Von Willebrand Factor Antigen Concentration in Dogs with Sepsis

Background: Von Willebrand factor (vWF) antigen concentration, a marker of endothelial activation, is increased in human patients with multiorgan failure, sepsis, or both, and is an independent predictor of survival.
Hypothesis/Objectives: vWF antigen concentrations are significantly higher in dogs with sepsis.
Animals: Fourteen dogs hospitalized with sepsis. Sepsis was defined as microbiologic or cytologic evidence of infection combined with systemic inflammatory response syndrome. Control dogs were healthy dogs, without evidence of disease.
Methods: Prospective, observational study. Dogs admitted to the intensive care unit with a diagnosis of sepsis were considered eligible for enrollment into the study. Exclusion criteria included a previous diagnosis of von Willebrand disease or a recent history of a plasma transfusion. Citrated plasma samples were collected for analysis of vWF antigen by ELISA. All samples were drawn from dogs during hospitalization. Data between populations were analyzed using nonparametric statistical analysis with a P value < .05 considered significant.
Results: Twenty-five dogs were enrolled; 14 dogs with sepsis and 11 control dogs. The median vWF antigen concentration in dogs with sepsis was 156% (range, 117–200%), which was significantly higher than healthy dogs (105%; range, 44–155%, P < .005). There was no difference between survivors and nonsurvivors with a median vWF antigen concentration of 144% (range, 136–201%) in survivors (n = 7) and 159% (range, 122–174%) in nonsurvivors (n = 7) ( P = .5).
Conclusions and Clinical Importance: vWF is increased in dogs with sepsis, possibly reflecting endothelial activation. Further exploration of endothelial function is warranted in critically ill dogs.     

Plasma von Willebrand Factor Antigen Concentration and Buccal Mucosal Bleeding Time in Dogs With Experimental Hypothyroidism

This study was undertaken to investigate the effects of hypothyroidism on buccal mucosal bleeding time and von Willebrand factor antigen (vWf:Ag) concentrations. Hypothyroidism was induced in 8 adult dogs by administration of iodine 131. Four healthy dogs acted as controls. Measurement of plasma vWf:Ag and serum thyroxine and triiodothy-ronine concentrations, and buccal mucosal bleeding time were made before induction of hypothyroidism, for 23 weeks after ¹³¹I administration, and during 5 weeks of levothyroxine supplementation. No significant changes in buccal mucosal bleeding times were noted during the study. After an insignificant increase in vWfAg concentration in hypothyroid dogs, levothyroxine treatment was associated with a significant decrease in vWf:Ag concentration in hypothyroid dogs when compared with controls. Results of this study suggest that hypothyroidism does not induce acquired von Willebrand's disease or significant defects in primary hemo-stasis. J Vet Intern Med 1996;10:60–64. Copyright © 1996 by the American College of Veterinary Internal Medicine .     

Effect of Desmopressin Acetate on Bleeding Times and Plasma von Willebrand Factor in Doberman Pinscher Dogs with von Willebrand''s Disease

Effects of desmopressin acetate (1-desamino-8-D-arginine vasopressin [DDAVP]) on plasma von Willebrand factor (vWf) were studied in 12 purebred Doberman pinschers confirmed to have von Willebrand's disease (vWd) (plasma vWf antigen [vWf:Ag] concentrations, less than 30 U/dl). Twelve dogs had subnormal plasma botrocetin cofactor (BCf) activity and 11 dogs had prolonged buccal mucosa bleeding times. Tranquilization of three dogs with lenperone and three dogs with xylazine did not induce significant changes in mean plasma vWf:Ag concentrations or mean BCf activities. Thirty and 120 minutes after administration of DDAVP (1 micrograms/kg subcutaneously), there was significant shortening of the mean buccal mucosa bleeding time. Ten dogs responded to DDAVP with increases in BCf activity which exceeded 10 U/dl at 30 or 120 minutes, or both, after the drug was administered. At the same time, increases in plasma vWf:Ag concentrations were smaller than the increases in BCf activity. It was shown by multimeric analysis that primarily the higher molecular weight forms of vWf increased in plasma in response to DDAVP.     

Changes in factor VIII activity and von Willebrand factor antigen concentration with age in dogs.

The factor VIII activity of 38 German shepherd puppies, 6-12 weeks old, submitted for diagnosis of haemophilia A was measured. Eight of these puppies had values higher than would be expected for haemophiliacs, but less than the reference range for adult dogs. A further sequential study of 21 puppies (6-26 weeks of age) indicated that the factor VIII activity of puppies is generally less than that of adult dogs until about 14 weeks of age. Changes in the concentration of von Willebrand factor antigen in the puppies were irregular. These variations are probably not sufficient to interfere with accurate diagnosis of haemophilia A in most affected young dogs, but may interfere with the detection of heterozygotes in young bitches.     

Efficacy of Fresh-Frozen Plasma and Cryoprecipitate in Dogs with von Willebrand's Disease or Hemophilia A

Here we report the comparative efficacy of fresh-frozen plasma (FFP) and Cryoprecipitate in the treatment of 2 inherited bleeding disorders in dogs. The dogs were divided into 3 groups, consisting of 4 Doberman Pinschers with type I von Willebrand's disease (vWD) (group I), 1 Scottish Terrier with type III vWD (group 2), and 4 German Shepherd Dogs with hemophilia A (group 3). In vWD, therapeutic efficacy was determined by the ability of the products to increase von Willebrand factor antigen (vWf:Ag) concentrations above 35 canine units (CU)/dL and to correct the prolonged buccal mucosal bleeding time. Therapeutic efficacy in hemophilia A was assessed by the ability of the products to increase the factor VIII coagulant (FVIII:C) activity above 30 CU/dL. In both groups 1 and 2, higher increases in vWf:Ag were achieved with Cryoprecipitate than with FFP, despite a significantly smaller total amount of vWf:Ag (in CU) being infused with Cryoprecipitate. The maximum vWf:Ag attained after infusion in group 1 was dependent on both the baseline vWf:Ag concentration and on the type of infusion product. The dogs with vWD in both groups also displayed a delayed increase in FVIII:C activity after infusion of both plasma products, which is characteristic of the disease. In group 3, Cryoprecipitate achieved similar increases in FVIII:C activity compared to FFP, although a significantly lesser amount of FVIII:C (in CU) was delivered with Cryoprecipitate. Six of the 9 dogs treated with FFP experienced adverse effects ranging from mild pruritus to pallor and weakness, whereas none of the 9 dogs treated with Cryoprecipitate had any observable adverse reactions ( P = .009). Based on its efficacy and safety, we recommend Cryoprecipitate over FFP for treatment or prophylaxis of hemorrhagic episodes in dogs with vWD or hemophilia A.     

Disposition of Antimony and Aminosidine Combination After Multiple Subcutaneous Injections in Dogs

The disposition of a combination of antimony (Sbv) (12.8 mg/kg) and aminosidine (AM) (10 mg/kg) in 10 healthy Beagle dogs after multiple subcutaneous injections is described. Sbvplasma concentrations were determined by atomic absorption spectrometry, and AM by ion-pair liquid chromatography, using a fluorimetric detector. Sbvreached Cmaxat 60 min, and for about 1 h plasma levels were homogeneously stabilized between 10.78 and 11.76 microgram/mL; by 12 h, Sbvplasma concentrations were close to the detection limit (0.3 microgram/mL). AM Cmaxvalues were recorded after 1 h (30.6+/-3.11 microgram/mL, mean +/- SD), and plasma levels reached values close to the detection limit (0.15 microgram/mL) between 7 and 8 h after injection. Sbvkinetic parameters did not appear modified by the presence of AM. Moreover, repeated injections of the combination did not modify the kinetic behaviour of the two drugs and did not alter the renal function of the animals. The superimposition analysis of the Sbvdata suggests that a twice daily injection of the metal at a dose of 12.8 mg/kg would be sufficient to maintain inhibitory Sbvconcentrations similar to those recorded in humans.     

A Comparison of Serum Concentrations of Penicillin After Intramuscular Injection and Subcutaneous and Deep Injection into the Dewlap in Cattle

Using an aqueous solution of sodium benzyl penicillin as the model substance, a comparison was made in cattle between absorption after intramuscular injection, and after subcutaneous and deep injection into the dewlap.The duration of supposed therapeutically effective serum concentrations using the 2 dewlap routes was longer than for the intramuscular route, although maximum concentrations were lower. The applicability of injection into the dewlap, especially the subcutaneous route, is discussed in relation to intramuscular injection.     

Desmopressin enhances the binding of plasma von Willebrand factor to collagen in plasmas from normal dogs and dogs with type I von Willebrand's disease.

A new in vitro von Willebrand factor-collagen binding activity (vWF:CBA) assay was used to assess qualitative changes in vWF in normal dogs and dogs with Type I von Willebrand's disease (vWD) following treatment with desmopressin acetate (DDAVP). Although DDAVP induced increases in vWF antigen concentrations at 1 hour postinfusion in both normal and vWD dogs (57% and 60% increases, respectively), there were disproportionately greater increases in vWF:CBA (96% and 103% increases). These results support the hypothesis that the enhanced hemostatic activity induced by DDAVP is, at least in part, due to the selective release of more functionally active vWF multimers. The assay, as described, provides a convenient means of simultaneously assessing vWF quantity and function before and after DDAVP administration.     

Evaluation of von Willebrand Factor During Pregnancy,Lactation and Oestrous Cycle in Bitches Affected and Unaffected by von Willebrand Disease

Plasmatic concentrations of von Willebrand Factor (vWF) increase during pregnancy in humans and dogs; however the mechanism of such increase is still not well defined. The aims of this study were: (i) to evaluate changes in vWF concentration during pregnancy and during the subsequent oestrous cycle in bitches affected and unaffected by von Willebrand Disease (vWD); (ii) to correlate the vWF levels and cortisol levels in both groups. Seven vWD affected (GI) and nine unaffected (GII) bitches were used. The animals were assessed during pregnancy, parturition, lactation and non‐gestational oestrous cycle in 11 moments (Pregnancy 1, Pregnancy 2, Parturition, Lactation 1, Lactation 2, Lactation 3, Anestrus, Proestrus, Oestrus, Diestrus 1, and Diestrus 2). The following tests were performed; measurement of von Willebrand factor antigen (vWF:Ag), albumin and cortisol. In both groups, vWF concentration remained stable during the non‐gestational oestrous cycle, but increased during pregnancy, with the highest value observed at parturition. Increases of 70% and 124% in vWF were seen in GI and GII, respectively, compared to anestrus. No correlation was found between vWF and cortisol. Values of vWF:Ag changed during pregnancy, with a peak at parturition, both in vWD affected and unaffected animals. Values of vWF were not altered in the different phases of the oestrous cycle following pregnancy in both groups. Evaluation of vWF during pregnancy can cause false negative results for vWD, but assessment can be performed at any point in the oestrous cycle of non‐pregnant bitches.     

Stability of canine factor VIII activity and von Willebrand factor antigen concentration in vitro

The in vitro stability of canine factor VIII activity, von Willebrand factor antigen concentration and the ratio of these two factors was studied. Samples were stored for up to 48 hours, either as plasma or as whole blood, at 4 degrees, 20 degrees and 37 degrees C. Factor VIII activity was generally stable in both plasma and whole blood samples for up to 48 hours at 4 degrees or 20 degrees C. The concentration of von Willebrand factor antigen was more stable in samples stored as plasma than whole blood, and for a shorter time than factor VIII activity. Consequently, the stability of the ratio of these two factors was relatively poor in vitro.     

Effect of desmopressin on plasma factor VIII and von Willebrand factor concentrations in Greyhounds

Objective To determine the effect of 1-Deamino-8-D-argi-nine vasopressin on plasma concentrations of von Willebrand factor and factor VIII in Greyhound blood donors, and to compare the response of 1-Deamino-8-D-arginine vaso-pressin injection on plasma concentrations of von Willebrand factor between groups with different resting plasma concentrations of von Willebrand factor.
Animals Fifteen Greyhound blood donors were used. Dogs were grouped into three categories depending on their von Willebrand factor concentrations.
Procedure Desmopressin was administered subcuta-neously at 1 mg/kg to all dogs. Plasma von Willebrand factor and factor VIII concentrations were measured before and 10, 20, 30, 45, 60, 90 and 120 min after desmopressin injection.
Results The von Willebrand factor and factor VIII concentrations in all dogs increased significantly and remained higher than base-line throughout the 2 h period.
Conclusion Desmopressin is useful in increasing von Willebrand factor concentrations in Greyhound blood donors, including those with low resting concentrations.     

The effects of desmopressin on plasma factor VIII/von Willebrand factor activity in dogs with von Willebrand''s disease.

Eight unanesthetized normal dogs and seven dogs with von Willebrand's disease (vWD) were given desmopressin (0.6 micrograms/kg, IV) in order to determine the effects of this drug on plasma Factor VIII/vWF activity. Seven of the normal dogs and four of the vWD dogs were administered an equal volume of saline (control infusion) on another occasion. The other three vWD dogs underwent major surgery after treatment with desmopressin. Plasma FVIII coagulant activity (FVIII:C), von Willebrand factor antigen (vWF:Ag), and FVIII-ristocetin co-factor activity (FVIII:RC) were quantitated before infusion and at 60 minutes postinfusion. Activities were expressed as a percentage of the activity of a pooled canine plasma (12 dogs) arbitrarily designated as having 100% FVIII:C, vWF:Ag, and FVIII:RC activity. Plasma FVIII:C activity increased by 28% in the normal dogs and by 37% in the dogs with vWD. Plasma vWF:Ag increased more than twofold in normal dogs after desmopressin treatment. In the vWD dogs the average increase was also twofold, however there was much greater variability between dogs with increases ranging from 1.2 fold to 2.4 fold. Plasma FVIII:RC activity almost doubled in normal dogs, however like vWF:Ag, the increases in vWD dogs were more variable. One vWD dog had no increase in FVIII:RC while in the remaining six dogs FVIII:RC increases ranged from 1.8 to 2.9 fold. The results of this study indicate that a single intravenous dose of desmopressin (0.6 micrograms/kg) causes a significant elevation in plasma vWF:Ag and FVIII:RC activity and a much lesser increase in FVIII:C activity in normal unanesthetized dogs.(ABSTRACT TRUNCATED AT 250 WORDS)     

DDAVP-induced increases in coagulation factor VIII and von Willebrand factor in the plasma of conscious dogs

Infusion of the vasopressin analogue DDAVP into five normal dogs at doses of 0.1-2.0 micrograms DDAVP per kg body weight induced dose-dependent increases in the plasma content of coagulation factor VIII and von Willebrand factor. Plasma concentrations of von Willebrand factor (determined antigenically as factor VIII-related antigen and functionally as coagglutinin cofactor activity) and coagulation factor VIII were measured immediately before and at 10, 30, and 120 min after 10-min intravenous infusions of DDAVP. The greatest increases in coagulation factor VIII were produced with the 2.0 micrograms/kg dose. Ten minutes after infusion the mean increase in coagulation factor VIII was 32 units/dl (concentrations of all indices were reported relative to concentrations in a standard canine plasma pool, arbitrarily assigned a concentration of 100 units/dl) and this increase did not change significantly throughout the duration of the experiment. At 10 min post-infusion, the mean factor VIII-related antigen concentration increased 81 units/dl (dose = 2.0 micrograms/kg) and did not change significantly for the duration of the experiment. The maximum mean increase in coagglutinin cofactor activity, 141 units/dl, occurred 10 min after infusion (dose = 1.0 microgram/kg). Coagglutinin cofactor activity decreased significantly from peak activity by 120 min post-infusion.     

黄芪多糖对vAMV感染雏鸡SOD活性的影响

3日龄肉用AA雏鸡禽成髓细胞性白血病强毒（vAMV）人工感染后,禽成髓细胞性白血病（AMB）发病率86．7％、死亡率70．0％,脾脏、胸腺、法氏囊、心脏、肝脏、肾脏及性腺超氧化物歧化酶（SOD）活性与健康雏鸡相比,T－SOD和Mn－SOD活性于10日龄时明显升高（P＜0．01）,于17日龄后则显著降低（P＜0．05,P＜0．01）,而Cu,Zn－SOD活性无显著变化（P＞0．05）。vAMV感染雏鸡注射黄芪多糖,AMB发病率64．1％、死亡率是51．3％,同对照组相比,黄芪感染组的T－SOD、Mn－SOD及Cu,Zn－SOD活性初期无显著差异（P＞0．05）,中后期则明显升高（P＜0．05,P＜0．01）。     

Effect of Desmopresssin in Normal Dogs and Dogs with von Willebrand's Disease

Desmopressin acetate (DDAVP(R)), a synthetic analogue of vasopressin was slowly administered intravenously to 12 healthy dogs of various breeds and 10 Doberman Pinschers with mild-to-moderate type I von Willebrand's disease at a dose of 0.3, 1.0 and 3.0 micro g/kg body weight. Plasma von Willebrand factor:antigen was measured by an electroimmunoassay prior to and 30, 60, 90, 120 and 180 minutes after desmopressin infusion. Desmopressin induced only very modest and statistically insignificant increases in von Willebrand factor in both groups. We conclude that the response to desmopressin as measured by circulating von Willebrand factor is much less pronounced in healthy dogs and in Doberman Pinschers with von Willebrand's disease than in humans.     

Dogs with heart diseases causing turbulent high-velocity blood flow have changes in platelet function and von Willebrand factor multimer distribution

The purpose of this prospective study was to investigate platelet function using in vitro tests based on both high and low shear rates and von Willebrand factor (vWf) multimeric composition in dogs with cardiac disease and turbulent high-velocity blood flow. Client-owned asymptomatic, untreated dogs were divided into 4 groups: 14 Cavalier King Charles Spaniels (Cavaliers) with mitral valve prolapse (MVP) and no or minimal mitral regurgitation (MR), 17 Cavaliers with MVP and moderate to severe MR, 14 control dogs, and 10 dogs with subaortic stenosis (SAS). Clinical examinations and echocardiography were performed in all dogs. PFA100 closure times (the ability of platelets to occlude a hole in a membrane at high shear rates), platelet activation markers (plasma thromboxane B2 concentration, platelet surface P-selectin expression), platelet aggregation (in whole blood and platelet-rich plasma with 3 different agonists), and vWf multimers were analyzed. Cavaliers with moderate to severe MR and dogs with SAS had longer closure times and a lower percentage of the largest vWf multimers than did controls. Maximal aggregation responses were unchanged in dogs with SAS but enhanced in Cavaliers with MVP (regardless of MR status) compared with control dogs. No significant difference in platelet activation markers was found among groups. The data suggest that a form of platelet dysfunction detected at high shear rates was present in dogs with MR and SAS, possibly associated with a qualitative vWf defect. Aggregation results suggest increased platelet reactivity in Cavaliers, but the platelets did not appear to circulate in a preactivated state in either disease.     

Effect of acepromazine, xylazine and thiopentone on factor VIII activity and von Willebrand factor antigen concentration in dogs

The effect of acepromazine maleate, xylazine and thiopentone on the packed cell volume, plasma protein content, factor VIII activity and von Willebrand factor antigen concentration of blood was studied in normal dogs. The same variables were measured in dogs with haemophilia A given acepromazine maleate and thiopentone. Both the packed cell volume and plasma protein content decreased after the administration of either acepromazine maleate or xylazine. Values were not changed further after administration of thiopentone. Changes in the haemostatic variables measured were generally small. Consequently, blood samples collected from dogs under the influence of premedicant doses of acepromazine maleate or xylazine, and when subsequently anaesthetised with thiopentone, are adequate for the assay of factor VIII activity and von Willebrand factor antigen concentration for establishing an animal's haemophilia A and von Willebrand's disease status.     

Plasma Antithrombin Activity as a Diagnostic and Prognostic Indicator in Dogs: A Retrospective Study of 149 Dogs

Background: Antithrombin (AT) is the major inhibitor of coagulation. In people, hypoantithrombinemia is associated with hypercoagulability, thrombosis, and poor prognosis. Veterinary studies, however, have not demonstrated similar prognostic significance. Thus, AT activity (ATA) in dogs currently is interpreted based on human medicine guidelines. Hypothesis: ATA can serve as a prognostic marker in dogs, as has been shown in people. Objectives: (1) To describe the clinical and clinicopathologic findings, diagnoses, and outcome of dogs with decreased versus normal ATA, (2) to identify diseases and mechanisms associated with hypoantithrombinemia, and (3) to assess ATA as a prognostic indicator. Animals and Methods: Retrospective study of 149 dogs with ATA measurement during their disease course. Results: Hypoantithrombinemic dogs had a higher proportion of leukocytosis, hemostatic abnormalities, hypoalbuminemia, and hyperbilirubinemia versus dogs with normal ATA. Hypoantithrombinemia commonly was present in immune‐mediated hemolytic anemia (IMHA), pancreatitis, hepatopathy, and neoplasia. It was associated with higher risk of mortality in the entire study population and for specific diseases (eg, IMHA, neoplasia). The odds ratio for mortality significantly and progressively increased when ATA was <60 and <30% (9.9, 14.7, respectively). A receiver operating characteristics analysis of ATA as a predictor of mortality showed an area under the curve of 0.7, and an optimal cutoff point of 60% yielded sensitivity and specificity of 58 and 85%, respectively. Conclusions and Clinical Importance: In dogs, ATA <60% indicates increased mortality risk, similarly to human patients, but ATA has limited value as a single discriminating factor in the outcome.