Dogs respond differently to the treatments,
so what works for some dogs may not work for others. It is extremely
important to discuss all the options before deciding on an appropriate
treatment program for your dog.
Therapy
Therapy of AIHA necessitates
a delicate balance between striving to control the disorder,
maintaining the body's ability to fight disease and avoiding
adverse side effects of therapeutic drugs. The initial goal is
to decrease the rate of hemolysis and allow recovery of the red
blood cell mass while preventing complications. While the treatment
of secondary IMHA should focus on eliminating the underlying
cause, treatment of AIHA aims to prevent formation of red blood
cell antibodies and to block or reduce receptors on neutrophils,
monocytes, and macrophages to prevent phagocytosis of antibody/complement
coated red blood cells..
The reduction of receptors
on phagocytic cells is accomplished by treatment with glucocorticoids
such as Prednisone and Dexamethasone.
Prednisone: a general immunosuppressive
- administered orally at
1 to 4 mg/kg/day, divided into two doses
- allow up to a week to
take effect
- decreases phagocytosis
by impairing receptors on phagocytic cells
- impairs T cell function,
killer cell function, phagocytic response to chemicals and cytotoxic
action
- suppresses lymphocyte
proliferation, interleukin-2 production, & IgG production
at high levels
- side effects include excessive
drinking, increased urination, increased appetite and weight
gain, abdominal enlargement, accumulation of fluid in the abdomen,
muscle atrophy, panting, heat intolerance, gastrointestinal problems
including ulceration and bleeding, pancreatitis, blood clots
resulting in pulmonary thromboembolism, skin thinning, bruising,
infections, hair loss, elevated liver enzymes, liver enlargement,
gastric ulcers, blood clots, & secondary infection of the
urinary or respiratory tract
Dexamethasone (.3-.9 mg/kg/day) is more potent
than Prednisone and can be administered intravenously or intramuscularly
as the initial treatment, but side effects can be more severe.
Prevention
of antibody formation is accomplished somewhat with glucocorticoids,
but patients that exhibit fulminant hemolysis, autoagglutination,
intravascular hemolysis or lack of response to glucosteroids
alone generally have high concentrations of serum antibody in
their blood so more potent immunosuppressive agents should be
considered.
Though
clinical studies have yet to determined the optimal drug combination
for specific disease states,
a
study showed significantly longer survival times for dogs given
Prednisone and Azathioprine compared with dogs given Prednisone
alone, Prednisone and Cyclophosphamide, or Prednisone, Cyclophosphamide
and Azathioprine.
Increased survival times for dogs given
Azathioprine were also shown in a subsequent study on the benefits
of Cyclophosphamide.
Azathioprine, aka Imuran: a general immunosuppressive used in combination
with Prednisone
- administered orally at
2 mg/kg once daily
- allow two to three weeks
to take effect
- inhibits T cells
- inhibits cell division
and cytokine production
- side effects include bone
marrow suppression, gastrointestinal irritation, liver damage,
pancreatitis
Cyclophosphamide,
aka Cytoxan: a
general immunosuppressive used in combination with Prednisone
- administered at 2 mg/kg
orally once a day for four days, then off for three; or every
other day, for up to eight weeks. If possible the drug should
be administered in the morning.
- allow two to three weeks
to take effect
- by inhibiting cell division
and cytokine production: inhibits both T and B cells
- administered also as a
single intravenous dose in dogs that require a blood transfusion
to inhibit an immune response to both the transfused blood and
the patient's own red blood cells
- side effects include bone
marrow suppression, gastrointestinal irritation, hemorrhagic
cystitis
Danazol: anabolic steroid used in combination
with Prednisone
- administered at 5-10 mg/kg
orally twice a day
- allow one to two weeks
to take effect
- incorporated into the
red cell membrane, stabilizing it and rendering the cells more
resistant to hemolysis
- block receptors on phagocytic
cells
- decreases circulating
levels of IgG and complement
- immune modulator by normalizing
the suppressor/helper T cell ratio
- reduces the need for prednisone
and avoids the side effects of long term prednisone use
- side effects include weight
gain, lethargy, masculinization, and increased liver enzymes.
Cyclosporine:
- administered 10 to 20
mg/kg/day orally or intramuscularly
- serum concentration needs
to be monitored to ensure adequate dosage and treatment
- therapeutic concentration
is 200-400ng/mL: toxic serum concentration is 600mg/dL
- inhibits activation of
T cells by interfering with the production of interleukin-2
- specifically inhibits
synthesis of cytokines, interleukin-2 and interferon by activated
T cells
- helper T cell immunosuppression
- side effects include vomiting,
diarrhea, anorexia, enlarged gums, weight loss, excessive loss
or growth of hair, warty growths, involuntary shaking and increased
susceptibility to infections
Intravenous
Human Gamma Globulin:
- administered intravenously
.5-1.5 g/kg intravenously over a 12 hour period.
- purified IgG from human
donors
- difficult to obtain since
it is also a drug used to treat AIDS patients
- competes with autoantibodies
for receptors
- enhance T suppressor cells
- impairs receptor mediated
phagocytosis & killer cell activity
- promotes release of immune
modulatory mediators
- no adverse side effects
have been seen
Leflunomide: experimental drug tested at UC/Davis
in the mid 90's, so far only used as a treatment with obstinate
cases
- inhibits proliferation
of B & T cells
- inhibits interleukin-2
and T cell dependent antibody production
- serum drug levels need
to be monitored to ensure adequate dosage and treatment
- administration of drug
needs to be discussed between treating vet and veterinarian that
participated or is familiar with the research
- not to be administered
with steroids.
Plasmapheresis is a process that removes autoantibodies
and complement components from the plasma. This lowers serum
concentration of antibodies targeting red blood cells and results
in a decreased rate of destruction. Special facilities and equipment
are needed to separate plasma from red blood cells and replace
with packed red blood cells suspended in suitable medium.
Splenectomy has been successful since the
extravascular destruction occurs mainly in the spleen. The spleen
is the source of plasma cells that produce antibodies against
antigens, so the major source of autoantibodies is removed. Most
likely to benefit are dogs with extravascular red cell destruction
or enlarged spleens. Splenectomy is approached with caution since
an enlarged spleen may represent the source of significant extramedullary
hematopoiesis (development of blood cells outside of the bone
marrow). Prior to considering a splenectomy a bone marrow aspirate
should be done to determine whether the bone marrow even has
the capability to make baby red blood cells. Significant erythroid
hyperplasia, production of baby red blood cells, should be present.
If a needle aspiration cytology of the enlarged spleen reveals
significant erythrophagocytosis, removal not only prevents the
erthrophagocytosis, it also removes a significant source of antibody
production. A possible reduction in the immunosuppressive drug
dosage is a benefit. It should be noted in the absence of the
spleen, the liver sometimes has been known to take over its duties.
Eicosapentanoic
acid is a therapy
mentioned in the Five
Minute Veterinary Consult, but I have no idea what it is. Please email me
if you do!
Oxygen A decrease in total red blood cell mass results
in insufficient oxygen delivery to bodily tissues, so patients
receiving transfusions may benefit from short term supplemental
oxygen.
Transfusions may be needed as a method of support
in animals with life threatening anemia (PCV<15%). The goal
of a transfusion is the maintenance of tissue oxygenation to
avoid damage to the vital organs while providing support and
giving time for the drugs to start to work.
- Whole blood: urged to
use crossmatched blood since transfusions may accelerate the
hemolytic crisis. Cytoxan may be given to decrease the potential
immune response.
- Oxyglobin is
a hemoglobin based oxygen carrying solution that can provide
oxygen carrying support for two to three days. Oxyglobin is advantageous to red blood cells in
the sense that there is no need for blood typing and crossmatching.
It also doesn't introduce addition foreign red blood cells into
the system that may "fuel the fire" of destruction.
Oxyglobin can discolor the skin, mucous membranes, eyes and urine.
Gastrointestinal
Protectants: protect the stomach from gastric
ulceration and bleeding while on steroids
- Cimetidine (Tagament):
reduces acidity,10 mg/kg, 3 or 4x a day.
- Famotidine (Pepcid ac):
inhibits gastric acid secretion, .25 mg/kg daily
- Misoprostol (Cytotec):
inhibits gastric secretion and presumably stimulates mucous production,
which acts as a barrier, 2-5 mcg/kg orally 2-3 times day.
- Sucralfate (Carafate):
.5-1 gm orally three or four times a day, coats stomach and binds
to ulcer, protecting it from acid and prevents bleeding.
Antimicrobial
Therapy: discuss
with your vet the administration of antibiotics to avoid secondary
infections due to a suppressed immune system.
Heparin Due to potentially harmful thromboplastic substances
released during hemolysis, patients that exhibit direct autoagglutination
of blood or intravascular hemolysis are at high risk for thromboembolic
disease, so heparinization should be considered to prevent a
possible onset of thromboembolism and disseminated intravascular
coagulation.
- administered 100-300 units/kg
3x a day subcutaneously.
- side effects include excessive
bleeding, bruising, bloody urine and bloody feces.
Anticoagulant
drugs, such as
Coumadin, aka Warfarin Sodium, can be given to reduce the clotting
ability of the blood.
Intravenous
fluids should be
administered with severe hemolysis to maintain vascular volume
and prevent kidney failure.
Complications
Hypoxia, a deficiency in the amount of
oxygen reaching bodily tissues and organs, may result in serious
and irreparable damage. The functioning of bodily organs is dependent
upon oxygen delivered by red blood cells, so when the red blood
cell count drops too low to deliver the much needed oxygen, hypoxia
and eventual necrosis may develop.
Thromboembolic
Disease is suspected
to occur due to thromboplastic substances released during hemolysis.
It can be compounded by glucocorticoid treatment, which can contribute
to an already existing hypercoagulable state. Though symptoms
of an embolism are hard to differentiate from side effects of
anemia, blood clots can be detected with ultrasounds and x rays.
High bilirubin levels, low levels of albumin and platelets in
the blood, elevated liver enzymes and use of intravenous catheters
are associated with the increased risk of pulmonary thromboembolism.
Heparin is commonly used to inhibit the growth of existing and
prevent further clots.
Disseminated
Intravascular Coagulation,
aka DIC, can accompany hemolysis due to the consumption of clotting
factors and platelets, which can result in mass hemorrhaging.
Monitoring blood platelet counts and smears for schizocytes can
provide early warning of DIC.
