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Canadian Researcher Reviews CVADs Side Effects in Immune Tolerance Therapy
 

A Canadian researcher published the results of a study on the side effects of the use of central venous access devices (CVAD) in delivering immune tolerance therapy (ITT) to hemophilia patients with inhibitors in a review article in the March 2009 issue of Haemophilia. The author of the study was Manuel D. Carcao, MD, Department of Pediatrics, Division of Haematology/Oncology Child Health Evaluative Sciences, Hospital for Sick Children at the University of Toronto, Canada.

Inhibitors result when the body’s immune system identifies infused factor VIII as a foreign substance and releases antibodies to attack it, thereby “inhibiting” the protein’s ability to form a blood clot. ITT is an effective therapeutic response to an inhibitor, particularly in hemophilia A patients with a factor VIII deficiency (FVIII). Considered an optimal approach by many clinicians, ITT, if successful, can eliminate the immune system reaction over time.

ITT involves high doses of factor product given regularly (once daily or several times per week), to train the body to accept the therapy by stopping the production of antibodies. The process is similar to allergy densitization treatments. Once the immune system accepts the presence of FVIII, tolerance is achieved and the inhibitor is essentially eradicated. This process, however, can take weeks or years. Although time-consuming and expensive, ITT is effective in approximately 70%-85% of FVIII inhibitor cases.

“By far, the most common and most problematic adverse events associated with being on ITT are those related to the need for a CVAD and complications arising from this. CVADs facilitate the repeated administration of coagulation factors (for purposes of treating or preventing bleeds or for ITT) in individuals with haemophilia and poor vascular access. They are particularly useful in the setting of young children who have small peripheral veins and need frequent infusion of factor,” explained Carcao.

Cacao described three of the most common CVAD-associated side effects: infection, device malfunction and thrombosis.

Infections are the most prevalent CVAD complication. They can occur at the device access point (local), in the tubing (regional) or systemwide. Infections are responsible for 70% of all CVAD removals. The removal and potential re-insertion of a CVAD will often cause an interruption in ITT, which can hinder success of the therapy. According to Carcao severe infection-related complications, such as septic arthritis, bacterial endocarditis, septicemia and death, are rarely reported. 

Device malfunctions are another complication of CVADs. Mechanical problems resulting in failure of the apparatus to function include catheter dislodgement or fracture, catheter migration and embolism, and port reservoir complications (erosion of the skin covering the port). Some of these require CVAD removal.

Patients with a CVAD can also experience clots resulting from venous thrombosis. If untreated, these clots can impede blood flow from the CVAD, cause complete obstruction in the CVAD and/or generate larger clots. A life-threatening pulmonary embolism could develop.

Carcao concludes his review by emphasizing the importance of proper CVAD care and maintenance, including regular “flushing” with heparin or saline to keep the line and tip clean. He also stressed the need for firm adherence to aseptic practices to prevent infection.

Source: Carcao M. Side-effects and venous access issues with immune tolerance therapy. Haemophilia (2009), 15, 494-500.

 

 

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