Treatment methods for patients with hemophilia now include prophylactic or immune tolerance regimens that require frequent regular infusions of clotting factor concentrate, often beginning at an early age. If such regimens are undertaken, central venous access devices (CVADs) may be utilized to facilitate venous access. Due to the increased use of CVADs in the bleeding disorders community and in response to frequent requests from hemophilia treatment center personnel for guidelines regarding their appropriate use, MASAC has developed the following recommendations:

1. Surgeons placing these devices in patients with bleeding disorders should do so only in conjunction with appropriate hemophilia treatment center planning and oversight.

2. Treatment centers should provide an adequate period of time for patients and families to learn appropriate CVAD care (See MASAC Recommendation #103, Standards and Criteria, Section I. A. 3.).

3. Clear guidelines for ongoing management, tracking and follow-up of patients/families with CVADs should be developed and instituted at treatment centers utilizing these devices. These guidelines should include the following:
a. Symptoms requiring immediate notification of a medical care provider should be outlined. A plan for intervention and reporting of fevers in patients with CVADs should be developed and clearly understood by patients/families and the treatment center staff.
b. Anticoagulant concentration, need for anticoagulant removal in small children or with repeated access at close intervals, and methods recommended for maintenance of line patency should be documented. For example, a child on routine prophylaxis receiving an infusion every other day or less frequently may not require removal and discarding of the heparin solution in the device. However, small patients (i.e., those less than 10 kilograms) or patients requiring daily or more frequent access and infusion (e.g., those with an inhibitor) should have the heparin in the catheter removed and discarded, as these patients are at risk of becoming therapeutically anticoagulated.
c. Use of antibiotic prophylaxis for invasive procedures including dental interventions should be emphasized. Patients with CVADs require the use of prophylactic antibiotics in association with dental work or other invasive procedures such as surgery. Issues with oral hygiene should be assessed and addressed on an ongoing basis.

4. Patients and families should review appropriate care of CVADs on a regular basis with their treatment center personal and should bring any questions regarding CVAD care to the prompt attention of their comprehensive center care team.

5. Repeated problems experienced with CVADs (e.g., line fracture or malfunction) should be reported to the Center for Devices and Radiologic Health (CDRH) of the FDA.

6. NHF supports the development of clinical trials to address factors contributing to and methods to minimize complications associated with these devices.

This material is provided for your general information only. NHF does not give medical advice or engage in the practice of medicine. NHF under no circumstances recommends particular treatment for specific individuals and in all cases recommends that you consult your physician or local treatment center before pursuing any course of treatment.

CHAPTERS: Please feel free to distribute this to your members.

PHYSICIANS: Please distribute this to physicians in your area who treat persons with hemophilia.

Appendix to MASAC Recommendation #115
Background Information
Prophylactic therapy, especially in the young child with hemophilia, has led to increased utilization of central venous access devices (CVADs). The most common of these devices are subcutaneously implanted Ports and PassPorts. These devices have potential risks as well as benefits that should be considered on an individual basis and adequately discussed with patients and families. Such discussions with patients and families will lead to a clearer understanding of the intensity of care required by patient/families, potential complications, and situations requiring contact with a medical care provider. The decision as to which CVAD is recommended for any particular patient is based upon a variety of factors including the patient's clinical circumstances, specific needs, past history with these devices, age and size, as well as the experience and comfort level of the treatment center personnel and surgeon with these devices. Several devices are available, including totally implanted Ports and PassPorts and externalized catheters such as Hickmans and Broviacs. PassPorts may be used in individuals wishing to have the reservoir peripherally located.

Two clear benefits of CVADs in patients with hemophilia are the ease of access and administration of replacement therapies to treat or prevent bleeding episodes and the reduction of long-term damage to peripheral veins. The use of CVADs has increased patient and family freedom from the need for immediate access to medical care. CVADs have decreased the fear of pain associated with venipuncture in children and decreased the need for visits to physicians, emergency rooms, and treatment centers for infusion therapy. The majority of patients and families can be taught appropriate care of these devices to provide a safe level of care at home.

There are many potential risks associated with the use of CVADs; chief among them are infection and thrombosis.

CVADs are foreign bodies that may become infected. Infection may arise due to inadequate sterile technique when accessing the device, but may also arise in face of appropriate sterile technique. Infections of CVADs are potentially serious and in some instances life threatening, as these devices are in direct communication with the blood supply and may lead to rapid growth of bacteria and overwhelming infection in the patient. The frequency of occurrence of line sepsis varies as reported in different publications depending upon the center and method of calculation. Calculated based upon the number of catheter days, the infection rate for Ports is approximately 0.4/1000 catheter days (1). If infection rates are calculated as a percentage of the population of all patients with Ports, the reported rate varies from 8-55% (2-5). Infections appear to be more common in children less than 2 years of age, children with inhibitors, children with a history of previous CVAD infection or thrombosis, and children whose lines have to be accessed frequently. Other risk factors for infection include poor oral hygiene and presence of dental cavities and/or abscesses. CVADs with more than one lumen have an increased risk of infection, at least in externalized lines. Some medical conditions are associated with an increased risk of infection, including those with immune system compromise such as HIV. Recurrent infections in one device should trigger a follow-up investigation of risk factors in the patient and discussion with the care provider about sterile techniques and ways to minimize further infection.

Thrombosis is the development of a clot in a blood vessel that may obstruct or occlude blood flow. Patients with hemophilia may develop blood clots despite their underlying bleeding disorder, especially in association with the use of CVADs. A clot may develop within the line or device itself, which is often treated with medications that dissolve clots. If the clot within the device cannot be dissolved, then the device may need to be removed and/or replaced. A clot that occurs within a blood vessel may also lead to removal of the device based upon the symptoms the patient has experienced, the extent of the clot, and the function of the line. Not all devices are replaced with another CVAD after a significant clot in the blood vessels has occurred. For example, some patients may develop extensive clots in the upper body venous system leading to arm and face swelling due to poor venous return. The long-term risks and consequences of thrombosis related to CVADs in hemophilic children are not currently known.

Other risks associated with CVADs include:
1. Line fracture and migration of the catheter into another area of the body, usually the heart or lungs.
2. Separation of the catheter from the reservoir of the CVAD leading to no blood return and infiltration of the infused material into the tissues surrounding the device.
3. Development of a hematoma (bruise or bleed) around the reservoir where the device is accessed.
4. Opening of the skin over the device exposing the CVAD, usually occurring over the reservoir. This is called dehiscence.
5. Leakage of the material injected or infused into the CVAD into the tissues surrounding the device if the needle is not correctly positioned.
6. Development of a tear in the material covering the reservoir, usually due to the use of improper needles for access.

1. Shapiro AD and Donfield SM. Infectious complications of central venous access devices (CVAD) in children with hemophilia. 2000; Haemophilia 6 (abst 18) 278.
2. Liesner RJ et al. Use of central venous catheters in children with severe congenital coagulopathy. British Journal of Hematology 1995; 91, 203-207.
3. Blanchette VS et al. Central venous access devices in children with hemophilia: an update. Blood Coagulation and Fibrinolysis 1997; 8(suppl 1), S11-S14.
4. Medeiros D et al. Contrast venography in young haemophiliacs with implantable central venous access devices. Haemophilia 1998;4, 10-15.
5. Warrier I et al. Experience with central venous catheter (CVC) in children with hemophilia. Haemost 1993; 69, 854 (Abstract)
6. Perkins JL et al. The use of implantable venous access devices (IVADs) in children with hemophilia. Journal of Pediatric Hematology/Oncology 1997; 19(4) 339-344.