Page 1256 - Small Animal Internal Medicine, 6th Edition

1228 PART XI Immune-Mediated Disorders

has been found to be dose-dependent. Doses of greater complement-mediated cell damage, and modulation of the
than 15 mg/kg PO q12h are associated with higher risk of release and function of proinflammatory cytokines. In dogs,
VetBooks.ir gastrointestinal toxicity. Mild suspected allergic reactions hIVIG binds to Fc receptors on mononuclear phagocytes,
thereby inhibiting phagocytosis. Whether other mechanisms
have been reported with use of the parenteral product. The
current recommended dose in dogs is 10 mg/kg PO q12h.
nary medicine to treat IMHA, pure red cell aplasia, myelofi-
The concentration of MPA in the plasma of cats following also play a role is unknown. hIVIG has been used in veteri-
administration of mycophenolate is highly variable, so the brosis, ITP, erythema multiforme, pemphigus foliaceus, and
safety and efficacy of this drug is unknown in cats (Slovak toxic epidermal necrolysis. Doses of hIVIG that have been
et al., 2017). used in dogs range from 0.25 to 1.5 g/kg; hIVIG is adminis-
tered as an intravenous infusion over 6 to 12 hours. Mild
thrombocytopenia and occasional vomiting have been
SPLENECTOMY reported in healthy dogs treated with hIVIG. The most
serious concern for use of hIVIG in dogs and cats is that
Splenectomy is an adjunctive therapy recommended in the administration of an infusion containing human protein
management of hematologic immune-mediated diseases could lead to sensitization and potential anaphylaxis if the
such as IMHA and ITP. Splenectomy is theorized to decrease treatment is repeated. There are few reports of anaphylactic
the number of mononuclear phagocytic cells available for reactions in dogs or cats treated with hIVIG despite repeated
phagocytosis of antibody-coated RBCs and platelets. It is administration in some case reports; however, anaphylaxis
typically recommended in dogs with IMHA or ITP resistant was reported to occur in a dog with myasthenia gravis
to medical therapy. There is evidence to support splenectomy treated with four doses of hIVIG. The other potential adverse
in dogs with ITP that relapse after tapering of prednisone effect documented in dogs is increased risk of thromboem-
and azathioprine therapy. The merits of splenectomy in dogs bolism. In a study of healthy dogs treated with hIVIG, a
with IMHA are less clear. One retrospective case series docu- prothrombotic and proinflammatory effect was demon-
mented a positive clinical response after splenectomy in 10 strated (Tsuchiya et al., 2009). Risk of thromboembolism is
dogs with IMHA that were not responding to immunosup- also a concern in people treated with hIVIG, especially in
pressive treatment. Nine of ten dogs survived to 30 days, and those already at risk. A high prevalence of thromboembo-
the hematocrit increased while transfusion requirements lism was reported in dogs with IMHA treated with hIVIG;
decreased after surgery. Interpretation of this study is diffi- however, whether this related to the underlying disease or
cult because most dogs were treated concurrently with the hIVIG treatment was not clear. The major limitation of
corticosteroids, and the positive outcome could have been a hIVIG treatment is the expense; consequently prospective
delayed response to medical treatment. Potential risks of studies of hIVIG treatment in veterinary medicine have been
splenectomy include hemorrhage and thromboembolic limited, and the evidence for its efficacy in disorders other
complications. The spleen is also an important site of extra- than canine ITP is weak. Immunoglobulin is currently most
medullary hematopoiesis, so splenectomy has the potential commonly used as an adjunctive treatment in dogs with
to impair RBC regeneration. severe ITP and as a rescue agent in dogs with immune-
mediated diseases (IMHA, myasthenia gravis, dermatologic
drug reactions, pemphigus foliaceus) that are not responding
HUMAN INTRAVENOUS to conventional immunosuppressive agents. Because of the
IMMUNOGLOBULIN rapid but short-acting effect of hIVIG on phagocytosis, the
most logical use is as a bridge to suppress phagocytosis in
Human intravenous immunoglobulin (hIVIG) is a prepara- diseases such as IMHA and ITP while waiting for other
tion of polyspecific IgG obtained by pooling the plasma of a immunosuppressive drugs to become effective; however,
large number (>1000) of healthy human blood donors. clinical studies to support this hypothesis are lacking except
hIVIG is available as either a solution or a lyophilized in canine ITP.
product, and a wide range of concentrations and vial sizes
are available. Numerous commercial products are available
and vary in price and availability (e.g., Gammagard S/D, PENTOXIFYLLINE
Baxter Healthcare Corporation, Deerfield, Ill; Gamimune N,
Bayer Pharmaceuticals, Leverkusen, Germany). hIVIG is the Pentoxifylline belongs to the methylxanthine drug class and
treatment of choice for immune-mediated thrombocytope- is a derivative of theobromine. Despite this derivation, the
nic purpura in people and is also used for the treatment of drug does not have cardiac or bronchodilatory effects. The
a wide variety of other immune-mediated diseases. Numer- major properties of pentoxifylline relate to its effects on the
ous mechanisms by which hIVIG modulates the immune immune system and blood viscosity. Pentoxifylline improves
system have been documented in humans, including the deformability of RBCs by unknown mechanisms. Pent-
decreased production of autoantibodies, possibly due to oxifylline also has a number of immunomodulating effects,
antiidiotypic antibodies in hIVIG, functional modulation of including inhibition of IL-1, IL-6, and tumor necrosis
T cells, decreased natural killer cell activity, blockade of factor-α, as well as inhibition of B- and T-cell activation.