Hemostatic Disorders Flashcards
What is primary hemostasis
Platelet plug formation
Steps of primary hemostasis (3)
1) Platelets adhered to exposure vWF on subendothelial collagen
2) Platelets release ADP
3) Platelets aggregate - release factors for binding
Receptors involved in platelet aggregation
GpIIa/IIIb or CD41/CD61
What is an important co-factor in secondary hemostasis
CALCIUM
What is secondary hemostasis
Fibrin clot formation
What happens in extrinsic pathway
1) Tissue Factor released from damaged cells 2) TF binds with plasma factor VII –> TF-VIIa
Factors in extrinsic pathway
TF and VII (Ca required)
What happens in intrinsic pathway
1) Exposed collagen binds and activates plasma factor XII 2) XII activates enzymatic cascade leading to Prothrombin Activator Complex
Which factors are involved in intrinsic pathway
XII, XI, IX, VIII
Factors in common pathway
X, V, II, I, XIII
Vitamin K factors
II, VII, IX, X
Sources of vitamin K
Diet Bacteria
Where is vitamin K needed as a co-factor
Liver
Causes of hemorrhage: vessels
1) Rhexis (bursting)
2) Trauma, inflammation, infection, endotoxin, type III hypersensitivity, collagen disorders, vitamin C deficiency
Causes of hemorrhage: platelets
1) Decreased production
2) Decreased function
3) Destruction (immune mediated thrombocytopenia - IMT)
4) Consumption (DIC)
Causes of hemorrhage: coagulation factors
Inherited deficiencies Acquired defects
Hemorrhage that is <3mm is
Petechial
Hemorrhage >1cm is
Ecchymosis
Petechial hemorrhage is caused by
Diapedesis
Ecchymosis is caused by
Damage to capillary beds
Inherited factor deficiencies (4)
II (Prothrombin) - affects dogs.
- Mild bleeding in adults
- Epitaxis and umbilicus bleed in puppies
VII - affects dogs
- Mild, more easily bruised
IX (hemophilia B) - affects dogs, cats, rarely horses
- Variable severity
- Severe in large dogs
X - affects cats and dogs
- Severe bleeding!
Acquired coagulation factor defects
Decreased production due to:
1) Severe liver disease
2) Vit K deficiency (deficiency of II, VII, IX, X, proteins c and s)
What causes acquired vit k deficiency
Moldy sweet clover
Warfarin
Sulaquinoxaline
What binds a heparin-like molecule on platelets, and inhibits factors IIa, Xa, and IXa on active site
Antithrombin III
What inactivates TF-VIIa complex of extrinsic pathway
TFPI
What inhibits factors Va and VIIa
Protein C/S (activated by IIa)
What do endothelial products inhibt
Platelets
What does tissue plasminogen A do
Activates fibrinolysis
List the antithrombotic mechanisms
1) Antithrombin III
2) TFPI
3) Protein C/S (vit K dependent)
4) Endothelial products
5) tpA
Whats a persistent thrombus in vessel lumen called
Thromboembolus
Whats a thrombus in the heart called
Mural thrombus
Causes of thrombus formation (4)
1) Reduced blood flow (cardiac insufficiency, hypovolemia, obstructions)
2) Turblent blood flow
3) Hypercoagulability (production of procoagulations, DIC, inflammation)
4) Endothelial injury, activation
A saddle embolism is a
Arterial thromboemboli
What are arterial thromboemboli usually caused by
Aortic thrombi dislodging and settling at a birfucation downstream
You find a pale, white emboli. Its likely a…
Arterial thromboemboli
You find a thrombus that is dark red and gelatinous. It’s likely a…
Venous thrombus
Venous thrombi formation
Blood stasis / slow blood flow They are large numbers of RBCs that are loosely incorporated due to slow blood flow
Where are venous thrombi typically found
Pulmonary veins
Which type of thrombi can result in pulmonary infarcts or right-sided heart failure
Venous thrombi
Which type of thrombi is common in cats with cardiomyopathies
Arterial thromboemboli
You see a thrombus that is yellow. What is it? Which part of the body are you likely in?
Postmortem thrombus Typically in heart, vessels
Steps of thrombolysis
1) Plasminogen binds to clot
2) Tissue plasminogen activator released from endothelium or ECM and binds to clot
3) Plasminogen —> Plasmin
4) Plasmin degrades fibrin, fibrinogen, Va, VIIIa, vWF, HMWK
5) Clot dissolves, leaving fibrin degradation products
How do larger, persistent thrombi dissolve? What can occur after?
By phagocytosis Granulation tissue forms after
Mural/occlusive thrombi are dissolved how?
Invaded by FIBROBLASTS Recanalization: form new vascular channels, providing alternative blood through and around the thrombus
What are the risks of recanalization
Increased blood turbulence at site of mural thrombus —> risk of more thrombi!
3 ways to remove a thrombus
1) Thombolysis
2) Phagocytosis
3) Fibroblast/recanalization
