What is the major regulatory enzyme for Thrombopoiesis?
Thrombopoietin
Where does Thombopoietin come from?
Continually produced by the liver, bone marrow, endothelium ect.
______ stimulates megakaryocyte production and differentiation
Thrombopoietin
Thrombopoietin binds to _____ in ciruclation
Platelets
When _____ numbers decrease there isn’t enough in ciruclation to pick up the thrombopoeitin, leading to increased thrombopoietin free in plasma that ciruclates to the bone marrow and stimulates production of _____
Platelets
Megakaryocytes
Platelets are part of _____ hemostasis
Primary
_____ Provides a surface for which secondary hemostasis occurs on
Platelets
How long does it take to form the primary hemostatic plug?
3-5 minutes
In the formation of the primary hemostatic plug, platelets adhere to exposed ______
Subendothelium
Once platelets adhere to subendothelium they undergo ____, leading to a shape change
Activation
After platelets are activated, they begin to secrete _____
Granules
After platelets have activated and secreted granules, they _____ to form a platelet plug
Aggregate
For platelets to adhere to the subendothelium they require ______Factor
Von Willebrand factor
Von Willebrand factor binds to ____ on the platelet surface and forms a bridge between the platelets and subendothelium
GP1b
During primary hemostasis, when platelets ____ , they start to undergo shape changes where they grow long extensions and increase their surface area by 3-5%
Activation
*Increase their surface area
The majority of negatively charged phospholipids are kept on the inside of the platelet, but when the platelet becomes activated they _____ their membrane in order to carry the negative charge on the outside
Flip
After platelets become activated, what two things are secreted in their granules?
Von Willibrand factor
Calcium
*Von willebrand factor calls more platelets to the site
During activation platelets secrete _____ which comes and coats the top of the negatively charged platelets, so the platelets become positively charged
Calcium
Calcium is secreted in platelet granules that coat the platelet with a positive charge which is important for creating the surface for the _____ factors to come down and bind to form fibrin
Coagulation
Once the granules are stimulated to form platelet aggregation, _____ binds to the platelets and starts bridging the adjacent platelets.
Fibrinogen
When _____ binds to activated platelets and bridges adjacent platelets is when you get formation of the platelet plug
Fibrinogen
True/False: Platelet aggregation is a reversible process
False
*Irreversible
Platelets provide a surface for formation and deposition of ____
Fibrin
Platelets activate their cytoskeleton to _____ the clot in order to facilitate wound closure and vessel patency
Retract
What laboratory tests are used to assess platelet concentration?
Blood Smear
Hematology analyzers
Spontaneous hemorrhage occurs when platelet numbers decrease below ______
20,000
What laboratory tests do we use to access platelet morphology?
Blood Smear
Hematology Analyzers
Increased MPV suggests increased ______
Thrombopoiesis
What does the presence of macrothromobocytes suggest?
Increased platelet production
What are the tests used in the clinical setting to evaluate platelet function?
Bleeding tests
*Buccal mucosal bleeding time or cuticle (toenail) bleeding time
What test do we use to access platelet production?
Bone Marrow Aspirate
*see if there are megakaryocytes or megakaryoblasts
In a thrombocytopenic patient, how should healthy bone marrow respond?
Production of Platelet precursors
*Megakaryocytes and Megakaryoblasts
What are the 5 mechanisms of Thrombocytopenia?
Production
Destruction
Sequestration
Loss
Consumption
Differential Diagnosis for Thrombocytopenia due to Loss of blood?
Hemorrhage
Two differential diagnoses for Thrombocytopenia due to Consumption of platelets
DIC
Vasculitis- ex. Ehrlichia and FIP
Differential Diagnosis for Thrombocytopenia due to Destruction
Immune-mediated Thrombocytopenia
Differntial Diagnoses for Thrombocytopenia due to Decreased Production
Bone Marrow Hypoplasia
Neoplasia- ex. Leukemia
Differential Diagnosis for Thrombocytopenia due to Sequestration
Splenomegaly
Splenic Torsion
Splenic neoplasia
Thrombocytopenia due to ______ is the only one that causes severe thrombocytopenia
Destruction
*Immune mediated thrombocytopenia
What are the two major mechanisms for Thrombocytosis?
Increased production
Increased distribution in plasma
What 4 diseases may cause reactive thrombocytosis?
Chronic inflammatory disease
Iron deficiency anemia
Chronic hemorrhage
IMHA
What 3 situations may cause reactive thrombocytosis?
Rebound from thrombocytopenia
Post-splenectomy
Excitement and exercise- splenic contraction
What mechanism is involved in Von Willebrands disease?
Decreased platelet adhesion
*Defects in the adhesion molecule that binds platelets during initiation of platelet plug- platelets float away and platelet plug is not formed
Von Willebrand is a carrier for Factor ____
VIII
True/False: In Von Willebrands disease the CBC will show a normal platelet count
True
In Von Willebrand disease, there will be a ____ bleeding time
Prolonged
What test would you run to confirm Von Willebrand disease?
Analyze Plasma for Von Willebrand Factor
What is the platelet associated bleeding pattern for Von Willebrand disease?
Prolonged Bleeding
What are the 4 Vitamin K dependent factors?
II, VII, IX, X
*KNOW THIS
What are the major blood systems in the dog?
Dog Erythrocyte Antigen (DEA)
Dal blood system
What are the two common DEA blood types in dogs?
DEA 1.1
DEA 1.2
*45% of population is DEA 1.1
What are the most antigenic blood types in the dog?
DEA 1.1
DEA 1.2
Do dogs have naturally occuring isoantibodies?
No
*1st exposure stimulates antibody production
What blood type is not always expressed in Dalmations?
Dal
*Ubituitous in all dogs except some dalmations lack the Dal antigen
What are the major blood systems in the cat?
The AB group system
The Mik system
Do cats have naturally occuring isoantibodies?
Yes
*All cats have naturally occuring alloantibodies
True/False: You shoud blood type all cats prior to transfusion
True
What Feline Blood type is associated with strong isoantibodies?
Type A
*Strong natural isoantibodies against type A. Do not give type A blood to a type B cat
True/False: It is okay to give type A blood to a type B cat
False
*cat will die due to strong antibodies against type A blood
True/False: You can give type B blood to a Type A cat without having a major reaction
True
*weak antibodies against type B blood
What are the 2 most antigenic blood types in the horse?
Aa and Qa
*implicated in neonatal isoerythrolysis
In a Major crossmatch, what is tested in the recipient and the donor?
Recipient- serum
Donor- Red Blood cells
Identifies antibodies against RBC antigens in the plasma of the recipient or donor
Crossmatching
When interpreting a crossmatch you should look for what two things?
Hemolysis
Agglutination
Whe performing a crossmatch, if there is agglutination it is a ____ crossmatch
Positive
No agglutination or hemolysis means you have a ____ crossmatch
Negative
If crossmatching comes back negative, due to no agglutination or hemolysis, the recipient is ____ to have a transfusion reaction from the donors Red blood cells
Not likely
In a crossmatch if agglutination or hemolysis are detected it is a _____ crossmatch
Positive
If a crossmatch comes back positive with agglutiation or hemolysis, the recipient is ____ for a transfusion reaction
at risk
*DO NOT TRANSFUSE
When a mare develops antibodies against the red blood cell antigens of her foal due to mating with a sire that has genes for offending red blood cell antigens
Equine Neonatal Isoerythrolysis
True/False: In neonatal isoerythrolysis the foal is born healthy but can become sick after ingestion of the mares colostrum
True
In what disease do foals ingest mares colostrum and absorb antibodies against their red blood cell antigens
Equine Neonatal Isoerythrolysis
Transfusion reaction that leads to mild extravascular hemolysis that occurs up to 3 weeks post-transfusion
Delayed hemolytic immune mediated reaction
Why might you get coagulopathy in a patient with liver disease?
Decreased synthesis of coagulation factors
Production of dysfuntional factors
*Leads to a tendency for BLEEDING
Syndrome caused by continued activation of coagulation and fibrinolysis
DIC
*disseminated intravascular coagulation
Syndrome that results in thrombosis of the microvasculature and depletion of coagulation factors leading to bleeding
DIC
How does the coagulation panel appear during the consumptive phase of DIC?
thrombocytopenia
prolonged PT and PTT
Increased FDP
*also decreased anti-thrombin and fibrinogen
The consumptive phase of DIC leads to _____
Bleeding
Phase of DIC that leads to thrombosis and organ dysfunction
Hypercoagulable
What type of bleeding patterns do you expect with DIC?
Petechia, Ecchymosis, GI bleeding
*Massive bleeding
DIC is caused by exposure of _____
Tissue factor
What type of bleeding pattern do you expect with Warfarin toxicosis?
Bleeding into thoracic cavity
Bleeding into Joint cavities
Bleeding into the brain
How does the coagulation panel appear for Warfarin?
normal platelet count
Prolonged PT and PTT
What 2 tests are used to access fibrinolytic activity?
Fibrin Degradation products
D-dimer
What are the two tests to access the intrinsic/common pathway? Which one is more sensitive
Activated Partial thromboplastin Time
Activated Clotting time
*Activated Partial Thromboplastin Time is more sensitive
What test is used to access the extrinsic/ common pathway?
Prothrombin Time
What test requires 70% deficiency of factor VII before prolongation is detected?
Prothrombin Time
*Extrinsic pathway
If the Prothrombin Time is prolonged, in the extrinsic pathway test, there is a _____ deficiency
Factor VII
What intrinsic pathway test requires 95% deficiency of the factor beore prolongation is detected
Activated Clotting Time
*Factor has to practially be wiped out
What two intrinsic pathway tests measure the time for fibrin clot formation?
Activated Partial Thromboplastin Time
Activated Clotting Time
What is the significance of a prolonged time with the Intrinsic pathway tests?
Deficiency of an Intrinsic or common pathway factor
*Could be any factor
How do you collect a sample for a coagulation test?
Clean Stick
*avoid collection from heparinized catheter
What tube do you use for collection of a sample for coagulation tests?
Sodium Citrate tube
When do you get falsely decreased platelet concentrations on the analyzer?
Clumping
Too big (macrothrombocytes)
Expression of which cofactor initiates coagulation?
Tissue Factor (Factor III)
What is the key factor that promotes amplification of secondary hemostasis?
Thrombin
During amplification, what four factors does Thrombin affect?
Va, VII, VIIIa, XI
What three factors contribute to coagulation efficiency?
Calcium
Factor V
Platelet Membrane
What coagulation factor has the shortest half life?
VII
Prior to ____ of a liver, you should screen for coagulation abnormalities
Biopsy
What are the 2 differentials for severe thrombocytopenia?
Immune mediated thrombocytopenia
DIC
How would you differentiate between DIC and Immune mediated thrombocytopenia on a CBC?
Immune mediated thrombocytopenia will have a lower platelet count
In Warfarin toxicosis, Warfarin inhibits _____ epoxide reductase
Vitamin K
*Warfarin inhibits the synthesis of Vitamin K. Vitamin K is needed for the blood to clot, therefore warfarin toxicosis leads to uncontrolled bleeding
What cofactor is required for antithrombin to inactivate thrombin?
Heparin
What are the two major end-products for fibrinolysis?
Fibrin Degradation products
D-dimers
