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“I Have a History of TTP or AHUS. Can I Become Pregnant?”
Table 12 Controversies and unresolved issues in TTP and AHUS
Reliable assays with rapid turnaround times are needed to improve the management of TTP
Fast blockers of VWF-platelet aggregation
These agents are needed for TTP with severe organ dysfunction or refractory to PEx
The beneﬁts of corticosteroids, commonly prescribed for acquired TTP, are questionable
The potential beneﬁts for de novo cases of acquired TTP remain to be determined
Prevention of late TTP relapses
ADAMTS13-guided prophylactic rituximab has been effective for late TTP relapses
More experience is needed to determine its optimal schedule and overall efﬁcacy
Alternatives of rituximab when it is ineffective or not tolerated
The efﬁcacy of cyclosporine A and acetylcysteine remains uncertain
Bortezomib (Yates et al. 2014) and other immunomodulation drugs deserve further investigation
Distinction between exacerbation and relapse
The current distinction is arbitrary
A biologic basis for the distinction remains elusive
Current mutation analysis does not identify all cases with defective complement regulation
It also does not provide overall assessment of the severity in regulation defects
Global quantitative assays of complement regulation defects are needed
Patients with certain C5 mutations that affect its binding with eculizumab
Eculizumab may not be effective
Alternatives therapies are needed
Duration of eculizumab therapy
In retrospective analysis, approximately 40 % of patients do well without maintenance therapy
A priori identiﬁcation of these patients would help abdicate unnecessary maintenance therapy
Inhibitors of C3 activation
Will the approach provide additional beneﬁt without serious adverse effects?
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PM. Mild to moderate reduction of a von Willebrand
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F, Martinez F, Ji W, Overton JD, Mane SM, NÃürnberg
G, AltmÃüller J, Thiele H, Morin D, Deschenes G,
Baudouin V, Llanas B, Collard L, Majid MA, Simkova
E, NÃürnberg P, Rioux-Leclerc N, Moeckel GW,
Gubler MC, Hwa J, Loirat C, Lifton RP. Recessive
mutations in DGKE cause atypical hemolytic-uremic
syndrome. Nat Genet. 2013;45:531–6.
Nishimura J, Yamamoto M, Hayashi S, Ohyashiki K,
Ando K, Brodsky AL, Noji H, Kitamura K, Eto T,
Takahashi T, Masuko M, Matsumoto T, Wano Y,
Shichishima T, Shibayama H, Hase M, Li L, Johnson
K, Lazarowski A, Tamburini P, Inazawa J, Kinoshita T,
Kanakura Y. Genetic variants in C5 and poor response
to eculizumab. N Engl J Med. 2014;370:632–9.
Noris M, Galbusera M, Gastoldi S, Macor P, Banterla F,
Bresin E, Tripodo C, Bettoni S, Donadelli R, Valoti E,
Tedesco F, Amore A, Coppo R, Ruggenenti P, Gotti E,
Remuzzi G. Dynamics of complement activation in
aHUS and how to monitor eculizumab therapy. Blood.
Sanchez-Luceros A, Farias CE, Amaral MM, Kempfer
AC, Votta R, Marchese C, Salviu MJ, Woods AI,
Meschengieser SS, Lazzari MA. von Willebrand
factor-cleaving protease (ADAMTS13) activity in
normal non-pregnant women, pregnant and postdelivery women. Thromb Haemost. 2004;92:1320–6.
Scully M, Thomas M, Underwood M, Watson H, Langley
K, Camilleri RS, Clark A, Creagh D, Rayment R,
McDonald V, Roy A, Evans G, McGuckin S, Ni AF,
Maclean R, Lester W, Nash M, Scott R, Brien
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nancy: presentation, management, and subsequent
pregnancy outcomes. Blood. 2014;124:211–9.
Tati R, Kristoffersson AC, Stahl AL, Rebetz J, Wang L,
Licht C, Motto D, Karpman D. Complement activation
associated with ADAMTS13 deﬁciency in human and
murine thrombotic microangiopathy. J Immunol.
Tsai HM. Thrombotic thrombocytopenic purpura and the
atypical hemolytic uremic syndrome: an update.
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Yates S, Matevosyan K, Rutherford C, Shen YM, Sarode
R. Bortezomib for chronic relapsing thrombotic
thrombocytopenic purpura: a case report. Transfusion.
of Thromboembolic Disease
Kamran M. Karimi and Peter Gloviczki
Acute venous thromboembolism (VTE) can present in a multitude of ways and is best regarded as a
spectrum of diseases rather than a single disease
entity. Clinical manifestations can be varied, and
patients can present with asymptomatic deep
venous thrombosis (DVT), symptomatic DVT,
asymptomatic pulmonary embolism (PE), and
symptomatic PE that can be mild, massive, or fatal.
Some patients can also present with paradoxical
embolism with systemic arterial embolization
through a patent foramen ovale (PFO) resulting in
stroke, acute limb, or visceral ischemia. Paradoxical
embolism, unfortunately, remains underappreciated in the medical community at large.
The most devastating complication of acute
DVT is PE. In patients with symptomatic DVT,
as many as 50–80 % may have radiographic evidence of asymptomatic PE. Conversely, in those
patients with symptomatic PE, asymptomatic
DVT can be found in 80 % cases (Buller et al.
K.M. Karimi, MD, FACS, RPVI (*)
Department of Vascular and Endovascular Surgery,
Covenant Clinic, Waterloo, IA, USA
P. Gloviczki, MD, FACS
Division of Vascular Surgery, Mayo Clinic,
Rochester, MN, USA
2005). Risk of death in patients with symptomatic PE is 18-fold higher than those with DVT
alone (Heit et al. 2006). It is not uncommon for
some patients to present with the dramatic clinical picture of phlegmasia cerulea dolens. Longterm complications of PE include pulmonary
hypertension. Chronic thromboembolic pulmonary hypertension (CTEPH) can develop in up to
4 % of patients after an initial episode of PE
(Pengo et al. 2004). It can manifest as exertional
dyspnea, edema, chest pain, and progressive
decline in the right heart function. Another serious long-term complication is postthrombotic
syndrome (PTS). PTS is a range of clinical presentations that can result from the chronic effects
of DVT. It is the most important late complication of DVT that results in signiﬁcant morbidity,
healthcare expenditure, and loss of productivity.
The annual health cost of PTS has been estimated at $200 million (Ashrani et al. 2009).
Signs and symptoms may include aching or
cramping pain in the involved extremity, heaviness, pruritus, edema, development of painful
superﬁcial varicosities, hyperpigmentation, and
venous ulceration (Coon et al. 1973). According
to some studies, severe PTS changes can be
found in 5 % of the US population. PTS can
present up to 20 years after the initial episode of
DVT (Mohr et al. 2000). Pathophysiologically
and as seen on sonographic studies, it is a result
of venous valvular incompetence and venous
luminal obstruction (Johnson et al. 1995; Budd
et al. 1990).
© Springer International Publishing Switzerland 2016
S.A. Abutalib et al. (eds.), Nonmalignant Hematology, DOI 10.1007/978-3-319-30352-9_47
K.M. Karimi and P. Gloviczki
A 35 year old 3 day post partum female presents
to the emergency department with acute loss of
function of the right side of her body. Clinical
picture is consistent with a left middle cerebral
artery stroke. On exam she also has left lower
extremity swelling and pain. She undergoes a full
workup for acute stroke.
Question 1. Which diagnostic test is most
likely to reveal the pathophysiology of the
stroke in this young patient?
Blood homocysteine levels
Patent foramen ovale (PFO) is present in
25 % of the adult population, and the vast
majority are hemodynamically insigniﬁcant. In
some adults PFO can serve as a conduit for paradoxical embolization into the systemic arterial
circulation. A strong association between PFO
and cryptogenic stroke has been established in
patients less than 55 years of age (Homma et al.
2010). PFOs with hypermobile septum (>9 mm,
also termed as aneurysms in literature); observable transatrial shunting at rest, i.e., without
Valsalva maneuver; and large physiologic
shunt, i.e., more than ten bubbles crossing the
interatrial septum over the three cardiac cycles,
are considered high risk for paradoxical
embolization and stroke (Thaler et al. 2013).
Randomized trial data has shown mixed results
in demonstrating clear superiority of percutaneous PFO closure over medical therapy and continues to be heavily debated and a selectively
performed procedure at certain institutions
(Agarwal et al. 2012; Meier et al. 2013;
Stortecky et al. 2015).
Question 2. She is also found to have left iliofemoral and popliteal vein DVTs. She makes
full recovery from her stroke. At 3-month
follow-up, she complains of pain, swelling, and
heaviness in her left lower extremity. She has
been on warfarin. Sonography shows chronic
thrombus in the iliofemoral and popliteal
veins with diminished ﬂow and no evidence of
an acute DVT. What other information is the
sonography likely to reveal?
A. Arteriovenous ﬁstula
B. Multiple deep venous varicosities
D. Femoral artery pseudoaneurysm
The pathophysiology of PTS is ambulatory
venous hypertension. Patients with PTS have
high ambulatory venous pressures. It has been
shown that patients with venous valvular incompetence and luminal obstruction have the highest
ambulatory venous pressures. Higher venous
pressures correlate with more severe postthrombotic morbidity.
Factors that predispose patients to the development of PTS (Ageno et al. 2003) are:
1. Delayed (>90 days) recanalization after the
initial episode of DVT.
2. Extent of valvular incompetence.
3. Anatomic distribution of the reﬂux and
obstruction. Incidence is three times higher in
proximal versus distal only DVT.
4. Recurrent DVTs.
5. High body mass index (>40).
The anatomic distribution of lower extremity
DVT can be deﬁned by three types:
1. Calf and infrapopliteal DVTs
2. Proximal DVT involving popliteal, femoral,
deep femoral, and common femoral veins
3. Iliofemoral DVT
Patients at risk for development of PTS, particularly those with iliofemoral DVT, should
be considered for interventional procedures in
addition to anticoagulation alone (Jaff et al.
Surgical Treatment of Thromboembolic Disease
A 57-year-old male with 3-month history of
anorexia, weakness, and progressive jaundice
presents with progressive swelling, increasing
pain, and bluish discoloration of his right lower
extremity. Workup shows a solid mass in the head
of the pancreas and DVT of the right iliofemoral
and popliteal veins. He is admitted to the hospital
and started on therapeutic doses of low molecular
weight heparin. Over the subsequent 24 h, the
pain and swelling in the right lower extremity
worsens and the lower leg starts turning white.
Question 3. What would be an appropriate
next step in management?
A. Double the dose of low molecular weight
B. Give a loading dose of warfarin.
C. Obtain MRI of the lower extremity.
D. Obtain a consultation with a vascular
The patient is developing phlegmasia; the ﬁrst
stage is phlegmasia alba dolens.
It is a form of severe extremity DVT that presents with a painful and swollen limb without signiﬁcant venous congestion, hence the name alba,
which means white. It involves major outﬂow
veins but spares collateral veins. The venous
drainage is decreased but present nevertheless.
There is preservation of tissue oxygenation, and
there is no ischemia in the early stages.
Colloquially it has also been called milk leg syndrome as historically it was seen in pregnant
females during the third trimester, resulting from
compression of the left common iliac vein against
the pelvic brim by the gravid uterus (Rutherford
et al. 1991).
Phlegmasia alba dolens can progress to
phlegmasia cerulea dolens. Literally, it means
painful blue edema. It is an uncommon but
severe form of symptomatic DVT that can result
from extensive thrombosis of the major venous
and collateral venous outﬂow obstruction. There
is massive ﬂuid sequestration as the outﬂow
impedance exceeds capillary oncotic pressure,
resulting in dramatic edema. This can further
affect perfusion and hence capillary level oxygenation which if prolonged in its progressive
state can lead to venous gangrene (Mumoli et al.
2012). Shock can ensue due to intravascular volume depletion, and increased interstitial pressure compounded by arteriolar vasospasm can
compromise arterial inﬂow. Underlying malignancy can be identiﬁed in 40–50 % of patients
who present with phlegmasia cerulea dolens
Venous gangrene is the terminal stage of acute
severe DVT resulting in irreversible tissue ischemia. It is accompanied by tissue loss, profound
biochemical derangements, and shock.
Patients with acute extensive DVT presenting
with phlegmasia and impending limb threatening
ischemia should be seen by the vascular surgical/
Question 4. In this scenario anticoagulation
alone is not sufﬁcient because?
A. Low molecular weight heparin is ineffective
in cancer-related DVT.
B. Low molecular weight heparin is ineffective
in malnourished patients.
C. The large thrombus burden can result in limb
D. Low molecular weight heparin should be
combined with antiplatelet agents to expedite
The rationale for anticoagulation in acute
DVT is to promote thrombus stabilization and
prevent its progression and reduce the risk of
PE. In cases of PE, it is to prevent recurrent
PE. Anticoagulation does not actively result in
thrombus dissolution but relies on the body’s
intrinsic ﬁbrinolytic mechanism to reduce the
thrombus load over time. In cases of phlegmasia,
time is of essence and progressive tissue ischemia puts the extremity at risk of gangrene.
Intrinsic ﬁbrinolysis is a slow chemical process,
whereas these patients need rapid thrombus
reduction and restoration of venous outﬂow.
K.M. Karimi and P. Gloviczki
Question 5. Lower extremity DVT is more
common on the right compared to the left.
True or false?
Left-sided DVTs are ﬁve times more common
than the right. This clinical scenario is called
May-Thurner syndrome and is commonly
encountered in surgical practice (Wolpert et al.
2002; Kibbe et al. 2004).
Anatomically, the left common iliac vein
(CIV) crosses between the right common iliac
artery (CIA) and L5 vertebra to join the inferior
vena cava (IVC). This anatomical arrangement
results in the compression of the left CIV and predisposes it to external trauma. Mechanical
obstruction from the rigid vertebral body posteriorly and a thicker and high-pressured artery anteriorly can lead to intimal hyperplasia and
subsequent venous obstruction. Iliofemoral DVTs
are ﬁve times more common in the left lower
extremity as compared to the right. Any treatment
strategy for left iliofemoral DVT should maintain
focus on this important anatomical factor.
A 25-year-old professional baseball player presents with severe pain and swelling in the right
upper extremity for 2 days. Workup shows extensive axillo-subclavian DVT.
Question 6. What is the most likely causative
factor for this DVT?
between the space bordered by the undersurface
of the clavicle and the superior surface of the ﬁrst
rib in the anterior most part of the thoracic outlet.
Extrinsic compression and repetitive forces can
lead to intrinsic damage and extrinsic scar tissue
formation. This is an area predisposed to injury
with movements of the upper extremity, and this
condition is therefore referred to as effort thrombosis. Although uncommon, it is more likely to
be seen in young active and otherwise healthy
Question 7. Which of the following is appropriate in the treatment of this patient?
A. Therapeutic doses of anticoagulation
B. Full immobilization and rest of the involved
C. Elevation and external compression with Ace
D. Thrombolytic therapy
E. All of the above
Anticoagulation is given to prevent thrombus progression. The involved extremity
should be placed in compression bandage and
elevated to reduce edema and tissue pressure.
Initial rest is advised for patient comfort. For a
young professional athlete, aggressive treatment with thrombolytic therapy aiming to
reduce thrombus burden and prevent longterm morbidity should be undertaken
A 27-year-old morbidly obese female presents
with acutely symptomatic DVT in the left iliofemoral vein. There are no respiratory symptoms.
She is started on anticoagulation.
A. Undiagnosed thrombophilia
B. Undiagnosed occult malignancy
C. History of repair of left tibial plateau fracture
5 months ago
D. Repetitive external trauma to the axillarysubclavian vein
Question 8. What is most likely to cause longterm morbidity?
This is Paget-Schroetter syndrome (Shebel
et al. 2006; Melby et al. 2008).
In the case of the upper extremity, the subclavian vein is vulnerable to injury as it passes
A. Adverse effects of anticoagulation
C. Postthrombotic syndrome
Surgical Treatment of Thromboembolic Disease
Several governing bodies including the
Society of Vascular Surgery (SVS) and the
American Venous Forum (AVF) have taken into
consideration the growing body of evidence
favoring thrombus removal in iliofemoral DVT
and axillo-subclavian DVT. Outcome analysis
from observational, clinical, and case-controlled
studies supports the beneﬁts and quality of life
improvement gains from therapies directed at
thrombus removal (Guyatt et al. 2012; Meissner
et al. 2012; Jaff et al. 2011). Currently, three
approaches, either alone or in combination, are
available to patients who will beneﬁt from thrombus removal:
sion. Moreover, since phlegmasia is likely to be
associated with cancer, shock, and renal dysfunction, CDT may not be a suitable option, and
open thrombectomy is the preferred method of
In this era systemic thrombolysis is rarely
employed for extremity DVT and only holds historic interest. Results of CDT/open venous
thrombectomy are far superior and complications
signiﬁcantly less compared to systemic thrombolysis. Systemic thrombolysis should only be
used if the patient cannot be transported to a
facility that can perform CDT or venous
1. Endoluminal approaches
2. Open venous thrombectomy
3. Systemic thrombolysis
Cases 3 and 4, Question
Of these three available options, generally
catheter-directed thrombolysis (CDT) techniques are the preferred first-line therapy. This
is due to their minimally invasive technique
and effectiveness as both a diagnostic and a
therapeutic tool. They allow the operator to
assess response to treatment clinically and
radiographically during ongoing therapy. They
also provide endoluminal access to interventional treatment for associated problems such
as May-Thurner syndrome and/or residual
venous stenosis from chronic thrombus
(Enden et al. 2012; Aziz et al. 2012). They are,
however, limited by the number of specialists
and institutions that can offer such therapy.
These approaches should also be weighed
carefully in patients with high risk of
Open venous thrombectomy is a safe and recognized treatment modality in patients who are
not otherwise candidates for CDT or where CDT
is not readily available. It is also the preferred
modality in the setting of advanced phlegmasia.
Additional surgical maneuvers, such as Esmarch
elastic bandage compression to achieve highgrade compression in order to push the thrombus
into a more proximal vein where it can be
removed, may be required. In rare cases fasciotomies may be deemed necessary to decrease
compartment pressure and increase tissue perfu-
Question 9. Why is catheter-directed thrombectomy superior to systemic thrombolysis in
Cases 3 and 4?
A. It is readily available at the majority of
B. It is cheaper and less labor intensive.
C. The thrombolytic agent is delivered directly
into the thrombus.
Acute thrombus is made up of cross-linked
ﬁbers of ﬁbrin. Plasmin degrades ﬁbrin into
ﬁbrin degradation products. In a thrombus plasmin is bound to ﬁbrin in its inactive precursor
form, plasminogen (Blomback 2001; Doolittle
et al. 2001). The principle behind CDT is to
deliver plasminogen activators (thrombolytic)
into the actual thrombus. This results in rapid
initiation of the ﬁbrinolysis. The advantages of
this technique are:
1. Smaller doses of thrombolytic agents are
required during CDT. This not only offers an
important safety advantage but increased concentration of the drug at the site of action
2. Direct delivery also reduces the chances of
interaction between active plasmin and circulating alpha2-antiplasmin and endothelial
plasminogen activator inhibitor-1 (Berridge
et al. 1991; Hirsch et al. 2006).
K.M. Karimi and P. Gloviczki
Cases 1, 2, 3, and 4, Question
Question 10. Which of the above cases are
most likely to beneﬁt from CDT with an
acceptable risk of bleeding?
Cases 1, 3, and 4
Cases 3 and 4
Cases 2, 3, and 4
Cases 1 and 2
The best radiographic and clinical results are
seen in patients in whom symptoms have been
present for 7 days or less. Thrombus greater than
14 days is less likely to respond to
CDT. Sonographic ﬁndings of hypoechoic (acute)
thrombus with hyperechoic (chronic), circumferential thrombus along the wall of the vein, with
no ﬂow on color Doppler, represent the most
common real-life situation. In our practice, these
are mostly cases of acute on chronic DVT. This
makes CDT of iliofemoral DVT or symptomatic
upper extremity effort thrombosis worth pursuing
in these cases. Even though the amount of thrombolytic agent is small, there is still a small risk
(2 %) of bleeding. In Case 2, there is a known
malignancy, and until a complete metastatic
workup can be completed, thrombolytics should
Surgical Technique (Mayo Clinic,
Rochester, MN Protocol)
Needle access is established with a micropuncture needle under ultrasonographic guidance.
The aim is to get into the vein with the ﬁrst pass,
in order to reduce the risk of access site complications. The tract of the wire is not lanced with a
blade to further reduce that risk. Preferred access
sites are the ipsilateral popliteal vein in the cases
of iliofemoral and ipsilateral basilic veins in the
cases of symptomatic axillo-subclavian DVT. We
prefer a seven- or eight-French sheath with a
radiopaque tip marker. Continuous unfractionated heparin is initiated through the sheath with a
goal of no more than a PTT 1.5 times normal.
After initial venography, the extent of the throm-
bus is determined. Wire and catheter access is
obtained across the involved segment of the
venous anatomy and into the normal veins
beyond the diseased segment. Depending on the
total duration of therapy, contrast venography is
performed daily to document radiographic
improvement or lack thereof.
Traditionally, the thrombolytic agent is delivered into the thrombus through a multi-side-hole
catheter. However, over the last two decades,
more advanced delivery systems have been developed to reduce the duration and cost of treatment.
These devices employ mechanical techniques
alone or in combination with pharmacologic
In our opinion pharmacomechanical thrombectomy (PMT) is superior to pharmacologic
therapy alone in terms of duration of treatment
and superior to mechanical thrombectomy alone
in terms of efﬁcacy (Vendantham et al. 2002).
Other groups have reported success with shorter
treatment durations when thrombolytics are delivered through specialized catheters that emit ultrasonic waves and render the thrombus increasingly
porous to the penetration of the lytic agent (Parikh
et al. 2008). Another attractive technique is that of
isolated segmental pharmacomechanical thrombolysis (ISPMT). The lytic agent is delivered in a
segment of the thrombus isolated by inﬂation of
balloons at each end of the vein. Mechanical
action mixes the lytic and breaks up the thrombus
which is then aspirated (Martinez Trabal et al.
2008). Other than CDT, all the more contemporary techniques focus on either enhancing the
penetration of the lytic into the thrombus or
mechanical forces to increase contact surface area
between the lytic and the thrombus. Commonly
used thrombolytics include:
1. Streptokinase (SK)
2. Tissue plasminogen activator (tPA)
3. Recombinant tissue plasminogen activator
It is our practice to perform contrast-enhanced
CT chest to rule out PE with IFDVT. In case of
established PE, extensive IFDVT, or radiographic
Surgical Treatment of Thromboembolic Disease
evidence of thrombus in the IVC, we place
All patients undergoing treatment with continuous infusion of lytics should be monitored
closely, preferably in the setting of an intensive
care unit (ICU). They should be monitored for
any signs of bleeding either from the venous
access site or remotely. Serial neurological exams
and evaluation of the access site should be performed routinely. Serial labs with CBC, coagulation proﬁle, and ﬁbrinogen levels should be
performed at least every 6 h. Fibrinogen level can
serve as a surrogate marker for bleeding.
Fibrinogen levels less than 150 mg/dL are associated with an increased risk of bleeding (Hirsch
et al. 1990; Tracy et al. 1992; Pharmacy
Healthcare Solutions 2005). In those circumstances, lytic infusion should be stopped for an
hour and restarted at a lower rate.
With the advent of site-directed therapy, systemic thrombolysis is rarely employed for cases
of DVT. However, certain groups of patients still
remain at risk for bleeding and should not be
treated with CDT.
Absolute contraindications are active internal
bleeding, intracranial space-occupying lesion,
and recent (<3 months) intracranial hemorrhage.
Relative contraindications are recent surgery
or major trauma, uncontrolled hypertension, documented atrial thrombus, coagulopathy, endocarditis, advanced cirrhosis, and the immediate
postpartum state (Working party on thrombolysis
in management of limb ischemia 2003).
Question 11. The patient in Case 4 continues
to show subacute-looking thrombus and
venous outﬂow obstruction 48 h after initiation of thrombolytic therapy. What would be
the appropriate next step?
A. Stop the CDT and discharge patient on
C. Add clopidogrel and aspirin to her medications.
D. Convert to open venous thrombectomy
E. Balloon angioplasty and stenting.
Balloon angioplasty and stenting in the preferred treatment for chronically diseased iliac vein.
Open venous thrombectomy generally reserved for
situations where CDT is either not available or
contraindicated. It can also be applied to patients
who have failed to show reasonable recanalization with CDT/PMT.
Surgical Technique (Comerota et al.
2012) With Mayo Clinical Institutional
This procedure is performed under general anesthesia. The conﬂuence of the femoral and deep
femoral veins is localized with sonography. The
distal great saphenous vein and the saphenofemoral junction are also identiﬁed. A cutdown is
performed and the veins are controlled with
Silastic vessel loops. A longitudinal incision is
made over the conﬂuence of the CFV and femoral vein; this allows intraluminal access into the
deep femoral vein. If there is a notable thrombus
in the femoropopliteal segment, then the lower
extremity is elevated and tightly wrapped in
Esmarch bandage starting from the toes extending to the groin. If there is persistent thrombus,
then Fogarty balloon catheters can be used to aid
thrombus retrieval. Cutdown on the posterior
tibial vein and direct ﬂushing with heparinized
saline are also useful adjuncts. The posterior tibial vein can also be cannulated for ascending
venography. Once infrainguinal thrombectomy is
achieved, focus is shifted to iliocaval thrombectomy. Access is obtained from the contralateral
CFV followed by placement of a 10- or 12-French
sheath. Following an iliocaval venogram and
intravascular ultrasonography (IVUS), catheter is
placed into the IVC. This determines the presence
or absence of thrombus in the IVC and also aids
in the measurement of the diameter of the
IVC. Thrombus in the IVC clearly increases the
risk of PE during thrombectomy. An appropriately sized balloon placed from the contralateral
K.M. Karimi and P. Gloviczki
CFV and inﬂated will reduce the risk of PE during thrombus manipulation. Valsalva positive
pressure breaths also reduce the risk of PE during
thrombectomy. Iliac vein thrombectomy is performed using an eight or ten Fogarty balloon
catheter under ﬂuoroscopic guidance. We also
use the adherent clot catheter to remove some of
the chronic thrombus. Completion venography
and IVUS are performed to assess the degree of
residual thrombus and to identify an underlying
venous stenosis. Iliac vein stenosis is treated with
balloon angioplasty using high-pressure noncompliant balloon. If there is residual stenosis, then
high-radial force stents are used. IVUS serves as
an excellent tool in the sizing of the stents. It is
our practice to create an arteriovenous ﬁstula
between the ipsilateral superﬁcial femoral artery
(SFA) and femoral vein using either a side branch
of the GSV or prosthetic material (polytetraﬂuoroethylene (PTFE)). The proximal end of the
PTFE grafts that are used for dialysis access grafts
is 4 mm in diameter and is ideal for this part of the
procedure. We place a Prolene suture marker with
a long tail and being in close to the subdermal
skin closure for easy identiﬁcation and ligation in
the future. Alternatively, a 6 mm externally supported graft can be used in a small-loop conﬁguration. The advantage of this is that percutaneous
closure with an amplatzer plug is possible 6 weeks
to 3 months after the procedure.
We measure the pressure in the CFV before
and after the creation of the arteriovenous ﬁstula.
Step-up in pressure more than 10 mmHg suggests outﬂow obstruction and should be imaged
and treated accordingly. In select case we also
perform duplex sonography of the DVF with a
hockey stick probe and ensure there is lowresistance systolodiastolic ﬂow in the CFV. Lack
of diastolic ﬂow also suggests outﬂow obstruction and should be addressed.
As with any vascular surgical procedure, excellent hemostasis is conﬁrmed at the end. Patients
are kept on anticoagulation with continuous drip
of unfractionated heparin or low molecular weight
heparin and converted to oral agents prior to discharge. With the advent of oral anticoagulants with
a more rapid onset of action compared to warfarin,
the traditional overlap period of 4–5 days of anticoagulation between parenteral agents and oral
agents can be circumvented. In patients where
metallic stents are placed, antiplatelet agents such
as aspirin or clopidogrel are also given.
Question 12. Patient in Case 4 achieves excellent radiographic results and still has some
edema. What additional treatment is warranted in this case?
A. High-dose furosemide
B. Whirlpool therapy
C. Graduated compression stockings
Earlier studies had shown that the daily use of
sized to ﬁt 30–40 mmHg graduated elastic compression stockings for 2 years after the initial episode of DVT decreases the risk of development of
PTS (Kanaan et al. 2012). These recommendations
are also part of the ACCP 12 guidelines. However,
this ﬁnding has not been corroborated by a recently
published placebo-controlled trial (Kahn et al.
2014). Compression stockings are widely used to
treat the progression of edema following DVT.
A 44-year-old business executive is brought to the
emergency department with sudden onset of shortness of breath and chest pain. He has recently
returned on a transpaciﬁc ﬂight. He is diaphoretic,
oxygen saturation on 100 % mask is 92 %, and
pulse is 132/min. EKG shows signiﬁcant right ventricular strain. He is found to have a saddle embolus
in his main pulmonary artery. Troponin and BNP
are elevated. He is intubated, started on therapeutic
anticoagulation, and transferred to ICU.
Question 13. In addition to anticoagulation,
which other therapeutic modalities should be
Placing the patient on ECMO