Hemostatic Abnormalities in Dogs With Hemangiosarcoma A. S. Hammer, DVM, C. G. Couto, DVM, C. Swardson, DVM, and D. Getzy, DVM
The hemostasis profiles of 24 dogs with histologically confirmed hemangiosarcoma were prospectively evaluated. Microangiopathic hemolysis was defined as the presence of schistocytes; disseminated intravascular coagulation was defined as I) thrombocytopenia, 2) fibrin(ogen) degradation products > 10 pg/mL, 3 ) prolongation of one or more coagulation times (activated partial thromboplastin time or one-stage prothrombin time) by greater than 25% of the control, 4) fragmented red blood cells (>l+ based on a semiquantitative grading scale), and 5) fibrinogen I 80 mg/dL. Three of the five criteria listed above had to be met for disseminated intravascular coagulation to be diagnosed. Fifty percent of the dogs were considered to have disseminated intravascular coagulation at presentation. Thrombocytopenia was present in 75% of the dogs and was the most common abnormality. The mean platelet count was 137,80O/pL. Twenty-five percent of the dogs died as a result of the hemostatic abnormalities. Only 12%of the dogs had microangiopathic hemolysis without other evidence of disseminated intravascular coagulation. Hemostatic abnormalities are present in many dogs with hemangiosarcoma a t the initial clinical presentation and represent an important clinical finding. (Journal of Veterinary Internal Medicine 1991; 511-14)
mangiosarcoma and are of clinical importance due to the high mortality associated with DIC.7
HEM, NGIOSARCOMA in the dog has been associated with hemostatic abnormalities such as disseminated intravascular coagulation (DIC) and microangiopathic hemolysis (MAH). To our knowledge, there are only nine published cases of DIC in dogs with hemangiosar~oma.'-~ Microangiopathic hemolysis has been associated with both spontaneous and experimentally induced hemangiosarcoma in this species."* The red blood cell fragmentation is believed to result from distortion and disruption of erythrocytes as they pass through fibrin deposits within vessels and abnormal tumor vasculature.',2,8Another report of ten dogs with hemangiosarcoma revealed that 90% were thrombocytopenic, and 80% had fragmented red blood c e k 6 Our clinical impression has been that dogs with hemangiosarcoma have a high prevalence of hemostatic abnormalities. We prospectively evaluated the hemostasis profiles of 24 dogs with histopathologically confirmed hemangiosarcorna to determine the prevalence of these abnormalities. We concluded that hemostatic abnormalities are present in a large number of dogs with he-
'-'
Methods Thirty-five dogs examined at the Veterinary Teaching Hospital-Ohio State University (VTH-OSU) between January 1983 and March 1989 were diagnosed by histopathology as having hemangiosarcoma. The histopathologic sections were retrospectively reviewed and 24 dogs were prospectively evaluated for hemostatic abnormalities at presentation. The coagulation tests included onestage prothrombin time (OSPT) using rabbit brain thromboplastin* and activated partial thromboplastin time (APTT) using rabbit brain cephalint; the endpoints for these tests were determined by fibrometer. The OSPT and APTT, respectively, were reported as a percent prolongation above the concurrently run control. Controls consist of pooled citrated plasma from a donor colony frozen and stored at -70°C. The reference ranges for the OSPT and APTT are 10 to 12 seconds and 18 to 24 seconds, respectively. Also determined were platelet count, fibrinogen concentration (heat precipita-
From the Department of Veterinary Clinical Sciences (Hammer, Couto) and the Department of Veterinary Pathobiology (Swardson, Getzy), the Ohio State University, College of Veterinary Medicine, Columbus, Ohio. Reprint requests: Alan Hammer, 1935 Coffey Road, Columbus, OH 43210.
* Baxter Healthcare Corporation,
Dade Division, Miami, FL. Activated Cephaloplastin Reagent, American Dade, Aguada, PR.
t Actin
11
12
Journal of Veterinary Internal Medicine
HAMMER ET AL.
TABLE1. Individual Data for Dogs With Hemangiosarcoma and Hemostasis Profiles
Tumor Site 1 right atrium
2 3 4 5 6 7 8 9
I0 II
12 13 14 15 16 17 I8 19 20 21 22 23 24
subcutaneous, kidney, liver liver spleen subcutaneous liver omentum subcutaneous spleen spleen right atrium spleen spleen spleen spleen liver, right atrium spleen liver, spleen right atrium, spleen subcutaneous spleen subcutaneous. lungs subcutaneous right atrium, lung
Platelets/pL
OSPT
APTT
(% prolongation
(% prolongation
above control)
above control)
56 32 38 0 -9 6 21 -5 25 21 190
32,000 28,000 3 1,000 148,000 349,000 45,000 344.000 92,000 75,000 28,000 16,000 3 1,000 64,000 370,000 430,000 45,500 140,000 43,000 133,000 I2 1,000 96,000 76,000 332,000 238,000
101
17 13 -13 20 -5 10
-3 6
15 27 4 31
52 21 54 8
I I38 -17 4 76 242 172 I35 14 6 55 40 41 I06 12 8 23 89 3 58
FDP
40 m / m L 10-40 &g/mL 10-40 pg/mL negative negative negative negative negative 40 pglmL 10-40 pg/mL 40 pg/mL negative >40 pg/mL negative negative >40 pg/mL negative 10-40 pg/mL negative negative negative 40 pg/mL negative 10-40 &mL
Fibrinogen (mg/dL)
I00 300 200 200 400 I00 110
200 600 200 25 155 94 NE NE I10
I20 I00 300 I00 200 200 200 300
Fragmented Red Blood Cells
0 I+ 2+ NE 0 0 I+ 0 2+ I+ I+ 2+ NE 2+ 0 0 2+ NE I+ 0 0 0 0 I+
Outcome
Diagnosis
euthanized alive euthanized alive alive died in DIC a1i ve euthanized euthanized died in DIC euthanized died* alive euthanized euthanized died in DIC euthanized died in DIC alive alive alive died in DIC alive died in DIC
DIC DIC DIC thrombocytopenia normal thrombocytopenia MAH thrombocytopenia DIC DIC DIC DIC thrombocytopenia MAH prolonged APTT DIC DIC DIC MAH thrombocytopenia thrombocytopenia DIC normal DIC
NE: not evaluated.
* Died due to causes unrelated
to hemostatic abnormalities
tion method'), and fibrin(ogen) split products (FDP) concentration (latex agglutination method$). The reference range for platelet counts is 150,000to 400,OOO/pL and for fibrinogen is 80 to 160 mg/dL; normal fibrin(ogen) degradation product concentration is less than 10 pg/mL. Fibrin(ogen) split products were reported as < I 0 pg/mL, 10 to 40 pg/mL, and >40 pg/mL. Microscopic examination of blood smears was performed to identify red blood cell fragmentation using the semiquantitative system of Weiss et a1.l' This system classifies schistocytosis based upon the average number of schistocytes per IOOOX microscopic field. One to two schistocytes per field are graded 1+; three to eight schistocytes per field are graded 2+; nine to 20 are graded as being 3+; and greater than 20 schistocytes are 4+. The average of five fields (lOOOX) was reported. The dogs were classified as having DIC if at least three of the following five criteria were present: thrombocytopenia (platelets < 15O,OOO/pL), FDPs > 10 pg/mL, prolongation of the APTT and/or OSPT by greater than 25% of the control, fragmented red blood cells 2 I + , and fibrinogen concentration I80 mg/dL. The diagnosis of MAH was made if 2 1 schistocytes were present. Disseminated intravascular coagulation and MAH could both coexist in the same patient. If no abnormalities were found, the dog's hemostatic status was classified as normal. Any other hemostatic abnormalities that
+
$ Thrombo-Wellcotest, Wellcome Diagnostics, Dartford, England.
did not fulfill the above criteria were described. The patients' immediate outcome (i.e., within 4 days of the hemostasis screen) was determined and recorded as alive, death related to hemostatic abnormalities, death unrelated to hemostatic abnormalities, or euthanized.
Results The data for individual dogs are listed in Table 1. There were 12 dogs (50%)with laboratory evidence of DIC and three dogs ( 12%) with microangiopathic hemolysis alone. Thrombocytopenia was the most common abnormality and was present in 18 dogs (75%). The mean platelet count for the 24 dogs was 137,8OO/pL. Six dogs (25%) had isolated thrombocytopenia without evidence of DIC or MAH. The distribution of the platelet counts is depicted in Figure 1. Two dogs (8%) were considered to have normal hemostasis profiles. In one dog, the only abnormality was a prolonged APTT. Fragmented red blood cells ( 2 1 +) were present in 1 1 dogs (46%) and represented the only abnormality in two of the dogs (8%). Six dogs (25%) died as a result of DIC and eight dogs (33%) were euthanized shortly after diagnosis and could not be evaluated for DIC as a cause of death. Nine dogs (37%) survived the immediate four-day, postoperative period following the initial hemostasis profile and one dog died due to causes unrelated to hemostatic abnormalities.
Vol. 5
. No. 1 , 1991
HEMOSTATIC ABNORMALITIES
13
30
20
FIG. 1. Distribution of platelet counts in 24 dogs with hemangiosarcoma.
10
0
150
Platelet Count (xl OOO/pL) Discussion The most clinically relevant finding of this study was that 50% of the dogs with hemangiosarcoma evaluated for hemostatic abnormalities by routine laboratory tests were diagnosed as having DIC based upon laboratory evidence alone. This confirms our clinical impression that dogs with hemangiosarcoma have a high prevalence of hemostatic abnormalities despite the paucity of reported cases in the veterinary literature. A survey of coagulation abnormalities in 100 dogs with neoplastic disease revealed that 8% had increased FDPs and 36% were thrombocytopenic.' There were only four dogs with hemangiosarcoma included in that survey. Although dogs with DIC were not specifically counted, the investigators implied that only 8% to 16% of the dogs studied had DIC. Based on the hemostasis results of the 24 dogs reported herein, dogs with hemangiosarcoma appear to have a greater risk for DIC than dogs with other types of neoplasia. Disseminated intravascular coagulation is important to recognize due to the associated high mortality rate.' Twenty-five percent of the dogs reported in this study died as a consequence of DIC (i.e., bleeding or thrombosis with attendant organ failure). This figure is probably falsely decreased by the fact that 33% of dogs were euthanized shortly after diagnosis. Other studies have found a mortality rate exceeding 80% in dogs with DIC.7 Thrombocytopenia was the most common abnormality, being present in 75% of the patients. The percentage of dogs with thrombocytopenia reported here is similar to that reported by Ng and Mills in ten dogs with hemangiosarcoma (90% of the dogs were thrombocyto-
'
penic).6 Despite the mean platelet count of 137,8OO/~L, the degree of thrombocytopenia was variable as depicted in Figure 1. Greater than one third of the dogs had platelet counts of less than 50,00O/pL. In addition to the thrombocytopenia, it is conceivable that at least some of the dogs probably had some degree of platelet dysfunction induced by the circulating FDPs." Approximately two thirds (24/35) of the dogs with hemangiosarcoma diagnosed during the study period had hemostasis profiles performed. Some bias based upon the history and physical examination was undoubtedly introduced as to which dogs were evaluated. However, the prevalence of DIC in the total population of dogs with hemangiosarcoma remains high (12 of 35 or 34%). Our data on the prevalence of MAH are similar to those reported in experimentally induced hemangiosarcoma. In our study, almost 50% of the dogs had MAH either directly or indirectly (i.e., DIC) related to hemangiosarcoma. In the dogs with experimentally induced hemangiosarcoma, 45% had anemia that was attributed primarily to MAH.' Five dogs in that study were evaluated for hemostatic abnormalities and only one had evidence of DIC.' Fifty-eight percent of the dogs with experimentally induced hemangiosarcoma had fragmented red blood cells in circulation.' This is similar to the 46% of dogs in this study with fragmented red blood cells. Other investigators found schistocytosis in 23% of dogs with splenic neoplasia. l 3 In summary, we conclude that DIC is a likely complication of hemangiosarcoma in dogs. Due to the high morbidity and mortality in dogs with DIC,7 hemostasis profiles should be performed to evaluate dogs suspected
14
HAMMER ET AL
of having hemangiosarcoma. Measures to control or prevent DIC (e.g., heparin, blood component therapy) in dogs with hemangiosarcoma may increase survival times by decreasing early mortality. References 1. Rebar AH, Hahn FF, Halliwell WH, et al. Microangiopathic he-
2. 3. 4.
5.
molytic anemia associated with radiation-induced hemangiosarcomas. Vet Pathol 1980; 17:443-454. Madewell BR, Feldman BF. Characterization of anemias associated with neoplasia in small animals. J Am Vet Med Assoc 1980; 176:419-425. Legendre AM, Krehbiel JD. Disseminated intravascular coagulation in a dog with hemothorax and hemangiosarcoma. J Am Vet Med Assoc 1977; 171:1070-1071. Zenoble RD, Gabbert NH. A possible case of disseminated intravascular coagulation and splenic hemangiosarcoma. Canine Practice 1977; 4:52-55. Crow SE, Bell TG, Wortman JA. Hematuria associated with renal hemangiosarcoma in a dog. J Am Vet Med Assoc 1980; 1761531-533.
Journal of Veterinary Internal Medicine
6. Ng CY, Mills JN. Clinical and haematological features of haemangiosarcoma in dogs. Aust Vet J 1985: 62:l-4. 7. Drazner FH. Clinical implications of disseminated intravascular coagulation. Compend Contin Educ Pract Vet 1982; 4:974981. 8. Bull BS, Kuhn IN. The production ofschistocytes by fibrin strands (a scanning electron microscope study). Blood 1970; 35: 1041 1 1. 9. Jain NC. Schalm’s Veterinary Hematology. 41h ed. Philadelphia: Lea and Febiger, 1988: 58-59. 10. Weiss DJ. Uniform evaluation and semiquantitative reporting of hematologic data in veterinary laboratories. Vet Clin Pathol 1988; I3:27-3 1. 1 1. Madewell BR, Feldman BF, O’Neill S. Coagulation abnormalities in dogs with neoplastic disease. Thrombosis and Haemostasis 1980; 44135-38. 12. Bick RL. Diseminated intravascular coagulation and related syndromes: A clinical review. Semin Thromb Hemost 1988; 14:299-338. 13. Johnson KA, Powers BE, Withrow SJ, et al. Splenomegaly in dogs: Predictors of neoplasia and survival after splenectomy. Journal of Veterinary Internal Medicine 1989; 3: 160- 166.
Book Review Veterinary Pediatrics
Johnny D.Hoskins As Dr. Hoskins stated in the preface for Veterinary Pediatrics, review papers and research articles have been published on the diagnostic, medical, and surgical disorders of the young dog and cat. Additionally, puppies and kittens have been studied as models for understanding the physiology, pathology, and therapy utilized in human neonates. Unfortunately, access to this information has been limited to prac’ticing veterinarians since the data have been scattered in various research journals and textbooks. Pertinent information has been accumulated in Veterinary Pediatrics to provide an excellent guide to the health needs of dogs and cats from birth to 6 months of age. Topics in veterinary Pediatrics include physical examination and radiography, behavioral development and disorders, drug and blood component therapy, the cardiovascular system, the respiratory system, the nervous system, the digestive system, the liver and pancreas, endocrine and metabolic systems, the urinary system, the hematopoietic system, the immune system, the musculoskeletal system, the skin, the lymphoid system, the eye, the ear, nutrition and nutritional disorders, toxicology, environmental injuries, and preventive health programs. The chapter on the liver and pancreas by
Sharon A. Center, William E. Hornbuckle, and Johnny D. Hoskins provides new information, i.e., normal values for routine biochemical indicators of hepatobiliary disorders in puppies and kittens during the first 4 weeks of life. The chapter on drug and blood component therapy by Craig E. Greene, Johnny Hoskins, and Jennifer M. Authement provides much needed information on therapeutic considerations for young animals. Informative discussions on the cause and therapy of neonatal hypoglycemia are given. Readers should be aware, however, that the formula for making 20% dextrose solution (p. 266) is wrong. The solution made by adding 30 ml of 50% dextrose to 500 ml of 5% dextrose is 7.5% dextrose, not 20% dextrose. I would not recommend that 20% dextrose be given intravenously to puppies; administering 7.5% dextrose is safer (see “Complications of Drug Therapy”, p. 34). The formula given for making 10%dextrose is also wrong. Noticeably missing from this textbook is a chapter on the reproductive system. Topics such as cryptorchidism, effects of prepubertal gonadectomy, and puppy vaginitis would be useful information to the practicing veterinarian. Nevertheless, Veterinary Pediatrics is an excellent book. It is hoped that a second edition will follow. Patricia N. Olson, DVM, PhD Fort Collins, Colorado
The hemostasis profiles of 24 dogs with histologically confirmed hemangiosarcoma were prospectively evaluated. Microangiopathic hemolysis was defined as the presence of schistocytes; disseminated intravascular coagulation was defined as I) thrombocytopenia, 2) fibrin(ogen) degradation products > 10 pg/mL, 3 ) prolongation of one or more coagulation times (activated partial thromboplastin time or one-stage prothrombin time) by greater than 25% of the control, 4) fragmented red blood cells (>l+ based on a semiquantitative grading scale), and 5) fibrinogen I 80 mg/dL. Three of the five criteria listed above had to be met for disseminated intravascular coagulation to be diagnosed. Fifty percent of the dogs were considered to have disseminated intravascular coagulation at presentation. Thrombocytopenia was present in 75% of the dogs and was the most common abnormality. The mean platelet count was 137,80O/pL. Twenty-five percent of the dogs died as a result of the hemostatic abnormalities. Only 12%of the dogs had microangiopathic hemolysis without other evidence of disseminated intravascular coagulation. Hemostatic abnormalities are present in many dogs with hemangiosarcoma a t the initial clinical presentation and represent an important clinical finding. (Journal of Veterinary Internal Medicine 1991; 511-14)
mangiosarcoma and are of clinical importance due to the high mortality associated with DIC.7
HEM, NGIOSARCOMA in the dog has been associated with hemostatic abnormalities such as disseminated intravascular coagulation (DIC) and microangiopathic hemolysis (MAH). To our knowledge, there are only nine published cases of DIC in dogs with hemangiosar~oma.'-~ Microangiopathic hemolysis has been associated with both spontaneous and experimentally induced hemangiosarcoma in this species."* The red blood cell fragmentation is believed to result from distortion and disruption of erythrocytes as they pass through fibrin deposits within vessels and abnormal tumor vasculature.',2,8Another report of ten dogs with hemangiosarcoma revealed that 90% were thrombocytopenic, and 80% had fragmented red blood c e k 6 Our clinical impression has been that dogs with hemangiosarcoma have a high prevalence of hemostatic abnormalities. We prospectively evaluated the hemostasis profiles of 24 dogs with histopathologically confirmed hemangiosarcorna to determine the prevalence of these abnormalities. We concluded that hemostatic abnormalities are present in a large number of dogs with he-
'-'
Methods Thirty-five dogs examined at the Veterinary Teaching Hospital-Ohio State University (VTH-OSU) between January 1983 and March 1989 were diagnosed by histopathology as having hemangiosarcoma. The histopathologic sections were retrospectively reviewed and 24 dogs were prospectively evaluated for hemostatic abnormalities at presentation. The coagulation tests included onestage prothrombin time (OSPT) using rabbit brain thromboplastin* and activated partial thromboplastin time (APTT) using rabbit brain cephalint; the endpoints for these tests were determined by fibrometer. The OSPT and APTT, respectively, were reported as a percent prolongation above the concurrently run control. Controls consist of pooled citrated plasma from a donor colony frozen and stored at -70°C. The reference ranges for the OSPT and APTT are 10 to 12 seconds and 18 to 24 seconds, respectively. Also determined were platelet count, fibrinogen concentration (heat precipita-
From the Department of Veterinary Clinical Sciences (Hammer, Couto) and the Department of Veterinary Pathobiology (Swardson, Getzy), the Ohio State University, College of Veterinary Medicine, Columbus, Ohio. Reprint requests: Alan Hammer, 1935 Coffey Road, Columbus, OH 43210.
* Baxter Healthcare Corporation,
Dade Division, Miami, FL. Activated Cephaloplastin Reagent, American Dade, Aguada, PR.
t Actin
11
12
Journal of Veterinary Internal Medicine
HAMMER ET AL.
TABLE1. Individual Data for Dogs With Hemangiosarcoma and Hemostasis Profiles
Tumor Site 1 right atrium
2 3 4 5 6 7 8 9
I0 II
12 13 14 15 16 17 I8 19 20 21 22 23 24
subcutaneous, kidney, liver liver spleen subcutaneous liver omentum subcutaneous spleen spleen right atrium spleen spleen spleen spleen liver, right atrium spleen liver, spleen right atrium, spleen subcutaneous spleen subcutaneous. lungs subcutaneous right atrium, lung
Platelets/pL
OSPT
APTT
(% prolongation
(% prolongation
above control)
above control)
56 32 38 0 -9 6 21 -5 25 21 190
32,000 28,000 3 1,000 148,000 349,000 45,000 344.000 92,000 75,000 28,000 16,000 3 1,000 64,000 370,000 430,000 45,500 140,000 43,000 133,000 I2 1,000 96,000 76,000 332,000 238,000
101
17 13 -13 20 -5 10
-3 6
15 27 4 31
52 21 54 8
I I38 -17 4 76 242 172 I35 14 6 55 40 41 I06 12 8 23 89 3 58
FDP
40 m / m L 10-40 &g/mL 10-40 pg/mL negative negative negative negative negative 40 pglmL 10-40 pg/mL 40 pg/mL negative >40 pg/mL negative negative >40 pg/mL negative 10-40 pg/mL negative negative negative 40 pg/mL negative 10-40 &mL
Fibrinogen (mg/dL)
I00 300 200 200 400 I00 110
200 600 200 25 155 94 NE NE I10
I20 I00 300 I00 200 200 200 300
Fragmented Red Blood Cells
0 I+ 2+ NE 0 0 I+ 0 2+ I+ I+ 2+ NE 2+ 0 0 2+ NE I+ 0 0 0 0 I+
Outcome
Diagnosis
euthanized alive euthanized alive alive died in DIC a1i ve euthanized euthanized died in DIC euthanized died* alive euthanized euthanized died in DIC euthanized died in DIC alive alive alive died in DIC alive died in DIC
DIC DIC DIC thrombocytopenia normal thrombocytopenia MAH thrombocytopenia DIC DIC DIC DIC thrombocytopenia MAH prolonged APTT DIC DIC DIC MAH thrombocytopenia thrombocytopenia DIC normal DIC
NE: not evaluated.
* Died due to causes unrelated
to hemostatic abnormalities
tion method'), and fibrin(ogen) split products (FDP) concentration (latex agglutination method$). The reference range for platelet counts is 150,000to 400,OOO/pL and for fibrinogen is 80 to 160 mg/dL; normal fibrin(ogen) degradation product concentration is less than 10 pg/mL. Fibrin(ogen) split products were reported as < I 0 pg/mL, 10 to 40 pg/mL, and >40 pg/mL. Microscopic examination of blood smears was performed to identify red blood cell fragmentation using the semiquantitative system of Weiss et a1.l' This system classifies schistocytosis based upon the average number of schistocytes per IOOOX microscopic field. One to two schistocytes per field are graded 1+; three to eight schistocytes per field are graded 2+; nine to 20 are graded as being 3+; and greater than 20 schistocytes are 4+. The average of five fields (lOOOX) was reported. The dogs were classified as having DIC if at least three of the following five criteria were present: thrombocytopenia (platelets < 15O,OOO/pL), FDPs > 10 pg/mL, prolongation of the APTT and/or OSPT by greater than 25% of the control, fragmented red blood cells 2 I + , and fibrinogen concentration I80 mg/dL. The diagnosis of MAH was made if 2 1 schistocytes were present. Disseminated intravascular coagulation and MAH could both coexist in the same patient. If no abnormalities were found, the dog's hemostatic status was classified as normal. Any other hemostatic abnormalities that
+
$ Thrombo-Wellcotest, Wellcome Diagnostics, Dartford, England.
did not fulfill the above criteria were described. The patients' immediate outcome (i.e., within 4 days of the hemostasis screen) was determined and recorded as alive, death related to hemostatic abnormalities, death unrelated to hemostatic abnormalities, or euthanized.
Results The data for individual dogs are listed in Table 1. There were 12 dogs (50%)with laboratory evidence of DIC and three dogs ( 12%) with microangiopathic hemolysis alone. Thrombocytopenia was the most common abnormality and was present in 18 dogs (75%). The mean platelet count for the 24 dogs was 137,8OO/pL. Six dogs (25%) had isolated thrombocytopenia without evidence of DIC or MAH. The distribution of the platelet counts is depicted in Figure 1. Two dogs (8%) were considered to have normal hemostasis profiles. In one dog, the only abnormality was a prolonged APTT. Fragmented red blood cells ( 2 1 +) were present in 1 1 dogs (46%) and represented the only abnormality in two of the dogs (8%). Six dogs (25%) died as a result of DIC and eight dogs (33%) were euthanized shortly after diagnosis and could not be evaluated for DIC as a cause of death. Nine dogs (37%) survived the immediate four-day, postoperative period following the initial hemostasis profile and one dog died due to causes unrelated to hemostatic abnormalities.
Vol. 5
. No. 1 , 1991
HEMOSTATIC ABNORMALITIES
13
30
20
FIG. 1. Distribution of platelet counts in 24 dogs with hemangiosarcoma.
10
0
150
Platelet Count (xl OOO/pL) Discussion The most clinically relevant finding of this study was that 50% of the dogs with hemangiosarcoma evaluated for hemostatic abnormalities by routine laboratory tests were diagnosed as having DIC based upon laboratory evidence alone. This confirms our clinical impression that dogs with hemangiosarcoma have a high prevalence of hemostatic abnormalities despite the paucity of reported cases in the veterinary literature. A survey of coagulation abnormalities in 100 dogs with neoplastic disease revealed that 8% had increased FDPs and 36% were thrombocytopenic.' There were only four dogs with hemangiosarcoma included in that survey. Although dogs with DIC were not specifically counted, the investigators implied that only 8% to 16% of the dogs studied had DIC. Based on the hemostasis results of the 24 dogs reported herein, dogs with hemangiosarcoma appear to have a greater risk for DIC than dogs with other types of neoplasia. Disseminated intravascular coagulation is important to recognize due to the associated high mortality rate.' Twenty-five percent of the dogs reported in this study died as a consequence of DIC (i.e., bleeding or thrombosis with attendant organ failure). This figure is probably falsely decreased by the fact that 33% of dogs were euthanized shortly after diagnosis. Other studies have found a mortality rate exceeding 80% in dogs with DIC.7 Thrombocytopenia was the most common abnormality, being present in 75% of the patients. The percentage of dogs with thrombocytopenia reported here is similar to that reported by Ng and Mills in ten dogs with hemangiosarcoma (90% of the dogs were thrombocyto-
'
penic).6 Despite the mean platelet count of 137,8OO/~L, the degree of thrombocytopenia was variable as depicted in Figure 1. Greater than one third of the dogs had platelet counts of less than 50,00O/pL. In addition to the thrombocytopenia, it is conceivable that at least some of the dogs probably had some degree of platelet dysfunction induced by the circulating FDPs." Approximately two thirds (24/35) of the dogs with hemangiosarcoma diagnosed during the study period had hemostasis profiles performed. Some bias based upon the history and physical examination was undoubtedly introduced as to which dogs were evaluated. However, the prevalence of DIC in the total population of dogs with hemangiosarcoma remains high (12 of 35 or 34%). Our data on the prevalence of MAH are similar to those reported in experimentally induced hemangiosarcoma. In our study, almost 50% of the dogs had MAH either directly or indirectly (i.e., DIC) related to hemangiosarcoma. In the dogs with experimentally induced hemangiosarcoma, 45% had anemia that was attributed primarily to MAH.' Five dogs in that study were evaluated for hemostatic abnormalities and only one had evidence of DIC.' Fifty-eight percent of the dogs with experimentally induced hemangiosarcoma had fragmented red blood cells in circulation.' This is similar to the 46% of dogs in this study with fragmented red blood cells. Other investigators found schistocytosis in 23% of dogs with splenic neoplasia. l 3 In summary, we conclude that DIC is a likely complication of hemangiosarcoma in dogs. Due to the high morbidity and mortality in dogs with DIC,7 hemostasis profiles should be performed to evaluate dogs suspected
14
HAMMER ET AL
of having hemangiosarcoma. Measures to control or prevent DIC (e.g., heparin, blood component therapy) in dogs with hemangiosarcoma may increase survival times by decreasing early mortality. References 1. Rebar AH, Hahn FF, Halliwell WH, et al. Microangiopathic he-
2. 3. 4.
5.
molytic anemia associated with radiation-induced hemangiosarcomas. Vet Pathol 1980; 17:443-454. Madewell BR, Feldman BF. Characterization of anemias associated with neoplasia in small animals. J Am Vet Med Assoc 1980; 176:419-425. Legendre AM, Krehbiel JD. Disseminated intravascular coagulation in a dog with hemothorax and hemangiosarcoma. J Am Vet Med Assoc 1977; 171:1070-1071. Zenoble RD, Gabbert NH. A possible case of disseminated intravascular coagulation and splenic hemangiosarcoma. Canine Practice 1977; 4:52-55. Crow SE, Bell TG, Wortman JA. Hematuria associated with renal hemangiosarcoma in a dog. J Am Vet Med Assoc 1980; 1761531-533.
Journal of Veterinary Internal Medicine
6. Ng CY, Mills JN. Clinical and haematological features of haemangiosarcoma in dogs. Aust Vet J 1985: 62:l-4. 7. Drazner FH. Clinical implications of disseminated intravascular coagulation. Compend Contin Educ Pract Vet 1982; 4:974981. 8. Bull BS, Kuhn IN. The production ofschistocytes by fibrin strands (a scanning electron microscope study). Blood 1970; 35: 1041 1 1. 9. Jain NC. Schalm’s Veterinary Hematology. 41h ed. Philadelphia: Lea and Febiger, 1988: 58-59. 10. Weiss DJ. Uniform evaluation and semiquantitative reporting of hematologic data in veterinary laboratories. Vet Clin Pathol 1988; I3:27-3 1. 1 1. Madewell BR, Feldman BF, O’Neill S. Coagulation abnormalities in dogs with neoplastic disease. Thrombosis and Haemostasis 1980; 44135-38. 12. Bick RL. Diseminated intravascular coagulation and related syndromes: A clinical review. Semin Thromb Hemost 1988; 14:299-338. 13. Johnson KA, Powers BE, Withrow SJ, et al. Splenomegaly in dogs: Predictors of neoplasia and survival after splenectomy. Journal of Veterinary Internal Medicine 1989; 3: 160- 166.
Book Review Veterinary Pediatrics
Johnny D.Hoskins As Dr. Hoskins stated in the preface for Veterinary Pediatrics, review papers and research articles have been published on the diagnostic, medical, and surgical disorders of the young dog and cat. Additionally, puppies and kittens have been studied as models for understanding the physiology, pathology, and therapy utilized in human neonates. Unfortunately, access to this information has been limited to prac’ticing veterinarians since the data have been scattered in various research journals and textbooks. Pertinent information has been accumulated in Veterinary Pediatrics to provide an excellent guide to the health needs of dogs and cats from birth to 6 months of age. Topics in veterinary Pediatrics include physical examination and radiography, behavioral development and disorders, drug and blood component therapy, the cardiovascular system, the respiratory system, the nervous system, the digestive system, the liver and pancreas, endocrine and metabolic systems, the urinary system, the hematopoietic system, the immune system, the musculoskeletal system, the skin, the lymphoid system, the eye, the ear, nutrition and nutritional disorders, toxicology, environmental injuries, and preventive health programs. The chapter on the liver and pancreas by
Sharon A. Center, William E. Hornbuckle, and Johnny D. Hoskins provides new information, i.e., normal values for routine biochemical indicators of hepatobiliary disorders in puppies and kittens during the first 4 weeks of life. The chapter on drug and blood component therapy by Craig E. Greene, Johnny Hoskins, and Jennifer M. Authement provides much needed information on therapeutic considerations for young animals. Informative discussions on the cause and therapy of neonatal hypoglycemia are given. Readers should be aware, however, that the formula for making 20% dextrose solution (p. 266) is wrong. The solution made by adding 30 ml of 50% dextrose to 500 ml of 5% dextrose is 7.5% dextrose, not 20% dextrose. I would not recommend that 20% dextrose be given intravenously to puppies; administering 7.5% dextrose is safer (see “Complications of Drug Therapy”, p. 34). The formula given for making 10%dextrose is also wrong. Noticeably missing from this textbook is a chapter on the reproductive system. Topics such as cryptorchidism, effects of prepubertal gonadectomy, and puppy vaginitis would be useful information to the practicing veterinarian. Nevertheless, Veterinary Pediatrics is an excellent book. It is hoped that a second edition will follow. Patricia N. Olson, DVM, PhD Fort Collins, Colorado
