Page 2269 - Hematology_ Basic Principles and Practice ( PDFDrive )

2016 Part XII Hemostasis and Thrombosis

Surgical Management in Hemophilia Ample evidence shows that prophylaxis must be commenced early
in life to prevent joint disease. This is referred to as primary prophy-
With appropriate management (factor replacement with or without laxis; prophylaxis started at a very young age (usually 2 years of age
other adjunctive hemostatic agents), intra- and postoperative hemor- or earlier) before joint disease has developed (generally, before or
rhages can be prevented in patients with hemophilia thus allowing immediately after the first joint bleed). In contrast, secondary pro-
for surgery to be performed safely in patients with hemophilia. Ideally phylaxis refers to continuous long-term prophylaxis started at a later
a multidisciplinary team is required to undertake surgery in a safe age (after 2 years of age) or after more than one joint bleed has
manner; physicians with expertise in the management of hemophilia occurred. The term tertiary prophylaxis has recently been coined to
patients should always be involved. Some surgeries might need to be refer to prophylaxis starting after there is established joint disease.
adapted for patients with hemophilia (e.g., bioprosthetic heart valves The term prophylaxis also encompasses short-term prophylaxis regi-
are preferable to mechanical valves to avoid the need for anticoagulant mens given after surgery or ICH.
therapy). Comparisons of different starting prophylactic regimens have
The most common surgical procedures in hemophilia are those shown that patients can be started on less intensive prophylaxis regi-
undertaken to manage the complications of joint bleeds. These mens and gradually escalated to full-dose regimens. Although full-
include surgical or arthroscopic synovectomy, nonsurgical (chemical dose regimens prevent bleeds more effectively than intermediate- and
or radionucleotide) synovectomy, various arthrodesis procedures, and low-dose schedules, they cost more and may not be feasible in less
joint replacement. affluent countries. In these countries, intermediate- or low-dose
An open surgical or arthroscopic synovectomy endeavors to prophylaxis regimens may be more affordable, and may still confer
remove the inflamed and thickened synovial tissue that is the source significant benefit.
of bleeding within the joint. Although it may reduce the frequency of Although prophylaxis has been used for decades it was only in the
bleeding, it does not improve joint mobility and may even worsen it. last 10 years that a randomized study comparing primary full-dose
Radionucleotide synovectomy has largely replaced chemical syno- prophylaxis with on-demand therapy in young children with severe
90
vectomy. This involves injection of a radioisotope (e.g., yttrium , hemophilia was undertaken. This study demonstrated 90% fewer
32
chromic phosphate P ) into the joint space to obliterate synovial bleeds in patients given primary prophylaxis and after only a few
tissue. Compared with surgical synovectomy, radionucleotide syno- years, these patients already had less joint damage than those treated
25
vectomy is less invasive, associated with a shorter hospital stay, and on demand. The benefits of prophylaxis include reduced hospital-
reduced clotting factor coverage. Consequently, the procedure is less ization, less time lost from school or work, improved school perfor-
costly than surgical synovectomy. Radionucleotide synovectomy is mance, and a reduced need for orthopedic surgery. Because of these
particularly useful for patients with inhibitors because there is a lower benefits, the World Health Organization, World Federation of
risk of bleeding. However, long-term safety data are lacking in Hemophilia, and many other national hemophilia organizations have
hemophilia. endorsed primary prophylaxis as the standard of care for children
Arthrodesis (surgical joint fixation) is particularly useful for with severe hemophilia. One other potential benefit of prophylaxis is
painful joints with greatly compromised mobility in which joint that early initiation of prophylaxis may reduce the risk of inhibitor
replacement is not easily undertaken (e.g., ankles). development, at least in the subgroup of patients with severe hemo-
Joint replacements (particularly of the knee and hip) are still philia with “good risk” F8 mutations. 20,26
commonly performed procedures in adults with hemophilia. The The approach to prophylaxis varies by center and country. In some
elbow, which is not amenable to arthrodesis or for the most part to centers and countries, all patients are given full-dose prophylaxis,
joint replacement, is often the most difficult joint to manage in while in others, prophylaxis is individualized based on the severity
patients with hemophilia. It is likely that there will be less need for and frequency of bleeding episodes. 27
surgical procedures with the initiation of prophylaxis regimens in Burdens of prophylaxis include the need for venous access and
early childhood. cost. Patients receiving full-dose prophylaxis often require a CVAD
or AVF for repeated factor administration. Furthermore, in the short
term, full-dose prophylaxis regimens in young children are threefold
Prophylactic Clotting Factor Replacement more expensive than on-demand therapy. However, the cost of
on-demand therapy increases over time because once joint bleeds
Experience has shown that if treated solely on demand, patients with occur, the subsequent joint damage triggers more bleeding. The social
hemophilia will experience frequent bleeds and will, over time, costs of joint damage are high in terms of lost time from school or
develop disabling joint disease. Prophylaxis regimens reduce bleeding work and limitations in vocational opportunities for adults with
and prevent or limit joint damage in patients with hemophilia. The arthropathy. Whereas the costs of treating patients on demand rise
longest experience with the use of prophylaxis comes from European over time, the cost of prophylaxis may stabilize or decrease when
24
centers in Sweden, the Netherlands, and Germany. Based on adults become less active.
numerous cohort studies, there is good evidence that patients who Although most children in Europe and North America are on
receive prophylaxis experience fewer bleeds and maintain better joint prophylactic regimens, prophylaxis is less routinely used in develop-
function than those treated on demand. There are several different ing countries. However, this trend appears to be changing with
prophylaxis regimens distinguished by dose and frequency of factor increasing use of intermediate- and low-dose prophylaxis regimens in
administration. The full-dose prophylactic regimen, often referred to developing countries.
as the Malmö regimen, involves administration of 25 to 40 IU/kg of
conventional FVIII every other day (minimum, 3 days/week) for
patients with hemophilia A and the same amount of FIX 2 days a Considerations for Treatment of Hemophilic
week for those with hemophilia B. Less intense “intermediate-dose” Bleeding in Adults
prophylaxis regimens involve the administration of 15 to 25 U/kg 2
to 3 times a week, and low-dose prophylaxis regimens call for the There is little doubt that regular prophylactic infusion of clotting
administration of dosages of 10 to 15 IU/kg given once or twice a factor concentrate is the treatment of choice for children and adoles-
week. cents. However, the role of prophylaxis in adults is less clear. Although
Of course, new protocols will be needed for the extended-half-life it may seem intuitive to maintain prophylaxis throughout life, this
concentrates and full-dose, intermediate-dose and low-dose prophy- strategy is expensive, and its benefits have not been formally evalu-
laxis regimens with these products remain to be defined. In addition, ated. Furthermore, there is some evidence that not all children who
these concentrates enable achievement of higher prophylactic trough received prophylaxis require continued prophylactic therapy as adults.
levels, which could further reduce the risk of bleeding and allow When prophylactic therapy is undertaken in adults, it should be
patients more flexibility in pursuing activities. administered in a manner best suited to the individual needs of the