Physiatrists’ Online Resource
Deep
Venous Thrombosis and Pulmonary Embolism In Spinal Cord Injury
Ronald Garcia,
MD
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CONTENTS
Epidemiology
Pathophysiology
Consequences of
Pulmonary Embolism
Diagnosis
Treatment
Prevention
-
Incidence
i.
Incidence in SCI range from 49 to 100% in the
absence of prophylaxis used in various studies. (Miranda, 2000)
ii.
The incidence of leg DVT and pulmonary embolism
is 3x higher in SCI patients than in the general population.
iii.
3rd
leading cause of death for all SCI patients in 1st
postinjury year
-
Cost
i.
Total cost per patient for objective diagnosis
and tx of acute venous thromboembolic disease has been estimated at approx US
$4000 (April 2000) – does not include cost for patient who incur long-term
sequelae (Miranda, 2000)
-
Chronology (Miranda, 2000; Lamb, 1993))
i.
Venous thrombosis has not been reported within
the first 3 days following SCI.
ii.
Thrombosis has been detected 5 days after SCI.
iii.
Highest frequency occurring in a window spanning
the first 14 to 21 days after injury and by sequential plebography up to 90
days after the trauma.
iv.
83% of symptomatic thromboembolism occurred
within the first 6 months after injury in 287 patients followed for a mean of
13.7 yrs after SCI.
v.
Within 6 weeks 1/3 of cases of DVT involve the
femoral or iliac veins and by 5 months all cases involved the calf veins.
-
Control of Venous Blood Flow in Healthy Individuals
i.
Average venous pressure is only 2 mm Hg which is insufficient to
return blood to the heart, particularly from the lower limbs.
ii.
Venous return to the right ventricle is ensured
by the presence of venous valves and by the massaging action of skeletal muscle
groups as they contract on the veins that pass between them (“skeletal muscle
pump”).
-
Rudolf Virchow postulated that a triad of factors predisposed to
venous thrombosis: (1) local trauma to the vessel wall, (2) hypercoagulability,
and (3) stasis. It is now believed that many patients who suffer pulmonary
thromboembolism (PTE) have an underlying inherited predisposition that remains
clinically silent until an acquired stressor occurs such as surgery, obesity,
or pregnancy.
-
Changes in SCI that Increase the Risk for DVT/PE
i.
Neurologic impulse
1. Temporary
or permanent removal of all neurologic impulses below the level or segment of
injury resulting in paralysis and subsequent venous stasis.
2. Initial
lesion in SCI is spinal shock resulting from hyperpolarization of spinal
cord neurons. This lasts up to 3 months following injury and is commonly followed
by spasticity. The absence of
Spasticity in patients with SCI has been found to be a positive predictor of
fatal PE.
ii.
Skeletal Muscle
1. Reduction
in muscle fiber cross-sectional area, decrease in number of capillaries per
muscle fiber, change in muscle fiber composition (elimination of type IA fibers
and increase in type IIA and IIB) leading to muscle atrophy leading to
decreased efficiency of skeletal muscle pump leading to venous stasis.
iii.
Vascular wall
1. Decrease
in venous distensibility and capacity and increase in venous flow resistance as
a result of vascular adaptations to inactivity and muscle atrophy.
2. Damage
t vessel walls may occur in SCI patients as direct result of trauma from the
original injury or indirectly from external pressure on the paralyzed leg.
iv.
Hemostatic
1. Increase
in Von Willebrand activity and antigen
level (higher in paralyzed pts compared to nonparalyzed) and factor VIII clotting activity noted with ratio of Von
Willbrand factor to factor VIII greater than 2.0 considered a predictor of DVT
in patient during the first 12 days after injury.
2. Decreased
fibrinolytic activity during the first 24 hours after injury.
3. Increased
platelet reactivity to collagen.
4. SCI
patients with end-stage renal disease were found to have lower levels of ATIII
and higher Factor XII and VII activity compared to controls.
III.
Consequences of Pulmonary Embolism
-
Pulmonary embolism can have the following effects:
i.
INCREASED PULMONARY VASCULAR RESISTANCE due to vascular
obstruction or neurohumoral agents including serotonin
ii.
IMPAIRED GAS EXCHANGE due to increased
alveolar dead space from vascular obstruction and hypoxemia from alveolar
hypoventilation in the nonobstructed lung, right-to-left shunting, and impaired
carbon monoxide transfer due to loss of gas exchange surface
iii.
ALVEOLAR HYPERVENTILATION due to reflex
stimulation of irritant receptors
iv.
INCREASED AIRWAY RESISTANCE due to
bronchoconstriction
v.
DECREASED PULMONARY COMPLIANCE
due to lung edema, lung hemorrhage, and loss of surfactant.
vi.
RIGHT VENTRICULAR DYSFUNCTION
1. Progressive
right heart failure is the usual immediate cause of death from PTE. As
pulmonary vascular resistance increases, right ventricular wall tension rises
and perpetuates further right ventricular dilatation and dysfunction.
Consequently, the interventricular septum bulges into and compresses an
intrinsically normal left ventricle. Increased right ventricular wall tension
also compresses the right coronary artery and may precipitate myocardial
ischemia and right ventricular infarction.
2. Underfilling
of the left ventricle may lead to a fall in left ventricular output and
systemic arterial pressure, thereby provoking myocardial ischemia due to
compromised coronary artery perfusion. Eventually, circulatory collapse and
death may ensue.
-
Nonimaging Diagnostic
Modalities- These are generally safer, less expensive, but also less specific
than diagnostic modalities that employ imaging.
i.
Blood Tests
1.
The quantitative plasma D-dimer
enzyme-linked immunosorbent assay (ELISA) level is elevated (>500 ng/mL) in more than 90 percent of patients
with PTE, reflecting plasmin's breakdown of fibrin and indicating endogenous
(though clinically ineffective) thrombolysis. The plasma D-dimer ELISA has a high negative predictive value and can
be used to help exclude PTE. However, D-dimer assay is non-specific. Levels increase in patients
with myocardial infarction, sepsis, or almost any systemic illness.
2.
Data from the Prospective Investigation of Pulmonary
Embolism Diagnosis (PIOPED) indicate that, contrary to classic teaching,
arterial blood gases lack diagnostic utility for PTE. Among patients suspected
of PTE, neither the room air arterial PO2 nor calculation of the
alveolar-arterial oxygen gradient can reliably differentiate or triage patients
who actually have PTE at angiography.
ii.
Electrocardiogram- Classic
abnormalities include:
1. sinus tachycardia;
2. new-onset atrial fibrillation or flutter
3. S wave in lead I, a Q wave in lead V3, and an
inverted T wave in lead V3. (S1Q3T3)
4. Often, the QRS axis is greater than 90°.
5. T-wave inversion in leads V6 to V4
reflects right ventricular strain.
-
Noninvasive Imaging
Modalities
i.
Chest Roentgenography- A
normal or near-normal chest x-ray in a dyspneic patient suggests PTE.
Well-established abnormalities include focal oligemia (Westermark's sign) (Figure 1),
a peripheral wedged-shaped density above the diaphragm (Hampton's hump) (Figure 2),
or an enlarged right descending pulmonary artery.
Figure 1. Chest
film showing relative paucity of pulmonary vessels on left (Westerman's sign).
ii.
Venous Ultrasonography
1.
Ultrasonography of the deep
venous system relies upon loss of vein compressibility as the primary criterion
for DVT. About one-third of patients with PTE have no imaging evidence of DVT.
In these situations, the clot may have already embolized to the lung or is in the
pelvic veins, where ultrasonography is usually inadequate. Therefore, the
workup for PTE should continue if there is high clinical suspicion, despite a
normal ultrasound examination.
2.
The reliability of venous ultrasonography is
well established for proximal leg DVT among symptomatic outpatients.
However, ultrasonography is notoriously insensitive for DVT screening among asymptomatic
inpatients
iii.
Lung Scanning
1. Lung scanning is the principal imaging test for the
diagnosis of PTE. Small particulate aggregates of albumin labeled with a
gamma-emitting radionuclide are injected intravenously and are trapped in the
pulmonary capillary bed. A perfusion scan defect indicates absent or decreased
blood flow, possibly due to PTE.
2. Ventilation scans, obtained with radiolabeled inhaled gases
such as xenon or krypton, improve the specificity of the perfusion scan.
Abnormal ventilation scans indicate abnormal nonventilated lung, thereby
providing possible explanations for perfusion defects other than acute PTE.
3.
A high probability scan for
PTE is defined as having two or more segmental perfusion defects in the
presence of normal ventilation.
4.
Lung scanning is particularly useful if the
results are normal or near-normal, or if there is a high probability for PTE.
The diagnosis of PTE is very unlikely in patients with normal and near-normal
scans but, in contrast, is about 90 percent certain in patients with
high-probability scans. Unfortunately, fewer than half of patients with
angiographically confirmed PTE have a high-probability scan. Importantly, as
many as 40 percent of patients with high clinical suspicion for PTE and
"low-probability" scans do, in fact, have PTE at angiography.
iv.
Echocardiography
1. This technique is useful for rapid triage of acutely ill
patients who may have PTE.
2. Bedside echocardiography can usually reliably differentiate
among illnesses that have radically different treatment, including acute
myocardial infarction, pericardial tamponade, dissection of the aorta, and PTE
complicated by right heart failure.
3.
Detection of right
ventricular dysfunction due to PTE helps to stratify the risk, delineate the
prognosis, and plan optical management.
Figure 3.
Pulmonary infarction caused by thrombo embolism: Hampton's hump as seen on CT
scan
v.
Spiral Computed Tomography Scan.
1.
A spiral (helical) computed tomography (CT) scan is performed by
coupling a high-speed rotating CT scanner to a worm gear that drives the
patient platform. Instead of discrete tomographic "cuts," a single
long spiral of data is obtained, and the computerized reconstruction creates
virtual cuts through the data to produce traditional-appearing images (Figure 3).
2.
A spiral CT scan offers several advantages over traditional CT scans.
The machines themselves are very fast, and the spiral technique permits very
rapid scanning over a large area, so that the entire lung may be imaged within
the time that a patient can breath-hold. The entire scan can be performed
during the first circulation pass of an injected bolus of venous contrast, and
vessels can be tracked from cut to cut at high spatial resolutions. These
"CT-angiograms" have shown great promise in the detection of PE by a
relatively noninvasive method.
3.
In one retrospective analysis, one half of pulmonary emboli seen on
chest CT scan were completely unsuspected by the clinician, and the other half
had been clinically believed to be not likely enough to warrantV/Q or
angiography.
4.
It is possible that invasive
pulmonary angiography will be completely replaced by spiral CT angiography
within the next few years.
-
Invasive Diagnostic
Modalities
i.
Pulmonary Angiography
1.
Selective pulmonary
angiography is the most specific examination available for establishing the
definitive diagnosis of PTE and can detect emboli as small as 1 to 2 mm. A
definitive diagnosis of PTE depends upon visualization of an intraluminal
filling defect in more than one projection. Secondary signs of PTE include
abrupt occlusion ("cut-off") (Figure 4)
of vessels; segmental oligemia or avascularity; a prolonged arterial phase with
slow filling; or tortuous, tapering peripheral vessels.
2.
Pulmonary angiography can be carried out safely
among properly selected patients at hospitals that perform at least several
studies per month. In PIOPED, the procedure resulted in death in five patients
(0.5 percent), two of whom had severe heart failure prior to the procedure.
3.
Angiography is most useful when the clinical
likelihood of PTE differs substantially from the lung scan result or when the
lung scan is of intermediate probability for PTE.
Figure 4.
Pulmonary angiogram. A, "Cutoff lesion."
ii.
Contrast Phlebography
1. This technique has been mostly replaced by ultrasonography.
Venography is costly, uncomfortable, and occasionally results in contrast
allergy or contrast-induced phlebitis. Contrast phlebography is worthwhile when
there is a discrepancy between the clinical suspicion and the ultrasound
result, or if it is clinically important to screen asymptomatic postoperative
or trauma patients at high risk for DVT. Phlebography is also useful for
diagnosing isolated calf vein thrombosis or recurrent DVT.
Back to Top
-
Untreated, the mortality of PE is 25% for the
first episode and 80% overall (including recurrences).
-
There are four closely related goals of
treatment:
i.
to prevent death from the current embolic event,
ii.
to reduce the likelihood of recurrent embolic
events, and
iii.
to minimize the long-term morbidity of the
event.
iv.
to prevent the development of pulmonary
hypertension as a late complication.
-
The major treatment modalities available are
anticoagulation, thrombolysis, embolectomy, and interruption of the venous
pathway between the primary thrombus and the pulmonary circulation.
-
Supportive and symptomatic therapy for the
patient should not be forgotten in the rush to diagnose and treat this
life-threatening condition.
i.
Pain relief often is needed,
ii.
oxygen may be helpful as a pulmonary
vasodilatator even when the patient is not hypoxemic, and
iii.
antidysrhythmic agents may be helpful in the
management of secondary dysrhythmias.
iv.
Shock must be managed with fluid resuscitation
and inotropic or pressor agents at the same time that thrombolytic therapy or
surgical intervention is being prepared.
v.
Supportive measures can buy time but should
never be used in place of a primary therapeutic intervention.
vi.
The ability of pressors to sustain a patient's
blood pressure is in no way predictive of a good outcome.
vii.
The need for these measures is an absolute
indication for thrombolysis or thrombectomy.
viii.
Volume expansion usually is not beneficial for a
hypotensive patient with massive PE. Even if volume expansion succeeds in
raising systemic blood pressure, the patient with acute pulmonary hypertension
already faces an excessive right ventricular afterload, thus volume expansion
will usually worsen right ventricular function.
ix.
If cardiotropic agents are desired, the pure
beta-agonist isoproterenol may be preferred because it is a more effective
dilator of pulmonary arterioles and thus helps decrease right ventricular
outflow resistance at the same time that it improves right ventricular
contractility.
x.
In the presence of frank shock from PE,
restoration of cardiac output and coronary perfusion pressure is of prime
importance and norepinephrine may be the preferred agent.
xi.
If pressor agents are unable to effect
hemodynamic stabilization, cardiopulmonary bypass should be instituted.
-
Anticoagulation
i.
Anticoagulation has been the
mainstay of therapy for patients with PE since the introduction of heparin into
clinical use in the 1930s.
ii.
Heparin reduces the overall
mortality of PE because it prevents the progression of clot and reduces the
risk of further embolic events; however, heparin is not capable of dissolving
clot that has already developed. In fact, the Urokinase Pulmonary Embolism
trial shows that the average size and extent of clot in the pulmonary arteries
are slightly worse after 24 hours of heparin therapy. Nonetheless, prompt
effective anticoagulation has been shown to reduce overall mortality to less than
10%.
iii.
In the absence of any
contraindication, heparin anticoagulation should be started as soon as the
diagnosis of PE is seriously entertained, without waiting for the results of
diagnostic tests. If anticoagulation is delayed, venous thrombosis and PE may
progress rapidly.
iv.
The two options for initial
anticoagulation are full-dose unfractionated IV heparin, and fractionated low
molecular weight (LMW) heparin given subcutaneously.
1. Early reports suggest that the two are approximately equal
in safety and efficacy and that LMW heparin may actually prove superior.
2. Subcutaneous unfractionated heparin is ineffective for
treatment of DVT or PE and should never be used for this purpose.
-
Unfractionated Heparin.
i.
At the first serious suspicion for thromboembolic disease, full-dose
unfractionated IV heparin is started. Patients with venous thromboembolism are
hypercoagulable and thrombophilic, thus the usual bolus dose of 80 U/kg heparin
is insufficient to produce a timely therapeutic anticoagulation. The initial bolus
dose should be at least 100 U/kg, and many clinicians recommend an initial
bolus of up to 150 U/kg. The initial bolus is accompanied by an IV infusion of
18 U/kg/hr. Adjustments should be made every 4 to 6 hours according to the
simplified schedule in Box 1 or some similar plan. An insufficient starting
bolus and an insufficient initial infusion rate are responsible for the most
common serious complication of heparin--failure of anticoagulation.
ii.
An activated partial thromboplastin time (aPTT) of at least 1.5 times
the control value is necessary for therapeutic effect in the management of DVT
and PE, and the risk of recurrence is 15 times higher if a therapeutic aPTT is
not achieved within the first 48 hours.
iii.
Unfractionated heparin is metabolized according to first-order kinetics
and has a half-life of 90 minutes.
iv.
With an appropriate bolus and drip, heparin is capable of producing a
stable prolongation of the aPTT to 1.5 times the control value within 5 hours,
yet one study finds that only 40% of patients achieve therapeutic effect within
the first 24 hours.
v.
Clinically effective anticoagulation is achieved with serum heparin
levels of 0.3 to 0.5 U/ml, and some authors believe that following the heparin
assay is preferable to monitoring the PTT.
|
BOX 1 Unfractionated IV Heparin for Thromboembolic Disease
If the aPTT is subtherapeutic (<1.5 times
the control value) rebolus with 5,000 U and increase the drip by 10%. If the aPTT is supratherapeutic (>2.5 times
the control value) decrease the drip 10%. If the aPTT is extremely high (>100
seconds) hold the heparin drip for 1 hour and decrease the drip 10%. |
In the
absence of contraindications, anticoagulation should be started at the first
suspicion of thromboembolic disease, without waiting for the results of
diagnostic tests.
The
initial bolus of IV heparin should be 100-150 U/kg.
The
initial infusion of IV heparin should be 18 U/kg/hr.
The
aPTT should be checked every 6 hours until stable, and heparin dosing should
be adjusted as follows:
-
Low Molecular Weight Heparin.
i.
A fractionated LMW heparin is available in the United States as
enoxaparin (Lovenox). Enoxaparin is approximately 3 times more active against
factor Xa than against factor IIa, in contrast to unfractionated heparin, which
affects the two factors nearly equally.
ii.
Peak activity after subcutaneous administration occurs in 3 to 5 hours,
and the therapeutic effect lasts approximately 12 hours. A fully
anticoagulating dose of enoxaparin for prophylaxis is 30 mg given
subcutaneously every 12 hours.
1.
The drug has a wide therapeutic window, and the prophylactic dosage is
not adjusted based on the patient's weight.
2.
There is some evidence that enoxaparin may be both safer and more
effective than unfractionated heparin for a variety of reasons, including the
prophylaxis of venous thromboembolism in general medical patients, cardiac
patients, surgical and orthopedic patients, pregnant patients, and trauma
patients.
iii.
The literature supports the safety and efficacy of a higher
("off-label") dose of 1 mg/kg enoxaparin given subcutaneously every
12 hours for treatment of acute DVT and PE in both adults and children.
iv.
Except in overdoses, there is no utility in checking the PT or the aPTT
because the aPTT is usually not prolonged even when the patient is fully
anticoagulated. Elevations of hepatic transaminases may occur rarely but are
readily reversible and have not led to any adverse outcomes.
Risks of Heparin.
The most
important risk associated with unfractionated heparin is that it will be
ineffective because of insufficient doses. All forms of heparin may cause
hemorrhagic complications, and all forms can induce an immune thrombocytopenia,
which most often appears 1 to 2 weeks after the initiation of treatment.
Heparin-associated thrombocytopenia (HAT) is very serious and can be fatal if
not recognized quickly and managed appropriately. In the late 1970s, heparin
was reported to be the most common cause of drug-related deaths in hospitalized
patients, with an overall complication rate of 10% to 15%. If significant
bleeding complications develop in the heparinized patient, 15 mg of protamine
sulphate (infused over 3 minutes) will usually reverse the anticoagulant effect
of unfractionated heparin, and 1 mg of protamine sulphate will reverse the
effect of approximately 1 mg of enoxaparin. Protamine is contraindicated in
patients allergic to fish.
-
Warfarin
i.
Starting warfarin or other vitamin K-inhibitors without giving heparin
will cause clot extension and recurrent thromboembolism in approximately 40% of
patients compared with 8% of those who receive full-dose heparin during the
period of initiation of warfarin.
1.
Protein C and factor VII have short half-lives compared with the other
vitamin K-dependent proteins
2.
Exhaustion of anticoagulant proteins causes an early hypercoagulable
state that is responsible for clot extension. This same phenomenon occasionally
causes warfarin-induced necrosis of large areas of skin or of distal
appendages.
3.
Warfarin (coumadin) should not be given to patients with thromboembolic
disease until after full anticoagulation with heparin has been accomplished.
Heparin should be continued for the first 5 to 7 days of oral warfarin therapy,
regardless of the PT, until procoagulant vitamin K-dependent proteins have been
depleted.
ii.
In the past, warfarin was not started until a patient had already been
heparinized for 5 to 7 days. There is some evidence that warfarin may be
started safely after just 1 to 3 days of effective heparinization.
iii.
The anticoagulant effect of warfarin is adjusted by varying the dose to
keep the International Normalized Ratio (INR) within some target range, which
depends on the clinical setting. In the United States, oral anticoagulation
after acute thromboembolism has traditionally used a lower target INR of 2.5 to
3.5. There is some evidence that a lower intensity of anticoagulation with a
target INR of 2.0 to 3.0 may be equally effective in patients without an
important underlying hypercoagulable state.
iv.
Of the two recommended ranges currently used in the United States, the
higher-intensity INR target range of 2.5 to 3.5 makes sense because the risk of
recurrent thromboembolism increases dramatically when the INR drops below 2.5
and decreases to nearly zero when the INR is kept above 3.0. Bleeding
complications do not rise dramatically until the INR is well above 4.0.
v.
At least 186 different foods and drugs have been reported to interact
with warfarin to increase or decrease the anticoagulant effects of the drug.
vi.
An abrupt temporary rise in the rate of recurrent venous
thromboembolism occurs immediately after the discontinuation of oral warfarin
regardless of whether the drug is continued for 4 or 6 weeks or for 3 or 6
months. This may be due to the transient hypercoagulable state that is caused
by the differential recovery of procoagulant and anticoagulant vitamin
K-dependent proteins.
-
Duration of Anticoagulation.
i.
Patients who fail to receive a full course of effective anticoagulation
after an initial 7- to 14-day course of treatment with heparin will have an
early recurrence of venous thrombosis. One study shows recurrence in 47% of
patients who were maintained on subcutaneous unfractionated heparin (which does
not produce a therapeutic anticoagulation), whereas none of the patients on a
full anticoagulating dose of coumadin had recurrence.
ii.
The optimum duration of anticoagulant therapy remains controversial,
but the best evidence suggests that 6 months of anticoagulation reduces the
rate of recurrence to half of the recurrence rate observed when only 6 weeks of
anticoagulation are given.
iii.
Long-term anticoagulation is indicated for patients with an
irreversible underlying risk factor or with recurrent DVT or recurrent PE.
-
Thrombolysis
There are three groups of patients for
whom thrombolysis is mandatory: the traditionally recognized group of patients
who are severely hemodynamically unstable, the further group of patients with
exhausted cardiopulmonary reserves, and the final group of patients who are
expected to have multiple recurrences of pulmonary thromboembolism over years.
Thrombolysis for other patients is often indicated but remains optional
according to the 1992 recommendations of the American Heart Association/World
Health Organization task force on the diagnosis, treatment, and prevention of
PE.
i.
Hemodynamic Instability.
1.
Thrombolysis is mandatory for any hemodynamically unstable patient with
PE because only thrombolysis or thrombectomy can produce a timely improvement
in the acute cor pulmonale of PE.
2.
Right ventricular dilatation, hypokinesis, and tricuspid regurgitation
caused by acute PE are immediately reversed or improved with lytic therapy but
not with heparin.
3.
Thrombolytic therapy has replaced surgery as the primary mode of treatment
for virtually every hemodynamically unstable patient with pulmonary
thromboembolism.
4.
Surgical thromboembolectomy now is reserved for patients who have
failed thrombolysis or who cannot tolerate lytic therapy.
5.
Empiric thrombolysis may be indicated in selected he modynamically
unstable patients, particularly when the clinical likelihood of PE is
overwhelming and the patient's condition is actively deteriorating. The overall
risk of severe complications from thrombolysis is low, and the potential benefit
in a deteriorating patient is extremely high because many such patients do not
survive long enough to obtain a confirmatory study.
ii.
Exhausted Cardiopulmonary Reserves.
1.
Even a mild degree of hypoxemia and hypotension from PE is clear
evidence that a patient's compensatory mechanisms have been overwhelmed and
that cardiac and pulmonary reserves are exhausted.
2.
Patients with hypoxemia and hypotension should receive immediate
thrombolysis unless there are strong contraindications. This category may be
extended to include patients with normal blood pressure and normal oxygenation
who have other severe underlying cardiac or pulmonary disease, such as a
patient with one lung or a patient with cardiomyopathy, because such patients
are at particularly high risk of death from any further pulmonary clot load.
iii.
Anticipated Recurrences of Embolism.
1.
Patients who are at special risk for recurrent PE deserve early
thrombolysis because even if they survive each acute event, they are at
extremely high risk for disabling chronic cor pulmonale from the gradual
accumulation of chronic pulmonary thrombus. Such patients include those with a
history of thromboembolism, those with a known irreversible coagulopathy, and
those who are permanently immobilized.
-
Mortality Reduction from Routine
Thrombolysis.
i.
Lytic therapy helps prevent
symptomatic pulmonary hypertension and chronic cor pulmonale by removing
large-vessel thrombous that otherwise becomes partially recanalized and leaves
affected vessels with a permanently reduced elastic distensibility, by
dissolving pulmonary capillary microemboli that raise pulmonary resistance and
reduce gas exchanging capability, and by reducing the rate of recurrent
embolization.
ii.
Although the pulmonary
angiogram and theV/Qscan often return to normal after a few months of
anticoagulation, when lytic therapy is not used large-vessel thrombus is
recanalized rather than dissolved, leaving affected vessels with permanently
reduced elastic distensibility. Besides this reduced large-vessel capacitance,
patients treated only by anticoagulation have a permanent residual small-vessel
pulmonary clot load. Such patients have an average pulmonary capillary volume
only 60% of normal at 2 weeks and at 12 months, whereas patients treated with
lytic agents have a normal pulmonary capillary volume at 2 weeks and at 12
months after therapy.
iii.
Carbon monoxide diffusion, a
primary measure of pulmonary gas exchange, also becomes normal immediately
after the administration of lytic agents but remains dramatically impaired
after 12 months when patients with PE are treated only with anticoagulants.
iv.
Recurrent embolization
despite anticoagulation is a common cause of progressive disability, but lytic
therapy has been shown to reduce recurrent embolization.
-
Risks of Thrombolysis for Venous Thromboembolism.
i.
Thrombolytic agents and heparin produce a similar incidence of systemic
bleeding complications, but thrombolysis causes more local bleeding than
heparin after invasive procedures. For example, significant bleeding occurs
with thrombolysis in only 4% of patients without angiography, but in 14% of
patients who receive thrombolytic agents after pulmonary angiography. For this
reason, patients who have a high-probabilityV/Qscan and a concordant clinical
likelihood should receive thrombolysis without first having an angiogram.
ii.
Fear of intracranial bleeding is the biggest deterrent to the routine
use of thrombolytic therapy for all patients with thromboembolic disease; 0.4%
of patients suffer an intracranial bleed after thrombolysis. The benefits of
thrombolysis must exceed this level of risk to be justified.
iii.
If serious noncompressible bleeding complications result from lytic
therapy, the infusion of lytic agent should be stopped.
1.
Fresh frozen plasma and cryoprecipitate may be effective at reversing
the lytic state.
2.
Aminocaproic acid (an inhibitor of plasminogen activators) may be given
as a 5 gm IV bolus administered over 30 minutes, followed by a maintenance
infusion of 1 gm/hr until the bleeding has resolved.
-
Embolectomy
i.
Surgical embolectomy (once known as
Trendelenburg's operation) was first performed in the early 1900s but did not
become truly practical until the introduction of cardiopulmonary bypass. In the
prethrombolytic era, immediate pulmonary embolectomy was the only effective
therapy for patients with massive PE and was indicated whenever
angiographically demonstrated bilateral emboli caused severe right-sided heart
failure and marked systemic hypotension that could not be managed with pressor
agents.
ii.
Today, embolectomy is reserved for the patient
with severe pulmonary or cardiac compromise who is not a candidate for
thrombolysis, for whom there is insufficient time to achieve thrombolysis, or
in whom thrombolytic therapy has failed.
iii.
The procedure carries an operative mortality of
approximately 25%, and the surgical literature suggests that no matter how
massive the embolism, patients who do not become hypotensive will do better
without surgery if further embolization can be prevented. For this reason, open
surgical embolectomy is rarely indicated except in the setting of profound or
refractory hypotension.
iv.
Transvenous catheter embolectomy is an
alternative approach in which a suction-tip catheter is placed in contact with
the thrombus under fluoroscopic guidance and the thrombus is held by suction
while the catheter is withdrawn.
-
Cardiopulmonary Bypass
i.
Portable percutaneous
(femorofemoral) cardiopulmonary bypass machines are increasingly available
within the ED, and patients with profound hypoxemia or shock from massive PE
are excellent candidates for emergency bypass with extracorporeal membrane
oxygenation. This temporizing measure can be instituted rapidly and will
support a subset of patients long enough for thrombolysis or surgical
embolectomy to correct the underlying problem.
ii.
The placement of large
femoral arterial and venous catheters for bypass is not a contraindication to
lytic therapy as the catheters are placed correctly and not removed until after
the lytic state has resolved.
-
Emergency Thoracotomy
i.
A patient with sudden
cardiovascular collapse and full cardiac arrest from PE will not be
resuscitated by traditional advanced cardiac life support (ACLS) protocols, but
there are several case reports of resuscitation by immediate bilateral
thoracotomy and massage of the pulmonary vessels to dislodge a saddle embolus
and restore circulation to at least a portion of the pulmonary vascular tree.
ii.
This procedure is entirely
appropriate in the patient with a proven diagnosis or a high clinical
probability of PE who has sudden arrest in the ED. To be of any value, the
procedure must be carried out immediately because conventional CPR will not
result in any oxygenated blood reaching the cerebral circulation. Open thoracotomy
is unlikely to be rewarding when a patient has cardiopulmonary collapse shortly
after the administration of a thrombolytic agent.
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VI.
Prevention
-
Prevention of Recurrence
i.
Approximately 25% of patients
who survive their first PE will have a clinically recognized recurrence, even
if appropriately diagnosed and treated.
ii.
Prevention is critically
important because if a patient survives the first few hours of a symptomatic
PE, most of the mortality risk and much of the morbidity are associated with
future recurrences.
iii.
Risk factors such as smoking,
pregnancy, oral contraceptives, obesity, or prolonged stasis should be
modified.
-
Heparin Prophylaxis
i.
Subcutaneous unfractionated heparin has no role in the treatment of
suspected or proven PE, whether acute or subacute, nor is it sufficient for
prophylaxis against recurrences in patients with prior thromboembolic disease.
When a patient with prior thromboembolic disease must undergo surgery or
enforced bedrest, full-dose anticoagulation is indicated because otherwise the
incidence of recurrence is virtually 100%.
ii.
Subcutaneous unfractionated heparin does play an important role,
however, in the routine prophylaxis of patients who lack any prior
thromboembolic history.
1.
Prophylactic subcutaneous unfractionated heparin is highly recommended
for postoperative patients and for medical patients whose activity is
restricted. A 1986 NIH conference examined combined studies of 12,000 patients
and finds that prophylactic low-dose heparin effects a 68% reduction in DVT and
a 49% reduction in PE.
2.
Prophylactic heparin can effect a 30% mortality reduction in a general
population of unselected medical patients.
3.
The recommended regimen for
subcutaneous unfractionated heparin for prophylaxis is at least 5,000 U
subcutaneously every 12 hours.
-
Gradient Compression Stockings.
i.
The ubiquitous white stockings known as antiembolic stockings or as Ted
hose produce a maximum compression of 18 mm Hg and are rarely fitted in such a
way as to provide even that inadequate gradient compression. They are of
limited efficacy in prophylaxis against thromboembolism.
ii.
True gradient compression stockings (30 to 40 mm Hg or higher) are
highly elastic and provide a gradient of compression that is highest at the
toes and gradually decreases to the level of the thigh.
1.
Compression stockings of this type have been proven effective in the
prophylaxis of thromboembolism. When 192 pulmonary disease patients at bedrest
in the hospital were randomized to four prophylactic regimens, DVT was proved
in 26% of control patients, in 12% of patients who had manually applied leg
bandages, in 2.5% of patients on subcutaneous heparin, in 5% of patients on
aspirin, and in none of the patients who wore gradient compression stockings. A
1994 meta-analysis calculated an odds ratio of 0.28 for gradient compression
stockings (compared with no prophylaxis) in patients undergoing abdominal
surgery, gynecologic surgery, or neurosurgery. Imperiale likewise finds that
gradient compression stockings and LMW heparin are more effective than any
other modalities in reducing the incidence of DVT after hip surgery and are the
only tested modalities that reduce the incidence of PE. In this study, there is
no significant reduction in the incidence of PE in patients given subcutaneous
unfractionated heparin, oral warfarin, dextran, or aspirin.
-
Intermittent Pneumatic Compression.
i.
Active pneumatic sequential compression devices for the legs are also
effective as prophylaxis against thromboembolism and offer risk reduction
comparable with that obtained with gradient compression stockings.
ii.
Hull finds venographic evidence of deep vein thrombosis in 77 (49%) of
158 control patients but in only 36 (24%) of 152 patients who received active
intermittent pneumatic compression after total hip replacement.
iii.
Unfortunately, the devices are new to many nursing units, and
compliance with orders for the devices is poor. External pneumatic compression
devices are incorrectly applied or are nonfunctioning in 22% of patients in an
ICU and in 52% of patients in a routine nursing unit.
-
Combined Prophylaxis.
i.
Combined therapies are more effective than any single modality of
prophylaxis.
ii.
Jeffery finds that gradient compression stockings alone reduced the
incidence of postoperative deep vein thrombosis by approximately 60%, and when
used in combination with subcutaneous heparin or with active pneumatic
intermittent calf compression the incidence of postoperative DVT is reduced as
much as 85%.
iii.
Many clinicians use a synergistic combination of all three proven
modalities: subcutaneous LMW heparin, 30 to 40 mm Hg gradient compression
stockings, and an active intermittent pneumatic leg compression device.
-
Vena Cava Filters.
i.
Transvenous implantation of an "umbrella" filtering device
within the vena cava may be necessary in the patient with an extremely high
risk profile,the patient who cannot tolerate a period of anticoagulation, the patient with proven recurrence of DVT or
PE despite adequate anticoagulation.
ii.
Transvenous filters such as the original Mobin-Uddin filter (no longer
available in the United States) and the newer Kim-Ray-Greenfield filter have
largely replaced the older technique of surgical ligation of the inferior vena
cava, which had a significant associated mortality and morbidity.
iii.
When properly positioned, vena cava filters prevent the largest thrombi
from passing upward into the pulmonary arteries and can reduce the mortality of
PE. Filters do not prevent smaller pulmonary emboli from reaching the pulmonary
circulation, and large emboli may bypass the filters or may originate above the
filter.
iv.
Vena cava filters are not a substitute for anticoagulation. Many
patients have died from PE with a vena cava filter in place.
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