Can you rule in immune-mediated thrombocytopenia?

Signalment:

Canine, Yorkshire Terrier, 11-year-old, female spayed, 15 lbs.

Clinical history:

The dog presents for acute onset of vomiting.

Physical examination:

The findings include rectal temperature 101.0° F, heart rate 140/min, respiratory rate 25/min, pink mucous membranes, normal capillary refill time, and normal heart and lung sounds. While shaving the dog for the ultrasound study, ecchymoses of the abdominal skin were noted. Abnormal physical findings are ecchymoses of the abdominal skin and moderately painful abdomen.

Table 1: results of laboratory tests

Laboratory results:

A complete blood count, serum chemistry profile and urinalysis were performed and are outlined in Table 1.

Radiographic review:

Survey thoracic and abdominal radiographs were done. The thoracic radiographs are normal. The abdominal radiographs show an enlarged spleen.

Ultrasound examination:

Thorough abdominal ultrasonography was performed. The dog was positioned in dorsal recumbency for the ultrasonography. The ultrasound images provided are from this dog's liver.

Ultrasound examination: Photos 1-3(L-R)

My comments:

The liver shows a uniform echogenicity. No cancerous masses noted within the liver parenchyma. The gallbladder is moderately distended, and its walls are slightly thickened and hyperechoic. The gallbladder does contain some sludge material and possibly multiple small calculi. The spleen shows uniform echogenicity - no cancerous masses noted. The left and right kidneys are similar in size, shape and echotexture. No cancerous masses or calculi were noted in either kidney. The urinary bladder is distended with urine and contains some urine sediment material - no cancerous masses or calculi noted. The stomach and intestines are normal. The pancreas shows uniform echogenicity.

Case management:

In this case, immune-mediated thrombocytopenia and chronic cholecystitis are the clinical diagnosis. The management of the immune-mediated thrombocytopenia should include prednisone at 2-4 mg/kg orally divided into twice-a-day administration and doxycycline.

In those areas known to have ehrlichiosis, it is not unusual to have both immune-mediated thrombocytopenia and canine ehrlichiosis occurring in the same dog at the same time. The abdominal pain detected on palpation is most compatible with a chronic cholecystitis.

When the gallbladder contracts from eating and/or movement, it causes abdominal pain, nausea and vomiting. I would manage the gallbladder disease with daily administration of antibiotics and Denosyl SD4. I would also consider feeding the dog exclusively a diet formulated for liver disease such as Prescription Diet L/D. I would recommend only medical care for the gallbladder disease right now and if the dog was not responding to medical care, then an exploratory laparotomy would be recommended for possible surgical removal of the gallbladder.

The total platelet count needs to be normal before any surgery is attempted.

Brief review

Immune-mediated thrombocytopenia is the most common cause of severe thrombocytopenia in dogs, and bleeding is typically associated with a total platelet count <40,000/µl.

Typical treatment recommendations for immune-mediated thrombocytopenia involve administration of various drugs. Corticosteroids (prednisone 2-4 mg/kg orally divided into twice a day administration or dexamethasone 0.2 mg/kg intravenously administered twice daily, if vomiting) are the primary treatment and act primarily to impair clearance of antibody-coated platelets by macrophages.

Vincristine (0.02 mg/kg intravenously one time) is also frequently administered as an initial therapy in addition to corticosteroids. Vincristine may increase total platelet counts in dogs with immune-mediated thrombocytopenia through several proposed mechanisms, including stimulation of thrombopoiesis, increased fragmentation of megakaryocyte cytoplasm to release new platelets, and impairment of macrophage activity, leading to decreased phagocytosis of platelets.

Because many dogs with immune-mediated thrombocytopenia respond to corticosteroids ± vincristine and that the cost and/or potential adverse effects of other immunosuppressive agents are considerable and their efficacy has not been well documented, administration of other immunosuppressive drugs, such as cyclosporin, azathioprine, danazol and intravenous immunoglobulin is withheld unless the dog fails to respond to corticosteroids ± vincristine or develops serious adverse drug effects (thromboembolism, gastrointestinal ulceration).

Splenectomy is generally not done unless splenic masses are identified. Blood transfusions may be required in dogs with immune-mediated thrombocytopenia experiencing extensive mucosal surface bleeding, which appears to occur most frequently into the gastrointestinal tract and may be difficult to quantify.

Packed RBC transfusions are administered to provide severely anemic dogs with the necessary oxygen-carrying support. Platelet transfusions (fresh whole blood, platelet-rich plasma or platelet concentrate) are not recommended in most dogs with immune-mediated thrombocytopenia because the platelets are destroyed within minutes to hours of transfusion.

However, in thrombcytopenic dogs with severe, uncontrolled or life-threatening bleeding, platelet transfusions are indicated and may provide short-term hemostasis despite the lack of a measurable increase in total platelet count assessed one and 24 hours post-transfusion. While there is a risk of life-threatening bleeding is dogs with immune-mediated thrombocytopenia, most dogs with immune-mediated thrombocytopenia, despite severe thrombocytopenia, experience minimal bleeding in the form of petechiae and ecchymoses and do not bleed excessively even during surgery, potentially because the young, large platelets noted with increased thrombopoiesis are more hemostatically active.

Thus, in dogs with immune-mediated thrombocytopenia exhibiting only a mild bleeding tendency and undergoing surgery (splenectomy or removal of a tumor suspected to be the antigenic stimulus for development of immune-mediated thrombocytopenia), platelet transfusions may not be necessary in the operative period but should be available in the event of excessive bleeding.

Gallbladder disease

The diagnosis of gallbladder disease is initiated by the veterinarian's suspicion that gallbladder disease might be present as based on the case history and physical examination and laboratory findings. Radiographic and/or ultrasonographic imaging, serum bile acid determinations, fine needle aspiration of gallbladder for cytology and culture, and possibly liver biopsy for histopathologic examination may follow the initial results.

The CBC may show mild to moderate nonregenerative anemia, neutrophilic leukocytosis with a left shift, thrombocytopenia, or other morphologic changes. Increased serum liver enzyme activities such as increased serum ALT and AST are reliable indicators of hepatocellular damage or cholestasis. Serum ALP and GGT activities increase in cholestasis. In cats, any increase in serum ALP activity indicates cholestasis. Hyperbilirubinemia may occur with active hepatocellular damage and also occur with cholestasis secondary to extrahepatic disease. Any degree of bilirubinuria in cats of any age is abnormal and suggestive of active liver disease.

The most practical method of assessing liver and/or gallbladder dysfunction in nonicteric dog or cat is serum bile acid determinations. Fasting and two-hour postprandial bile acid concentrations has the same normal range values irrespective of age and will be increased with primary or cholestatic liver and/or gallbladder disease.

Survey abdominal radiography and ultrasonography may be helpful in diagnosing gallbladder diseases, identifies distinct liver/gallbladder masses, mineralization and cholelithiasis.

Ultrasound-guided fine needle aspiration of the gallbladder for cytology is relatively safe procedure for diagnosing some gallbladder diseases. Gallbladder aspirates may be obtained from a nonsedated animal placed in either dorsal or right lateral recumbency. The abdomen is clipped and prepared as for ultrasonography, and a 1-inch or 1.5-inch, 22-gauge needle is advanced into the gallbladder under guidance of the ultrasound beam.

A single gentle aspiration with a 6-ml syringe will usually yield adequate numbers of cells for cytologic evaluation and for bacterial culture. Smears of the gallbladder aspirate are then made, and the slides are stained with a cytologic stain such as Wright's-Giemsa. Exploratory laparotomy and surgical biopsy can also be performed, with the advantage of being able to visualize the liver lobes, gallbladder and extrahepatic biliary system.

Abdominal ultrasound

Cholecystitis and cholelithiasis are considered by many people to be uncommon in dogs and cats - a frequently quoted statement by many veterinarians and veterinary textbooks that is incorrect. Because of routine use of abdominal ultrasonography, many dogs and cats are now being diagnosed with acute and chronic gallbladder diseases. Cholecystitis often leads to vague signs of vomiting, fever and abdominal pain. The usual cause of cholecystitis is thought to be a bacterial infection from ascending bacteria from gastrointestinal tract or from hematogenous bacteria. When cholecystitis becomes severe, gallbladder necrosis and rupture may occur, with subsequent biliary peritonitis.

Ultrasonography identifies increased gallbladder wall thickness and echogenicity; dilated, tortuous bile ducts and concurrent cholelithiasis. Antimicrobial therapy based on bacterial culture and sensitivity test results is the optimal treatment for cholecystitis. Severe cases of cholecystitis, such as emphysematous or necrotic cholecystitis, may be treated surgically with cholecystectomy.

Choleliths

Choleliths occur in older dogs and cats as well. Choleliths are usually composed of cholesterol, bile acids, pigments, calcium and protein. Diet and cholecystitis are predisposing causes for cholelith formation. The clinical signs and diagnostic approach to cholelithiasis are similar to that used for cholecystitis.

Treatment of cholelithiasis may be either surgical or medical. Cholecystectomy can be performed for cholelithiasis, which will prevent recurrence. Medical therapy may include antimicrobial agents and commercial canine diet formulated for liver disease. Extrahepatic bile duct obstruction can occur in older cats, usually secondary to cholelithiasis, inspissated bile or parasitic infection. Choleliths in cats contain cholesterol, bilirubin derivatives and calcium. Occasionally, bile sludging secondary to increased mucosal uptake of bile fluid can result in overt inspissation of bile with biliary obstruction. Biliary obstruction and choleliths result in anorexia, vomiting, fever, icterus and acholic (depigmented) stools in severely affected animals.

Cats of any age may be affected with a fluke infection of the biliary tract or pancreas. Signs associated with a fluke infection are similar to other causes of biliary obstruction. Diagnosis of flukes is made by routine fecal sedimentation or use of formalin-ether sedimentation techniques to identify the typical-appearing fluke eggs. Occasionally, fluke eggs may be detected in abdominal fluid or liver cysts.

Optimal treatment for liver and pancreatic flukes is praziquantel (20 to 30 mg/kg single time or daily for three days). Parasitized cats with severe liver disease secondary to biliary tract obstruction may have a guarded prognosis.