Page 670 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

Fluid Therapy with Macromolecular Plasma Volume Expanders 657

signs in an autosomal recessive hereditary albumin defi- a low degree of substitution and a low C2/C6 ratio. 169
ciency in rats. 107 Interestingly, affected rats have marked This opens up the possibility for development of HES
hypercholesterolemia. products with higher MW (and thus potentially better
In our clinical experience and in experimental stud- intravascular persistence) but minimal effects on coagula-
ies, 182 animals with severe hypoproteinemia (COP, tion. With repeated administration, the small colloid
<11 mm Hg) may exhibit peripheral edema but rarely molecules are constantly excreted, and the relative con-
develop pulmonary edema. In dogs with centration of larger molecules increases. This fact explains
hypoalbuminemia, hydroxyethyl starch has been shown why many studies reporting clinically relevant bleeding
to result in clinical improvement of peripheral edema or refer to patients who received repeated doses of colloid
ascites. 150 The role of macromolecules in maintaining over a period of days.
the selective permeability of the microvascular bar- The exact mechanism of action by which coagulation is
rier 46,102 provides a rationale for the prophylactic use of affected still is not fully understood; however, great prog-
albumin or artificial colloid. It is, however, most impor- ress has been made over recent years. Older studies
tant to diagnose and treat the underlying cause of the reported reductions in factor VIII and von Willebrand’s
hypoproteinemia rather than administer palliative colloid factor (greater than those expected by dilution) and
therapy. Furthermore, if large ongoing losses are present, weakened clot formation. 2–4,68,69,82 Colloid molecules
as can be the case with protein losing nephropathies and may impair the action of endothelial adhesion molecules,
enteropathies, colloid support may not be effective. 106 thereby reducing endothelial release of von Willebrand’s
37
TREATMENT factor. Decreases in vWF and factor VIII may also occur
due to binding with HES molecules and accelerated elim-
COMPLICATIONS AND ination of the complex. 88 In essence, colloids can cause an
ADVERSE EFFECTS acquired type 1 form of Von Willebrand disease (VWD).
Dogs that already have mild to moderate VWD may expe-
rience severe reductions in VWF and factor VIII follow-
EFFECTS ON HEMOSTASIS ing colloid infusion. Colloids should be avoided in
The debate about whether artificial colloids cause known cases of VWD. Platelet dysfunction independent
abnormalities in coagulation is largely redundant because of von Willebrand factor is also present; its mechanism
all of the older, higher molecular weight artificial colloids has not been fully elucidated but is at least in part due
can cause abnormalities of primary and secondary hemo- to the ability of HES molecules to coat the surface of
stasis. The more important question is whether these platelets and interfere with ligand binding. 52
coagulopathies are clinically relevant. Despite many stud- The reductions in factor VIII (FVIII), which is
ies supporting a lack of clinically relevant bleeding, there stabilized by vWF in circulation, accounts for the mildly
also is a large amount of clinical and experimental evi- prolonged activated partial thromboplastin times that
dence documenting serious, potentially life-threatening have been observed in people after HES administration. 81
bleeding after administration of hydroxyethyl starches Hydroxyethylstarches decrease agonist-induced expres-
and dextran. 6,21,42,162,172 This apparently conflicting evi- sion and activation of platelet integrin aIIbß3 (formerly
dence implies that coagulation abnormalities are clinically known as GPIIb/IIIa). 62 Integrin aIIbß3 on the surface
relevant only in some cases. The effects on coagulation of the platelet binds fibrinogen, and therefore plays a vital
appear to be directly related to the intravascular concen- role in platelet aggregation and formation of a platelet
tration of artificial colloid. 172 Higher plasma plug. It has also been shown that HES molecules coat
concentrations of colloid may occur after larger doses, the surface of the platelet, limiting binding of ligands
repeated administration, or reduced intravascular degra- to cell surface receptors, which may decrease function
dation. However, although high molecular weight has of platelets independent of the integrin aIIbß3
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been considered to be one of the key factors in determin- blockade.
ing coagulation effects of HES products, 164 in general a The clinical relevance of platelet dysfunction after HES
reduction in molecular weight has also been associated administration has been manifest in people as increased
with a reduction in degree of substitution. Recent postoperative blood loss or increased transfusion
intriguing work evaluating the coagulation effects of requirements in some patient populations. 20 Neverthe-
products with differing MW but the same low degree less, some studies in surgical patients have also shown
of substitution (HES 130/0.42, HES 500/0.42, and no significant increase in blood loss. 80,94 Trials in postop-
HES 900/0.42) that demonstrated similar effects on erative patients that have used rapidly degradable HES
coagulation for all three preparations suggests that solutions found no difference in rates of blood loss and
molecular weight has less effect than the degree of substi- transfusion requirements when compared to albumin or
tution. 95 A further study evaluating HES 700 with vary- gelatin. 88 A recent pooled analysis of studies in major sur-
ing degrees of substitution and C2/C6 ratios suggests gery comparing HES 130/0.4 (Voluven) and HES 200/
that effects on coagulation are minimized when there is 0.5 (Starquin) found that estimated blood loss and