Hemostasis Flashcards
what are the 4 components of hemostasis?
- Primary hemostasis (vasoconstriction, primary platelet plug)
- Secondary hemostasis (clotting cascade)
- Fibrinolysis (control clot size)
- Wound healing
What are the three key components of primary emostasis?
- vessels –> vasoconstriction
- von Willebrand factor
- Platelets
Endothelium can do two things, what determines their function?
Normally anticoagulant - inhibit platelet aggregation
Pro-coagulant upon traumatic stimulation
von Willebrand factor is a __________ agent
Cross linking
What makes vWF?
Endothelium
Megakaryocytes
Platelets (alpha granules)
What is vWF function?
cross links activated platelets
cross links platelet to collagen
binds and stabilizes factor VIII (circulates as a complex)
What stimulates the vasoconstriction in primary hemostasis?
endothelial damage –> immediate local reflex of vasoconstriction
How is the vasoconstriction maintained?
activated platelets - TXA2
Tissue factor
Coagulation by-products
What does TXA2 do?
vasoconstrictor and potent platelet aggregator
What opposes the function of TXA2?
PGI2 (prostacyclin) and Aspirin (irreversibly blocks formation of TXA2 by platelets)
What are the platelets 4 major steps during primary hemostasis?
- Rolling
- Adhesion and shape change
- Secretion of granule content
- Aggregation
What may interfere with platelet rolling?
Anemia - platelets go to center of vessel
Normal blood flow encourages margination
What are essential for platelet adhesion?
vWF and gp1b/IXa (vWF receptor on platelet)
vWF is essential for adhesion to subendothelium (collagen)
What does the shape change of a platelet do during primary hemostasis?
exposes occult membrane receptor and leads to expulsion of contents
What are the granules in a platelet?
Alpha granules
Dense granules
What is in an alpha granule?
- Adhesion proteins (vWF, fibrinogen, thrombospondin)
- Growth modulators (PF-4, TGF beta, thromboplastin)
- Coagulation factors (V, XI, HMWK, fibrinogen)
What are in dense granules?
Energy and signaling (ATP, ADP, calcium=factor V, serotonin, and histamine)
What are two aggregation linkers?
vWF
fibrinogen (platelet to platelet)
What are two aggregation receptors?
gp1b/IXa
gp2b/IIIa
What is factor I, V, XII, and III?
I - fibrinogen
V- Ca
XII - Haegman factor
III - Tissue factor
What would we test if we were concerned about a primary hemostasis problem?
Vessels, platelets, or vWF
Signs/physical exam findings of primary hemostasis.
- Petechiation (not common with vWD)
- Ecchymoses
- Body surfaces
- Mucosal bleeding (epistaxis, GI, Hematuria)
- Cutaneous bruising
- Prolonged wound bleeding/oozing (tooth extraction or venipuncture)
What 4 mechanisms are considered for primary hemostasis?
- Thrombocytopenia
- Vasculopathies (vessels)
- von Willebrand Disease (linking)
- Thrombopathies (defective function) or thromboasthenias (weak adhesion to platelets)
What are the four main mechanisms for thrombocytopenia?
Sequestration
Production
Utilization
Destruction
What are three organs contributing to thrombocyte sequestration?
Spleen
lung
liver
What are the 6 important features of DIC?
- Thrombocytopenia
- Prolonged PT
- Prolonged PTT
- Decreased ATIII
- Schistocytes
- Increased FDP or D-dimers
What is the normal platelet life span for dog, cat, and other?
Dog: 5-7 days
Cat: 1.5 days
Other: 5-8 days
If there were platelet counts < 20,000 what would you think it could be?
Primary Immune mediated thrombocytopenia (ITP)
“Destruction”
What could cause infectious vasculitis?
- Rickettsia
- Parasitic (heartworm)
- Gram negative bacteria
- Viral
- Leishmaniasis
What is the #1 inherited hemostasis disease?
vWD
What are three key altered functions in vWD?
- platelet adherence –> defective platelet plug
- Platelet aggregation –> defective platelet plug
- Stabilization of Factor VIII –> may have prolonged aPTT
What are the different types of vWD?
Type I: Most mild bleeding tendencies. Doberman Pinscher #1 breen predisposed. Decrease in total numbers.
Type II: Moderate severity. Decrease in larger multimers. German shorthair pointers
Type III: Lethal. Severe bleeding tendencies. No or small amounts of vWF. Scottish terrier, Chasapeake Bay Retriever.
What tests are run to look for vWD?
BMBT
aPTT
When someone says Aleutian mink, you say ___________
Chediak Higashi Syndrome
What is Chediak Higashi Syndrome?
Granule disorder - lack dense granules in platelets. Also a disorder in other cell types (neutrophils) making it a systemic condition
What cat breed is #1 for chediak Higashi Syndrome?
Persian
What is Glanzmann Thrombasthenia?
Aggregation disorder: gpIIb/IIIa
What diagnostic tools do you use for primary hemostasis?
General baseline (CBC, chem, U/A) Platelet # (blood smear is best) BMBT (platelets, vessels, vWF) vWF:Ag \+/- clot retraction
What is the purpose of a clot retraction?
tests selected platelet functions (cross linking and fibrinogen)
Grade 1+ - 4+
4+ is most retraction and ideal
2-3+ is compromised function
1+ almost no retraction - ineffective
T/F
clot retraction time is affected by vWF
False
what does the BMBT test for?
evaluates primary hemostasis
cut isnt deep enough to stimulate any fibrin
normal BMBT
< 4.0 minutes in anesthetized and non ansthetized dogs
< 3.3 in cats
is the BMBT normal in animals with secondary hemostasis issues?
yes
When is it safe to say there is vWD based on the BMBT?
When it is prolonged in a Doberman with unknown vWf:Ag
vWf:Ag concentrations < 20%
Clinical defects for secondary hemostasis problems
Large SQ hemorrhage Large hematomas Hemarthrosis Deep muscles Cavitary hemorrhage
What factors are in the extrinsic pathway?
TF and VII
What factors are in the common pathway?
X
V
Thrombin (II)
Fibrinogen (I)
What factors are in the intrinsic pathway?
XII
XI
IX
VIII
What human error can cause an error in clotting times?
A bad stick (activates TF b/f we test)
Sample from catheter (heparin flushes are used)
What tube is use to take samples for clotting times?
Blue top (citrate)
What should the anticoagulant to blood ratio be? Why is this ratio so important?
1:9
The test adds Ca to the sample so we need to make sure there is the set amount of Ca in there that the test is expecting
T/F
Always use a vacutaner to collect samples for clotting times
True
What does the PT look at?
Extrinsic and common pathway
TF, VII, X, V, thrombin, fibrinogen
What does the aPTT look at?
Intrinsic and common pathway
IX, XI, XII, VIII, X, V, thrombin, fibrinogen
What does the ACT look at? What does ACT stand for?
Intrinsic and common pathways
Activated clotting time
What does RVVT stand for? What does it test?
Russell viper venom test
Common pathway
What does TT test stand for? What does it test?
Thrombin time
Testing fibrinogen!!!!! You need thrombin to convert fibrinogen
What does a prolonged TT value mean?
Due to decrease or abnormal fibrinogen or reaction inhibitors
When will the PT or PTT be prolonged?
with < 30% normal factor quantity
What % of factor quantity needs to be reached to cause prolonged ACT?
< 5% of normal quantity
What is required to do an accurate ACT? What sample type is used?
platelets >10,000
whole blood in ACT tube
How is the ACT calculated? What is unique about this test?
How long it takes to form a clot
Does not have phospholipid in this test. It relies on the phospholipid on the platelet surface.
What are some factors (3 major) that contribute to anticoagulation? What is the sequelae to each step.
- ATIII + Heparin: ATIII alone won’t do much –> inactivates thrombin and X + others
- Thrombomodulin + thrombin –>activates protein C + reduces thrombin availability –> proteolysis of V and VIII
- Edothelial secretions (PGI2, NO, ADPase) –> vasodilation, inhibition of platelet aggregation
What do endothelial cells produce?
vWf tPA PG-I (prostacyclin) NO ADPase
Why shouldn’t FDPs be used alone in dx DIC? What is more suggestive of clot formation
FDP can be from increased fibrinogen during inflammatory disease
D-dimers
What are D-dimers?
Fragments of cross -linked fibrin in a clot
What are the vitamin K dependent clotting factors?
II (thrombin), VII, IX, X, Protein C, and Protein S
T/F
There are no known tissue factor deficiencies
True
What is Hemophilia A?
deficiency in Factor VIII
Most common inherited coagulopathy
< 2% VIII - spontaneous bleeding and bleeding with minor trauma
What is Hemophilia B?
Deficient in Factor IX
Less common than hemophilia A
To remember: think “B9”
What happens with Factor XII deficiency? What is the other name for this factor?
XII activates plasminogen
Thrombosis: do not exhibit bleeding tendencies
Hageman factor
What animals naturally lack F XII?
Bird
Reptile
Marine mammal
Why does liver disease contribute to prolonged PT and aPTT?
Decreased synthesis of coag factors and inhibitors
Diminished absorption of fat soluble vitamin K
What may cause Vitamin K antagonism?
Rodenticide: Warfarin, pindone, bromadiolone, brodifacoum
Coccidiostat - sulfaquinoxaline
What does early vitamin K antagonism look like? Late?
Early: prolonged PT (extrinsic) due to decrease VII
Late: prolonged PT and PTT due to decrease II, IX, X
What are at least 7 problems that DIC can happen secondary to?
Neoplasia obstetric problems Shock Trauma Heat stroke Snake bite Pancreatitis IMHA Infections (viral, bacterial, protozoal, parasitic)
What are the three triggers for DIC?
- Tissue factor activation –> extrinsic path (trauma, Inflammation)
- Endothelial damage –> intrinsic path, platelets
(toxins - hypoxia - acidosis) - Direct cascade activation (venoms)
DIC laboratory findings
Thrombocytopenia Schistocytes Prolonged aPTT and PT Decrease in fibrinogen (except horses) Increased FDPs and/or D-dimers Decreased ATIII
What is the DIC pathophysiology?
Simultaneous activation of coagulation and fibrinolysis (+platelet consumption)
- Microvascular fibrin formation
- Thrombosis (block - ischemic damage- necrosis)
- Hemorrhage (consume and deplete clotting factors)
