Hem 5 - Platelets and Hemostatis Flashcards
platelets - what are they formed by, what do they look like, what do they form, what do they participate in
-Formed by cytoplasmic fragmentation of megakaryocytes in the bone marrow
-Small disc-shaped structures, no nucleus, scattered cytoplasmic
granules
- Granules contain several substances that are important for
hemostasis (e.g. ADP, serotonin, thromboaxane, histamine, fibrinogen
that promote contraction of nearby platelets or assist in thrombus formation.)
- Also: Factors involved in wound healing - PDGF, TGF-β
-Form “plugs” – seal defects in damaged vessels rapidly
- Also participate in inflammation (and can clump at
inflammatory sites)
how long is maturation for platelets
2-5 days
platelet kinetics - what is involved in regulation, circulation, pools, clearance
-Production and maturation regulated by Thrombopoietin and IL-11
-Circulate for about 10 days
-Sizeable splenic and non-splenic (bone marrow, lungs, liver) pools
-“Old” platelets are cleared by macrophages
platelet function - hemostasis (what is it, what does it involve, end result)
-Hemostasis is a complex and highly regulated process in which platelets aggregate and specific coagulation
factors are sequentially activated causing polymerization of fibrin, resulting in a local change in blood from a fluid to a solid state to prevent blood loss.
-Involves interactions between blood vessels, platelets and coagulation factors that are involved in the formation and subsequent dissolution of blood clots
primary vs secondary vs tertiary homeostasis
primary = formation of the hemostatis platelet plug
secondary = stabilization of the platelet plug by fibrin clot
tertiary = dissolution of the fibrin clot
primary hemostasis - life span, what happens when increased blood flow
- Primary hemostasis is short lived.
- If the blood flow is increased, the soft plug could be sheared from the injured surface, possibly creating emboli and allowing hemorrhage to re-start.
hemostasis - what prevents it in normal conditions
In normal physiological conditions, hemostasis is prevented by the
endothelium that acts as a physical barrier and secretes platelet inhibitory products, such as prostacyclin (PGI2) and nitric oxide
what happens when platelets are activated
When activated, they become sticky and contract (collapse inward) - growth factors from within are released, recruiting nearby platelets to do the same!
what is the first thing that happens after damage that leads to events of primary hemostasis
- Vasoconstriction to decrease blood flow and diminish blood loss
Vessel spasms! Squeezes down to decrease blood flow to the site of injury
Then, collagen, basement membrane, and other layers of sub epithelium is exposed to blood cells (which never see these proteins)
what happens with vessel injury and von willebrand factor
With vessel injury, platelets adhere to von Willebrand factor (vWf) in the
subendothelium via the platelet membrane receptor GPIb-IX.
Primary Hemostasis
vWf attracts platelets and they all stick to it - never seen by platelets in bloodstream b/c subendothelium
(Causes contraction via actin to release serotonin, ADP, and Thromboxane. Likely also sticking to collagen and all sorts of other proteins)
what leads to the formation of the platelet plus that suppresses blood loss
- Serotonin released by platelets maintains vasoconstriction
-ADP attracts more platelets to the area
-Thromboxane A2 promotes platelet aggregation, degranulation, and vasoconstriction
problems in primary hemostatis = petechia - what leads to it, what do we see it with
-Low numbers or functionally abnormal platelets are associated with primary hemostasis problems – these lead to petechial hemorrhages (petechia)
-seen with = Low Platelet
Number, Abnormal Platelet
Function, Absence of (or
abnormal) von Willebrand factor
(vWf) (also called “Factor VIII related
antigen”)
tests for primary hemostasis - normal counts for different species , what do you need to consider if counts above that but petechia is seen
-platelet number and function:
- Normal dogs and cats should have platelet counts of >200,000/μl
- Normal horses and cows should have platelet counts of >100,000/μl
- Bleeding, that can attributed solely to thrombocytopenia, does not actually occur unless platelet counts are < 30,000/μl
-If counts are above that, but petichiae are seen, consider:
- Measurement of platelet adhesion
- Platelet aggregation tests
secondary hemostasis - what happens at this step, what is it defined as, what does it involve
- Secondary hemostasis is defined as the generation of fibrin through the coagulation cascade.
- This involves soluble circulating coagulation factors,which act
as enzymes [which require activation] and cofactors (calcium and platelets/platelet membranes)
secondary hemostasis - basic events, whatare the enzymes called, cascades
- The basic events of secondary hemostasis involve the activation of specific enzymes in one of two different sequential cascades that lead to polymerization of fibrin and
filling of the vascular defect by consolidating the platelet plug.
-The enzymes are called clotting factors, they commonly require calcium and phospholipid as co-factors.
-The two different cascades are called the “contact” (intrinsic) and “tissue factor” (extrinsic) pathways. These pathways converge at a “common” pathway which leads to fibrin formation
