Wednesday, September 10, 2008

crashing and burning

this was not a successful week for my patients - despite intensive management of them. sometimes nature wins, no matter how much we as doctors struggle against it.

i had 3 heartbreaking cases that i poured myself into - all were euthanized. a heat stroke, an IMHA (immune-mediated hemolytic anemia), and a dog with aspiration pneumonia that developed during a routine dental.

i guess i'll start with my IMHA.

julius was an older cocker spaniel that came in through the emergency service. he presented to his vet collapsed with white mucus membranes. the vet took one look at the signalment (cocker spaniel) and chief complaint (anemia/collapse) and sent him straight to us without conducting any bloodwork. he knew on presentation that in all likelihood we were dealing with primary IMHA.

IMHA is a disease in which the body decides to destroy the red blood cells. it can occur by itself or concurrently with ITP (immune-mediated thrombocytopenia). this is when the body also destroys platelets - which are crucial for clotting. the two together are called Evan's syndrome.

when IMHA happens, the body's immune system coats red blood cells with antibodies, leading to their removal from circulation. this can happen via the normal pathway of red blood cell destruction (in the spleen) which leads to extravascular hemolysis. or it can happen inside the veins (intravascular hemolysis). intravascular is usually considered worse. IMHA is fairly common in cocker spaniels. in primary IMHA, the underlying cause is never determined and is likely a genetic predisposition. in secondary IMHA, there is a known underlying cause like drugs (sulfa drugs can cause this), cancer, or tick-borne diseases like Lyme disease or Rocky Mountain spotted fever. in cockers, it's usually primary IMHA. but you always look for the other diseases - just to be sure.

treatment for this disease is to suppress the immune system. recent research suggests that the best outcome is achieved by using a combination of steroids (prednisone orally), azathioprine (a purine antagonist that interferes with DNA/RNA synthesis), and low-dose aspirin (at low doses, aspirin is not an anti-inflammatory/pain drug but inhibits platelet aggregation and prevents clots from forming). with the exception of the aspirin, neither of the other treatments are exactly benign. steroids come with a host of negative side effects, and azathioprine can cause pancreatitis and occasionally acute liver failure.

when i saw julius, i ran bloodwork - which looked surprisingly good. his PCV (packed cell volume) - a measure of what percent of his blood is actually cells - was 15% (normal in dogs 35-45%). 15% is the borderline for transfusing or not. when i put his blood on a slide, it instantly agglutinated. this isn't the same as clotting. agglutination is where all the red blood cells stick together - which REALLY - isn't what clotting is (i know it sounds the same). the red blood cells are sticking together because of all the antibodies on their surfaces, as opposed to platelets and clotting factors forming clots. see the picture for the difference. at any rate, he was obviously an IMHA. but was he primary or secondary to something else? given his older age, i was worried about cancer.

we did the IMHA "special" - tick titers, thorax and abdominal xrays, as well as full panel bloodwork. i was pleased to find that his liver, kidney, and other values were all within normal ranges.

we held off on the transfusion with strict orders to have his PCV checked every 4 hours, and if it dropped below 15% to transfuse. when i left him for the night, julius was wagging his stump of a tail, eating like crazy, and giving kisses to anyone who would tolerate him. he was a truly sweet cocker spaniel (a rarity).

i arrived the next morning to find julius still eating and chipper, but his PCV had dropped to 11%. we transfused him and he seemed to do well for a while. on the second day, he developed purulent nasal discharge and a high fever indicative of a respiratory infection like canine influenza. it was very strange and a very uncommon occurrence with IMHA.

and then on day 3, he started to turn yellow and i knew things were not going in our favor. i expected this. the drugs we started him on usually take a minimum of 2-3 days to work (sometimes up to a week) - so i knew he would get worse before he got better. it was no surprise. why yellow, perhaps you're wondering? when red blood cells are broken down, they release a substance called bilirubin as part of their metabolism. this is usually cleaned up and handled by the liver. however, in IMHA - the liver becomes overwhelmed and cannot keep up so that bilirubin builds up in the blood. it's a pigment - and it's color is....drumroll...yes, you guessed it...yellow. you can see the color in the sclera of the eye, the gums, and the skin (if it's bad enough). julius was turning highlighter yellow.

i rechecked his bilirubin and to my dismay found it to be 21.5 (normal 0.1-0.9). what did that mean to me? that julius was hemolyzing (destroying) his transfusion rapidly. i rechecked his PCV - and it was 13% (it had come up to 20% after the transfusion). on top of that, julius had started vomiting and having diarrhea, as well as abdominal pain. i was worried - because azathioprine has the side effect of causing pancreatitis (inflammation of the pancreas)- a debilitating and sometimes fatal in its own right disease. i checked his amylase and lipase - 2 questionable markers of pancreatitis. both were through the roof. i conducted a snap test for pancreatitis and it was positive (but that test has a HOST of its own problems). my clinicial suspicion was mostly based on the severe abdominal pain he demonstrated when i palpated his abdomen.

i also noted at the time that his ALT (a liver value that marks acute damage) had gone off the charts. not a good sign at all...indicating possible impending liver failure.

i stopped his azathioprine and switched him to a 2nd line immunosuppressive - cyclosporine.

he continued to decline. he went from eating and wagging his stump to laterally recumbent and barely responsive. his mother was crushed, and so was i. here, after 3 days of intensive care, he went from looking great to looking like he was dying. he just got worse and worse.

stumped at the rapid progression of his other GI diseases - i took him to ultrasound and was stunned to find his abdomen full of blood. not only was he hemolyzing his blood - he was bleeding into his abdomen. i rechecked his platelet count - which was low - but not Evan's syndrome low. it didn't explain the bleeding. acute pancreatitis didn't explain the bleeding either.

i was left full of questions with no answers. julius meanwhile was in a stupor. his mother - crying quietly - told me that she wanted to stop. i agreed that it was time, that i thought we'd lost the battle. julius went quietly, without a struggle.

in the end, i was left with more questions than answers. julius had IMHA, yes...but why did julius go into acute liver failure? was the pancreatitis really 2ndry to the azathioprine? why did he bleed into his abdomen? was there something i could have done differently? did he have cancer somewhere?

the only question to which i have an answer is did i do the best i could and did i give julius gold standard care? i can answer those both with a resounding yes. still, it hurt to tell his mother that there was nothing more that i could do for him. it hurt to give up, even though i knew it was time.


Amy said...

Is IMHA the same as DIC?? or is it the animal equivalent?

Homeless Parrot said...

no, DIC is a different disease altogether. in IMHA the immune system attacks and lyses the red blood cells leading to anemia.

in DIC, the homeostasis of the blood system gets out of whack and the body starts making clots inappropriately throughout the body. tons of clots form and then the body has used up all its clotting factors AND all its platelets. the pathway then goes the other way - and the animal (or person) bleeds to death.

very, very different. DIC is usually in response to a huge systemic insult. IMHA is a random thing that happens to some dogs.