Blood. 2002 May 1;99(9):3102-10.

How we diagnose and treat deep vein

thrombosis.
Hirsh J1, Lee AY.
Author information

1
Henderson Research Centre, and the Department of Medicine,
McMaster University, Hamilton, Ontario, Canada.
jhirsh@thrombosis.hhscr.org

Abstract
Making a diagnosis of deep vein thrombosis (DVT) requires both
clinical assessment and objective testing because the clinical
features are nonspecific and investigations can be either falsely
positive or negative. The initial step in the diagnostic process is to
stratify patients into high-, intermediate-, or low-risk categories using
a validated clinical model. When the clinical probability is
intermediate or high and the venous ultrasound result is positive,
acute symptomatic DVT is confirmed. Similarly, when the probability
is low and the ultrasound result is normal, DVT is ruled out. A low
clinical probability combined with a negative D-dimer result can also
be used to rule out DVT, thereby obviating the need for
ultrasonography. In contrast, when the clinical assessment is
discordant with the results of objective testing, serial venous
ultrasonography or venography is required to confirm or refute a
diagnosis of DVT. Once a patient is diagnosed with an acute DVT,
low-molecular-weight heparin (LMWH) is the agent of choice for initial
therapy and oral anticoagulant therapy is the standard for long-term
secondary prophylaxis. Therapy should continue for at least 3
months; the decision to continue treatment beyond 3 months is made
by weighing the risks of recurrent thrombosis and anticoagulant-
related bleeding, and is influenced by patient preference. Screening
for associated thrombophilia is not indicated routinely, but should be
performed in selected patients whose clinical features suggest an
underlying hypercoagulable state. Several new anticoagulants with
theoretical advantages over existing agents are undergoing
evaluation in phase 3 studies in patients with venous
thromboembolism.
Blood. 2010 Jan 7;115(1):15-20. doi: 10.1182/blood-2009-09-241851. Epub 2009
Oct 30.
The new oral anticoagulants.
Garcia D1, Libby E, Crowther MA.
Author information

1
University of New Mexico, MSC08-4630, 900 Camino de Salud NE,
Albuquerque, NM 87131-0001. davgarcia@salud.unm.edu
Abstract
Although their first application in clinical practice occurred in the
1940s, vitamin K antagonists remain the only form of oral
anticoagulant medication approved for long-term use. Although the
available vitamin K antagonists are highly effective for the prevention
and/or treatment of most thrombotic disease, the significant
interpatient and intrapatient variability in dose-response, the narrow
therapeutic index, and the numerous drug and dietary interactions
associated with these agents have led clinicians, patients, and
investigators to search for alternative agents. Three new orally
administered anticoagulants (apixaban, dabigatran, and rivaroxaban)
are in the late stages of development and several others are just
entering (or moving through) earlier phases of investigation. These
novel anticoagulant medications are being studied for the prevention
and treatment of venous thromboembolism, the treatment of acute
coronary syndromes and the prevention of stroke in patients with
atrial fibrillation. This review summarizes published clinical trial data
pertinent to apixaban, dabigatran, and rivaroxaban.
Ann Intern Med. 2004 Jun 1;140(11):867-73.
Fondaparinux or enoxaparin for the initial
treatment of symptomatic deep venous
thrombosis: a randomized trial.
Bller HR1, Davidson BL, Decousus H, Gallus A, Gent M, Piovella F, Prins
MH, Raskob G, Segers AE, Cariou R, Leeuwenkamp O, Lensing AW; Matisse
Investigators.
Author information

Abstract
BACKGROUND:
The current standard initial therapies for deep venous thrombosis are
low-molecular-weight heparin and unfractionated heparin. In a dose-
ranging study of patients with symptomatic deep venous thrombosis,
fondaparinux had efficacy and a safety profile similar to those of low-
molecular-weight heparin (dalteparin).
OBJECTIVE:
To evaluate whether fondaparinux has efficacy and safety similar to
those of enoxaparin in patients with deep venous thrombosis.
DESIGN:
Randomized, double-blind study.
SETTING:
154 centers worldwide.
PATIENTS:
2205 patients with acute symptomatic deep venous thrombosis.
INTERVENTION:
Fondaparinux, 7.5 mg (5.0 mg in patients weighing <50 kg and 10.0
mg in patients weighing >100 kg) subcutaneously once daily, or
enoxaparin, 1 mg/kg of body weight, subcutaneously twice daily for at
least 5 days and until vitamin K antagonists induced an international
normalized ratio greater than 2.0.
MEASUREMENTS:
The primary efficacy outcome was the 3-month incidence of
symptomatic recurrent venous thromboembolic complications. The
main safety outcomes were major bleeding during initial treatment
and death. An independent, blinded committee adjudicated all
outcomes.
RESULTS:
43 (3.9%) of 1098 patients randomly assigned to fondaparinux had
recurrent thromboembolic events compared with 45 (4.1%) of 1107
patients randomly assigned to enoxaparin (absolute difference, -0.15
percentage point [95% CI, -1.8 to 1.5 percentage points]). Major
bleeding occurred in 1.1% of patients receiving fondaparinux and
1.2% of patients receiving enoxaparin. Mortality rates were 3.8% and
3.0%, respectively.
LIMITATIONS:
Follow-up was incomplete in 0.4% of fondaparinux-treated patients
and 1.0% of enoxaparin-treated patients.
CONCLUSIONS:
Once-daily subcutaneous fondaparinux was at least as effective (not
inferior) and safe as twice-daily, body weight-adjusted enoxaparin in
the initial treatment of patients with symptomatic deep venous
thrombosis.
 TINJAUAN PUSTAKA

Arterioscler Thromb Vasc Biol. 1995 Feb;15(2):258-68.

Venous thrombosis-associated inflammation and attenuation

with neutralizing antibodies to cytokines and adhesion
molecules.
Wakefield TW 1, Strieter RM, Wilke CA, Kadell AM, Wrobleski SK, Burdick MD, Schmidt R, Kunkel
SL, Greenfield LJ.
Author information

Erratum in

Arterioscler Thromb Vasc Biol 1995 Apr;15(4):550.

Abstract
Thrombosis and inflammation are closely related. However, the response of the vein wall
to venous thrombosis has been poorly documented. This study examines the hypothesis
that venous thrombosis is associated with an inflammatory response in the vein wall. In a
rat model of inferior vena caval thrombosis, vein wall was temporally examined for
inflammation by assessment of histopathology, leukocyte morphometrics, and cytokine
levels. Animals were killed 1 hour and 1, 3, and 6 days after thrombus induction. Our
findings demonstrated an early (day 1) neutrophil infiltration into the vein wall followed by
a later (days 3 and 6) monocyte/macrophage and lymphocyte response. Cytokines were
elevated only under conditions of venous thrombosis. Levels of epithelial neutrophil
activating protein-78 (ENA-78), tumor necrosis factor-alpha (TNF), interleukin-6, and
JE/monocyte chemoattractant protein-1 (JE/MCP-1) increased over the 6-day period,
while macrophage inflammatory protein-1 alpha (MIP-1 alpha) peaked at day 3 after
thrombus induction. Additionally, rats were passively immunized with neutralizing
antibodies to TNF, ENA-78, MIP-1 alpha, JE/MCP-1, intercellular adhesion molecule-1
(ICAM-1), and CD18 compared with control antibodies. The most effective antibody early
after thrombus induction for attenuating vein wall neutrophil extravasation was anti-TNF
(P < .01). The monocyte/macrophage extravasation was inhibited most by anti-ICAM-1
followed by anti-TNF (P < .01). These findings demonstrate that venous thrombosis is
associated with significant vein wall inflammation that is partially inhibited by neutralizing
antibodies to cytokines and adhesion molecules.
 NCBI

Clin Med Res. 2010 Dec; 8(3-4): 168172.

doi: 10.3121/cmr.2009.866
PMCID: PMC3006583
Virchows Contribution to the
Understanding of Thrombosis and Cellular
Biology
David R. Kumar, BS,* Erin Hanlin, BS, Ingrid Glurich, PhD, Joseph J.
Mazza, MD, and Steven H. Yale, MD
Author information Article notes Copyright and License information
This article has been cited by other articles in PMC.

Few physician-scientists have contributed as much to the

fundamental understanding of the pathophysiology of cellular
biology as Rudolf Virchow. His contribution to the cellular
biomedicine paradigm along with the germ theory of Pasteur
and Koch formed the basis for many of the medical advances of
the twentieth century.1 He was one of the first physicians to
examine disease at the cellular level, arguing that the origin of
disease was caused by cellular pathology. One area that he
studied extensively, and in which he has left lasting
contributions to modern medicine, was in the area of
thrombosis, specifically venothromboembolism (VTE). For
much of the later half of the twentieth century, the so-called
Virchows Triad has formed the basis for understanding the
pathogenesis of VTE and is still widely used to assess VTE
risk.2 In order to assess and appreciate the applicability of
Virchows Triad to current medical practices, it is important first
to examine how the principals of Virchows original theory of
thrombosis continue to be applicable to modern day theory.
Go to:
VIRCHOW AT A GLANCE
Virchow was born in Pomeranian Prussia on October 13, 1821,
and attended the Friederich-Wilheim Institute, a division of the
University of Berlin, graduating in 1843.3 His writings as a
student were as diverse as his later work and included essays
such as Rheumatic Disease, Particularly of the Cornea and
Only the Liberal Minded Can Gain Insight into the Future of
Medicine.3 After graduation, Virchow quickly gained success
as a clinician and researcher, and was appointed company
surgeon at the military medical center Charit Hospital in 1845,
at the age of 24.3 He presented a paper to an audience consisting
mainly of his superiors entitled On the Need and Correctness of
Medicine Based on a Mechanistic Approach in which he
emphasized the need for research based on clinical observation,
experimentation in animals, and necropsy.4 In 1856, Virchow
published a collection containing ten years of previous work
titled Collective Treatises on Scientific Medicine, which
contained his detailed studies of embolization following venous
thrombosis.4 In 1847, he taught courses in pathological
anatomy, and with Reinhardt as co-author, published the first
volume of Archives for Pathological Anatomy and Physiology
and Clinical Medicine.3
Go to:
POLITICS
Virchow was active in politics and medical reform. In 1847, a
typhus epidemic occurred in Upper Silesia, a Prussian province
inhabited by a Polish minority. Virchow was appointed to
survey the medical situation. In his report, he admonished the
government for the epidemic and stated, the answer to the
question of how to prevent outbreaks in Upper Silesia is quite
simple: education, together with its daughters, freedom and
welfare.5 His experiences in Upper Silesia were to be the
foundation for his political career. He argued that the physician
is the natural attorney for the poor, and that the improvement
of medicine would eventually prolong human life, but
improvement of social conditions could achieve this result now
more rapidly and more successfully.6,7 In Prussia, the mid to
late 19th Century was dominated by Nationalistic views that de-
emphasized the importance of individual liberties and interests.8
As a result, many of Virchows proposed ideas that were aimed
at the health and well-being of the individual were considered
radical or extreme. In addition to being a proponent for
democracy, the separation of church and state, and social
welfare programs, some of Virchows other ideas included
medical care for the impoverished, prohibition of child labor,
protection for pregnant women, decrease of the work day in
hazardous jobs, and improved working conditions.7,9
Revolutionary at the time, these principles have become
commonplace in 21st century politics.
The idea of medical social justice would permeate most of his
life. He participated in the revolutions in Berlin and was elected
to the Berlin City Council, where his focus was on improving
public health by developing systems for water and sewer
disposal, advocating for school physicians, and providing input
to cities and states in the planning of hospitals.10 He also played
a crucial role in establishing the capitals medical statistics,
which monitored and recorded death rates, infant mortality, and
causes of death.11 Consequently, this improved the standard of
care as it gave physicians and health care workers a way to
measure outcomes and focus on areas that needed improvement.
He co-founded the German Progressive Party and was elected
into the Prussian parliament and later to the Reichstag.3 He
stood in staunch opposition to Prussian Chancellor Otto von
Bismarck, who was so incensed that the Chancellor challenged
Virchow to a duel. All his work for medical reform and social
justice has earned him the modern title of the father of social
medicine.7
As a result of his political stance regarding the epidemic in
Upper Silesia, Virchow was suspended from Charit in 1849.
Upon his dismissal from Charit, he was able to secure a
professorship at the University of Wrzburg in Bavaria and
became Chair of the Department of Pathological Anatomy.9,12
He was later asked to return to Berlin to teach pathological
anatomy, but agreed only under the condition that a special
building to house a new pathological institute be erected;
consequently, the Berlin Pathological Institute was built.9,12
The institute would train many scientists who would later
become leaders in their fields including Friedrich von
Recklinghausen, who served as one of Virchows assistants, and
William Osler, who stayed at the institute for 3 months in
1873.3,13
In 1858, Virchow presented a series of 20 lectures to a group of
practicing physicians in Berlin at the Institute of Pathology.10
These lectures were subsequently published that same year in a
book entitled Cellular Pathology as Based upon Physiological
and Pathological Histology (English Translation).11,14 He was
the first to postulate that the basic units of life are the self-
reproducing cells of living bodies, and he summarized this cell
theory with the Latin phrase omnis cellula a cellula [all cells
arise from cells].11,15,16 Although Schleiden (1838) and
Schwann (1839) had previously described cells as building
blocks of all plants and animals, Schwanns theory was that the
intercellular substance called the cytoblastema was the origin of
new cells.15,17 Virchow, on the other hand, argued that new
cells arose from old cells and that the intercellular space was
excreted by existing cells.3,15,17
It was also during these lectures that Virchow outlined what has
become the modern paradigm for pathology. Virchow theorized
that pathogenesis originated at the cellular level from single
cells. This theory would later be called cellular pathology. He
outlined systematic methods for the field of pathology based on
experimentation and observation, and demonstrated that cell
theory applied to both diseased and healthy tissue.16,17 Virchow
noted that the organism as a whole did not become diseased but
instead only certain cells or group of cells. In his lecture
Physiological and Pathological Tissues, Virchow stated that
every pathological structure has a physiological prototype.15 In
attempting to explain the transition between the physiological
and the pathological before the word mutation had been coined,
Virchow wrote, In the place of the law of continuity, therefore,
we must place something else. And here, I think, the doctrine
that has the strongest claim to our attention is histological
substitution. Here Virchow was attempting to define what
would later be coined metaplasia.15
Go to:
EARLY WORK ON THROMBOSIS
Virchow began his research of thrombosis and pulmonary
embolism by describing a blood clot as a network of fibers
where blood cells have become embedded.14 Virchow created
the terms thrombosis and embolism and argued that a clot in the
pulmonary arteries or veins is not de novo but instead originates
in the peripheral vascular system.4,14 He described the
pathogenesis of pulmonary embolization as a process wherein:
New masses of coagulum deposit themselves from the blood
upon the end of the thrombus layer after layer. The thrombus is
prolonged beyond the mouth of the branch into the trunk in the
direction of the current of the blood, shoots out in the form of a
thick cylinder farther and farther, and becomes continually
larger and larger. It is these prolonged plugs that constitute the
source of real danger; it is in them that ensues the crumbling
away, which leads to secondary occlusions in remote vessels.
Thus we see that as a rule all the thrombi from the periphery of
the body produce secondary obstructions and metastatic
deposits [emboli] in the lungs.14

He noted that the symptoms of pulmonary embolism ranged

from sudden death to silent emboli.18
In 1856, Virchow described the consequences of a pulmonary
embolus that migrated from the venous circulation, which later
came to be known as Virchows Triad.4,19,20 As it is has come
to be known today, the triad consists of stasis, vessel damage,
and hypercoagulability, and is used to describe the etiology and
assess the risk of thrombosis, especially of deep vein thrombosis
(DVT.)2,19
Standing the test of time, it is still believed that at least 2 of
these 3 factors occurring concurrently increase a patients risk of
developing DVT; stasis is thought to be the most predominant
of the 3 factors, and when combined with either
hypercoagulability or vessel damage a clot usually forms.21
Abnormalities of rheological properties of blood cells caused by
such factors as turbulence at bifurcations and large vessels
burdened by an irregular lumen (eg, atheroma or stenotic
regions) results in stasis.22 Clinically, stasis may be manifest by
such factors as immobilization; limb paralysis due to stroke,
plaster cast or spinal injury; heart failure; varicose veins; and
chronic venous insufficiency.23 Vascular damage is the result of
any abnormality affecting the vessel wall resulting in disruption
to the endothelium.22 Direct or indirect vessel injury may arise
from recent surgery, central venous catheter, trauma,
chemotherapy, vasculitis, sepsis, and hyperhomocysteinemia.23
Finally, abnormalities in platelets as well as in the coagulation
and fibrinolytic pathways contribute to hypercoagulability.22
Go to:
ATTRIBUTION OF VIRCHOWS TRIAD
Recently, there has been much debate surrounding the origin of
Virchows Triad, which has resulted in a closer inspection of his
experiments on thrombosis and emboli (1856) to determine if
his findings have indeed become misinterpreted over
time.4,20,24 In fact, mention of a Virchows Triad does not occur
in either books or journal articles until 1950 and even later than
that in major pathology texts.4,20
In his description about 200 years prior to Virchow, Richard
Wiseman, a surgeon to King Charles II, provides two factors,
depending of the Part or from some other pressure upon the
Vessel and by its own [the bloods] grossness, to explain
thrombosis. These factors have now come to be known as
stasis and hypercoagulability respectively, which are two of
the three tenets of Virchows Triad.4 Gabriel Andral, who is
considered the founder of hematology, observed in 1830,
decades before Virchow, that stasis, inflammation of the
endothelium, and an increased tendency for the blood to
coagulate are all risk factors for venous thrombosis.20,24
The humoral theory of disease, presuming that all diseases start
in the blood, was still an important component of medicine at
the start of Virchows career. The age of Romanticism still
permeated medicine in Germany in the 19th century, with
hypotheses being put forward based on little evidence and little
importance placed on observation and experimentation.8,9,13,25
Robert Froriep, a professor of Virchow who exposed him to the
more progressive scientific ideas of France and England,
challenged Virchow to disprove the notion that phlebitis
dominates all pathology, a claim made by French pathologist
Jean Cruveilhier.3,4,16,20 Not only was phlebitis believed to be
the precursor for all diseases, but it was also thought to be the
cause of pulmonary thrombosis.4,20 Lastly, many of Virchows
contemporaries believed that thrombi in the pulmonary arteries
formed de novo in the pulmonary circulation rather than initially
forming in the venous circulation.4,19
Virchow approached his experiment with the goal of
demonstrating that inflammation is secondary to thrombosis,
and pulmonary thrombosis does not occur in situ but arises in
the venous circulation.4 After performing a series of
experiments in which foreign objects were introduced into the
jugular vein of dogs, it was observed that the blood was able to
carry these foreign bodies to the pulmonary arteries.4,19 These
experiments supported the hypothesis that the inflammation is a
secondary phenomenon to thrombosis, and pulmonary emboli
result from thrombus within the venous circulation.4,19 Virchow
then examined the pulmonary embolus in greater detail and
stated:
In all cases the blood formed more or less extensive clots
around the introduced body the list of possible consequences
of the obstruction could be grouped into three categories;
Phenomena due to the irritation of the vessel and its
surroundings;
Phenomena due to blood coagulation;
Phenomena due to the interruption of the bloodstream26

While this can be misconstrued to be the factors involved in

increasing ones risk for DVT (ie, endothelial damage,
hypercoagulability, and stasis), it is clear that Virchow was
trying to explain the consequences of a pulmonary
embolism.4,20 However, we may be able to overlook this
nuance if we realize that the three factors resulting from a
thrombus are the same factors involved in the formation of a
thrombus.4,19 The fact that Virchow never appeared to link the
two should not detract from his findings. Similar to the way in
which advances are brought forth in other disciplines, it is
through the collective work of many that lead to the most
 ground-breaking and revolutionary discoveries. It was as a result
of Virchows emphasis on clinical observation, experimentation,
pathological anatomy, and the desire to obtain evidence to
support his hypotheses that allowed for the breakthrough to
finally occur.4

CMAJ. 2006 Oct 24;175(9):1087-92.

Diagnosis and treatment of deep-vein thrombosis.

Scarvelis D1, Wells PS.
Author information

Erratum in

CMAJ. 2007 Nov 20;177(11):1392.

Abstract
Deep-vein thrombosis (DVT) is a common condition that can lead to complications such
as postphlebitic syndrome, pulmonary embolism and death. The approach to the
diagnosis of DVT has evolved over the years. Currently an algorithm strategy combining
pretest probability, D-dimer testing and compression ultrasound imaging allows for safe
and convenient investigation of suspected lower-extremity thrombosis. Patients with low
pretest probability and a negative D-dimer test result can have proximal DVT excluded
without the need for diagnostic imaging. The mainstay of treatment of DVT is
anticoagulation therapy, whereas interventions such as thrombolysis and placement of
inferior vena cava filters are reserved for special situations. The use of low-molecular-
weight heparin allows for outpatient management of most patients with DVT. The
duration of anticoagulation therapy depends on whether the primary event was idiopathic
or secondary to a transient risk factor. More research is required to optimally define the
factors that predict an increased risk of recurrent DVT to determine which patients can
benefit from extended anticoagulant therapy.

PMID:

17060659

PMCID:

PMC1609160

DOI:
 10.1503/cmaj.060366
[Indexed for MEDLINE]
Free PMC Article

Circ Res. 2011 May 13;108(10):1284-97. doi: 10.1161/CIRCRESAHA.110.233056.

Microparticles in hemostasis and thrombosis.

Owens AP 3rd1, Mackman N.
Author information
Abstract
Blood contains microparticles (MPs) derived from a variety of cell types, including
platelets, monocytes, and endothelial cells. In addition, tumors release MPs into the
circulation. MPs are formed from membrane blebs that are released from the cell surface
by proteolytic cleavage of the cytoskeleton. All MPs are procoagulant because they
provide a membrane surface for the assembly of components of the coagulation protease
cascade. Importantly, procoagulant activity is increased by the presence of anionic
phospholipids, particularly phosphatidylserine (PS), and the procoagulant protein tissue
factor (TF), which is the major cellular activator of the clotting cascade. High levels of
platelet-derived PS(+) MPs are present in healthy individuals, whereas the number of
TF(+), PS(+) MPs is undetectable or very low. However, levels of PS(+), TF(+) MPs are
readily detected in a variety of diseases, and monocytes appear to be the primary cellular
source. In cancer, PS(+), TF(+) MPs are derived from tumors and may serve as a useful
biomarker to identify patients at risk for venous thrombosis. This review will summarize
our current knowledge of the role of procoagulant MPs in hemostasis and thrombosis.

PMID:

21566224

PMCID:

PMC3144708

DOI:

10.1161/CIRCRESAHA.110.233056
[Indexed for MEDLINE]
Free PMC Article

Med Clin North Am. 2003 Nov;87(6):1157-64.

Calf deep venous thrombosis should be treated with
anticoagulation.
Deitcher SR1, Caprini JA.
Author information
Abstract
A 50-year-old man with hypertension presents with a 2-day history of right calf swelling
and pain. Venous duplex ultrasound reveals a right soleal vein thrombosis. He denies
history of bleeding, renal disease, and symptoms suggestive of pulmonary embolism
(PE). Physical examination is unrevealing except for calf tenderness, redness, warmth,
and swelling. He is ambulatory. A decision is made to treat the calf deep venous
thrombosis (DVT) with anticoagulation.

PMID:

14680297
[Indexed for MEDLINE]

BMC Cardiovasc Disord. 2014; 14: 178.

Published online 2014 Dec 8. doi: 10.1186/1471-2261-14-178
PMCID: PMC4292826
Should we look for silent pulmonary
embolism in patients with deep venous
thrombosis?
Maria Jos Garca-Fuster, Maria Jos Fabia, Elena Furi, Gernot
Pichler, Josep Redon, Maria Jos Forner, and Fernando Martnez
Author information Article notes Copyright and License information

Go to:
Abstract
Background
Asymptomatic or silent pulmonary embolism (S-PE) in patients
with deep vein thrombosis has been the focus of numerous
publications with the objective of determining the incidence of
S-PE and assessing whether its existence has any clinical or
therapeutic consequences that outweigh the risks associated with
the diagnostic tests performed and the increased healthcare
costs. The objectives were to assess the incidence of S-PE using
computed tomography angiogram (CTA), to understand the
epidemiological factors that might trigger embolism, and to
assess whether D-dimer (DD) predicts the existence of S-PEs.
Methods
A prospective and consecutive assessment of 103 hospitalized patients with lower
limb DVT in the absence of PE symptoms, using CT scan. DD was quantified before
anticoagulation. The risk factors and characteristics of the DVT were studied. A
three-year follow-up assessing risk recurrence and clinical outcome was performed.

Results
The incidence of S-PE was 66%. In 77% of these cases, the main and lobar
pulmonary arteries were affected. Iliac and femoral DVTs most often produced S-PE.
ROC curve with a DD value higher than 578 ng/ml provided good sensitivity but low
specificity to identify patients with S-PE. Diagnosis entailed higher hospitalization
expenses. No significant recurrence rate of thrombotic events was observed in the S-
PE group during the follow-up.

Conclusions
The incidence of S-PE in lower-limb DVT is high, but in the absence of symptoms,
diagnosis does not appear to be necessary, as there are no short- or long-term clinical
or therapeutic consequences.
Keywords: Pulmonary embolism, Deep vein thrombosis, D-dimer

Arterioscler Thromb Vasc Biol. 2010 Apr;30(4):669-74. doi: 10.1161/ATVBAHA.109.200766.

Indications for catheter-directed thrombolysis in the

management of acute proximal deep venous thrombosis.
Patterson BO1, Hinchliffe R, Loftus IM, Thompson MM, Holt PJ.
Author information
Abstract
Deep vein thromboses (DVTs) cause significant morbidity and mortality in the general
population. Oral anticoagulation therapy may reduce thrombus propagation but does not
cause clot lysis and therefore does not prevent postthrombotic syndrome (PTS).
Catheter-directed thrombolysis (CDT) can be used to treat DVTs as an adjunct to
medical therapy, but there is no consensus defining exact indications. Current evidence
suggests that CDT can reduce clot burden and DVT recurrence and consequently
prevents the formation of PTS compared with systemic anticoagulation. Appropriate
indications include younger individuals with acute proximal thromboses, a long life
expectancy, and relatively few comorbidities. Limb-threatening thromboses may also be
treated with CDT, although the subsequent mortality remains high. A number of
randomized controlled trials are currently under way comparing the longer-term
outcomes of CDT compared with anticoagulation alone. Initial reports suggest that
venous patency and valvular function are better maintained after CDT. The effectiveness
of combined pharmacomechanical thrombectomy and the role of vena cava filters need
to be investigated further before strong recommendations can be made. The reported
short-term outcomes following catheter-based intervention for DVT are encouraging in
selected patients. Further evidence is required to establish long-term benefits and cost-
effectiveness.

PMID:

20237328

DOI:

10.1161/ATVBAHA.109.200766

CMAJ October 24, 2006 vol. 175 no. 9 doi: 10.1503/cmaj.060366

Review
Diagnosis and treatment of deep-
vein thrombosis
Dimitrios Scarvelis, Philip S. Wells
+
Author Affiliations
From the Departments of Medicine (Scarvelis, Wells) and of
Community Medicine and Epidemiology (Wells), the Division of
Hematology (Scarvelis, Wells), and the Ottawa Health Research
Institute (Scarvelis, Wells), University of Ottawa, Ottawa, Ont.
Correspondence to:
Dr. Dimitrios Scarvelis, Division of Hematology, The Ottawa
Hospital, Rm. 462, 737 Parkdale Ave., Ottawa ON K1Y 1J8; fax 613
761-4840; dscarvelis@ottawahospital.on.ca
Abstract
Deep-vein thrombosis (DVT) is a common condition that can lead to
complications such as postphlebitic syndrome, pulmonary embolism and
death. The approach to the diagnosis of DVT has evolved over the years.
Currently an algorithm strategy combining pretest probability, D-dimer
testing and compression ultrasound imaging allows for safe and
convenient investigation of suspected lower-extremity thrombosis. Patients
with low pretest probability and a negative D-dimer test result can have
 proximal DVT excluded without the need for diagnostic imaging. The
mainstay of treatment of DVT is anticoagulation therapy, whereas
interventions such as thrombolysis and placement of inferior vena cava
filters are reserved for special situations. The use of low-molecular-weight
heparin allows for outpatient management of most patients with DVT. The
duration of anticoagulation therapy depends on whether the primary event
was idiopathic or secondary to a transient risk factor. More research is
required to optimally define the factors that predict an increased risk of
recurrent DVT to determine which patients can benefit from extended
anticoagulant therapy.

Format: Abstract

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J Thromb Haemost. 2009 May;7(5):879-83. doi: 10.1111/j.1538-7836.2009.03294.x. Epub 2009 Jan 19.

Definition of post-thrombotic syndrome of the leg for use in

clinical investigations: a recommendation for standardization.
Kahn SR1, Partsch H, Vedantham S, Prandoni P, Kearon C; Subcommittee on Control of
Anticoagulation of the Scientific and Standardization Committee of the International Society on
Thrombosis and Haemostasis.
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Abstract
SUMMARY:
The post-thrombotic syndrome (PTS) is increasingly recognized to be a common and
important complication of deep venous thrombosis (DVT). Because there is no 'gold
standard' objective test to establish its presence, PTS is diagnosed primarily on the basis
of the presence of typical symptoms and clinical signs in a limb that was affected by DVT.
As a wide variety of definitions of PTS have been used by researchers, it is difficult to
compare data across studies and to formally combine data in meta-analyses. In a step
towards standardization of the measurement of PTS in clinical studies, available scales
and evidence to support their utility to diagnose PTS and to classify its severity were
reviewed and discussed at the Control of Anticoagulation Subcommittee of the
International Society on Thrombosis and Haemostasis (Vienna, July 2008)