Peripherally inserted central catheter (PICC)-related venous thrombosis

. Some estimates suggest that PICCs are responsible for over one-third of all upper extremity
DVTs, suggesting that the arm veins are perhaps the most thrombotic sites in which a central
venous catheter can be placed .Even when used for short- (days) or medium-term (weeks)
treatment, PICCs carry a substantial risk of thrombosis that should be carefully considered
prior to use. PICCs appear to be associated with a greater risk for venous thrombosis overall
(superficial and deep thrombosis) compared with centrally inserted catheters (CICCs;
including ports), particularly in those who are critically ill or who have malignancy. The
incidence of deep vein thrombosis (DVT) for PICCs is between 5 and 15 percent for
hospitalized patients and 2 and 5 percent for ambulatory patients. , central catheter use was
associated with a 14-fold increased risk for upper extremity DVT, without a significantly
increased risk for pulmonary embolism. PICCs were associated with a higher risk compared
with CICCs.

Risk factors associated with PICC thrombosis can be categorized as patient-, provider-, and
device-related factors . The best way to prevent DVT is to avoid a device unless absolutely
necessary. Among patient factors, prior history of DVT (especially if such an event occurred
within 30 days), obesity, hematological malignancies, critical illness, and comorbidities such
as diabetes and obstructive lung disease have been linked to PICC-related DVT Device
factors — The device factors most associated with PICC-related DVT include the size of the
catheter, which, in turn, is related to the number of catheter lumens, and catheter tip location.
As with centrally inserted catheters, the incidence of PICC-related DVT increases with
increasing number of lumens, and for left-sided catheters . PICCs traverse a greater length of
vein, and, although the catheter is small relative to the central veins, the catheter may occupy
the entire internal diameter of the peripheral vein into which it is inserted [9]. The increase in
thrombogenicity of PICCs is explained, in part, by their insertion route; PICCs are placed into
the smaller, peripheral veins of the upper extremity, typically in the arm (eg, brachial vein,
basilic vein), where they occupy a greater fraction of the cross-sectional area of the vein. This
property (termed the catheter-to-vein ratio) is a key factor associated with PICC-related DVT
the brachial vein provides the greatest cross-sectional area when placing a PICC
Alternatively, puncture of veins that are more proximal to the chest (eg, the axillary vein in
the deltopectoral groove) provides access to larger-caliber vessels and results in lower rates
of DVT . In general, the greater the number of PICC lumens, the greater the size of the
catheter and resultant vein size that is necessary. The larger diameter of double- or triple-
lumen catheters occupies a greater cross-sectional area of the smaller peripheral (compared
with axillosubclavian) vein, leading to more stasis.

Catheter tip location is another important device factor. PICC tips should reside at the
cavoatrial junction (CAJ) or the right atrium (RA), where blood flow is greatest and risk of
DVT is lowest. PICCs that do not terminate in this location (ie, those in the middle to
proximal third of the superior vena cava) are associated with sevenfold greater rates of DVT.
Similarly, power injection of contrast dye may promulgate tip malposition and is important to
consider when using PICCs for radiographic studies

CLINICAL FEATURES AND DIAGNOSIS Most catheter-related thromboses (PICCs and

centrally inserted venous catheters [CICCs] alike) remain clinically silent . It is estimated that
3 to 10 percent of patients with PICC-related deep vein thrombosis (DVT) exhibit symptoms.
Most events occur within the first 7 to 14 days of catheter insertion (ie, dwell time) and
accumulate as catheter dwell times increases . Complete or partial occlusion, or difficulty
infusing or aspirating from the PICC, is not necessarily a sign of PICC-related thrombosis.
Intraluminal precipitation of drugs or minerals, blood products, or kinking of the catheter
from extraluminal causes can create this clinical picture. Furthermore, formation of fibrin
tails or sheaths (thin, slender structures that wrap around the catheter or the distal end of the
device) can also lead to catheter dysfunction. The term catheter thrombosis should be
reserved for radiographic evidence of thrombosis involving the vein in which a catheter
resides. Most PICC-related DVT does not occur at the site of insertion but in the deep veins
of the upper extremity, typically at the junction of the axillary and subclavian veins.
Superficial vein thrombosis (redness, pain, and swelling over the site of skin puncture and
catheter entry) was a common occurrence among older-generation PICCs that were made of
silicone but not now .Patients often complain of arm or forearm pain or swelling in the setting
of central vein thrombosis. Measurement of limb circumference (which should be
documented at baseline when a PICC is placed) is an objective and helpful way to assess an
increase in girth. As thrombosis progresses, dilation of the veins of the upper extremity,
chest, and neck may result as collaterals develop to bypass the obstruction. Pulmonary
embolism (PE) is rare with PICC-related DVT. However, PICC use has been linked to
development of lower extremity thrombosis and may increase the risk of PE from this
location

, diagnosis of PICC-related DVT is best made by Doppler-enhanced ultrasound for upper

extremity thromboses .However, the performance drops significantly for central thromboses
involving the subclavian or chest veins when anatomic structures and vessel depth limit
compression and visualization. If suspicion for DVT remains high in spite of negative
ultrasound, additional testing is recommended using venography (computed tomography,
catheter based) with or without use of highly sensitive D-dimer

Treatment of PICC-related thrombosis includes symptomatic care, anticoagulation, and

possibly thrombolysis. Symptomatic care includes extremity elevation, warm or coll
compresses, and oral nonsteroidal anti-inflammatory agents (NSAIDs). Whether to remove
the catheter depends upon whether it is functional and necessary.

Anticoagulation — Guidelines for the treatment of venous thromboembolism disease

recommend at least three months of uninterrupted systemic anticoagulation for catheter-
related upper extremity DVT (including PICC-related DVT) involving deep veins of the
upper extremity (brachial, axillary, subclavian) . While both warfarin and low-molecular-
weight heparin (LMWH) may be used, LMWH is preferred in patients with cancer and
catheter-related DVT . Although no recommendations regarding direct oral anticoagulants
exist for catheter-related upper extremity DVT, one study reported favorable faster resolution
of PICC-related DVT with low rates of bleeding in those treated with rivaroxaban compared
with traditional agents Anticoagulation should be continued for as long as the PICC catheter
remains in place. However, data supporting this recommendation are scant and largely
extrapolated from retrospective cohort studies and trials involving lower extremity DVT

Thrombolysis — Interventional techniques may also be used to treat PICC-related DVT,

especially if the burden of thrombosis is large or if there is concern for phlegmasia.
Thrombolysis can be considered for patients who meet the following criteria: severe
symptoms that do not improve with anticoagulation, thrombosis spanning both the subclavian
and axillary veins, good performance status, symptoms <14 days, life expectancy >1 year,
and low risk for bleeding . Although phlegmasia involving the upper extremities is rare, a
case series and report of 37 patients found that it commonly occurred in the setting of
indwelling vascular catheters; concomitant lower extremity thrombosis was associated with
worse outcomes Catheter-directed thrombolysis with infusion of tissue plasminogen activator
(tPA) over a 12- to 24-hour period has been used to manage such cases with reasonable
success (50 to 90 percent clot lysis) but with an increased risk of bleeding (10 percent). In
addition, mechanical thrombectomy with tPA infusion with or without angioplasty or stent
placement of the affected vessel has been attempted for severe cases of central venous
outflow obstruction.

Handling the catheter — As with other central venous catheters, routine PICC removal in the
setting of DVT is not recommended. Rather, several factors should be considered in this
respect, including:●Is the catheter clinically necessary? ●Is the PICC functional (that is, does
it aspirate or infuse to achieve the intended clinical purpose)? ●Is the PICC tip centrally
located? PICC tips that do not terminate at the cavoatrial junction or right atrium should be
repositioned to ensure that the device is located in the ideal position. ●Is there a concern for
infection associated with the catheter?

Resolution of thrombosis is faster if the PICC catheter can be removed while anticoagulation
is instituted. However, removal and reinsertion of a catheter in the contralateral upper
extremity is unwise as it is known to be associated with high risk of recurrent thrombosis. An
important exception is if the PICC is nonfunctional, as removal may help resolution of
thrombosis and avoid complications such as bacteremia that may occur in the setting of
thrombus. Removal of the PICC should be considered if symptoms persist despite systemic
anticoagulation or if thrombosis is associated with bacteremia

COMPLICATIONS Complications of PICC-related deep vein thrombosis (DVT) can be

classified as local versus systemic. Local complications include phlebitis and inflammation of
the affected vein ultimately leading to scarring and venous stenosis. These changes have
important implications for patients, especially those with chronic kidney disease; prior PICC
placement is among the most important predictors of arteriovenous graft or fistula failure and
threatens the success of dialysis in these individuals Although less frequent than in the lower
extremities, pulmonary embolism may also occur with PICC-related DVT. Post-thrombotic
syndrome, while infrequent, has also been described with PICC-related DVT and may lead to
chronic pain, swelling, and/or extremity discoloration

●Removing devices promptly when they are no longer necessary is another important
recommendation as most events occur within the first 7 to 14 days of dwell and accumulate
over catheter dwell times. Ensuring appropriate catheter tip location and sizing of catheter to
veins to prevent stasis are also key prevention strategies. Systemic use of venous
thromboembolism prophylaxis (eg, subcutaneous heparin or low-molecular-weight heparin)
is not associated with reduction in the risk of either centrally inserted venous catheter
(CICC)- or PICC-related DVT.
Catheter-related upper extremity venous thrombosis

Intravenous catheters cause endothelial trauma and inflammation, which can lead to venous
thrombosis. The majority (70 to 80 percent) of thrombotic events occurring in the superficial
and deep veins of the upper extremity are due to the presence of intravenous catheters. The
remainder are due to mechanical compression from anatomic abnormalities (ie, venous
thoracic outlet syndrome) Superficial thrombophlebitis due to peripheral catheters is
generally self-limited once the catheter is removed. Thrombosis involving the deep veins (ie,
subclavian, axillary, brachial) can lead to pulmonary embolism and long-term sequelae in
spite of adequate therapy. Pulmonary embolism from upper extremity sources accounts for
approximately 6 percent of cases

The main superficial veins of the upper extremity include the cephalic, basilic, median
antebrachial, median antecubital, and accessory cephalic

The deep veins of the upper extremity include the paired ulnar, radial, and interosseous veins
in the forearm; paired brachial veins of the upper arm; and axillary vein. The axillary vein
becomes the subclavian vein at the lower border of the teres major muscle

The most common site of deep vein thrombosis for centrally placed catheters is the internal
jugular vein . For PICC catheters, the brachial, axillary, or subclavian veins may be involved.
Thus, great caution should be used when considering intravenous access options in patients
who may require hemodialysis access in the future due to the relatively high incidence of
PICC-associated venous thrombosis.

Risk factors — Catheter diameter/number of lumens — The diameter of the catheter relative
to the size of the vein determines whether or not blood will flow freely around the catheter or
stagnate [23-25]. For a vein of similar size, thrombosis is more likely with a large-diameter,
centrally placed catheter (eg, plasmapheresis, dialysis, multilumen catheters) compared with
a small-diameter catheter (eg, single lumen). Peripheral versus central insertion — PICCs
appear to be associated with a greater risk for venous thrombosis overall (superficial and deep
thrombosis) compared with centrally inserted catheters (CICCs), including those attached to a
port, particularly in those who are critically ill or who have malignancy Malposition of the tip
of a central catheter may be associated with an increased risk of venous thrombosis. Prior
catheter infection is also a risk factor for the development of catheter-induced thrombosis
Prior deep vein thrombosis also increases the risk for catheter-induced upper extremity
venous thrombosis Prothrombotic states — The presence of a number of congenital or
acquired systemic prothrombotic conditions may increase the risk for catheter-induced upper
extremity venous thrombosis . It is well documented that factor V Leiden and prothrombin
gene mutation 20210 are risk factors for non-catheter-related UEDVT. Oral contraceptives
may increase the risk for catheter-related UEDVT when used in a patient with prothrombotic
mutations, such as prothrombin 20210 or factor V Leiden . Chemical irritation — Chemical
phlebitis can also occur as a reaction to the catheter material, or the infused drugs. Common
culprits include potassium chloride, diazepam, antibiotics (eg, vancomycin and oxacillin),
chemotherapy agents, and hypotonic (<250 mosmol/kg) or hypertonic (>350 mosmol/kg)
electrolyte solutions

.)
CLINICAL PRESENTATION The symptoms and signs of venous thrombosis are related to
local effects and to embolization, either to the pulmonary circulation or, paradoxically, to the
systemic arterial bed.. Obstruction of upper extremity flow may cause congestion of the
collateral veins of the shoulder and chest wall on the affected side. The patient may or may
not take notice of the venous patterning that results. Thrombosis of the deep veins can be
asymptomatic or present with mild symptoms. Inability to draw blood from
catheter — Inability to withdraw blood from or infuse into an indwelling catheter in an
otherwise asymptomatic patient is a common occurrence. Mechanical problems account for
40 percent of catheter occlusions, while thrombi account for the remainder. Differentiating
these two mechanisms is not possible solely on clinical grounds, and radiographic evaluation
by plain film (to detect overt malposition) or injection of contrast material into the catheter is
needed . Inability to infuse through a catheter is virtually always mechanical and is usually
due to a tight anchoring suture or a subcutaneous kink. Occluding thrombus usually does not
originate in the lumen of the catheter but rather begins as a "fibrin sheath" encasing the
catheter tip. The fibrin sheath blocks the withdrawal of blood from the catheter by creating a
one-way valve over the catheter tip, impairing the ability to withdraw blood from the catheter
but allowing infusion through it, the so-called "withdrawal occlusion." Propagation of
thrombus around the catheter ultimately prevents both infusion and withdrawal from the
catheter.

Symptomatic — The clinical manifestations of catheter-related venous thrombosis are

variable, and patients are often only mildly symptomatic, while some have more debilitating
symptoms.

Phlebitis — Phlebitis refers to an inflammatory reaction within the vein, usually due to
thrombus, which gives rise to clinical findings of pain, tenderness, induration, and/or
erythema along the course of a vein. While phlebitis does not represent infection, it is
sometimes difficult to differentiate from infection, and phlebitis predisposes to and often
leads to infected lines/veins. Superficial phlebitis with or without thrombosis of the vein is
frequently associated with the use of peripheral intravenous catheters (eg, basilic or cephalic
veins) and is more common in patients who are immunocompromised (eg, burns, transplant).
Patients with central catheters, particularly peripherally inserted central catheters (PICCs),
can also present with phlebitis of the superficial veins. PICCs can cause extensive superficial
thrombophlebitis due to the length of vein traversed by the catheter. Superficial phlebitis due
to peripheral venous catheters is generally a benign, self-limited disorder once the catheter is
removed. The phlebitic reaction in deeper veins leads to pain and tenderness overlying the
insertion site of the catheter. Induration, erythema, or congestion of tributary veins may be
appreciated at the base of the neck, infraclavicular fossa, shoulder, or arm depending upon
the location and type of catheter. The differential diagnosis of these symptoms in patients
with underlying malignancy includes local tumor invasion, malignant lymphadenopathy, and
bone metastasis, which may be complicated by pathologic fracture (especially of the
clavicle).Suppurative (infected) thrombophlebitis causes significant local symptoms, and the
patient may be toxic with bacteremia or fungemia. Suppurative thrombophlebitis can be
initiated by infection of catheter-associated thrombus. Purulent material may emanate from
the catheter exit site in patients with tunneled catheters.

Extremity edema — Obstruction of the major thoracic veins can cause edema (usually
unilateral) of the arm and hand, depending upon the extent of collateral venous flow from the
upper extremity. Swelling is often exercise dependent and presents only when the arm is used
vigorously. In some patients, the edema is a subjective symptom, described as a feeling of
fullness in the fingers with rings feeling "too tight."

If bilateral UEDVT is suspected in a patient with bilateral upper extremity edema, it can be
distinguished from more generalized fluid retention by the absence of lower extremity edema.

Embolization — A high index of suspicion for occult subclavian vein thrombosis is necessary
when evaluating a susceptible patient with symptoms suggestive of pulmonary emboli or
acute neurologic insult. Symptoms consistent with embolization in an otherwise
asymptomatic patient with a central catheter may provide the first clues to the presence of
UEDVT. This possibility is often overlooked clinically. Although low, the risk of
embolization is not negligible. Fatal pulmonary embolism has been reported, even in patients
treated with anticoagulants The incidence of pulmonary embolus is relatively low for both
catheter-related and spontaneous upper extremity deep vein thrombosis The incidence is
higher in patients with cancer.

Clinical prediction score — A clinical score for predicting the presence of upper extremity
deep vein thrombosis (DVT). A risk score was generated from the following four
parameters●Presence of a catheter or access device in a subclavian or jugular vein or a
pacemaker (plus 1 point)●Unilateral pitting edema (plus 1 point)●Presence of localized pain
in that extremity (plus 1 point)●Another diagnosis at least as plausible (minus 1 point)
Total scores were then rated as low probability (zero points or less, prevalence of upper
extremity DVT 9 to 13 percent), intermediate probability (one point, prevalence 20 to 38
percent), or high probability (2 to 3 points, prevalence 64 to 70 percent).

DIAGNOSTIC EVALUATION Duplex ultrasonography Venography — Venography may

be indicated if clinical suspicion for UEDVT is high and the ultrasound is negative or
nondiagnostic. For mechanical catheter problems, instillation of intravenous contrast into the
lumen of the catheter under fluoroscopy may readily demonstrate the presence of thrombus at
the tip of the catheter.Digital subtraction venography can be performed if an aggressive
diagnostic approach is required. Venography requires cannulation of either a peripheral vein
or other central vein (eg, subclavian, femoral). Because poor venous patency is one of the
reasons that indwelling catheters are needed in the first place, access for venography can be
challenging.

TREATMENT Phlebitis — There are limited data to guide management of upper extremity
superficial vein thrombosis. Fortunately, it appears that pulmonary embolus from superficial
phlebitis is very rare. The initial management of superficial phlebitis related to peripheral
intravenous catheters consists of discontinuing the intravenous infusion and removing the
peripheral catheter. Symptomatic care includes extremity elevation, warm or cool
compresses, and oral nonsteroidal anti-inflammatory agents (NSAIDS). Topical NSAIDs
may also be effective in relieving local burning associated with superficial phlebitis. It has
been shown for spontaneous lower extremity superficial thrombophlebitis that patients who
are not anticoagulated have a higher incidence of persistent pain and thrombus
recurrence/extension. Based upon a systematic review of randomized trials, anticoagulation is
suggested in patients with lower extremity superficial vein thrombosis who are at risk for
deep vein thrombosis. Extrapolating from these data, it would be reasonable to also consider
anticoagulation for patients with upper extremity superficial vein thrombosis who are at risk
for deep vein thrombosis (eg, superficial thrombosis in proximity to the deep veins,
thrombophilia).
Patients with proximal basilic or cephalic vein thrombosis who remain symptomatic (eg,
edema, pain) in spite of catheter removal may also be considered for treatment to manage
symptoms. As with superficial thrombophlebitis of the lower extremity, anticoagulation in
these patients should be highly effective in alleviating symptoms, especially in the setting of
malignancy. Whether anticoagulation improves the future patency of the superficial veins has
not been adequately investigated. The duration of therapy under these circumstances needs to
be guided by clinical judgment. Ultrasound can be repeated if symptoms progress to rule out
extension into the deep venous system. The catheter insertion site should also be monitored.
Excessive pain may indicate suppurative phlebitis, chemical phlebitis, or extravasation of
infused fluid into the subcutaneous tissues. Additional treatment, including surgery, may be
required to manage extravasation injuries. Antibiotics should be initiated if there is any
concern for suppurative thrombophlebitis.

Deep vein thrombosis — For patients with upper extremity deep vein thrombosis (UEDVT),
embolization (either to the pulmonary circulation or, paradoxically, to the arterial
circulation), while less common compared with lower extremity DVT, is still a serious
problem. Thus, therapy for UEDVT is also directed toward preventing this complication.,
anticoagulation should also be effective for preventing embolization of thrombi from the
thoracic veins, although treatment failures occur Catheter-induced UEDVT is generally
managed more conservatively compared with primary (spontaneous) UEDVT. The more
aggressive approach used with spontaneous UEDVT therapy is due to a higher incidence of
postphlebitic sequelae. post-thrombotic syndrome (PTS) following upper extremity deep
venous thrombosis in adults ranged from 7 to 46 percent. Residual thrombosis and
axillosubclavian vein thrombosis were associated with PTS, but catheter-associated UEDVT
was associated with decreased risk.

Anticoagulation — anticoagulant therapy with a goal of relieving acute symptoms and

preventing embolization remains the cornerstone of therapy . In patients with acute UEDVT
involving the axillary or more proximal veins, we recommend anticoagulation, as described
for lower extremity DVT, provided there are no contraindications, with or without catheter
removal. For isolated brachial vein thrombosis, the intensity and duration of anticoagulation
is uncertain, and decision-making should be individualized. The type and intensity of
anticoagulant therapy with catheter-induced UEDVT should be similar to that given to
prevent embolization of thrombi from the deep veins of the legs. We suggest initial therapy
with parenteral anticoagulants (low-molecular-weight heparin [LMWH], fondaparinux,
unfractionated heparin) followed by a vitamin K antagonist (eg, warfarin) or LMWH.
Sufficient data are lacking to recommend the use of a direct oral anticoagulant (DOAC) for
the management of the acute phase of catheter-induced UEDVT.
Routine removal of the catheter is not recommended. In patients who have an ongoing need
for the catheter, it is reasonable to administer anticoagulant therapy without catheter removal,
provided the line remains functional and well positioned . The optimal duration of
anticoagulation when the catheter stays in place has not been standardized. The ACCP
guidelines recommend continuing anticoagulation as long as the central venous catheter
remains in place, especially in patients with cancer. If the catheter needs to be removed, there
are currently no data to indicate whether central venous catheter removal should be preceded
by a brief period of anticoagulation to minimize risk of embolization.
There is uncertainty about the need to anticoagulate patients with thrombosis confined to the
brachial vein. The risk of long-term chronic venous sequelae from venous obstruction at this
site generally appears to be quite small. The ACCP guidelines favor anticoagulation for up to
three months if the thrombosis is symptomatic, is associated with cancer, or the catheter
remains in place

Asymptomatic thrombosis — Treatment of asymptomatic UEDVT is more controversial and

less well defined than treatment of symptomatic thrombi. While asymptomatic thrombi in the
leg are well recognized as a source of embolization, the rate of this or other complications
with asymptomatic subclavian vein thrombosis is not known . Consequently, the risk/benefit
analysis of any potential treatment cannot be determined. However, there is no theoretical
reason to believe that the risk of embolization is different than that of symptomatic
subclavian vein thrombi, unless the thrombus is chronic in nature. In addition, asymptomatic
UEDVT can cause permanent obstruction in the subclavian vein and may interfere with
subsequent catheter placement, resulting in loss of central venous access on the affected side.

Deep vein fibrinolysis — Although some authors have advocated the use of interventions
such as catheter-directed fibrinolytic therapy for catheter-induced UEDVT, there is no hard
evidence that better outcomes are achieved compared with more conservative therapy with
anticoagulation. These interventions are time-consuming, expensive, and not without
morbidity. Since thrombolytic therapy is indicated to minimize long-term symptoms, the
impact of this potential problem on the patient's quality of life should first be determined.

Catheter-directed fibrinolytic therapy would seem logical for individuals with significant
symptoms in the acute stages of thrombosis (symptoms less than 14 days), who have low risk
for bleeding and good long-term prognosis relative to their underlying disease and whose
lifestyles require vigorous use of the affected arm. On the other hand, a patient with limited
life expectancy from his or her coexistent medical problems, who does not require extensive
and vigorous use of his or her arm, would probably do just as well with conservative therapy.

Catheter management

Functioning — Maintenance of the catheter is justified if it is mandatory, functional, in the

correct position, and not infected. Anticoagulation is instituted and clinical symptoms
monitored closely for signs of improvement for as long as the catheter is present . Worsening
of symptoms while anticoagulated indicates a need to remove the line and repeat the duplex
examination.

Occluded — Occluded catheters are often removed and replaced. However, many patients
have limited access sites, and salvage of a catheter that has a thrombotic (ie, not mechanical)
occlusion can be attempted with the instillation of fibrinolytic agents . The decision to use
thrombolytic therapy for refractory thrombi is mainly clinical, considering the available
resources (drug availability, outpatient infusion pumps, etc.) and the degree of need for rapid
restoration of catheter function. For thrombotic occlusions unresponsive to two or more
boluses of a thrombolytic agent, objective diagnosis with radiologic techniques is advisable,
since many instances will be due to mechanical problems (eg, fibrin sheath) amenable only to
mechanical solutions.
Thrombolytic agents that have predominantly been studied for this indication include tissue-
type plasminogen activator (t-PA) or alteplase, and urokinase . In the United States and
elsewhere, alteplase (Cathflo, Activase) is more commonly used to manage catheter
occlusion. Alteplase is available in 2-mg vials for use in this setting. For adults or children
weighing ≥30 kg, one or two doses of 2 mg (1 mg/mL) of alteplase (tissue-type plasminogen
activator) with a recommended dwell time of 30 to 120 minutes per dose are generally
successful in restoring catheter function. Lower-weight patients should receive a reduced
dose adjusted to catheter lumen volume. The efficacy and safety of local instillation of
alteplase was confirmed with catheter function restored in 74 and 90 percent after one or two
doses, respectively

Urokinase is not available in the United States and has been found to be less effective
compared with alteplase . Outside of the United States, urokinase may still be in use.
Guidance on urokinase dosage for the management of dysfunctional central venous catheters
has been published for use in the United Kingdom with suggested doses of urokinase (Syner-
Kinase) 10,000 IU for each lumen using a PushLock technique or dwell time of 30 to 60
minutes . For persistent withdrawal occlusion or for hemodialysis catheters, a higher dose of
urokinase (25,000 IU per lumen) is recommended. The value of intraluminal lytic enzyme
infusion is unknown.

THROMBOSIS PREVENTION Routine prophylactic systemic anticoagulation is not

recommended for patients with indwelling central venous catheters .Various society
guidelines do not recommend routine prophylactic anticoagulation for the sole purpose of
preventing catheter-related thrombosis, even in patients with cancer. Nevertheless,
prophylactic heparin may have a role in some high-risk patients when the perceived risk of
thrombosis outweighs the risk of bleeding and the burden of anticoagulation. High-risk
factors include previous venous thrombosis, bulky disease, or hereditary thrombophilia