Coags Flashcards
Intima factors
endothelial layer
vwf
tissue factor
prostacyclin
no
media factors
subendothelial layer
collagen
fibronectin
Undamaged endothelium does not express
Tissue factor or collagen
Endothelial cells modulate hemostasis by synthesizing and secreting:
Procoagulants (initiators of coagulation)
Anticoagulants (inhibitors of coagulation)
Fibrinolytics (to dissolve the clot)
Endothelial cells release mediators….
Vasoconstrictors
Vasodilators- NO
von Willebrand factor (vWF) do what….
Adherence of platelets to the subendothelial layer
Tissue factor does what
Activates the clotting cascade pathway when injury to the vessel occurs
Some of these mediators control blood flow by vasoconstriction
thromboxane A2, adenosine diphosphate [ADP])
control blood flow by vasodilation
nitric oxide, prostacyclin
Coagulation factors function
Coagulation
Collagen function
Tensile strength
Fibronectin function
Mediates cell adhesion
Thrombomodulin function
Regulates anticoagulation pathway
Antithrombin III function
Degrades factors XII, XI, X, IX, II
Tissue pathway factor inhibitor function
Inhibits tissue factor
Plasminogen function
Converts to plasmin
tPA function
Activates plasmin
Urokinase function
Activates plasmin
Vasoconstiction mediators
serotonin, Thromboxane A2
adenosine diphosphate
Nitric Oxide function
Vasodilates, promotes smooth muscle relaxation
Prostacyclin function
Vasodilates, inhibits aggregation, promotes smooth muscle relaxation
media collagen function
A potent and important stimulus for platelet attachment to the injured vessel wall
media fibronectin function
Facilitates the anchoring of fibrin during the formation of a hemostatic plug
Adventitia Controls blood flow by ….
influencing the vessel’s degree of contraction
The endothelial cells produce ….
nitric oxide and prostacyclin, which influence the adventitia
Nitric oxide’s ability to influence and promote smooth-muscle relaxation results in …..
vascular vasodilation
Once the vessel vasodilates, the increase in blood flow limits the activity of procoagulant mediators by…..
simply washing the procoagulant mediators away
Nitric Oxide Synthesis occurs where and how
This metabolic reaction occurs within the endothelial lining
Under the influence of nitric oxide synthetase (NOS), L-arginine is converted to nitric oxide
NO -> activates soluble guanylate cyclase, subsequently producing a second messenger, cyclic guanosine monophosphate, that causes muscle relaxation
Eicosanoids refered to as
Collectively referred to as prostanoids or eicosanoids
Prostacyclin
Leukotriene
Thromboxane
Prostacyclin is a …..
lipid molecule produced in the endothelial cells from prostaglandin
A powerful vasodilator, prostacyclin also interferes with platelet formation and aggregation
smm eicosanoids factors
prostaglandins
PGE2
PGF2
4 Phases of Hemostasis and Coagulation
Vascular phase (Vascular spasm)
Primary hemostasis (Formation of platelet plug)
Secondary hemostasis (Coagulation and formation of fibrin)
Fibrinolysis (Lysis of clot)
Vascular Phase
spasm/constrict of smm done by endothelins -> fibroblasts
Vasoconstriction “may” slow down or stop bleeding
Localized in injured area
Primary Hemostasis
happens after spaces -> attract plat -> plat plug
Initiates the phases of platelet formation….
Adherence
Activation
Aggregation
Where are plat located in the bv
they tend to be pushed aside, strategically positioned near the vessel-wall surface where they can then “react” in the event of injury
plat formation , life span’ concentration
They are formed in the bone marrow from megakaryocytes
Maintain a concentration count of approximately 150,000 to 300,000/mm3
1-2 weeks lifespan
plat cleared by….
Cleared by macrophages in the reticuloendothelial system and the spleen
Spleen sequesters up to 1/3 of the circulating PLT for later us
Glycoproteins responsibility
Adheres to injured endothelium, collagen and fibribogen
GpIb sticks/attaches PLT to vWF
GpIIb-IIIa complex links activated PLT together to form a plug
Gp2b, 3a inhibitor mediations
ranexa, integrelin
Phospholipids responsibility
Substrates to prostaglandin synthesis
Produce thromboxane A2 which activates PLT
Actin and myosin
responsibility
Contraction to form the PLT plug
Thrombosthenin responsibiilty
PLT contraction
ADP responsiblity
PLT activation and aggregation
Calcium responsbility
Plays a role in the coagulation cascade
Fibrin-stabilizing factor
responsbility
Cross links fibrin
Serotonin responsibility
Activates nearby PLT
Growth factor responsiblity
Repairs damaged vessel walls
Adherence
vWF mobilizes from within the endothelial cells and emerges from the endothelial lining
Glycoprotein Ib (GpIb) receptors emerge from the surface of the platelet
The purpose of GpIb is to attach to vWF and attract platelets to the endothelial lining
vWF makes platelets “sticky” and allows them to adhere to the site of injury
Activation
tissue factor ->conformational transformation-> activated
Structure swells and becomes oval and irregular
From the platelet surface, two other major glycoproteins, IIb and IIIa, project themselves outward
The purpose of the GpIIb-IIIa receptor complex is to link other activated platelets together in an effort to form a primary platelet plug
When this action is complete, the platelets seal and heal the site of injury within the blood vessel
Aggregation
As platelets undergo this metamorphosis, they release the alpha and dense granules, the contractile granules, thrombin, and many important mediators into the blood in an effort to promote procoagulant activity
These mediators are responsible for platelet aggregation to form a primary unstable clot
When injury is minute and less threatening, this primary plug is enough to maintain hemostasis
When the injury is large, activation of the coagulation clotting cascade is required for permanent repair to create and stabilize a secondary clot to cease bleeding
fibrin production requires….
all the clotting factors
single most important protein involved in clotting
fibrin
fibrin formation
A series of enzymatic reactions (clotting cascade) that ultimately activate prothrombin to thrombin, the enzyme that converts soluble fibrinogen to fibrin
factor 1
fibrinogen
liver
not vitmain k depednednt
factor 2
prothrombin
liver
vit K dependendt
factor 3
name; Tissue Factor or Thrombo-plastin
Source; Vascular wall and extracellular membrane; released from injured cells
factor 4
name; Calcium
source; diet
factor 5
name; Proaccelerin
source; Liver
not vitamin K dependent
factor 7 name and source
name; Proconvertin
source; Liver
vit K dependent
factor 7 name and source
name; Proconvertin
source; Liver
vit K dependent
factor 8 C name and source
name; Antihemo-
philiac factor
source; liver
not vit K dependent
factor VIII:vWF name and source
name; vonWillibrand’s Factor
source; vascular endothelial cells
factor 9 name and source
name; christmas factor
source; liver and other tissue
vit K dependent
factor 10 name and source
name; Stuart-Prower Factor
source liver
vitmain K depedneent
factor 11 name and source
name; Plasma thromboplastin antecedent
source; Liver
factor 12 name and source
name; Hageman Factor
souce; liver
factor 13 name and source
name; Fibrin Stabi-
lizing factor
source; liver
Liver factors that are vitamin k dependent
2,7,9,10
Warfarin works on what pathways
extrinsic
Extrinsic Pathway
Tissue factor release from sub-endothelium during trauma. Tissue factor activates the extrinsic pathway
Factor X activation; Tissue factor activates factor 7; 7 activates 10 in the presence of factor 4 (calcium)
Prothrombin activator and platelet phospholipids activate factor 2 (thrombin); Factor 5 accelerates the positive feedback mechanism (increase production of prothrombin activator)
Clot forms within 12 to 15 seconds
For 37 cents, you can purchase the extrinsic pathway
Intrinsic Pathway
Slower process
12,11,9,8-> collagen -> factor 12-> 11 (activated by stilmulation of kinogen and accellerated by prekalcerin) -> factor 9 activation-> factor 9a -> factor 10 ……..
Common Pathway
Prothrombin activator changes prothrombin (II) to thrombin (IIa)
Prothrombin changes fibrinogen to fibrin in the presence of calcium
Fibrin is added to the aggregated platelet plug.
Activated fibrin-stabilizing factor (XIIIa) cross-links fibrin-fibers to complete the clot
Clot is formed. Stays in place until vascular tissue is repaired.
When is fibrinolysis activated
When the clotting cascade is activated, so is the process of fibrinolysis.
labs and meds for intrinsic pathway
hepatin, ptt, act
extricnsic pathway meds and labs
coumadin, pt, inr
mechanism for fibrinolysis
release of tissue plasminogen activator (tPA) by damaged endothelial cells
urokinase function
urokinase is produced and released by the kidneys as a means of prevent small clots getting lodged in the kidney tissue
fibrinogenic factors
Kallikrien and neutrophil elastase
These circulating activators will then convert plasminogen to plasmin, which then breaks down fibrin
circulating activators that convert plaminogen to plasmin
TPA & UPA
plasmin breaks down fibrin to fibrin degradation products (split products)
PLT values
150,000 to 300,000/mm3
Bleeding time values
3-10 min
PT values
12-14 sec
aPTT values
25-35 sec
TT (Thombin time) value
30 secs
ACT (activated clotting time) values
80-150 secs
Fibrinogen values
> 150 mg/dl
Most common hereditary bleeding disorders
vWF Disorder
Diagnosis vWF Disease
PT and aPTT = normal
BT is prolonged
Hematologist to analyze labs
Treatment for vWF Dz
Correct the deficiency of vWF
Using desmopressin
By the transfusion of the specific factor
Cryoprecipitate
how does DDAVP work
A synthetic analogue of vasopressin and stimulates the release of vWF by endothelial cells
DDAVP dose
intravenously at a dose of 0.3 µg/kg in 50 mL of normal saline over 15 to 20 minutes
DDAVP time effect
effect in 30 minutes and lasts from 6 to 8 hours
When do we give to to them; give it when get to OR or before in preop , consider redosing during sx.
The side effects of DDAVP
Headache, stupor, hypotension, tachycardia, hyponatremia, and water intoxic
In order to decrease water intoxication, hyponatremia, and consequent seizures, the administration of water, orally or intravenously, should be restricted ______ after the use of the drug
4-6 hrs
Cryoprecipitate risk
In common preparation, the cryoprecipitate is not submitted to viral attenuation and, therefore, poses an increased risk of infection
if pt unresponsive to ddavp w/ vWF use…..
Cryoprecipitate
Cryoprecipitate raises the fibrinogen levrl by….
1 unit raises the fibrinogen levels by 50 mg/dL
what is Factor VIII concentrate and when do we give it
Factor VIII concentrate is prepared from the pool of plasma from a large number of donors
It undergoes viral attenuation
Contains F VIII and vWF
Given preoperatively and during surgery
Anesthesia Consideration for clotting disorders
General anesthesia- avoid epidurals
Arterial puncture is not recommended
avoid IM
Patients with coagulopathies undergoing neuroaxial block results in…..
increased risk of developing a hematoma and compression of neurological structures
how does heparin work
Heparin inhibits thrombin (thrombin needed to convert fibrinogen to fibrin)
Heparin derives its anticoagulant effect by activating antithrombin III
labs to monitor heparin
PTT and ACT
reversal for heparin
Heparin’s anticoagulant effect is rapidly reversible by protamine (+ polypeptide forming a stable complex neutralizing heparin)
LMWH vs UFH
LMWHs -effective at VTE prophylaxis compared to UFH (more specific)
LMWHs have a more predictable pharmacokinetic response, fewer effects on platelet function, and a reduced risk for heparin-induced thrombocytopenia (HIT)
Monitoring of LMWHs is not performed routinely
Coumadin works by….
Interferes with hepatic synthesis of vitamin K–dependent coagulation factors: factors II, VII, IX, X
reversal for coumadin and how long does it take
Vitamin K reverses coumadin anticoagulation - takes 6-8 hours to correct
coumadin more rapid reversal option….
More rapid reversal - prothrombin complex concentrates, recombinant factor VIIa and FFP
Fibrinolytics act by ….
converting plasminogen to plasmin, which in turn cleaves fibrin, thereby causing clot dissolution
common fibrinolytic
Tissue plasminogen activator (tPA), streptokinase (SK), and urokinase (UK)
Anti-Fibrinolytics works by
inhibits the conversion of plasminogen to plasmin
medications that are Anti-Fibrinolytics
Antifibrinolytic agents–tranexamic acid, ε–aminocaproic acid, and aprotinin
what is Disseminated Intravascular Coagulopathy
Systemic activation of the coagulation system simultaneously leads to thrombus formation and exhaustion of platelets and coagulation factors
underlying disorders may precipitate DIC
trauma, amniotic fluid embolus, malignancy, sepsis, or incompatible blood transfusions
DIC expected labs
Reductions in PLT,
prolongation PT, PTT, and thrombin time (TT),
elevated concentrations of soluble fibrin degradation products
tx for DIC
blood component transfusions to replete coagulation factors and platelets consumed in the process
treat the cause
what is contraindicated in DIC
Antifibrinolytic therapy
what is Factor V Leiden
Factor V is a protein for normal clotting
When enough fibrin has been made, a substance called activated protein C inactivates factor V, helping stop the clot from growing any larger than necessary
Factor V Leiden is an abnormal version of factor V that is resistant to the action of activated protein C
Activated protein C cannot easily stop factor V Leiden from making more fibrin
Mutations in genes for factor V (factor V Leiden)
Factor V Leiden is associated with
an increased risk of developing an episode of DVT (with or without a PE)
when is screening for Factor V leiden
pregnancy
Tx factor V leidan
Because of high risks of DVT and PE, patients are on anticoagulants….. + being pregnant
Common anticoagulation options include warfarin, unfractionated heparin, and LMWH
Factor 5 Levidan in preganncy
First presentation of DVT, repeated missed abortions, and recurrent late fetal losses
what is Heparin-induced Thrombocytopenia
HIT describes an autoimmune-mediated drug reaction occurring in as many as 5% of patients after exposure to unfractionated heparin or (rare cases) LMWH
hallmark of findings of HIT
The hallmark of findings is a decrease in PLT < 100,000
Thrombocytopenia occurring 5 -14 days after initial therapy
Hit results in….
platelet activation and potential for venous and arterial thromboses
Evidence suggests that HIT is mediated by …..
immune complexes (composed of IgG antibody, platelet factor 4 [PF4], and heparin)
Patients developing HIT during heparin therapy experience substantially increased risk for …..
thrombosis (absolute risk 30%-75%).
TX for HIT
D/C heparin STAT (i.e., including unfractionated heparin, heparin-bonded catheters, heparin flushes, LMWH)
Alternative non-heparin anticoagulation must be administered concurrently
Heparin is usually substituted for….. in HIT
a direct thrombin inhibitor (i.e., bivalirudin, lepirudin, argatroban)
What is a synthetic factor Xa inhibitor
Fondaparinaux - to treat VTE. Off labelled use
Typically, PF4/heparin immune complexes clear from the circulation within….
3 months
If possible, patients experiencing HIT should avoid……
avoid future exposure to unfractionated heparin
