Coagulation & dissolution of a blood clot Flashcards
Steps to blood clotting (general)
Vasoconstriction, platelet aggregation, clot strengthening, and clot dissolution
Normal hemostasis for coagulation is
a balance between generation of hemostatic clots and uncontrolled thrombus formation
The extrinsic pathway is
plasma mediated, initiation of hemostasis
AKA: primary hemostasis
key: tissue factor
The intrinsic pathway
amplifies and propagates hemostasis
AKA- secondary hemostasis
Key: thrombin
The common pathway results
in an insoluble fibrin clot
Preoperative coagulation testing should be based on
patient’s history and planned surgery
patient’s history is why you should check lab values
Agents that impact the coagulation cascade include
antiplatelets, anticoagulants, thrombolytics, procoagulants
There are more than ____ substances that affect blood coagulation
50
At normal homeostasis, _____ predominates but when a vessel is ruptured, _______ are activated
anticoagulants; procoagulants
Fibrinolysis is
the orderly breakdown of a stable blood clot
Hemostasis is regulated by interactions between
the blood vessel walls, circulating platelets, and clotting proteins in the plasma
Normally, vascular endothelium provides a
non-thrombogenic surface- antiplatelet or profibrinolytic surface
Damage to the endothelium exposes
the underlying extracellular matrix and elicits a contraction (vasoconstriction)
Thrombin, hypoxia, and high fluid sheer stress can
also induce prothrombotic endothelial changes
When platelets are exposed to the extracellular matrix in damaged endothelium they undergo
a series of biochemical and physical alterations
adhesion, activation, and aggregation
Normal concentration of platelets is
150,000-400,000 per microliter
spontaneous bleeding <50,000 micrograms/L
Lethal <10,000 micrograms/L
The life of a platelet is
8-12 days
Platelets are formed in
the bone marrow
A thrombocyte is a
thrombus/clot+ cells
Platelet adhesion occurs due to
exposure to subendothelial matrix proteins allows platelets to undergo a conformational change to adhere to the vascular wall
Von willebrand factor is produced in the
endothelium and platelets
vWF is released by
endothelial cells and by activated plateletes
vWF’s primary function is to
bind other proteins
it is particularly important as a bridging molecule between the subendothelial matrix and platelets forming a cross links
glycoprotein IIb/IIIa; glycoprotein Ib/factor IX/factor V receptor complex
The GPIb-V-IX complex binds
von Willebrand factor, allowing platelet adhesion and platelet plug formation at sites of vascular injury
Absence of GP1b-V-IV receptor is known as
Bernard Soulier syndrome
Von Willebrand factors is mainly activated in conditions of
high blood flow and shear stress
Deficiency of vWF shows primarily in
organs with small vessels such as skin, GI, and uterus
Von willebrands disease is diagnosed by
measuring the amount of vWF in a vWF antigen assay and the functionality of vWF with binding assays
factor VIII is also measured
Type 1 vWD is a
failure to secrete vWF into circulation or vWF being cleared more quickly than normal; mild, often undiagnosed until bleeding following surgery, easy bruising, or menorrhagia
Type 2 vWD is a
qualitative defect and bleeding varies- decreased ability to bind to GPib
decreased ability to bind to VIII
Type 3 vWD is
most severe, homozygous defective gene, complete absence of production of vWF
leads to extremely low levels of VIII since it does not exist to protect VIII from proteolytic degradation
Platelet type Von Willebrand disease is
a defect of the platelet’s GPIb receptor
vWF is normal, the platelet receptor GPIb is abnormal
We need to figure out which type of Von Willebrand’s disease they have in order to
know how to treat them
What medications are GPIIb/IIIa inhibitors?
considered a class of antiplatelets; includes abciximab, integrilin, and aggrastat
GpIIb/IIIa inhibitors work by
blocking the ability of fibrinogen to form around the aggregated platelets
as a result, no fibrinogen bridging of platelets to other platelets can occur
Platelet activation causes platelets to
develop pseudopod-like membrane extensions to increase platelet surface area
Platelet recruitment occurs when
platelets release granular contents resulting in recruitment and activation of additional platelets
Medications that are thromboxane A2 inhibitors include:
aspirin- inhibits the ability of COX enzyme to synthesize the precursors of thromboxane within platelets
Naproxen- nonselective COX inhibitor
P2Y12 receptors further amplify
the response to ADP and draw forth the completion of aggregation
ADP receptor antagonist medications include:
prodrugs: ticlopidine, clopidogrel (Plavix), and prasugrel (Efient)
direct acting: ticagrelor (brilinta) and cangrelor (kengrexal)
_____ completes the formation of a platelet plug
platelet aggregation
Activators released during the activation phase
recruit and amplify the response of additional platelets to the site of injury
Newly activated glycoprotein IIb/IIIa receptors on the platelet surface bind
fibrinogen to provide for cross-linking with adjacent platelets
The key step in blood clotting is
the conversion of fibrinogen (I) to fibrin (Ia) by thrombin (IIa)
Soluble fibrinogen is converted to
insoluble fibrin
Following platelet adhesion, activation, and aggregation, the
blood clot begins to form
the plasma protein fibrinogen breaks down to produce fibrin which becomes cross-linked into a stable mesh
coagulation factors are then activated and initiate the coagulation cascade
The classic description of coagulation includes initiation of
the coagulation cascade via the intrinsic or extrinsic pathway
The intrinsic pathway is triggered when
blood contacts a negatively charged surface (i.e. exposed subendothelial collagen)
The extrinsic pathway is activated when
blood contacts cells outside the vascular endothelium
-nonvascular cells express a membrane protein called tissue factor (III) which initiates this pathway
The common final pathway is where
the intrinsic and extrinsic pathways converge with the activation of factor X
Most coagulation factors are _____ with some exceptions_____
enzymes; vWF and tissue factor (III) are glycoproteins)
Most coagulation factors are synthesized
via the liver except for calcium (IV) comes from diet & von Willebrand is synthesized in endothelial cells and platelets
Factors ___, ____, ___, and _____ are Vitamin K dependent for utilization
II, VII, IX, and X
The intrinsic pathway of coagulation begins with
damage to the blood vessels themselves
Formation of the primary complex on collagen and thrombin generation by way of factor
XII and ultimately merges to the common pathway and activates factor X
The intrinsic pathway is also known as the
contact activation system
The extrinsic pathway is also known as the
tissue factor pathway
The extrinsic pathway is the initial step in
plasma-mediated hemostasis
Following damage to the blood vessel,
factor VII comes into contact with tissue factor and forms an activated TF-VIIa complex
The TF-VIIa circulating the plasma activates
factor X to promote the conversion of X to Xa
The common pathway of coagulation depicts
thrombin generation and subsequent fibrin formation- prothrombin II is cleaved by activated factor X to produce thrombin IIa
Factor X takes
prothrombin and turns it into thrombin
Prothrombin gets activated to
thrombin
Thrombin activates
fibrinogen to form fibrin
Fibrin creates
covalent bonds and cross-linking of fibers create a meshwork in all directions of blood cells, platelets, and plasma which adhere to the surface of damaged blood vessel
After a clot is formed, the
actin and myosin of the platelets trapped in the fibrin mesh interact in a manner like that in muscle contraction
Clot lysis occurs when
plasminogen (normally found in the blood) is activated to plasmin
Tissue plasminogen activator
is released from the tissue, vascular endothelium, plasma, and urine to activate clot lysis
Plasmin is an
enzyme which digests fibrin fibers, fibrinogen, Factor V, Factor VIII, prothrombin, and factor XII
Exogenous plasminogen activators such as
streptokinase are used clinically to dissolve intravascular clots
Thrombolytics are
more capable of dissolving newly formed clots (platelet rich and weaker fibrinogen bonds)
-older clots have more cross-linking and re more compacted= more difficult to dissolve
Thrombolytics possess inherent
fibrinolytic effects or enhance the body’s fibrinolytic system by converting endogenous pro-enzyme plasminogen to the fibrinolytic enzyme plasmin
Prothrombin time evaluates the
evaluates the extrinsic pathway
sensitive to factors II, VII, and X
Partial thromboplastin time indicates the
indicates the performance of the intrinsic pathway
ACT is
reliable for high heparin concentrations
influenced by hypothermia, thrombocytopenia, and coagulation deficiencies
Visoelastic testing
TEG & Rotem- global assay for whole blood clotting including coagulation factors, inhibitors, anticoagulant drugs, platelets, and fibrinolysis
Platelet function tests
involve centrifugation of platelet blood to obtain platelet-rich plasma
Heparin concentration measurements
increasing concentrations of protamine are added to samples of heparin containing blood and time to clot is measured
Bleeding time
incision is made on the forearm and the amount of time it takes for bleeding to stop is recorded
ACT normal value
80-150 seconds
Fibrinogen normal value
> 150 mg/dL
aPTT normal values
25-35 seconds
Thrombin time normal values
<30 seconds
INR normal values
0.9-1.2
Prothrombin time normal values is
12-14 seconds
Bleeding time is
3-10 minutes
Platelet count is
150,000-400,000
