Artifactual Prolongation of the Activated Partial Thromboplastin Time Associated With Hemoconcentration in Dogs

An inappropriate blood-to-anticoagulant ratio can cause an artifactual prolongation of the activated partial thromboplastin time (APTT) and prothrombin time (PT). In a drug safety study in dogs, we observed a 4-to 5-second increase in the APTT from baseline coincident with increased hematocrit values (56% to 65%) secondary to drug-induced vomiting and diarrhea. The PT and platelet counts were unchanged, and there was no clinical evidence of bleeding associated with venipuncture. Although we were unable to sample the same dogs to investigate the possible effect of hemoconcentration on the prolonged APTT, the question was addressed by an in vitro study. The hematocrit value for citrated blood samples collected from healthy beagle dogs was increased by the addition of aliquots of red blood cell/plasma mixtures in vitro while maintaining a 9:1 blood-to-anticoagulant ratio. There was a 2-to 4-second prolongation of the APTT associated with hematocrit values of 55% to 61 %, but the PT was not prolonged. Adjustment of the blood-to-anticoagulant ratio corrected the prolongation. This study emphasizes the important relationship of the blood-to-anticoagulant ratio when measuring coagulation tests in hemoconcentrated samples.     

Observations on blood coagulation after snakebite in dogs and cats

Blood samples from 13 cases of snakebite, 6 in dogs and 7 in cats, were tested for activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrin/fibrinogen degradation products (FDP). Four cases were tested for fibrinogen concentration. Based on the results of a commercially available ELISA test, 9 cases were caused by tiger snakes (Notechis scutatus) and 1 case by a brown snake (Pseudonaja textilis). Three other cases had clinical signs and increased creatine phosphokinase values which suggested tiger snake envenomation. Although the period post-envenomation varied, results indicated a marked prolongation of the APTT and PT in 5 of 6 dogs. Three of these 5 dogs also had increased FDP values and 3 (of 3 examined) were hypofibrinogenaemic. Clinical manifestations of this coagulopathy were: haematoma formation after venepuncture (3 cases), gingival petechiae (1 case) and hyphaema (1 case). In contrast, there was minimal or no prolongation of the APTT and PT values, and no increase in FDP, in all 7 cats. Furthermore, no cat exhibited clinical signs of a coagulopathy.     

Measurement of prothrombin time (PT) and activated partial thromboplastin time (APTT) on canine citrated plasma samples following different storage conditions

Samples from 75 clinically ill dogs were utilised in the study. APTT and PT tests were performed immediately on fresh citrated plasma samples (Fresh). The remaining plasma was stored at -20 degrees C for less than 4 months (n=36 samples) or between 4 and 7 months (n=39 samples). In batches of five, frozen samples were thawed rapidly and APTT and PT tests were performed on the thawed samples immediately (0RT) and after storage at room temperature (23 degrees C, range: 22-25 degrees C) for 24h (24RT) and 48h (48RT). The median APTT value from the (0RT) samples was significantly longer than that obtained from fresh samples (15s vs. 13.2s) but the PT value was not statistically different (7.8s vs. 7.6s). The median APTT (15s) and PT (7.5s) results from the (24RT) samples were not statistically different to those from the (0RT) samples (APTT: 15s, PT: 7.6s) but both tests were significantly longer (APTT: 16.5s, PT: 9.2s) from the (48RT) samples. We concluded that long term batching and freezing of clinical samples at -20 degrees C is acceptable for measurement of PT but not of APTT. We demonstrated that APTT and PT results do not change following storage of samples at room temperature for 24h but storage for 48h may lead to statistically and clinically significant changes (values at least 25% higher than the high value of the laboratory's reference interval) in both clotting times.     

Effects of meloxicam on the haemostatic profile of dogs undergoing orthopaedic surgery

The buccal mucosal bleeding time (BMBT), prothrombin time (PT), activated partial thromboplastin time (APTT) and intraoperative bleeding score (IBS) of 38 dogs that underwent orthopaedic surgical procedures and received meloxicam orally and/or parenterally were measured. Fourteen of the dogs (group A) received a single subcutaneous dose of 0.2 mg/kg meloxicam at premedication, 18 dogs (group B) received 0.1 mg/kg meloxicam orally daily for five days followed by a single subcutaneous dose of 0.2 mg/kg meloxicam preoperatively, and six dogs (group C) received 0.5 ml of normal saline subcutaneously at premedication. No statistically significant differences among the groups were detected in relation to the mean (SD) values of BMBT, PT and IBS before and after the surgery, or in the values of APTT in group A. In group B there was a small but significant increase in APTT after the surgery, but all the measurements were within the normal range for dogs.     

Effect of three loading doses of warfarin on the international normalized ratio for dogs

OBJECTIVE: To evaluate effect of 3 loading doses of warfarin sodium on the international normalized ratio (INR) for dogs. ANIMALS: 18 dogs weighing between 25 and 30 kg. PROCEDURE: Dogs were randomly allocated into 3 groups and received 2, 4, or 6 mg of warfarin administered orally once a day for 2 days after surgery for bilateral iliac artery grafting. Activated partial thromboplastin (APTT) and prothrombin times (PT) were measured before and after treatment. Prothrombin time also was reported as an international normalized ratio. RESULTS: The APTT were not significantly different among groups before or after treatment. The INR and PT were significantly increased in all groups after treatment. The INR and PT of the 6-mg group were significantly greater than those of the 2-mg and 4-mg groups. None of the dogs had clinical evidence of bleeding. CONCLUSIONS AND CLINICAL RELEVANCE: A warfarin loading dose of 6 mg/d can be safely administered for 2 days to dogs weighing between 25 and 30 kg. Anticoagulation can be achieved safely in dogs in 2 days by use of warfarin. The effects of warfarin can be monitored with the INR.     

Evaluation of a bench-top coagulation analyzer for measurement of prothrombin time, activated partial thromboplastin time, and fibrinogen concentrations in healthy dogs

OBJECTIVE: To evaluate a bench-top coagulation analyzer for determination of prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen concentration in healthy dogs. ANIMALS: 55 healthy adult dogs. PROCEDURES: PT, APTT, and fibrinogen concentration were determined by use of the coagulation analyzer. Values were compared with results obtained independently by a conventional laboratory. RESULTS: Correlations (with 95% confidence intervals) between the coagulation analyzer and conventional laboratory values were 0.760 (0.610 to 0.857), 0.700 (0.448 to 0.721), and 0.896 (0.878 to 0.918) for PT, APTT, and fibrinogen concentration, respectively. Using linear regression, comparison of data from the coagulation analyzer and the conventional laboratory provided equations relating the coagulation analyzer values with values from the conventional laboratory and suggested that APTT and fibrinogen values from the coagulation analyzer and conventional laboratory were approximately the same within expected random variation. Prothrombin time values for the coagulation analyzer were significantly offset from the PT values for the conventional laboratory but still were correlated reasonably well with the conventional laboratory values. CONCLUSIONS AND CLINICAL RELEVANCE: By use of the mechanical method of analysis, fibrinogen concentrations obtained with a bench-top coagulation analyzer correlated well with results for a conventional laboratory, indicating that the coagulation analyzer is a reliable instrument for determination of this coagulation variable. Coagulation analyzer results for PT and APTT correlated less strongly with those for the conventional laboratory, but they would still be considered clinically reliable.     

Effects of haemolysis, lipaemia and bilirubinaemia on prothrombin time, activated partial thromboplastin time and thrombin time in plasma samples from healthy dogs

Interferences caused by haemolysis, lipaemia and bilirubinaemia on prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT in normal canine plasma samples were studied using commercially available reagents and a steel ball coagulometer. Haemolysis significantly interfered with APTT (P = 0.0076) and TT (P = 0.0292). Regression analysis showed that TT was significantly shortened as haemoglobin concentrations increased. Lipaemia increased as demonstrated by regression analysis. Bilirubin significantly interfered with PT (P=0.0003) and APTT (P=0.002). Although statistically significant, none of the differences found were of clinical relevance.     

The activated partial thromboplastin time of diluted plasma: variability due to the method of fibrin detection.

The purpose of this study was to determine the effects of the dilution of plasma (1/3 in saline) on the kinetics of fibrin generation in the activated partial thromboplastin time (APTT) assay. The diluted APTT is considered to increase the sensitivity of the APTT test however, studies in our laboratory using an electro-optical fibrin detection system failed to show significant differences in APTT values obtained with diluted and undiluted canine plasma. Seventeen plasmas, including plasmas moderately and markedly deficient in intrinsic factor activity were assayed in the undiluted and diluted APTT assay using two methods for fibrin endpoint detection; a visual "tilt-tube" technique and an electro-optical detection system. In the former technique the endpoint was the formation of a visible fibrin web or clot; in the latter procedure the end point was the first detection of a change in optical density of the plasma. Optical density changes during fibrin formation were also recorded ( thrombokinetograms ). The results indicated that the electro-optical fibrin detection system failed to identify a prolongation of the APTT as a result of 1/3 plasma dilution; a prolongation that was consistently observed with the visual fibrin detection technique. Plasma dilution however, did significantly reduce the rate of fibrin production as indicated by the thrombokinetogram profile. It was concluded that the dilution of plasma with saline, as has been used to increase the sensitivity of the APTT assay procedure, has little effect on the time of onset of fibrin formation in a given plasma. The major effect appears to be on the way in which fibrin forms in that the polymerization/crosslinkage events associated with macroscopic fibrin production are delayed.     

Comparison of prothrombin time, activated partial thromboplastin time, and fibrinogen concentration in blood samples collected via an intravenous catheter versus direct venipuncture in dogs

OBJECTIVE: To compare prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen concentration in canine blood samples collected via an indwelling IV catheter and direct venipuncture. ANIMALS: 35 dogs admitted to an intensive care unit that required placement of an IV catheter for treatment. PROCEDURES: Blood samples were collected via IV catheter and direct venipuncture at the time of catheter placement and 24 hours after catheter placement. Prothrombin time, APTT, and fibrinogen concentration were measured. RESULTS: 5 dogs were excluded from the study; results were obtained for the remaining 30 dogs. Agreement (bias) for PT was -0.327 seconds (limits of agreement, -1.350 to 0.696 seconds) and 0.003 seconds (limits of agreement, -1.120 to 1.127 seconds) for the 0- and 24-hour time points, respectively. Agreement for APTT was -0.423 seconds (limits of agreement, -3.123 to 2.276 seconds) and 0.677 seconds (limits of agreement, -3.854 to 5.207 seconds) for the 0- and 24-hour time points, respectively. Agreement for fibrinogen concentration was -2.333 mg/dL (limits of agreement, -80.639 to 75.973 mg/dL) and -1.767 mg/dL (limits of agreement, -50.056 to 46.523 mg/dL) for the 0- and 24-hour time points, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Agreement between the 2 techniques for sample collection was clinically acceptable for PT, APTT, and fibrinogen concentration at time 0 and 24 hours. It is often difficult or undesirable to perform multiple direct venipunctures in critically ill patients. Use of samples collected via an IV catheter to monitor PT and APTT can eliminate additional venous trauma and patient discomfort and reduce the volume of blood collected from these compromised patients.     

Diagnosis of disseminated intravascular coagulation in dogs admitted to an intensive care unit.

OBJECTIVE: To describe and evaluate hemostatic function in critically ill dogs with clinical signs of diseases that predispose to disseminated intravascular coagulation (DIC). DESIGN: Prospective case series. ANIMALS: 59 critically ill dogs (affected dogs) with clinical signs of diseases known to predispose to DIC and 52 clinically normal dogs (control dogs). PROCEDURE: Activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin clotting time (TCT), plasma fibrinogen concentration, serum concentration of fibrin and fibrinogen-related antigens (FRA), and plasma antithrombin III (AT III) activity were determined for all dogs. Results from affected dogs were compared with those of control dogs. In some affected dogs, postmortem tissue specimens were examined for evidence of microvascular thrombosis. A diagnosis of DIC was made by fulfilling at least 3 of the following criteria: 1) abnormal aPTT, PT, or TCT value, 2) low plasma fibrinogen concentration, 3) low plasma AT III activity, 4) high serum FRA concentration, or 5) low platelet count. To evaluate the severity of hemostatic dysfunction, 3 arbitrary categories (mild, moderate, and severe) were proposed. RESULTS: A diagnostic strategy based on moderate hemostatic dysfunction identified DIC in 16 of 59 (27.1%) affected dogs. The AT III activity was < 70% in 15 of 16 dogs with DIC. Microvascular thrombosis was observed in tissue specimens from 7 of 8 affected dogs. Serum FRA and plasma fibrinogen concentrations did not contribute in establishing a diagnosis of DIC. CONCLUSIONS AND CLINICAL RELEVANCE: A diagnosis of DIC can be made when hemostatic dysfunction is moderate in dogs with clinical signs of diseases associated with DIC.     

Laboratory evaluation of hemorrhagic coagulopathies in small animal practice

Assessment of animals with a suspected hemorrhagic diathesis of unknown cause(s) should be methodical. Most acquired coagulopathies result from thrombocytopenia. A platelet estimate (from a blood smear) and/or a platelet count on a fresh blood sample therefore are useful first steps in case evaluation. If thrombocytopenia is present, the most likely causes are immune-mediated destruction of platelets, DIC, or megakaryocytic hypoplasia. These diagnoses can be pursued by further test, including antiplatelet antibody assays (for example, the platelet factor 3 tests or an ELISA test), measurement of FDP, and bone marrow biopsy, respectively. If the platelet count is normal, a buccal mucosa bleeding time test is a useful second step. If this is prolonged, most likely causes are vWD or a thrombocytopathy (functional platelet defect). von Willebrand's disease can be diagnosed by measurement of vWf concentration or activity. A normal bleeding time does not exclude a diagnosis of vWD, but suggests that the functional activity of vWf is not compromised markedly. If the bleeding time is normal, APTT and PT should be measured. A prolonged APTT with normal PT, in the clinical setting, implies a deficiency of factor XI, IX, or VIII. A prolonged PT with normal APTT indicates factor VII deficiency. Prolongation of both APTT and PT usually is caused by a deficiency of several factors and is seen most often in cases with vitamin K deficiency or antagonism. Obviously, if a particular cause is suspected from the case history or for other reasons, appropriate tests should be evaluated at the beginning. If these do not confirm the provisional diagnosis, the just-described protocol might be a useful one to follow.     

Pharmacokinetics and pharmacodynamics of a therapeutic dose of unfractionated heparin (200 U/kg) administered subcutaneously or intravenously to healthy dogs

BACKGROUND: Heparin treatment has been recommended for dogs in hypercoagulable states such as disseminated intravascular coagulation, however, potential benefits have to be balanced against the bleeding risk if overdosage occurs. A better understanding of the pharmacology of heparin and tests to monitor heparin therapy in dogs may help prevent therapeutic hazards. OBJECTIVES: The purpose of this study was to evaluate the effects of 200 U/kg of sodium unfractionated heparin (UFH) on coagulation times in dogs after intravenous (IV) and subcutaneous (SC) administration and to compare these effects with plasma heparin concentrations assessed by its antifactor Xa (aXa) activity. METHODS: 200 U/kg of UFH were administered IV and SC to 5 healthy adult Beagle dogs with a washout period of at least 3 days. Activated partial thromboplastin time (APTT), prothrombin time (PT), and plasma aXa activity were determined in serial blood samples. RESULTS: After IV injection, PT remained unchanged except for a slight increase in 1 dog; APTT was not measurable (>60 seconds) for 45-90 minutes, and then decreased gradually to baseline values between 150 and 240 minutes. High plasma heparin concentrations were observed (maximal concentration = 4.64 +/-1.4 aXa U/mL) and decreased according to a slightly concave-convex pattern on a semilogarithmic curve, but returned to baseline slightly more slowly (t240-t300 minutes) than did APTT. After SC administration, APTT was moderately prolonged (by a ratio of 1.55 +/-0.28 APTT t0, range 1.35-2.01) between 1 and 4 hours after administration. Plasma aXa activity reached a maximum of 0.56 +/-0.20 aXa U/mL (range 0.42-0.9 U/mL) after 132 +/-26.8 minutes; this lasted for 102 +/-26.8 minutes. Prolongation of APTTs of 120-160% corresponded to plasma heparin concentrations of 0.3-0.7 aXa U/mL. CONCLUSIONS: As in humans, the pharmacokinetics of UFH in dogs was nonlinear. Administration of 200 U/kg of UFH SC in healthy dogs resulted in sustained plasma heparin concentrations in accordance with human recommendations for thrombosis treatment or prevention, without excessively increased bleeding risks. In these conditions, APTT can be used as a surrogate to assess plasma heparin concentrations. These findings need to be confirmed in diseased animals.     

Hemostatic Disorders in Cats: A Retrospective Study and Review of the Literature

Hemostasis profiles from 101 cats presented for medical or surgical evaluation to The Ohio State University Veterinary Teaching Hospital from 1986 through 1991 were reviewed retrospectively; 69% were abnormal. Commonly identified abnormalities included a mixed hemostatic defect compatible with disseminated intravascular coagulation, thrombocytopenia, isolated prolongation of the activated partial thromboplastin time (APTT), and prolongation of both the APTT and one-stage prothrombin time. The most common disorders associated with abnormal hemostasis profiles in this study were liver disease, neoplasia, and feline infectious peritonitis.     

Prothrombin, activated partial thromboplastin, and proteins induced by vitamin K absence or antagonists clotting times in 20 hyperthyroid cats before and after methimazole treatment

The effect of daily doses of 5-15 mg of methimazole on the platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), and proteins induced by vitamin K absence or antagonists (PIVKA) clotting time in 20 hyperthyroid cats was determined. No significant (P > .05) difference was found in median platelet count. PT, APTT, or PIVKA clotting time before treatment compared to median values at 2-6 weeks or > or =7-12 weeks of methimazole treatment. No cat had a prolonged APTT at any time. At 2-6 weeks of methimazole treatment, 1 cat each developed thrombocytopenia or prolonged PIVKA clotting time despite initially normal values. Three cats had abnormal coagulation tests (prolonged PT [n = 1] and PIVKA clotting time [n = 3]) before treatment that fluctuated during treatment. Excluding the 3 cats that had abnormal PIVKA clotting time before treatment, prolonged PIVKA clotting time developed in 6% (1/17; 95% confidence interval, 0-28%) cats treated with methimazole for 2-6 weeks. Seemingly. doses of methimazole commonly used to treat hyperthyroidism in cats do not cause alteration in PT and APTT, and only rarely prolong PIVKA clotting time. Nevertheless, abnormal PIVKA clotting time may explain bleeding tendencies unassociated with thrombocytopenia in methimazole-treated hyperthyroid cats.     

Interaction of bovine neutrophils in Pasteurella haemolytica mediated damage to pulmonary endothelial cells

The purpose of these studies was to determine mechanisms of pulmonary tissue damage mediated by Pasteurella haemolytica and interaction with bovine neutrophils. Bovine pulmonary artery endothelial cell monolayers were treated with various combinations of P. haemolytica factors including bacterial culture supernatant (CS) and purified LPS, with and without bovine neutrophils. Damage to endothelial cells was monitored by 51Cr release, cell detachment rate, and morphological changes. At 5 h post-treatment (PT) bacterial factors produced very little toxic change in cells, however, by 22 h PT both crude leukotoxin and LPS caused high levels of cytotoxicity and detachment. Neutrophils did not augment toxicity mediated by LPS, but actually protected endothelial cells from low levels of LPS. When the LPS component of CS was neutralized with polymyxin B, leukotoxin mediated neutrophil killing resulted in extensive endothelial cell damage. These results suggest that LPS may directly injure endothelial cells and this toxic effect may be reduced by neutrophils. However, neutrophil killing by leukotoxin may also contribute to endothelial cell damage in the absence of LPS.     

Agreement in histologic assessments of the pituitary pars intermedia in aged horses

OBJECTIVE: To evaluate concordance among veterinary pathologists in the assessment of histologic findings in the pars intermedia of pituitary gland sections from aged horses with mild signs suggestive of pituitary pars intermedia dysfunction (PPID). Sample Population-10 pituitary glands from aged horses. PROCEDURE: 7 pathologists were provided with signalment, clinical signs, and a single H&E-stained pituitary gland section from 10 aged horses with mild signs suggestive of PPID. Pathologists described histologic findings for each section and stated whether findings were consistent with PPID. Agreement among pathologists and with antemortem diagnostic test results was calculated. RESULTS: Overall, only fair agreement was found among the pathologists as to which horses had histologic findings consistent with disease (mean +/- SE kappa value, 0.34 +/- 0.069). Interpretation of individual sections varied, with minimal agreement (4 or 5/7 pathologists) for 5 of 10 sections evaluated. Postmortem assessment was in agreement with an antemortem endocrine diagnostic test result 79% of the time. CONCLUSIONS AND CLINICAL RELEVANCE: Validation of antemortem diagnostic testing for PPID in horses often relies on the results of postmortem histologic evaluation. The lack of consensus in histologic interpretation of pituitary glands from aged horses with mild clinical signs in our study indicates that postmortem histologic evaluation of pituitary glands is an inappropriate standard in validation of antemortem diagnostic tests for detection of early PPID. Caution should be used when interpreting diagnostic test results in horses in which early PPID is suspected.     

Thrombotest (PIVKA) Test Results in 25 Dogs with Acquired and Hereditary Caogulopathies

In the veterinary literature, it has been suggested that a prolongation in the thrombotest (PIVKA test) is a sensitive and diagnostic indicator of anticoagulant rodenticide intoxication. We evaluated prothrombin time (PT), activated partial thromoplastin time (aPTT), and PIVKA indicator in 25 bleeding dogs: 7 with inherited coagulopathies. All dos with acquired coagulopathies had prolonged PIVKA values when compared to the normal controls. Factor VII deficient dogs had a prolonged PIVKA and PT test result, whereas dogs with intrinsic coagulopathies only had an aPTT prolongation. A three-fold increase of the PIVKA or PT values was highly suggestive of an anticoagulant rodenticide poisoning compared to other acquired coagulopathies. Prolonged PIVKA resuls were not specific for anticoagulant rodenticide intoxication in our group of bleeding dogs.     

Antithrombin III activity (residual thrombin activity) in plasma from non-medicated or heparinized horses

Two synthetic substrate assays (fluorometric and chromogenic) were used to measure antithrombin-III (AT-III) activity (residual thrombin activity) in non-medicated and heparin (sodium) treated horses. In 18 non-medicated horses the fluorometric substrate assay (FSA) values were similar to previous reports but they reflected inconsistent trends and larger deviations in the heparin-treated groups (Group 2: 40 and 100 U/kg IV, n=6; Group 3: 240 U/kg IV, n=5; Group 4: 80 U/kg IV followed by 160 U/kg SC, n=8) when compared to the chromogenic substrate assay (CSA) values. The CSA values for the 18 non-medicated horses indicated a higher AT-III activity (lower residual thrombin activity) than the FSA. AT-III activity was quantified in 18 non-medicated horses (29 mg/dl) and compared well with values for humans (30 mg/dl) and dogs (40 mg/dl). Plasma heparin concentrations, determined by the FSA, correlated well with the therapeutic range (1.5 fold to 2.5 fold prolongation of the activated partial thromboplastin time (APTT) normal value) and values reported for humans. The effect of heparin therapy on AT-III activity in four treatment regimens was evaluated. AT-III activity was not significantly affected (with one exception) by a single dose of intravenous (IV) heparin (40 and 100 U/kg) nor by repeated subcutaneous (SC) injections of heparin (240 U/kg). A transient increase in residual thrombin activity was measured 12 h after an intravenous (80 U/kg) injection of heparin. Large doses of heparin (80 U/kg IV followed by 160 U/kg SC) given every 12 h produced a progressive prolongation of the APTT. In this group the APTT remained prolonged 48 h after the last treatment.     

一种新兽用止泻中药复方制剂对大鼠的急性及亚慢性毒性试验

为了解一种新兽用止泻复方制剂的安全性,本试验对该复方制剂进行了经口急性毒性和亚慢性毒性研究。急性毒性试验采用最大给药剂量法对20只Wistar大鼠进行经口灌服制剂。亚慢性毒性试验将80只Wistar大鼠随机分为4组,每组20只,经口染毒剂量分别为3 000、1 500、750和0 g/kg体重,连续染毒30 d。试验期间观察一般临床状况,每周测量大鼠体重并据此调整染毒剂量。试验结束后测定试验动物血液学、血清生化指标,并进行大体解剖学观察,称取各组主要脏器并计算脏器系数,对高剂量组和对照组大鼠的主要脏器进行组织病理学观察。急性毒性试验结果显示,该制剂经口染毒LD₅₀均大于5 g/kg体重时,所有大鼠均存活。亚慢性毒性剖检发现,高剂量组除个别大鼠心脏、肺脏、睾丸（♂）出现轻度淤血外,其他各剂量组的实质器官均未发现异常变化;血液学指标中除高剂量组的单核细胞比率、红细胞压积水平显著下降（P<0.05）外,其余各组各项指标均在正常范围内,与对照组无显著差异。结果表明,在本试验条件下,根据WTO有关外源性化学物急性毒性分级标准,该制剂属实际无毒物质;亚慢性毒性试验也未发现该制剂对大鼠的生长发育产生影响,短期重复应用至少在1 500 mg/kg饲喂条件下无亚慢性毒性。