Immune-mediated Hematopoetic Disorders

Question 1

In many cases of IMHA macrophages recognize erythrocytes coated with complement and/or immunoglobulin to target them for phagocytosis. What type of hemolysis is this associated with?

Answer 1

Macrophages = extravascular

Question 2

How are spherocytes formed in IMHA?

Answer 2

Macrophage phagocytosis of immunoglobulin and complement (c3b) coated RBCs causing extravascular hemolysis

Question 3

Ghost erythrocytes are indicative of intravascular hemolysis. What is the pathogenesis of how these cells form in cases of IMHA?

Answer 3

Complement fixation to MAC causes intravascular RBC lysis

Question 4

What is the pathophysiology of intravascular hemolysis and why does it carries a poorer prognosis?

Answer 4

Free hemoglobin, iron, and heme cause oxidative damage

Prevents NO from doing its job in maintaining vasodilation and inhibiting platelet aggregation

Free cell fragments (phospholipids) promote coagulation

Causes pro-inflammatory state -> DIC

Question 5

What are the clinical signs/laboratory findings that

might be associated with intravascular vs. extravascular hemolysis?

Answer 5

Intravascular: icterus, bilirubinemia/uria, HEMOGLOBINEMIA/URIA*

Extravascular: icterus, bilirubinemia/uria, organomegaly

Question 6

What are inciting causes of secondary IMHA?

Answer 6

Infectious

Chemical

Neoplasia

Other immune-mediated disease

Question 7

What is Evans’ syndrome?

Answer 7

IMHA with IMTP

Question 8

What is Warm agglutinin disease? What is cold agglutinin disease?

Answer 8

Agglutination and/or hemolysis occurs at specific temp

Warm: at body temp

Cold: below body temp

Question 9

What diseases other than IMHA that can result in spherocyte

or ghost cell formation?

Answer 9

Spherocytes: fragmentation/microangiopathy, zinc toxicosis, hypophosphatemia, envenomation, blood transfusion, burns

Ghost cells: any cause of intravascular hemolysis, hemolysis of sample from difficult blood draw or prolonged storage

Question 10

What are the expected clinicopathologic findings in cases of IMHA?

Answer 10

Anemia

Poikilocytosis -Ghost cells, Spherocytes

Agglutination

Neutrophilia

Monocytosis

Question 11

What does a positive Coombs’ test indicate? What is the utility of this test in a patient with auto-agglutination and signs/lab data supportive of IMHA?

Answer 11

Positive agglutination

No utility, don’t need to do Coomb’s

Question 12

What are some reasons a Coombs’ test may give a false negative result?

Answer 12

Low Ab titer

Technical issues

Question 13

Can a Coombs’ test differentiate primary from secondary immune-mediated hemolytic anemia?

Answer 13

No

Question 14

What factors have been identified that carry a poorer prognosis in canine IMHA cases?

Answer 14

Intravascular hemolysis

Hyperbilirubinemia (>10 mg/dL)

Question 15

What do we know about IMHA in the cat?
What conditions have been associated with secondary IMHA in the cat?

Are there any factors that have been associated with a better prognosis? A worse prognosis?

Answer 15

Neoplasia, lymphoma, FIP, mycoplasma, FeLV, other inflammation/infection

Better prognosis: primary IMHA, lymphocytosis, hyperglobulinemia

Worse: higher total bilirubin, older age

Question 16

What is the pathophysiology of primary and secondary ITP?

Answer 16

Primary: targets fibrinogen receptor (glycoprotein iib/iiia)

Secondary: molecules adsorbed to platelet surface

Question 17

What are some general causes of secondary ITP?

Answer 17

Infections

Chemical

Neoplasia

Concurrent immune-mediated disease

Question 18

What are the clinical signs and clinicopathologic findings associated with ITP?

Answer 18

Clinical Signs:

Petechia, ecchymoses, bruising, pale MM
Epistaxis, other bleeding (GI, oral, vaginal, ocular, cerebral)
Hematuria
Stiffness, lethargy, weakness, anorexia

Clin path:

Severe thrombocytopenia, +/-increased MPV, anemia

Question 19

How do you categorize the severity of a thrombocytopenia and how does this relate to risk of hemorrhage?

Answer 19

Platelet #

Marked: < 30K, spontaneous or induced bleed

Moderate: 30 - 100K, induced or no bleed unless plt defect

Mild: 100K - lower RI: no bleed unless plt defect

Question 20

What is the general signalment of animals with the various autoimmune disorders discussed? Are any age-groups overrepresented? Any breeds?

Answer 20

IMHA:
2-7 yrs, Cocker spaniel, schnauzer, collie, english springer, poodle, OES

ITP:
Middle age, cocker, poodle, sheepdog