Chapter 6. Treatment of established catheter-related thrombosis

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6.1. Data extraction
6.2. Data analysis
6.3. Discussion
6.4. Recommendations: treatment of established catheter-related thrombosis


The literature search retrieved no prospective randomized study.

 

HTA Questions

Studies included

HTA 1: Treatment of CVC Thrombosis: LMWH + VKA

2 prospective non-randomized studies

[SAVAGE1999] [KOVACS2007]

1 retrospective study

[TRAN2010]

HTA 2: Treatment of CVC Thrombosis: CVC removal

1 retrospective study

[FRANK2000]

HTA 3: Treatment of CVC thrombosis: thrombolytic therapy

2 retrospective studies

[PUCHEU1996][SCHINDLER1999[J1] ]

 


 [J1]cette étude est mentionnée comme propsective dans les SOR. J’ai regardé l’abstract sur PubMed, mais ce n’est pas dit. Je n’ai pas accès au full paper. Confirmez vous la nature retrospective?

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6.1. Data extraction

6.1 Data Extraction: Cliquez pour télécharger

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6.2. Data analysis

 

LMWH + VKA

Studies

2 prospective non-randomized studies

[SAVAGE1999] [KOVACS2007]

1 retrospective study

[TRAN2010]

Agreement

Not applicable, poor quality (39, 46 and 64 patients)

Quality of evidence

Very low (observational studies, serious limitations, serious imprecision)

Results

There are insufficient data to determine the efficacy and tolerance of LMWH + VKA for treating CVC-VTE.

Catheter removal

Studies

1 retrospective study

[FRANK2000]

Agreement

Not applicable

Quality of evidence

Very low (observational study, serious limitations)

Results

There are insufficient data to conclude on the efficacy and tolerance of CVC withdrawal for treating CVC-VTE. There are no data on the optimal timing between withdrawal and the initiation of anticoagulant therapy.

Thrombolytics

Studies

2 retrospective studies

[PUCHEU1996][SCHINDLER1999]

Agreement

Yes

Quality of evidence

Very low (observational studies, serious limitations, very serious imprecision)

Results

There are insufficient data to determine the efficacy and tolerance of systemic or localized thrombolytic therapy for treatment of CVC-VTE.

Nonetheless thrombolysis can be used even with intensive chemotherapy.

 

Conclusions
There is no evidence in cancer patients with catheter-related thrombosis to support:

  • The withdrawal of a non-infected, functioning, well-positioned CVC
  • The use of LMWH + VKA or long-term LMWH
  • Thrombolytic therapy via the catheter or systemic thrombolysis.

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6.3Discussion

Central venous catheters/access devices (CVC or CVAD) are an essential part of therapy for cancer patients, facilitating blood sampling, drug and intravenous fluid/nutrition delivery and blood product administration. One of the unavoidable complications associated with this convenience is CVC-associated VTE. In one prospective study of 444 consecutive cancer patients, 19 patients (4.3%) suffered a symptomatic CVC-related DVT at a median of 30 (range 6-162) days post-catheter placement, corresponding to an incidence of 0.3 per 1000 catheter-days (95%CI: [0.2-0.5]) [LEE2006]. A prospective study of 2144 patients with peripherally inserted central venous catheters (PICC) found a similar rate of thrombosis (3%) [EVANS2010]. Consequently, treatment of CVC associated thrombosis is a routine part of contemporary oncology practice. Our systematic review of studies evaluating the treatment of CVC-associated thrombosis found 2 non-randomized prospective studies of anticoagulation [SAVAGE1999] [KOVACS2007], 1 retrospective study of CVC removal [FRANK2000],
2 retrospective studies of localized or systemic thrombolysis [PUCHEU1996] [SCHINDLER1999] and 1 retrospective study with a variable treatment approach (thrombolysis, CVC removal and anticoagulation) [TRAN2010]. Although both the studies on anticoagulation and the two studies on thrombolysis found evidence of a favorable treatment response, the level of evidence was very poor. Current recommendations are therefore based upon expert opinion and treatment choice is left to the discretion of the treating physician.

The experts do not recommend catheter removal if all the following conditions are met: (i) the distal catheter tip is in the right position (at the junction between the superior vena cava and the right atrium), (ii) the catheter is functional (good blood reflux), (iii) the catheter is mandatory or vital for the patient, and (iv) there is no fever or any sign or symptom of infected thrombophlebitis. In contrast, catheter removal is warranted if there is a prime risk factor for thrombosis (catheter too short, misplaced, etc. ). There are no reliable data on the optimal duration of anticoagulant treatment after catheter removal.

The basis for this recommendation is several-fold:

  • 1. CVC-associated VTE represents a triggered episode of VTE associated with the CVC and the coagulopathy associated with the underlying cancer and its treatment.
  • 2. The risk for recurrence is high, as long as the CVC remains in place, therefore treatment should continue until the CVC is removed.
  • 3. Most cancer patients will need another form of central venous access after CVC removal. Placement of another CVC will likely place them at high risk for recurrent CVC-VTE.
  • 4. It is likely that underlying activation of coagulation associated with this triggered event will abate in a time course similar to that of other triggered VTE (i.e. surgery, trauma); therefore at least 3 months of anticoagulation should be sufficient.
  • 5. Once the CVC has been removed and at least 3 months of anticoagulation have been completed, patients with CVC-VTE should be at low risk for recurrent VTE, as their thrombotic event required the presence of a CVC as a local trigger.
  • 6. Two prospective studies (although of limited quality) have demonstrated the efficacy of primary anticoagulation in the treatment of CVC-related VTE [SAVAGE1999] [KOVACS2007].
  • 7. CVC removal is associated with the theoretical concern of thromboembolism on catheter withdrawal.
  • 8. Thrombolytic therapy may by superior to anticoagulation as regards thrombus dissolution and vessel patency, but will also likely be associated with a greater risk of bleeding complications [MEWISSEN1999].

Randomized studies investigating the treatment of CVC-VTE are warranted to improve the evidence basis for the treatment of this common complication of cancer therapy.
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6.4 Recommendations: treatment of established catheter-related thrombosis

R1. [J1] For the treatment of symptomatic CRT in cancer patients, anticoagulant treatment is recommended for a minimum of three months. In this setting, LMWH are suggested. Oral VKA can be used.

The CVC can be kept if it is functional, well-positioned, non-infected and shows good evolution under close surveillance.

Whether the CVC is kept or removed, no standard approach in term of duration of anticoagulation is established.

Quality of evidence

Very low

Balance between desirable and undesirable effects

Undetermined

Values and preferences

Subcutaneous injections if LMWH

Costs (resource allocation)

Catheter withdrawal is associated with additional costs

Level of recommendation

Best practice

 


 [J1]rien sur les thrombolytiques ?

Dans les SOR il était écrit :

Published data have shown the feasibility of thrombolytic therapy, including in patients treated with intensive chemotherapy (Level of evidence: D).

Thus, the experts proposed that, based on published data, the administration of thrombolytic drugs for the treatment of CVC-associated thrombosis may only be considered in specific circumstances, in which the thrombotic risk is superior to the risk associated with the use of these drugs: i.e. in the event of superior vena cava thrombosis associated with recent, poorly-tolerated, vena cava syndrome objectively confirmed (at least on a thoracic CT scan and/or opacification of the superior vena cava) or imperative maintenance of a CVC.