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Clinical Laboratory Sciences
Terms in this set (111)
Not bleeding (hemo = blood, -stasis = standing still)
Primary, secondary and fibrolysis
What are the three phases of hemostasis?
What is the main component of the primary phase of hemostasis?
Fibrin mesh (aka coagulation cascade)
What is the main component of the secondary phase of hemostasis?
Process to dissolve a blood clot
After the coagulation cascade
When does fibrinolysis occur?
What is the most important part of a platelet granule?
They play a role in initiation of the coagulation factor cascade
What role does platelets play in primary hemostasis?
Endothelial cells die and slough off causing the subendothelial collagen is exposed. Platelets come in and cover the denuded area so new endothelial cells spread out to replace lost ones.
What do platelets do in their normal daily maintenance role?
No, secondary hemostasis is not needed
Would secondary hemostasis occur after platelets perform their normal "daily" duties?
In larger injuries
When would secondary hemostasis be needed?
This is because the area of endothelium is very large or there is greater damage to the vessels.
The platelets aggregate and undergo several changes to initiate the coagulation cascade.
Why would secondary hemostasis occur after a large injury? What do the platelets do to initiate secondary hemostasis?
How many days does it take from stimulation of the megakaryoblast to produce platelets?
How many days do platelets normally circulate for?
Splenic, hepatic and marrow macrophages
What are platelets removed by?
2/3 of platelets are circulating
1/3 of platelets are in the spleen
In a healthy resting state how are the platelets distributed between circulation and the spleen?
Splenomegaly, blood then pools in the splenic sinusoids, causing the platelets to be sequestered leading to thrombocytopenia
What would happen if the blood is sequestered in the spleen?
Abnormal platelet function
What are the three categories of platelet disorders?
Petechia, ecchymosis and epistaxis
What would be seen with severe thrombocytopenia (<20,000/uL)?
S - sequestration/spurious
P - decreased production
U - increased utilization (consumption)
D - increased destruction
What mechanisms can cause thrombocytopenia?
No, it is not common
Regarding thrombocytopenia, is sequestration common?
Yes, it is common
Regarding thrombocytopenia, is spurious common?
Mild to moderate severity
Normal sized platelets
no evidence of bleeding problems
What are some characteristics for sequestration? (thrombocytopenia)
Delayed sample handling
What are some characteristics for spurious? (thrombocytopenia)
Platelets and MPV usually are small
Bone marrow aspirate reveals decreased or absent megakaryocytes
Spleen is normal size
What are some characteristics of decreased production? (thrombocytopenia)
Immune - injury to megakaryocytes
Adverse drug reactions
Idiopathic marrow failure
What are some diseases or mechanisms that cause decreased production? (thrombocytopenia)
What diseases or disease processes are relative to myelophthisis?
Disseminated Intravascular Coagulation (DIC)
What disease is associated with platelet utilization (consumption)? (thrombocytopenia)
No, it is a syndrome of a disease
Is DIC a disease?
Have to treat underlying disease process to have resolution
How do you treat DIC?
Widespread activation of hemostasis; consumes platelets and coagulation factors
What happens during DIC?
Regarding thrombocytopenia, is decreased production regenerative or non-regenerative?
Yes, they are usually regenerative. MPV will be increased and a bone marrow aspirate will reveal adequate or increased numbers of megakaryocytes.
Regarding thrombocytopenia, are destruction and utilization (consumption) regenerative?
What are some diseases or mechanisms that may cause platelet destruction? (thrombocytopenia)
Same mechanisms as immune-mediated anemia; platelets coated with antibodies are removed from circulation by macrophages
What happens during immune-mediated thrombocytopenia?
Increased platelet production
What is thrombocytosis?
Yes it is common, but usually has no clinical significance
Is thrombocytosis common?
Excitement (splenic contraction due to epinephrine release)
Megakaryocytic or megakaryoblastic anemia (rare)
What are some mechanisms when thrombocytosis can occur?
Von Willebrand Disease
What disease is associated with inherited platelet dysfunction?
Uremia or drugs (aspirin)
What diseases are associated with acquired platelet dysfunction?
A protein produced by endothelial cells
What is the Von Willebrand factor (vWF)
Found in plasma and attached to collagen of the subendothelium
Where is the vWF found?
vWF is exposed, platelets then attach to collagen via vWF and platelets are activated.
What happens when subendothelium is exposed?
Recruits more platelets to the site and links them together using another receptor.
What happens after platelets are activated?
The covering of platelets allows new endothelium to grow under the platelet "blanket"
What do platelets allow for when linking together?
No adhesion of platelets to subendothelium and bleeding is prolonged
What is the result of Von Willebrand disease?
Platelet counts - manual (rarely done) or automated, both must be confirmed by blood film evaluation (platelet estimate)
Platelet estimate - done by looking at the blood film, reliable, not precise, will identify clumped platelets
Buccal mucosal bleeding time (BMBT) - test of primary hemostasis, measure of time to bleeding ceases
What are some ways to evaluate platelets in a laboratory setting?
Thrombocytopenia - test is contradicted
Thrombopathia (platelet dysfunction) - hereditary/acquired
Von Willebrand's disease
What would a prolonged BMBT tell you?
Platelet membrane phospholipid
What is essential for activation and maintenance of the coagulation phase?
Deep hematoma formation
What are some clinical signs of defects in the coagulation cascade?
Blood accumulation in the pleural space
What is hemothorax?
Blood accumulation in the peritoneal cavity
What is hemoabdomen?
Bleeding into the joint cavity
What is hemarthrosis?
A deep hematoma formation
What is shown in the picture?
What is shown in the picture?
What arm of hemostasis, primary or secondary, occurs early on?
Formed by the cleavage of fibrinogen, then polymerized
Plasma protein produced in the liver
What is fibrinogen?
Platelet membrane phospholipid or exposure to collagen
What starts the process of polymerization?
Sequential interaction of clotting factors
What continues the process to form fibrin?
Forms a mesh around platelets and the two become a clot
What does fibrin do?
Activation of factor XII (12)
What does the intrinsic system start with?
Initiated in vivo - collagen, platelet phospholipids and endotoxins
Initiated in vitro - glass or clay compounds
What initiates the activation of factor XII (12)?
What prevents initiation of the intrinsic system?
Which factor in the intrinsic system participates in several positive feedback loops to drive a burst of activation?
Results in polymerization of fibrin by thrombin
What occurs after the intrinsic system or extrinsic system activates the common system?
All are in the plasma
Where are the initiators in the intrinsic pathway?
Tissue thromboplastin (factor III)
What initiates the extrinsic system?
Phospholipid membrane released by injured tissues/cells
What is factor III?
Factor VII - a plasma protein
What does factor III activate?
Generates fibrin from fibrinogen
Promotes platelet aggregation
Activates coagulation factors
Activated inhibitors of fibrinolysis
Describe thrombin's "pro-thrombotic role" in hemostasis
In high local concentration - degrades activated clotting factor
Describe thrombin's "anti-thrombotic role" in hemostasis
Citrate - binds to calcium
What additive is in a blue top tube to prevent clotting?
APTT and ACT
What tests are used to detect problems in the intrinsic system?
APTT, ACT and PT
What tests are used to detect problems in the common system?
What test is used to detect problems in the extrinsic system?
What test is used to detect problems in the last part of the common pathway (fibrinogen to fibrin)?
Because fibrin is digested by the enzyme plasmin to break down blood clots
Why don't we turn into a giant blood clot?
At the same time as coagulation
When is plasmin formation initiated?
Breaks polymerized fibrin or fibrinogen down to fibrin(ogen) degradation products (FDPs)
What does plasmin do?
In tissue injury
When do FDP's increase?
By the liver
What are FDP's removed by?
When do you see an increase in FDP's?
How are test results for FDPs reported?
Inflammation, internal bleeding, decreased clearance (liver disease)
When do we commonly see a mild increase (1:5) in FDP's?
Common in DIC
When do we see a marked increase (1:20) in FDP's?
What is another test for FDP's?
Unlike FDP's, D-Dimers do not ________________ with breakdown of fibrinogen, only with _____________.
It is more specific for DIC than FDPs
Because the D-Dimer test only increases with fibrin, what syndrome is it more specific for?
Dogs and horses
What species are D-Dimer tests commonly used for?
Factors II, VII, IX and X
What factors do rodenticides inhibit?
EDTA, it binds to calcium and is irreversible
What additive does a purple top have that would make it unfit to use for coagulation testing?
When there is sufficient antithrombin III (ATIII)
When will heparin inhibit clotting?
Almost all coagulation factors, especially thrombin
What does antithrombin III inhibit?
In the liver
Where is ATIII produced?
What does decreased ATIII activity promote?
DIC, sepsis, heparin therapy
ATIII deficiency is seen with increased utilization (consumption) such as....
ATIII deficiency is seen with decreased production such as....
ATIII deficiency is seen with increase loss such as....
Factor VIII, IX
What inherited factor deficiencies in the intrinsic system are most commonly seen?
Dogs, cats, horses, cattle
What species are factor VIII deficiencies most commonly seen in?
Dogs and cats
What species are factor IX deficiencies most commonly seen in?
Hemophilia A is associated with factor _____
Hemophilia B is associated with factor _____
Factor VII (7) deficiencies with minimal bleeding.
What inherited factor deficiencies in the extrinsic system are seen?
What species has seen factor VII deficiency?
Prolonged aPTT and ACT, with a normal PT
Individuals with a factor VIII (8) and IX (9) defect will show what on their laboratory findings?
Prolonged PT, normal aPTT and ACT
Individuals with a factor VII (7) defect will show what on their laboratory findings?
False, they effect more than one
T/F Acquired coagulation abnormalities effect only one arm of the coagulation cascade
Factors II, VII (7), IX (9) and X (10)
What factors can be decreased with vitamin K deficiency or warfarin poisoning?
Prolonges PT, aPTT and TT
What are some consequences of DIC?
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