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“I Have a History of TTP or AHUS. Can I Become Pregnant?”

“I Have a History of TTP or AHUS. Can I Become Pregnant?”

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H.-M. Tsai

Table 12 Controversies and unresolved issues in TTP and AHUS


ADAMTS13 assays

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

Preemptive rituximab

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?


Cornec-Le GE, Delmas Y, De PL, Doucet L, Ogier H,

Benoist JF, Fremeaux-Bacchi V, Le MY. Adult-onset

eculizumab-resistant hemolytic uremic syndrome

associated with cobalamin C deficiency. Am J Kidney

Dis. 2014;63:119–23.

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C, Sarode R. Relapsed thrombotic thrombocytopenic

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G, Lebranchu Y, Zuber J, Loirat C. Genetics and out-

come of atypical hemolytic uremic syndrome: a

nationwide French series comparing children and

adults. Clin J Am Soc Nephrol. 2013;8:554–62.

Lattuada A, Rossi E, Calzarossa C, Candolfi R, Mannucci

PM. Mild to moderate reduction of a von Willebrand

factor cleaving protease (ADAMTS-13) in pregnant

women with HELLP microangiopathic syndrome.

Haematologica. 2003;88:1029–34.

Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S,

Bedrosian C, Bingham C, Cohen DJ, Delmas Y,

Douglas K, Eitner F, Feldkamp T, Fouque D, Furman

RR, Gaber O, Herthelius M, Hourmant M, Karpman

D, Lebranchu Y, Mariat C, Menne J, Moulin B,

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Zimmerhackl LB, Goodship T, Loirat C. Terminal

Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome

complement inhibitor eculizumab in atypical

hemolytic-uremic syndrome. N Engl J Med.


Lemaire M, Fremeaux-Bacchi V, Schaefer F, Choi M,

Tang WH, Le Quintrec M, Fakhouri F, Taque S, Nobili

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.

Hematol Oncol Clin North Am. 2013a;27:565–84.

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JP, Foerster J, Rodgers GM, Paraskevas F, Glader B,

Arber DA, Means Jr RT, editors. Wintrobe’s clinical

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Lippincott Williams & Wilkins; Chapter 48. 2013b.

Tsai HM. A mechanistic approach to the diagnosis and

management of atypical hemolytic uremic syndrome.

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cerebral ischemia caused by thrombotic thrombocytopenic purpura. Eur J Haematol. 2003;70:183–5.

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Machin SJ, Scully M. Rituximab for thrombotic

thrombocytopenic purpura: benefit of early administration during acute episodes and use of prophylaxis to

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R. Bortezomib for chronic relapsing thrombotic

thrombocytopenic purpura: a case report. Transfusion.


Surgical Treatment

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

e-mail: kamrankarimimd@gmail.com

P. Gloviczki, MD, FACS

Division of Vascular Surgery, Mayo Clinic,

Rochester, MN, USA

e-mail: gloviczki.peter@mayo.edu

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


Case 1

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

Contrast echocardiogram

D-dimer assay

12-lead EKG

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

C. Venous




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

Case 2

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

(Donati 1995).

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/

interventional team.

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

thrombus dissolution.

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?

A. True

B. 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.

Case 3

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

(Thompson 2012).

Case 4

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

B. Chronic




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

improves efficacy.

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

be avoided.

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


4. Tenecteplase

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

retrievable filters.

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).

Case 4

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


B. Give





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

Practice Modifications

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.

Case 4

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.

Case 5

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

Intravenous nitroglycerin

Intravenous beta-blocker

Thrombolytic therapy

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