Coagulation Part 2: Disorders of Coagulation

Question 1

describe giant/shift platelets

Answer 1

1. giant platelets or shift platelets
   -larger than RBCs
   -will function normally
   -suggests accelerated thrombopoiesis (platelet regeneration)
   -MPV generally increased

Question 2

describe thrombocytopenia

Answer 2

4 causes: SPUD; often more than 1 mechanism involved; need to exclude the presence of platelet clumps that may falsely decrease the platelet count and increase MPV

Sequestration: trapping of platelets within the spleen, usually causes a mild, transient decrease in platelet counts; due to splenomegaly, splenic congestion, splenic neoplasia

Production;
-decreased production: due to
1. bone marrow diseases; will see other cytopenias; due to aplastic anemia, toxins, and other causes
2. infectious diseases: ehrlichia and other rickettsial organisms; viral organisms (FeLV/FIV, parvovirus)
3. macrothrombocytopenia (CKCS): nonpathogenic: idiopathic condition in Cavalier King Charles Spaniels due to both abnormal platelet morphology and decreased platelet production; will have fewer, larger platelets; decreased platelet count with increased MPV, normal plateletcrit; platelets normal in function

Utilization: increased
-indicates increased platelet consumption due to DIC, vasculitis, endocarditis, SEVERE acute blood loss from hemorrhage

Destruction:
1. Immune-mediated thrombocytopenia: can be primary or secondary; will see marked thrombocytopenia with normal coagulation testing

-primary: autoantibodies targeting platelets and megakaryocytes; breed predispositions

-secondary: antibody production triggered by an inciting cause; neoplasia, infectious disease, drugs, vaccines; RULE out all secondary causes before diagnose primary

Question 3

describe thrombocytosis

Answer 3

1. commonly seen but not often clinically significant but can predispose to thrombosis
2. divided into primary and secondary (reactive, most common)

Question 4

describe primary thrombocytosis

Answer 4

1. very rare; associated with a persistent, extreme thrombocytosis
2. due to a neoplastic cause: essential thrombocytopenia, acute megakaryoblastic leukemia, chronic myoproliferative diseases
3. patients may have an increased risk of thrombosis or hemorrhage, depending on platelet function

Question 5

describe reactive (secondary) thrombocytosis

Answer 5

several causes:

1. increased production: due to inflammation, recovery from recent thrombocytopenia, chemotherapeutic drugs, iron deficiency
2. redistributive or physiologic: epinephrine mediated or exercise = splenic contraction and transient thrombocytosis
3. decreased removal: recent splenectomy, seen post-op
4. excess cortisol: endogenous (Cushings) or exogenous (glucocorticoid admin)

Question 6

describe abnormal platelet function

Answer 6

thrombopathy or thrombocytopathy;

can be inherited or acquired; associated with
1. adherence or aggregation
2. surface membrane receptors
3. abilit to synthesice and release products

platelet count normally WRI or increased!

Question 7

what are causes of congenital platelet dysfunction?

Answer 7

1. von willebrand disease: most common hemostatic disorder in dogs (esp dobermans, scotties, shelties, rare in others)
   -a deficiency or abnormality of vWF due to either
   –quantitative or qualitative defect
   –acquired vWD (is uncommon in vet med)
2. clinical signs of vWD:
   -prolonged bleeding from wounds
   -mucosal hemorrhage: not seen until vWF <35%
3. diagnosis of vWD:
   -definitive requires assessment of vWF concentration and/or function
   -use vWF antigen concentration (vWF:Ag assay); ELISA method is gold standard:
   –citrated or EDTA plasma is frozen immediately after collection
   –storage time at room temp in whole blood can falsely INCREASE vWF
   –clotting and in vitro hemolysis can falsely DECREASE vWF
   -can also use electrophoresis, functional assays, genetic assays (determine carrier status)

Question 8

what is a cause of acquired platelet dysfunction?

Answer 8

hyporesponsive platelets

due to:
1. drugs: NSAIDs (cox inhibitors), calcium channel blockers
2. liver or renal failure (uremia)
3. marked elevation in globulins (hyperglobulinemia)
4 infectious diseases (FeLV, ehrlichia)
5. DIC

Question 9

what are the 2 disorders of the extrinsic pathway?

Answer 9

assessed via P(e)T!

1. inherited factor 7 deficiency or inhibition: seen in beagles, mild disease associated with bruising
2. acquired factor 7 deficiency or inhibition:
   -associated with early vitamin K deficiency or inhibition, since factor 7 has the shortest half life it will be the first to go
   -only PT will be prolonged

Question 10

describe disorders of the intrinsic pathways (5)

Answer 10

assessed via P(i)TT!

1. hereditary factor 12 deficiency/Hageman’s disease:
   -prolonged ACT or PTT with no clinical bleeding; more common in cats than dogs
2. hereditary factor 11 deficiency/Hemophilia C:
   -mildly prolonged bleeding seen after surgery; seen in dogs and holstein cattle
3. hereditary factor 9 deficiency/Hemophilia B:
   -X chromosome linked = more common in males;
   -affected males have variable clinical signs and spontaneous internal hemorrhage can occur
   -affected females are usually carriers
   -seen in dogs and cats
4. hereditary factor 8 deficiency/hemophilia A:
   -most common inherited coagulation factor disorder!
   -X chromosome linked = more common in males
   -affected males and females like hemophilia B, but seen in dogs, cats, SHEEP, CATTLE, HORSES
5. vitamin K antagonism or deficiency: factors 2. 7, 9, 10:
   -often affects multiple pathways: both PT and PTT prolonged, but will see PT prolonged first bc factor 7 has the shortest half life
   -antagonism due to rodenticides, moldy sweet clover
   -deficiency due to liver or GI disease

Question 11

describe common pathway disorders

Answer 11

1. cause prolonged PT and PTT
2. hereditary is rare but can see
   -factor 10 deficiency in dogs and cats or
   -fibrinogen deficiency in goats and dogs
3. acquired is usually associated with multi-pathway disorders

Question 12

describe multple pathway disorders

Answer 12

1, vitamin K antagonism or deficiency (2, 7, 9, 10)
2. liver failure: decreased production of coag factors
3. DIC: consumes factors
4. multiple factor deficiency is very rare; usually congenital diseases only affect one factor

Question 13

describe disseminated intravascular coagulation

Answer 13

1. syndrome in which disseminated, consumptive coagulation and fibrinolysis occurs
2. initially starts as a hypercoagulable state with widespread, excessive activation of hemostasis that generates excess thrombin and microvascular thrombi
3. gradual consumption of clotting factors exceeds the rate of synthesis and leads to hypercoagulable state and increased risk of hemorrhage
4. always SECONDARY to another condition that causes excessive consumption: neoplasia, heatstroke, IMHA, envenomation, sepsis, heartworm disease
5. triggered by excessive tissue factor release from:
   -damaged endothelial cells
   -neoplastic cells
   -endotoxin stimulated cells

Question 14

list consequences of DIC

Answer 14

1. disseminated thrombi: tissue ischemia, organ failure, death
2. hemorrhage: petechiae, ecchymoses, spontaneous bleeding
3. fragmentation anemia: an RBC shearing injury, evidenced by acanthocytes, schistocytes, spherocytes, and keratocytes (messed up RBCs)

Question 15

describe diagnosis of DIC

Answer 15

1. clinical suspicion:
   -physical evidence of bleeding disorder
   -initial phase of DIC may have no clinical signs
2. lab findings: (5)
   -prolonged PT/PTT: due to depletion of coag factors, multiple pathways involved

-mod to severe thrombocytopenia: due to increased utilization or consumption

-increased FDPs and D dimers: due to increased fibrinolysis

-cytologic evidence of fragmentation injury to RBCs: schistocytes, etc.

-others: normal to increased fibrinogen (may be masked by concurrent inflammation), increased BMBT, decreased antithrombin III (prevents coagulation)