Thromboelastographic results and hypercoagulability in dogs with surgically treated hepatocellular adenoma and carcinoma: A Veterinary Society of Surgical Oncology prospective study

Background

The most common haemostatic abnormality in dogs with cancer is hypercoagulability. A transient hypercoagulability has been documented in people with hepatocellular carcinoma (HCC) that resolves within weeks following hepatic tumour resection.

Objective

The objective was to compare the haemostatic status of dogs with liver tumours and healthy control dogs, by comparing coagulation and thromboelastography (TEG) measurements at three time points.

Methods

Liver tumour and healthy control dogs receiving surgery for liver lobectomy and ovariohysterectomy, respectively, were prospectively enrolled. All dogs had blood collected at three time points: pre-operative, 24 h post-operative and ~2 weeks post-operative. Haematological and haemostatic values were compared across time points in each group using repeated measures ANOVA tests.

Results

Ten and eight dogs were enrolled for the liver and control groups, respectively. Platelet count was significantly higher in the liver group than the control group at all time points, but within the normal range (pre-operative: 438.7 vs. 300.9 × 10⁹/L, p = .0078; 24 h post-operative: 416.2 vs. 283.9 × 10⁹/L, p = .0123; 10–14 days post-operative: 524.6 vs. 317.3 × 10⁹/L, p = .0072). The measure of the overall coagulant state (G-value) was significantly increased for the liver group compared to the control group at all time points (pre-operative: 15.6 vs. 8.6 d/sc, p = .0003; 24 h post-operative: 18.3 vs. 11.2 d/sc, p = .039; 10–14 days post-operative: 15.1 vs. 9.6 d/sc, p = .015).

Conclusion

The liver group was hypercoagulable based on elevated G-values at all time points compared to the control group. This hypercoagulability was attributed to the effect of hepatic tumours alone, and not secondary to surgery and anaesthesia.     

Effect of Two Pretreatment Techniques on Preventing Membrane Fouling

Ultrafiltration membrane was used to filter the Yangtze River water by powder activated carbon (PAC) pretreated, such as Tai Lake water by coagulation-sedimentation pretreatment. The changes of organic polar content were compared in each process. Combined with the scanning electron microscope(SEM) photographs of the membrane, the mechanism of slowing down membrane fouling by PAC and coagulation-sedimentation pretreatment was studied. The results showed that hydrophobic organic compounds were the main factors of membrane fouling, while hydrophilic organics had less impact. When the dosing quantity of PAC filtered by ultrafiltration membrane was 20 mg/L to pre-treat the water samples of Yangtze River, and that of polyaluminium chloride was 25 mg/L for the pretreatment of Tai Lake water samples, the flux could be recovered effectively after backwashing compared with filtering the two raw water directly. The cake layer formed on the surface of the membrane was looser after pretreatment, and could be discharged easily by periodic backwashing, The cake layer could prevent hydrophobic organic matters deposit on the surface of membrane directly, which will slow down the membrane fouling and improve the chemical safety of the membrane effluent.     

The role of tissue factor and tissue factor pathway inhibitor in health and disease states

Objective – To review the veterinary and human literature on the role of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in health and disease states.
Data Sources – Original research articles and scientific reviews from both human and veterinary literature were searched for relevance to TF and TFPI.
Human Data Synthesis – Interest in both TF and TFPI has grown widely over the last several years. The impact TF plays in coagulation, inflammation, angiogenesis, tumor metastasis, and cellular signaling has become apparent. Treatment with TFPI for severe sepsis has been examined and is still currently under investigation. Inhibition of the TF pathway is being studied as an aid in the treatment of neoplasia. The important physiologic and pathophysiologic role these molecules play has only begun to be understood.
Veterinary Data Synthesis – There is a paucity of publications that discuss the importance of TF and TFPI in veterinary medicine. An enhanced understanding of the TF pathway in human medicine, in experimental animal models treating sepsis with TFPI, and in animal models demonstrating the proangiogenic properties of TF provides relevance to veterinary medicine.
Conclusion – It is apparent that TF and TFPI are important in health and disease. An enhanced understanding of the physiologic and pathophysiologic roles of these factors provides better insight into coagulation, inflammation, angiogenesis, disseminated intravascular coagulation, and tumor metastasis. This greater understanding may provide for the development of therapeutics for sepsis, disseminated intravascular coagulation, and neoplasia.     

Development of a hamster model of Chlamydophila pneumoniae infection

The purpose of the study was to evaluate haemostatic function in cattle with abomasal displacement (AD) and to reflect the occurrence of disseminated intravascular coagulation (DIC). Ten adult cattle with left displacement of abomasum (LDA) (group I), 10 adult cattle with right displacement of abomasum with volvulus (RDA) (group II) and 10 clinically healthy adult cattle (control group) were used as material. Numbers of platelets (PLT) and coagulation tests (activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), serum fibrin/fibrinogen degradation products (FDPs), fibrinogen) were measured before the surgical treatment of cattle with LDA and RDA. APTT was prolonged only in group II compared with the control and group I (p<0.05). However, when the individual values of coagulation profiles of each cow were evaluated, two cattle in group I and three cattle in group II had at least three abnormal coagulation profiles, which reflect the occurrence of DIC. These cattle died after surgical treatment. The two cattle with LDA had abnormal APTT, FDPs and PLT values; three cattle with RDA had abnormal APTT, PT, TT, FDPs and PLT values. APTT (5 cases), FDPs (5 cases) and thrombocytopenia (5 cases) were the three most common abnormal tests on coagulation profile in the cattle with LDA and RDA. The results of the study indicate that cattle with AD had a spectrum of haemostatic dysfunction and that DIC was a significant risk factor for mortality.     

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.     

Validation of human recombinant tissue factor-activated thromboelastography on citrated whole blood from clinically healthy dogs

BACKGROUND: Thromboelastography (TEG) is an analytical method that enables global assessment of hemostatic function in whole blood (WB) with evaluation of both plasma and cellular components of hemostasis. TEG has a largely unused potential in the diagnostic workup and monitoring of dogs with hemostatic disorders and it may be a valuable supplement to traditional coagulation parameters. OBJECTIVES: The objective of this study was to establish a clinically applicable reference interval for a TEG assay using recombinant human tissue factor (TF) as the activator on citrated WB from clinically healthy dogs and to evaluate the stability of citrated WB stored for 30 minutes (T30) and 120 minutes (T120) at room temperature (RT). Additionally, we evaluated the analytical variation in reaction time (R), clotting time (K), angle (alpha), and maximum amplitude (MA). METHODS: Blood was collected from 18 clinically healthy dogs. Duplicate TEG analyses with TF as the activator at a concentration of 1:50,000 were performed on canine citrated WB at T30 and T120. R, K, a, and MAwere analyzed. RESULTS: Mean TEG values at T30/T120 were R = 5.61/4.91 minutes, K = 4.20/3.34 minutes, alpha = 45.33/50.90 degrees , and MA = 47.96/50.19 mm. Significant differences in these values were observed after storage for T30 and T120 at RT, with a tendency towards hypercoagulability at T120. The mean coefficients of variation were low. CONCLUSIONS: Canine citrated WB can be used for TEG analysis with human recombinant TF as the activator when stored at RT for T30 or T120. At both time points, the analytical variation was low, suggesting that TEG analysis may be of value in evaluating dogs with hemostatic disorders. A fixed time point should be chosen for serial measurements.     

Effects of oxidative modification of lipoproteins on blood coagulation and fibrinolysis

AIM: To study the effects of oxidative modification lipoproteins on blood coagulation and fibrino-lysis in vitro. METHODS: Normal human plasma VLDL, LDL and HDL, which were isolated by density gradient ultracentrifugation method, were oxidatively modified by Cu²⁺ and HOCl method. N-VLDL, Ox-VLDL, N-LDL, Ox-LDL, N-HDL, Ox-HDL were added to the reaction system which consisted of mixed fresh normal plasma respectively, prothrombin time (PT), activated partial thrombplastin time (APTT), plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (t-PA) and platelet aggregation were measured according to the direction of the kits. RESULTS: The relative electrophoretic mobility (REM), absorbance at 234nm and TBARS of oxidized VLDL, LDL and HDL mediated by HOCl or Cu²⁺ were significantly higher than that of the control group (P<0.01). N-VLDL, N-LDL and N-HDL had no effect on PT, APTT, t-PA, PAI-1 and platelet aggregation. The PT and APTT of Ox-VLDL, Ox-LDL and Ox-HDL were significantly shorter than that of the control group (P<0.05 and P<0.01). The platelet aggregation of Ox-VLDL, Ox-LDL and Ox-HDL were significantly stronger than that of the control group (P<0.01). The Ox-VLDL and Ox-LDL were higher in t-PA and lower in PAI-1 than that of the control group (P<0.05 and P<0.01), but the Ox-HDL had no influences on t-PA and PAI-1 activity. CONCLUSIONS: N-VLDL, N-LDL and N-HDL have no effects on blood coagulation and fibrinolysis in vitro. Ox-VLDL, Ox-LDL and Ox-HDL enhance blood coagulation and thrombosis. Ox-VLDL and Ox-LDL enhance t-PA activity and decreased PAI-1 activity, but Ox-HDL does not affect the fibrinolysis activity.     

制皂废水物化处理的探讨

以制皂废水经脱硫除尘塔后的出水为研究对象,通过气浮和混凝沉降的中试对比,提出混凝沉应用于出塔水的处理的工艺条件及组合混凝剂的最佳投加量。实验表明,混凝沉降能有效降低制皂废水的COD浓度,处理水可回用于脱硫除尘;同时,混凝沉降后出水可生化性较好,通过生化处理,可实现达标排放。