Page 2266 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 135 Hemophilia A and B 2013

For persons with hemophilia, all vaccines should be given with Until the 1970s, this entailed the use of plasma or cryoprecipitate.
care using the smallest gauge needle possible (#25 or #27) and apply- Plasma contains small amounts of FVIII and FIX. Consequently,
ing pressure to the injection site for about 5 minutes. Vaccinations when plasma is used as the source of clotting factor replacement, large
should be given subcutaneously rather than intramuscularly. This is volumes are needed. Cryoprecipitate contains a higher concentration
a matter of some debate, however, because the majority of carefully of FVIII, and in the past was commonly used for hemophilia A
administered intramuscular injections can be given safely. Neverthe- treatment. However, neither plasma nor cryoprecipitate is virally
less, there is an increased risk of hematoma formation after intramus- inactivated. Consequently, both of these blood products carry a risk
cular injections. Subcutaneously administered vaccinations appear to of viral transmission. This limitation, together with issues of volume
16
produce the same immune response as those given intramuscularly. and convenience, has rendered these products obsolete for manage-
The enhanced safety of subcutaneous injections renders this the ment of bleeding in persons with hemophilia.
preferred route. Plasma-derived clotting factor concentrates became available in
the 1970s. In the early 1980s, it became evident that these concen-
trates were contaminated with HIV and hepatitis C. 17,18 Consequently,
Avoidance of Aspirin and Other Medications thousands of hemophilia patients worldwide were exposed to these
devastating viral illnesses, and many died of AIDS or of complications
19
Persons with hemophilia already have a severe bleeding disorder, and of hepatitis C. Out of this tragedy came the development of safer
this can be exacerbated by aspirin. NSAIDs may also interfere with factor concentrates—plasma-derived concentrates that were subjected
platelet function and should be avoided if possible. Cyclooxygenase-2 to effective viral inactivation methods, including solvent detergent,
inhibitors have less of an effect on platelet function than traditional pasteurization, vapor treatment, nanofiltration, and dry heating—as
NSAIDs. For older persons with hemophilia with coexistent cardio- well as recombinant clotting factors. Currently administered plasma-
vascular disease, aspirin, other antiplatelet agents, or anticoagulants derived clotting factor concentrates are not associated with HIV,
may be indicated, but such patients require coordinated care by an hepatitis B, or hepatitis C seroconversion. In theory, there still is a
experienced cardiologist and a hemophilia specialist. small risk of transmission of viruses and prions from plasma-derived
concentrates. Plasma-derived concentrates are generally classified as
high purity (containing only the desired factor and very little else) or
Treatment of Bleeds intermediate purity (containing the desired factor but with other
factors present). In the case of FVIII, intermediate-purity products
When a bleed occurs in a patient with hemophilia, immediate treat- generally contain VWF (e.g., Alphanate [Grifols], Humate [CSL-
ment is required to halt further bleeding. Rapid treatment prevents Behring], and Wilate [Octapharma]), and intermediate-purity FIX
expansion of the bleed, accelerates healing, and reduces the risk of products are prothrombin complex concentrates (PCCs, e.g., Beriplex
permanent disability. The longer the delay in providing treatment, [CSL Behring], Octaplex [Octapharma], and Proplex [Shire]), which
the more bleeding that will ensue, and consequently the longer it will in addition to FIX, contain factors II, VII, and X, as well as protein
take to completely resorb the blood. Rapid treatment of joint bleeds C and S. In general, PCCs are no longer used for the management
will minimize damage to the joint and prompt treatment of muscle of bleeding in patients with hemophilia B because of the risk of
bleeds will limit expansion and reduce the risk of pseudotumor for- thrombosis. In the late 1980s, recombinant factor concentrates were
mation or compartment syndrome. Rapid treatment of ICH may be developed. First-generation recombinant products were stabilized by
life saving and will minimize morbidity. The capacity to administer the inclusion of albumin in the final product. Second-generation
rapid treatment is enhanced if the patient/family is able to administer products no longer contained albumin in the reconstituted prepara-
factor at home (see box on Home Care). tion but were still exposed to human plasma-derived albumin during
the manufacturing process. Third-generation products have no
exposure to human or animal proteins and are stabilized with sucrose.
Coagulation Factor Concentrates Until now, most recombinant FVIII concentrates have been derived
from a full-length (as opposed to B domain–deleted) complementary
One of the main components of treating bleeds in hemophilia is DNA (cDNA) constructs. However, many of the extended half-life
replacement of the missing coagulation factor to achieve hemostasis. FVIII concentrates (including the recently licensed Fc Fusion FVIII
Eloctate [Biogen]) currently being developed are B domain deleted.
Recombinant factor concentrates have traditionally been more
expensive than their plasma-derived counterparts, but they have
Home Care generally supplanted plasma-derived concentrates for hemophilia
Hemophilic treatment is best administered in the patient’s home. Having treatment because of increased safety and small volume of infusion.
a patient or other caregiver able to administer factor allows for prompt Until recently, there was only one licensed recombinant FIX (Benefix
treatment of bleeds and facilitates prophylaxis. Teaching patients and [Pfizer]). A second recombinant (regular acting) FIX (Rixubis [Shire])
families how to administer clotting factor concentrates is labor intensive and two extended half-life FIX (Alprolix [Biogen] and Idelvion [CSL-
and usually falls to a dedicated hemophilia clinic nurse. It often takes Behring]) were recently licensed and several more extended half-life
a long time before families become skilled at factor infusions. Most products are close to approval.
boys with hemophilia older than the age of 3 years can be treated at All brands of traditional recombinant FVIII concentrates have
home after the parents are taught how to administer factor. In some exhibited similar efficacy and have generally been thought to have
children, poor venous access precludes routine factor delivery; these similar rates of inhibitor development.
children often require implantation of a central venous access device
(CVAD) such as a port-a-cath or creation of an arterial-venous fistula The efficacy of a factor concentrate primarily relates to its phar-
(AVF). The teaching of home care is complex. Good sterile technique macokinetic properties (recovery and half-life), and in this respect
is critical to avoid CVAD or AVF infections. Later in life, children can until recently all available plasma-derived and recombinant concen-
be taught how to self-administer factor through peripheral veins. This is trates have had similar pharmacokinetic properties.
generally done in children between the ages of 8 and 12 years of age. The recovery of factor concentrate refers to the increase in factor
Treatment of bleeds generally consists of more than just hemostatic level achieved immediately after infusion of a given amount of factor.
support (factor concentrates or DDAVP). For example, epistaxis and With all FVIII concentrates, administration of 1 IU/kg of FVIII
oral bleeding benefit from the use of antifibrinolytic therapy, and rest increases the FVIII level by approximately 2%. Therefore to achieve
and physiotherapy are important components of the treatment of a FVIII level of 100% in an individual with severe hemophilia, a dose
joint bleeds (see section on hemarthroses). The use of ice, which is
routine in hemostatically normal people with musculoskeletal injuries, of 50 IU/kg is needed. FIX has a volume of distribution twice that
is controversial in hemophilia because cooling may impair hemostasis. of FVIII, and 1 IU/kg has traditionally been thought to increase the
FIX level by 1%. However, the recovery of recombinant FIX is