Disseminated Intravascular Coagulation in Cattle with Abomasal Displacement

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1 Disseminated Intravascular Coagulation in Cattle with Abomasal Displacement Kemal IRMAK ), Kürşat TURGUT ) ) Department of Internal Medicine, Faculty of Veterinary Medicine, University of Selcuk, 4203, Campus, Konya-TURKEY. *: Contact address: Department of Internal Medicine, Faculty of Veterinary Medicine, University of Selcuk, 4203, Campus, Konya-TURKEY. kirmak@selcuk.edu.tr, Tel /274, Fax: ABSTRACT The purpose of the study was to evaluate the 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), ten adult cattle with right displacement of abomasum with volvulus (RDA) (Group II) and ten 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. Activated partial thromboplastin time was only prolonged 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, 2 cattle in group I and 3 cattle in group II had at least 3 abnormal coagulation profiles, which reflect the occurrence of DIC. These cattle died after surgical treatment. These 2 cattle with LDA had abnormal APTT, FDPs and PLT values. 3 cattle with RDA had abnormal APTT, PT, TT, FDPs and PLT values. The three most common positive tests on coagulation profile of group I and II were found to be APTT (5 cases), FDPs (5 cases), thrombocytopenia (5 cases). Results of the study indicated that cattle with AD had a spectrum of hemostatic dysfunction and DIC was a significant risk factor for mortality. Key word: Coagulation profile, Cattle, Abomasal displacement. INTRODUCTION Abomasal displacement occurs most frequently in high yielding cows during early lactation (Breukink, 99; Hund and Nelson, 995; Turgut and Ok, 997). While LDA, in which the abomasum is trapped between the rumen and the left abdominal wall, is more commonly diagnosed, RDA is usually accompanied by a degree of volvulus, in which the rotation of the proximal duodenum, abomasum and omasum occur, and is therefore a more serious problem (Wallace, 989; Jean et al., 989; Constable, 99). There have been many papers describing the diagnosis and treatment of AD as well as the theory of causation, pathophysiology, and prognosis (Yamahato, 982a; Yamahato, 982b; Muylle et al., 990; Breukink, 99). However, there is no report evaluating the coagulation profiles in cattle with abomasal displacement. There is only one study in which APTT and PT have been evaluated in cows with LDA, and no difference has been found (Ogurtan et al., 2003). Disseminated Intravascular Coagulation is a continuously progressing process, it can be subdivided into three phases: phase I; compensated activation of the haemostatic system, phase II; decompensated activation of

2 the haemostatic system, phase III; full-blown DIC (Muller-Berghaus et al., 999). The pathologic process is characterized by widespread fibrin deposition in the microcirculation with subsequent ischemic damage and by the development of a hemorrhagic diathesis caused by the consumption of procoagulans and hyperactivity of fibrinolysis (Morris, 990b). In large animals DIC has been described in association with forms of localized and/or systemic septic processes (e.g., salmonellosis, metritis, mastitis), neoplasia, gastrointestinal disorders (e.g., strangulating intestinal obstruction, acute enteritis, protein-losing enteropathy), renal disease, and hemolytic anemia (Morris, 990b). Numerous laboratory tests of haemostasis may be abnormal during DIC; however, no one test consistently or specifically provides a definitive diagnosis (Morris, 990b). The minimum laboratory data needed to evaluate haemostasis in large animals are the PLT, plasma fibrinogen contents, PT (extrinsic system), APTT (intrinsic system), and FDPs. The results of these tests will also vary according to the severity and fulminant nature of the process and the time of sampling (Blood et al., 983; Morris 990a). The purpose of the study reported here was to evaluate the haemostatic function in cattle with AD and to reflect the occurrence of DIC. MATERIALS AND METHODS Animals: In this study, ten adult cattle with LDA (Group I), ten adult cattle with RDA (Group II) and ten clinically healthy adult cattle (Control Group) were used as material. All of these cows were Holstein. Ages of the animals varied from 3 to 7 years. Their mean (± sd) age was 4±.5 years. All were in early lactation (7 to 2 days) and have been fed with high concentrate diet. On admission the animals had been ill on average for 3 days. Clinical examinations: The cattle with AD showed loss of appetite, decreased rumen motility and milk production, and little or scant defecation. All animals were examined with regard to abdominal ausculopercussion, ballotment of abdomen for splashing sound, rectal examination and abdominal ultrasonography. After tentative diagnosis of AD, the diagnosis was verified by operation. Venous blood samples (K-EDTA) for haematological examination (PLT) and sodium citrate added blood samples for coagulation tests (APTT, PT, TT, FDPs, fibrinogen) were taken from the jugular vein before the surgical treatment of AD. Haematological examinations: The number of platelets were measured by automatic haemocell counter (Medonic, Ca530). Coagulation testing: 9 ml of venous blood sample for the determination of APTT, PT, TT, fibrinogen and FDPs concentrations were collected into collection tubes including ml of 3.8 % sodium citrate and centrifuged at 500 g for 5 minutes. The plasma samples were separated from blood within 30 minutes of blood collection and measurements were performed within 2-24 hours. The activated partial thromboplastin time (STA-CK Prest 5, Kit Cat. No: 00597) and PT (STA - Neoplastine Cl Plus, Kit Cat. No: 00597) were measured by STA analyser. TT (Thromboquik TM ; Product no: 3555) and fibrinogen (Fibriquik ; Product No: 35529) were measured by Thromblyser-XR (Organon Teknika). FDP were determined by Latex agglutination test methods using FDP plasma kit (Kit Cat. No: 00540; Organon Teknika Corp; Durham, NC, USA). 2

3 Statistical analysis: FDPs were compared with Kruskal-Wallis test statistic. Anova Duncan test has been used for other analyses. A value of P< 0.05 was considered statistically significant for all analyses. (SPSS for Windows; Statistical Package of Social Science, SPSS Inc. USA) RESULTS All cattle in group II had various degree of volvulus ( o ) Table shows the mean±sd APTT, PT, TT, fibrinogen and PLT values in group I, II and the control group and their statistical significance. Mean±SD and median FDPs concentrations are also given in table. Individual values of all cattle are given in table 2. Only APTT was prolonged 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, 2 cattle in group I (case 4 a and 5 a ) and 3 cattle in group II (case 3 b, 6 b and 9 b ) had at least 3 abnormal coagulation profiles (APTT >54.0 sec, PT 30.9 sec, TT >3.6 sec, FDPs >5 µg/ml, PLT 50x03/mm3), which reflect the occurrence of DIC (Table 2). These cattle (case 4 a and 5 a in group I; case 3 b, 6 b and 9 b in group II) died after surgical treatment (Table 2). Case 4 b and 5 a (cattle with LDA) had abnormal APTT, FDPs and PLT values. Case 3 b, 6 b and 9 b (cattle with RDA) had abnormal APTT, PT, TT, FDPs and PLT values (Table 2). One cow in group II (case b ) with normal coagulation profile results also died after surgical treatment. The highest and lowest values for the control group of cattle were APTT 50.0 sec, PT 26.9 sec, TT 3.6 sec, FDPs <5 µg/ml, PLT 68x03/mm 3 (Table 2). DISCUSSION Left displacement of abomasum (LDA) is a common condition of dairy cattle in which the abomasum is trapped between the rumen and the left abdominal wall rather than being in its normal position to the right of the ventral midline (Jean et al., 989). Right displacement of the abomasum (RDA) is usually accompanied by a degree of volvulus, in which the rotation of the proximal duodenum, abomasum and omasum occur. Thus, RDA with volvulus is a more serious problem (Wallace, 989; Constable, 99). In this study, all cattle with RDA (group II) had various degree of volvulus ( o ). And, 2 cattle with LDA and 3 cattle with RDA and volvulus died despite surgical treatment. Table. The mean±sd activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen and numbers of platelet (PLT) values, mean±sd and median serum fibrin/fibrinogen degradation products (FDPs) concentrations in group I (LDA), II (RDA) and the control group and their statistical significance. PARAMETERS Control Group (n:0) Mean±SD LDA (n:0) Mean±SD RDA (n:0 Mean±SD APTT (sec) 36.49±8.43a 45.63±26.24ab 63.38±30.58b * PT (sec) 24.0± ± ±8.04 TT (sec) 25.30± ± ±4.99 Fibrinogen (mg/dl) ± ± ±69.38 FDPs (μg/ml) Mean±SD Median ± ± ±0.5 PLT (0 3 /mm 3 ) 26.20± ± ±92.78 *: P<0.05 FDPs graded = <5 (µg/ml), 2= 5-20 (µg/ml), 3= >20 (µg/ml) 3

4 Table 2. Individual values of activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), serum fibrin/fibrinogen degradation products (FDPs), fibrinogen and numbers of platelet (PLT) in group I a (LDA), II b (RDA) and the control c group of cattle. Case No APTT (sec) PT (sec) TT (sec) FDPs (μg/ml) Fibrinogen (mg/dl) PLT (0 3 /mm 3 ) a < a a < a* a* a < a < a < a < a < b* < b < b* b < b < b* b < b < b* b < c < c < c < c < c < c < c < c < c < c < *: Death cows after surgical treatment The laboratory diagnosis of DIC is usually based on the prolonged APTT, PT, thrombocytopenia, hypofibrinogenemia, finding FDPs, schistocytes in blood smears, and decreased concentrations of coagulation factors (usually factors V, VIII) and antithrombin III add additional weight to the diagnosis. TT is also prolonged. Excessive coagulation is reflected by reduced plasma concentrations of platelets, coagulant and anticoagulant proteins, and increased concentrations of coagulant by-products. Fibrinolysis is indicated by elevated FDPs or reduced concentrations of fibrinolytic and antifibrinolytic proteins. No single laboratory test is, however, pathognomic for the disease (Jain, 993; Morris, 990b). A diagnosis of DIC is assumed, when at least three of five tests included in a coagulation profile are abnormal (Ritt et al., 997). In our study, the most common three tests of coagulation profiles found to be altered were APTT (2 cases), FDPs (2 cases), thrombocytopenia (2 cases) in the group I (case 4 a, 5 a ) and APTT (3 cases), FDPs (3 cases), thrombocytopenia (3 cases) in the group II (case 3 b, 6 b, 9 b ) (Table 2). 4

5 Activated partial thromboplastin time test is used to evaluate the intrinsic and common pathways. The most common cause of prolonged APTT is increased consumption of clotting factors during DIC. Liver failure and vitamin K deficiency prolong APTT, since factors II, VII, IX, and X are tested. A disseminated coagulopathy should be manifested by several abnormalities in the coagulation profile, although variable use, synthetic rates, and the half-lives of clotting factors may result in abnormality of only one clotting time (APTT or PT) (Morris, 990a). In this study, prolonged APTT was found to be common coagulation profile abnormality in cattle with LDA and RDA. Increased serum concentration of FDPs reflects the proteolytic action of plasmin on fibrin and/or fibrinogen at a rate that exceeds the clearance capacity of the mononuclear phagocyte system. Measurable serum FDPs generally indicate increased fibrinolysis response to excessive activation of coagulation (i.e., DIC); however, severe inflammatory processes, hemorrhagic disorders, or postoperative states that cause extensive intravascular fibrin deposition may elevate serum FDPs significantly. Primary (spontaneous) hyperfibrinolysis occur in people in association with chronic liver disease, neoplasia, or cardiopulmonary bypass; however, this cause for elevated serum FDPs has not been described in large animals (Morris, 990a). Finding of FDPs in 2 cattle with LDA (case 4 a, 5 a ) and 3 cattle with RDA (case 3 b, 6 b, 9 b ) in this study could be the result of DIC. Two cattle with LDA (case 4 a, 5 a ) and 3 cattle with RDA (case 3 b, 6 b, 9 b ) had thrombocytopenia (a platelet count less than 50,000/μl) in this study. Excessive consumption of platelets to fulfil their normal role in hemostasis occurs during DIC. The platelet count is a useful test for monitoring the rate and severity of consumption or destruction. Other components of the hemostatic system should be evaluated (e.g., PT, APTT, FDPs), since thrombocytopenia may be only part of a disseminated coagulopathy (Morris, 990a). Thrombocytopenia together with prolonged APTT and FDPs may show that DIC might develop in these cattle. Prothrombin time is a measure of the extrinsic and common pathways of coagulation. The most common cause of prolonged PT is increased consumption of clotting factors during DIC. Thrombin time is a measure of the rate of fibrinogen to fibrin conversion. It is prolonged when fibrinogen is less than 60 mg/dl, fibrinogen is nonfunctional, or FDPs are present that interfere with fibrin polymerization. Since hypofibrinogenemia is rare in large animals, a prolonged thrombin time most likely would indicate the presence of FDPs (Morris, 990a). Prolonged PT (case 6 b ) and prolonged TT (case 9 b ) together with prolonged APTT, FDPs and thrombocytopenia support the development of DIC in these cases. Hypofibrinogemia may result from impaired hepatic synthesis, increased consumption during DIC, degradation during primary hyperfibrinolysis, or uncompensated loss during massive hemorrhage. In spite of these mechanisms, reduced plasma fibrinogen is rare under any circumstances in large animals (Morris 990a). Hypofibrinogenemia is an uncommon manifestation of DIC in large animals and, when present, should strongly suggest concomitant liver dysfunction (Morris, 990b). Hypofibrinogenemia was not found in cattle with AD in this study. This could be the result of exclusive production of fibrinogen by liver and as an acute-phase reactant, being rapidly released in response to a variety of inflammatory and procoagulant stimuli. DIC is a recognized syndrome of abnormal hemostatic function. Most cases can be traced to platelet activation and/or the release of thromboplastins into the circulation from tissue damage in various conditions. Tissue necrosis and inflammation are common inciting causes of DIC through the release of procoagulant or of thromboplastin-like substances and the initiation of the coagulation sequence. Stagnant blood flow, acidosis, and hypoxia favor endothelial damage and DIC (Turgut, 2000). Development overstretching of abomasal wall, 5

6 thrombosis, vagus nerve damage, abomasal necrosis and peritonitis in the cases of AD, especially RDA with volvulus may cause the release of procoagulant and/or thromboplastins and incite DIC. Results of the study indicated that cattle with AD had a spectrum of hemostatic dysfunction and DIC was a significant risk factor for mortality. REFERENCES Blood, D.C., Radostits, O.M. and Henderson, J.A., 983. Veterinary Medicine, Sixth Edition, Bailliere Tindall. London., Breukink, H.J., 99. Abomasal displacement, etiology, pathogenesis, treatment and prevention. The Bovine Practitioner., 26, Constable, P.D., 99. Abomasal volvulus in cattle: Etiology and prognosis., New Orleans., proc 9 th ACVIM forum, Hund, J.C. and D. R. Nelson., 995. Right-sided abomasal displacement in dairy cattle. Vet. Med., 90, Jain, N.C., 993. Essentials of Veterinary Haematology, Lea&Febiger, Philadelphia., Jean, G.ST., Constable, PD., Hull, B.L., Rings, D.M., 989. Abomasal volvulus in cattle following correction of left displacement by casting and rolling., Cornell Vet. 79 (4), Morris, D.D., 990b. Disease of Hematopoietic and Hemolymphatic systems. In : Smith, B. P., (ed)., Large Animal Internal Medicine. The C. V. Mosby Company. Philadelphia., Morris, D.D., 990a. Alterations in the Clotting Profile. In : B.P. SMITH (ed). Large Animal Internal Medicine, The C.V. Mosby Company, Missouri, USA, Muller-Berghaus, G., Ten Cate, H. and Levi, M., 999. Disseminated intravascular coagulation: clinical spectrum and established as well as new diagnostic approaches., Thrombosis and Haemostasis- F.K. Schattauer Verlagsgesellschhaft mbh (Stuttgart) 82 (2) Muylle, E., Hende, C.V.D., Sustronch, B. and Deprez, P., 990. Biochemical profiles in cows with abomasal displacement estimated by blood and liver parameters. J. Vet. Med. A. 37, Ogurtan, Z., Ok, M., İzci, C. and Ceylan, C., Activated partial thromboplastin time and prothrombin time in cows with left displacement abomasums. Indian Vet. J., 80 (3), Ritt, M.G., Rogers, K.S. and Thomas, J.S., 997. Nephrotic syndrome resulting in thromboembolic disease and diseminated intravascular coagulation in a dog. J. Am. Anim. Hosp. Assoc. 33, Turgut, K., Hemostazis: Koagülasyon ve Trombosit Bozuklukları. Veteriner Klinik Laboratuvar Teşhis. Bahçivanlar Basım. San. A. Ş. Konya., Turgut, K. and Ok, M., 997. Ruminatlarda abdominal ağrı olan veya olmayan anoreksi ve abdominal gerginlik ile karekterize hastalıklar. Veteriner Gastroenteroloji. Bahçivanlar Basım. San. A. Ş. Konya., Wallace, C.E., 989. Reticulo, omasal, abomasal volvulus in dairy cows. The Bovine Practitioner, 24, Yamahato, H., 982a. Clinical and pathological studies on the etiological factors of bovine abomasal displacement and atony. I. Clinical cases. Jpn. J. Vet. Sci., 44 (39), 5-6. Yamahato, H., 982b. Clinical and pathological studies on the etiological factors of bovine abomasal displacement and atony. II. Clinical cases. Jpn. J. Vet. Sci., 44 (54),