26,47
during catheter-directed or PMT is uncertain. Asingle clinical trial looked into the effectof lter implantation during
percutaneous DVT procedures and found that while lters
reduce the incidence of iatrogenic PE, they provide no mortality benets.
48
In contrast, two retrospective cohort studies
found no difference in PE incidence when groups of patients
undergoing percutaneous DVT interventions with or without
lters were compared.
49,50
Due to the scarcity of studies, few
guidelines address the placement of lters during DVT thrombolysis or thrombectomy; those that do recommend the use
of lters for select patients who, in their physician’s expert
assessment, are at high risk of developing iatrogenic PE.
24.7 COMPRESSION STOCKINGS AND
CHOICE OF ANTICOAGULATION
Compression stockings and anticoagulation therapy are
often the mainstay of treatment for DVT. While there is no
evidence that compression stockings reduce the incidence of
PTS, the ACCP
symptom relief if necessary. For maximum effect, application
of compression stockings as soon as possible after DVT diagnosis may be very important to their long-term effectiveness.
The appropriate anticoagulation regimen and duration
of treatment have been addressed in several guidelines.
Figure
anticoagulation regimens based on the recommendations
of the ACCP and NICE.
duration is determined by the patient’s comorbidities, the
inciting event causing the DVT, and the presence of PE.
Anticoagulation can be discontinued after 3 months for
patients with transient risk factors such as surgery under
general anesthesia, connement to bed, cesarean section,
estrogen therapy, pregnancy and postpartum period, and
leg injury resulting in reduced mobility. Treatment for
cancer-associated thrombosis can be provided for 3–6
months, followed by re-evaluation for possible extension.
Finally, for patients requiring long-term treatment, the
extended-phase duration should be tailored to the individual patient and is not specied in the guidelines. However,
it is recommended that patients be re-evaluated at least
once a year.
While aspirin is not recommended as an alternative to
extended-phase anticoagulation therapy, it can be considered for patients who are no longer candidates or decline
long-term anticoagulation.
17
and NICE26 guidelines suggest their use for
24.3 presents an algorithm for the selection of
17,26
Anticoagulation therapy
17,26
17,26
17,25,26,47
18,47,50
Ancoagulaon indicated
https://t.me/med1917
Cancer-associated
thrombosis?
References 257
24
Yes
No
Anphospholipid
DOACs preferred
Apixaban or LMWH preferred for
syndrome-associated
thrombosis?
paents with luminal GI malignancy
LMWH alone or LMWH transioned
to VKA if DOACs unsuitable
Yes
VKA
preferred
No
DOACs preferred
Alternave: LMWH
transioned to VKA
Treatment for 3 to 6 months
followed by re-assessment
Possible extension if
malignancy not cured
Treatment for 3
months
Consider long-term
extension if
regimen well
tolerated
Transient risk
factors:
Treatment
for 3 months
Unprovoked VTE or
persistent risk factors:
extended-phase with
DOACs
alternave: VKA if DOACs
unsuitable
re-evaluaon at least on
an annual basis
24.3 Algorithm for anticoagulation regimen selection. Abbreviations: DOACs: direct oral anticoagulants; LMWH: low-molecu-
lar-weight heparin; VKA: vitamin K antagonists; VTE: venous thromboembolism; GI: gastrointestinal.
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CHAPTER
25
https://t.me/med1917
Prevention of deep
venous thrombosis
Jeffrey J. Siracuse and David McAneny
25.1 INTRODUCTION
Deep venous thrombosis (DVT) and pulmonary embolism
(PE) are major concerns for hospitalized patients, especially
those who have undergone operations. Venous thromboembolic (VTE) events are among the leading causes of preventable postoperative deaths.
is one of the highest-yield methods of reducing postoperative morbidity and mortality, and it has been a focus of
quality improvement.
patients are at risk for subsequent VTE events, post-thrombotic syndrome, venous claudication, and long-term
sequelae such as pulmonary hypertension.
The initial assessment of a patient, particularly a surgical
patient, should include both personal and family histories
of VTE events. Proper risk assessment also weighs clinical
factors such as comorbidities, underlying acute and chronic
conditions, and planned procedures or operations.
Assessment of VTE risk should be performed among all
hospitalized patients and guide determinations about prophylaxis, ranging from early ambulation to mechanical
lower extremity compression devices, to pharmacological
prophylaxis. Proper VTE prophylaxis is cost-effective, can
reduce related morbidity and mortality, and is associated
with a low risk of bleeding.
shown to improve outcomes, particularly in patients undergoing operations. Prolonged courses of chemoprophylaxis,
extending beyond hospital discharge in select patients at
particularly high risk, have also reduced the likelihood of
postoperative VTE.
lating VTE risk, including the American College of Chest
Physicians (ACCP) score and the Caprini risk assessment
2–4,6,9
model.
2–3
2
Several systems are valuable in calcu-
1–4
Prophylaxis against VTE
In addition to acute harm, these
2–4
5–8
2
Targeted prophylaxis has been
25.2 RISK ASSESSMENT MODELS
AND RISK-COMMENSURATE
PROPHYLAXIS
Risk factor assessments have developed over time from
generalized measures to patient-specic designs. In 2008,
the ACCP released guidelines for classifying VTE risk in
hospitalized patients.
10
These consisted of broad categories
that focused upon the reason for hospital admission. Categories were “Low Risk” (minor surgery in mobile patients
and fully mobile medical patients), “Moderate Risk” (most
general surgery, gynecology, and urology operations and
more sedentary medical patients), and “High Risk” (hip or
knee arthroplasty, major trauma, and spinal cord injuries).
Rogers et al. published data from the Patient Safety
in Surgery Study to develop a risk assessment model for
VTE, in collaboration with the National Surgical Quality Improvement Program. While VTE occurred in only
0.63% of patients undergoing vascular and general surgery
operations, its associated 30-day mortality was 11.2%.
The investigators identied 15 variables that were independently associated with VTE risk, including female
gender, high American Society of Anesthesiologists class,
ventilator dependence, preoperative dyspnea, cancer, recent
chemotherapy, preoperative blood transfusion, hypoalbuminemia, hyperbilirubinemia, hypernatremia, anemia,
operation type, emergency operation, and postoperative
wound infection.
Joseph Caprini developed a detailed patient-centered
risk assessment model that has evolved over time. The
original protocol (Figure25.1) was derived from a prospective analysis of 20 risk factors among 538 general
surgery patients.
(35%), moderate- (49%), and high-risk (17%) groups.
Only 10% of the low-risk patients received prophylaxis
versus 42.1% of the moderate- and 76% of the high-risk
cohorts. Later iterations of the Caprini risk assessment
model have increased the number of variables nearly two-
2
VTE risk was subsequently divided into four catego-
fold.
ries—low, moderate, high, and highest.
factors comprised acute spinal cord injury; hip, pelvis, or
leg fracture; knee or hip arthroplasty; recent polytrauma;
and recent stroke. In 2013, the Caprini score was further
expanded to include body mass index, operation duration, malignancy, smoking, diabetes, and blood transfusions (Table25.1).
been validated in multiple trials, and its implementation
in individual centers is correlated with a decreased incidence of postoperative VTE. Protocols have been embedded in the electronic medical record (EMR) to facilitate
order entry and improve compliance, and these renements have reduced VTE rates in multiple surgery special-
11–17
ties.
Modications of the Caprini scoring system at
7
6
These patients were stratied into low-
5
The highest risk
2
The Caprini classication system has
7
DOI: 10.1201/9781003328971-28
259259
260 Chapter 25 Prevention of deep venous thrombosis
https://t.me/med1917
Risk Factor
1 point
Age 40-60 years
Minor surgery (<45 minutes) is planned
Past major surgery (< 1 month)
Visible varicose veins
History of inflammatory bowel disease
Swollen legs (current)
Overweight or obese (BMI>25)
Heart aack
Congesve heart failure
Serious infecon (for example, pneumonia)
Lung disease (for example, COPD)
On bedrest or restricted mobility
Other risk factors
Oral contracepves or hormone replacement therapy
Pregnancy or postpartum (<1 month)
History recurrent spontaneous aboron
2 points
Age 61-74
Major surgery (> 45 minutes)
Leg plaster or brace
Central venous access
Current or past malignancies (except non-melanoma skin)
Paent confined to bed (>72 hours)
3 points
Age 75 years or more
History of DVT/PE
Family history of blood clots
Personal or family history of hypercoagulability
5 points
Serious trauma
Elecve major lower extremity arthroplasty
Hip/pelvis, or leg fracture
Stroke (<1 month)
Spinal cord injury resulng in paralysis
25.1 Original risk score fore assessment and prophlaxis by
Caprini JA, Arcelus JI, Hasty JH, Tamhane AC, Fabrega F.
Clinical assessment of venous thromboembolic risk in surgical
patients. Semin Thromb Hemost. 1991;17(3 Suppl):304–12.
6
our medical center include conferring 5 points for operations longer than 6hours, excluding thyroid and breast
cancers from the “present cancer” category, regarding
laparoscopy as equivalent to laparotomy, mandating the
scoring system in the EMR with “hard stops,” and providing the chance to opt out (with mandatory explanations
of this decision); ve risk score categories and corresponding levels of prophylaxis rigor; and required calculations
of the Caprini score at admission, immediately after the
operation, and upon discharge (Figure
25.2).
The risk of VTE can persist for several weeks after
operations, particularly among patients with malignancies. Furthermore, during an era in which hospital stays
have been eliminated or decreased in duration, some
patients may receive an insufcient amount of inpatient prophylaxis.
2
The Caprini score identies high-risk
patients who are candidates for an extended duration
of low-molecular-weight heparin prophylaxis beyond
hospital discharge. Among these select patients, 30 days
of chemoprophylaxis further reduce rates of VTE.
18,19
Therefore, pharmacological prophylaxis should continue after hospital discharge for patients who have elevated risk scores.
2
Surgeons at our medical center use Caprini scores
to define five risk levels and standardize risk-commensurate prophylaxis, including specific recommendations
about medications and their duration (Table25.2). We
administer 7–10 days of “extended prophylaxis” to
patients with Caprini scores 5–8 and 30 days of prophylaxis for scores 9 or higher. The extended courses provide low-molecular-weight heparin injections to select
patients following discharge from hospital. During the
past decade, this protocol has resulted in a substantial
and sustained reduction in the odds ratio of postoperative VTE.
2,16,17
Our team has a special interest in patients who develop
“breakthrough” VTE events despite having received prophylaxis in accordance with standards of care. We determined that perioperative sepsis, emergency operations, and
multiple operations put patients at signicant risk of VTE
complications even with typical anticoagulation, and we
have developed a protocol of “enhanced prophylaxis” for
these patients. This program adjusts dosages of low-molecular-weight heparin based upon anti–factor Xa levels to
ensure sufcient prophylaxis.
2,16
TABLE 25.1 Differences between the 2005 and 2013 versions of the Caprini Risk Score
BMI >25 kg/m
Operative time Minor surgery (≤45 min) = 1 point
Malignancy Current or history of cancer = 2 points Current or history of cancer = 2 points
Behaviors Not a risk factor Current smoking = 1 point
Other Not risk factors Insulin-dependent diabetes = 1 point
Abbreviations: BMI, body mass index.
Caprini 2005 Caprini 2013
2
Major surgery (>45 min) = 2 points
>40 kg/m
Minor surgery (≤45 min) =1 point
Major surgery (>45 min) = 2 points
Major surgery >2 h = 3 points
Chemotherapy = 1 point
Blood transfusion = 1 point
2
Risk Factor
t3
https://t.me/med1917
1 poin
Age 40-59 years Age 75 years or more
Minor surgery plannedHistory of DVT/PE
Recent major surgery (< 1 month) Family history of DVT/PE
Varicose veinsPresent chemotherapy
History of inflammatory bowel diseasePosive factor V Leiden
Swollen legs (current)Posive prothrombin 20210A
Obesity (BMI>30) Elevated serum homocysteine
Acute myocardial infarcon (<1 month) Posive Lupus ancoagulant
Congesve heart failure (<1 month) Elevated ancardiolipin anbodies
Sepsis (<1 month) Heparin-inducedthrombocytopenia (HIT)
Serious acute lung disease (<1 month) Other thrombophilia-Type
Abnormal pulmonary funcon(COPD)5 points
Medical paent currently at rest Major surgery lasng over 6 hours
Oral contracepves or hormone replacement therapyElecve major lower extremity arthroplasty
Pregnancyor postpartum (<1 month) Hip/pelvis, or leg fracture (<1 month)
Historyrecurrent spontaneousaboron Stroke (<1 month)
2 points Acute spinal cord injury (paralysis) (<1 moth)
Age 60-74
Major surgery (> 45 minutes)
Arthroscopic surgery
Laparoscopic surgery (>45 minutes)
Leg plaster or brace
Central venous access
Prior cancer (except non-melanoma skin)
Presentcancer(except breast or thyroid)
Paent confined to bed (>72 hours)
25.2 Current Boston Medical Center Caprini risk assessment.
25.3 Prophylaxis regimens 261
points
25
25.2.1 Machine learning applications of
the Caprini Risk Score
placebo, although the devices are most efcacious at reducing the risk of VTE when used in combination with phar-
macological prophylaxis.
As risk assessment models become more intricate, future
efforts may incorporate natural language processing
(“machine learning”) to extract patient risk factors from the
EMR and reliably calculate the probability of postoperative
2,11,17,18
VTE.
While this approach may eventually reduce the
time and effort necessary for clinicians to complete assessments, limitations of the EMR will still require clinicians to
make certain queries, especially eliciting high-yield factors
such as personal and family histories of VTE.
2,11
25.3.2 Inferior vena cava filter
Inferior vena cava (IVC) lters are primarily used when a
contraindication to anticoagulation exists. However, these
lters can migrate, fracture, and actually promote thrombosis. As a result, many quality initiatives encourage timely
retrieval of temporary IVC lters.
Interventional Radiology guidelines advise against routine
placement of IVC lters in the setting of trauma and major
operations and among patients who can be anticoagulated
25.3 PROPHYLAXIS REGIMENS
25.3.1 Mechanical prophylaxis
for established VTE.
placed for prophylaxis; instead, they should be reserved for
the presence of VTE when patients cannot tolerate thera-
peutic anticoagulation.
Postoperative VTE prophylaxis can include early ambulation, graduated compression stockings, and intermittent pneumatic compression. In fact, a core component
of Enhanced Recovery After Surgery (ERAS) programs is
early ambulation in addition to promptly removing catheters and drains, limiting opioids, and feeding early.
15,19
A Cochrane analysis demonstrated that graduated compression stockings reduce the risk of postoperative DVT
among general surgery and orthopedic surgery patients,
with or without other modalities of prophylaxis.
Pneumatic compression devices are commonly used in
hospital settings.
21,22
A meta-analysis demonstrated that
20
intermittent pneumatic compression is more effective than
25.3.3 Unfractionated heparin
Heparin functions by binding to antithrombinIII, block-
ing several factors in the coagulation cascade, particu-
larlythrombin (factor IIa) andfactor Xa. The inactivation
of thrombin disrupts the conversion of brinogen to brin.
The half-life of unfractionated heparin is 60–90 minutes,
and it is administered subcutaneously two or three times
daily to provide VTE prophylaxis. Side effects include
bleeding and heparin-induced thrombocytopenia, although
unfractionated heparin can be safely prescribed to patients
with end-stage renal disease.
21,22
23,24
The Society for
24
IVC lters are rarely and selectively
26,
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25.3.4 Low-molecular-weight heparin
Enoxaparin is a low-molecular-weight heparin and can
be injected subcutaneously. It has a longer half-life than
unfractionated heparin and so can be administered once
daily for prophylaxis. Enoxaparin is contraindicated in
patients with end-stage renal disease. In a randomized trial
of extended prophylaxis among patients undergoing total
hip arthroplasty (THA) and total knee arthroplasty (TKA),
enoxaparin was associated with fewer symptomatic VTE
events than were seen in patients who had received aspirin
alone (1.8% vs 3.5%).
High-risk patients may benet from escalating doses
of enoxaparin. Protocols titrating enoxaparin based upon
anti-Xa levels may be benecial for prophylaxis. This type of
regimen requires diligence among surgeons and pharmacists
as well as support embedded in the EMR. It will be interesting to determine the impact of protocol compliance and
anti-Xa levels upon the incidence of VTE.
decreased the incidence of VTE in trauma patients.
27
28
This strategy has
28–30
25.3.5 Fondaparinux
Fondaparinux is a selective factor Xa inhibitor that can
offer VTE prophylaxis. Fondaparinux is injected subcutaneously once daily and has 100% bioavailability. Its
onset of action is instant, its half-life is 17–21hours, and
its clearance is renal. Fondaparinux is a viable alternative
when heparin agents are contraindicated.
31
25.3.6 Rivaroxaban
Rivaroxaban is an oral direct factor Xa inhibitor. With a
half-life of 5–9 hours, it can be delivered once daily for
VTE prophylaxis, although it is contraindicated in patients
with end-stage renal disease. When compared to enoxaparin in the RECORD trial, rivaroxaban started 6–8hours
after THA and TKA was more effective in reducing the
incidence of the composite of symptomatic VTE and allcause mortality at 2 weeks.
major bleeding was similar for both cohorts at 2 weeks
(0.2% for both) and at the end of the planned medication
period (0.3% vs 0.2%).
32
In addition, the incidence of
25.3.7 Apixaban
Apixaban is another oral direct factor Xa inhibitor, but it
can be given to patients who have end-stage renal disease.
Its half-life is 9–14hours. In a randomized trial of patients
undergoing THA and TKA, apixaban was more effective
than enoxaparin in reducing the likelihood of VTE, and it
did not impart a greater risk of bleeding.
33
25.4 PROPHYLAXIS GUIDELINES
25.4.1 American College of Chest
Physicians
The current ACCP guidelines were issued in 2012 and analyzed medical patients, nonorthopedic surgery patients, and
orthopedic surgery patients.
3,4,8
For acutely ill nonsurgical
patients who are hospitalized (but not in an intensive care
unit) and at increased risk of VTE, the ACCP guidelines
recommend pharmacological prophylaxis with either
low-molecular-weight heparin, unfractionated heparin, or
fondaparinux. The guidelines do not recommend extended
prophylaxis when patients are mobile. For acutely ill hospitalized medical patients considered to be at low risk of
VTE, the ACCP standards advise against the use of pharmacological or mechanical prophylaxis. For acutely ill hospitalized medical patients at increased risk of thrombosis
but who are either bleeding or are at high risk for major
hemorrhage, the recommendations promote mechanical
measures with graduated compression stockings or intermittent pneumatic compression devices. For critically ill
patients (in an intensive care unit), the recommendations
include low-molecular-weight heparin or unfractionated
heparin; for patients at high risk for bleeding, mechanical
prophylaxis is preferred until the bleeding risk subsides.
The ACCP recommends no pharmacological or mechanical prophylaxis for nonorthopedic surgical patients when
VTE risk is very low (<0.5%). Early ambulation should
sufce. For patients at low VTE risk (∼1.5%), the guidelines suggest mechanical prophylaxis with intermittent
pneumatic compression. Moderate risk (∼3%) patients are
to receive low-molecular-weight heparin, unfractionated
heparin, or mechanical prophylaxis with intermittent pneumatic compression. High-risk patients are managed with
mechanical prophylaxis and either low-molecular-weight
heparin or unfractionated heparin. In high-risk patients
undergoing abdominal or pelvic operations for cancer, the
ACCP proposes 4 weeks of low-molecular-weight heparin
for prophylaxis. For patients at moderate or high risk of
VTE and at high risk of bleeding, mechanical prophylaxis is
advised until the prospects of bleeding decrease sufciently
to permit prophylactic anticoagulation. The standards do
not support either IVC lter placement for prophylaxis or
empiric sonographic lower extremity vein surveillance.
For orthopedic surgery patients, the ACCP guidelines
propose VTE prophylaxis for a minimum of 10–14 days,
with the option of extending prophylaxis to 35 days.
Low-molecular-weight heparin is the preferred medication, along with intermittent pneumatic compression
during the hospital stay. Mechanical prophylaxis is advised
for patients who have an increased risk of bleeding, and
apixaban is suggested for patients who decline injections.
The ACCP does not advocate either IVC lter placement
for prophylaxis or lower extremity surveillance with vein
ultrasonography after orthopedic operations.
3
8
25.4.2 American Society of Hematology
The American Society of Hematology released updated
VTE prophylaxis guidelines in 2018. For acutely ill medical patients, the standards include pharmacological anticoagulation with either unfractionated heparin, enoxaparin,
or fondaparinux, although the low-molecular-weight formulations are preferred. The society recommends unfractionated heparin or enoxaparin for critically ill medical
patients. Mechanical prophylaxis is advised for patients
in whom pharmacological prophylaxis is contraindicated.
Extended courses of prophylaxis beyond hospital discharge
are not recommended for medical patients.
34
25.5 Caprini risk assessment model 263
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25.5 CAPRINI RISK ASSESSMENT
MODEL
25.5.1 Joint arthroplasty
In a series of 873 patients, low-risk (dened as Caprini
scores ≤9 in arthroplasty) THA and TKA patients were
prescribed aspirin 81 mg twice daily for 6 weeks. High-risk
(Caprini >9 in arthroplasty) THA patients received oral
apixaban 2.5 mg twice daily for 5 weeks, and high-risk
TKA patients received oral apixaban 2.5 mg twice daily
for 12 days followed by aspirin 81 mg twice daily for 4
weeks. The overall incidence of VTE in the entire series
was 0.2%, including two DVTs in low-risk patients and
no events in the high-risk group. The rate of symptomatic
DVT after TKA was 0.35%, and there were no VTE events
after THA. Prior to the implementation of this protocol,
the overall rate of VTE had been 0.78% for hip and knee
arthroplasty. Bleeding complications were low and did not
differ between the groups.
25.5.2 Application of the Caprini Risk
Score in ambulatory surgery
patients
A NSQIP analysis revealed a 30-day incidence of VTE of
just 0.15% following outpatient operations, and so prophylaxis in that setting should be individualized. Independent risk factors included current pregnancy, active cancer,
age 41years or older, body mass index 40 kg/m
operative time 120 minutes or longer, arthroscopic surgery, and varicose vein operations. The weighted risk index
identied a 20-fold variation in 30-day VTE rates between
low- (0.06%) and highest-risk (1.18%) patients. More
investigations are warranted to guide prophylaxis for outpatient surgery.
36
25.5.3 Application of the Caprini Risk
Score in low-risk operations
Our Boston Medical Center team investigated the value of
the Caprini score in directing prophylaxis following operations that are thought to confer a low risk for VTE. One
study involved a retrospective review of 881 patients who
underwent lumpectomy or mastectomy (with or without
axillary surgery and/or reconstruction). The overall VTE
rate was 0.68%, but all of these patients were in the highor highest-risk categories. No patients at low or moderate
risk developed a VTE. Notably, none of the ve patients
who developed VTE complications after discharge had
been prescribed the recommended extended chemoprophylaxis. Conversely, none of the high- or highest-risk patients
who received appropriate extended prophylaxis developed
a VTE event. There was no correlation between bleeding
and chemoprophylaxis, whether applied solely in the hospital or for extended courses beyond discharge.
Another study assessed VTE and bleeding episodes
among patients undergoing thyroid or parathyroid operations. In this series of 978 consecutive patients, 27.7%
qualied as being at high or highest risk of developing a
35
2
or higher,
37
VTE. The only patient who developed a DVT was in the
highest-risk category but did not comply with the prescribed extended course of VTE prophylaxis. The overall
hematoma rate was 1.5%, consistent with historic reports,
but only one of these patients had received extended prophylaxis.
can identify high-risk patients who may benet from VTE
chemoprophylaxis, even with extended courses, as well
as low-risk patients who require no chemoprophylaxis.
This distinction is particularly important for operations in
which hemorrhage presents special concerns, although chemoprophylaxis did not seem to promote bleeding in either
of these series.
38
These studies demonstrate that the Caprini protocol
25.5.3.1 Application of the Caprini Risk Score
in medical patients
The Caprini risk assessment model is not widely used
for VTE risk assessment in internal medicine.
ysis from the University of Michigan yielded a VTE rate
of 1.05% within 90 days of hospital admission among
63,548 medical patients. The mean risk score was 4.9, and
there was a positive linear correlation between the development of VTE events and scores ≤10. Pharmacological
prophylaxis reduced the VTE rate by 15%, although no
specic Caprini score cutoff established a clear benet
for prophylaxis.
patients with malignancies showed that the Caprini score
would have identied 82.4% of VTE events and recommended pharmacological prophylaxis.
has also been highly predictive of VTE among patients who
were admitted for stroke.
nonsurgical hospitalized patients include the Padua Prediction Score as well as the IMPROVE score.
39
Asingle-center analysis of hospitalized
40
The Caprini score
41
Other risk prediction scores for
42
2
An anal-
25.5.4 Application of the Caprini Risk
Score in patients with COVID-19
Investigators retrospectively examined inpatients with
COVID-19 to dene the predictive ability of the Caprini
risk assessment model in this setting, and they identied a
signicant correlation between the Caprini value and the
likelihood of VTE. Scores were calculated twice, initially by
the physician upon admission and later by the investigator
based on data available at discharge or death. The series
utilized the 2005 Caprini score and a modied version
of the score that also included D-dimer elevation and the
severity of COVID-19 symptoms. The primary endpoint
was symptomatic VTE, and patients received prophylactic
or therapeutic enoxaparin based upon clinical condition.
The original 2005 Caprini score provided the highest predictability when it was calculated at discharge or death.
43
25.5.5 Practical advice for implementing
the Caprini risk assessment model
Principles of standardization, automation, and ease of use
have guided the implementation of the Caprini risk assessment model in the EMR at many institutions, including
ours. Numerical VTE risk scores are automatically added to
25
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