Coagulation (final) Flashcards
Describe Hemostasis
Normal hemostasis is a balance btw clot generation, thrombus formation, andcounter-regulatory mechanisms that inhibit uncontrolled thrombogenesis or premature thrombus degradation
Slide 2
3 Goals of Hemostasis
to limit blood loss from vascular injury
maintain intravascular blood flow
promote revascularization after thrombosis
Slide 2
What are the 2 stages of Hemostasis?
Describe each…
Primary: Immediateplatelet deposition at the endovascular injury site
Leads to the initial platelet plug formation
Only adequate for minor injury
Secondary: clotting factors activated
Stabilized clot formed and secured with crosslinked fibrin
Slide 3
What is the Vascular Endothelial Role?
Vascular endothelial cells have antiplatelet, anticoagulant, and profibrinolytic effects that inhibit clot formation
Slide 5
Describe the anti-clotting mechanisms of endothelial cells
-are negatively charged to repel platelets
-produce platelet inhibitors such as prostacyclin and nitric oxide
-excrete adenosine diphosphatase, which degrades -adenosine diphosphate (ADP), a platelet activator
-increase protein C, an anticoagulant
-produce Tissue Factor Pathway Inhibitor (TFPI), inhibiting factor Xa & TF-VIIa complex
-Synthesize tissue plasminogen activator (t-PA)
Slide 5
____ play a critical role in hemostasis and are derived from ____
Platelets and megakaryocytes
Slide 6
Nonactivated platelets circulate as ____ with a lifespan of ____
discoid anuclear cells and 8-12 days
Slide 6
normally, ~ ____ of platelets are consumed to ____ with ____ new platelets formed daily
10%
support vascular integrity
1.2-1.5 X10^11
Slide 6
2 important things about the platelet membrane
1) contains numerous receptors
2) has a surface canicular system, which increases membrane surface area
Slide 6
Describe the process of platelets undrgoing hemostasis
Damage to endothelium exposes the underlying extracellular matrix (ECM), which contains collagen, von Willebrands factor, and other platelet-adhesive glycoproteins
Upon exposure to ECM, platelets undergo 3 phases of alteration:
-adhesion
-activation
-aggregation
Slide 7
Describe Adhesion of platelets
Adhesion: occurs upon exposure to ECM proteins
Slide 8
Describe activation of platelets
What are 2 types of storage granules in platelets?
Activation: stimulated when platelet interacts w/collagen & tissue factor (TF), causing the release of granular contents
Plts contain 2 types of storage granules: alpha granules and dense bodies
-Alpha granules: contain fibrinogen, factors V & VIII, vWF, Plt-derived growth factor & more
-Dense bodies: contain ADP, ATP, calcium, serotonin, histamine, epinephrine
Slide 8
Describe aggregation of platelets
Aggregation: occurs when the granular contents are released, which recruit and activate additional platelets, propagating plasma-mediated coagulation. Activated glycoprotein IIb/IIIa receptors on plt surface bind fibrinogen, promoting fibrin crosslinking
Slide 8
Each stage of the platelet cascade requires what?
Assembly of membrane-bound activation tenase-cmplexes
Each tenase complex is composed of
1) a substrate (inactive precursor)
2) an enzyme (activated coagulation factor)
3) 3) a cofactor (accelerator or catalyst)
4) 4) calcium
Slide 9
Describe the intrensic pathway
Beginning w/XIIa, it was initially thought to occur only in response to endovascular contact with negatively-charged substances (glass, dextran)
Current understanding is the intrinsic pathway plays a more minor role in theinitiation of hemostasis, and is more an amplification system to propagate thrombin generation initiated by the extrinsic pathway
Slide 13
Describe the extrensic pathway
The Extrinsic pathway is the initiation phase of plasma-mediated hemostasis
Begins endothelial injury, exposing TF to the plasma
TF forms an active complex with VIIa (TF/VIIa complex)
TF/VIIa complex binds to and activates factor X, converting it to Xa
TF/VIIa complex also activates IX→ IXa in the intrinsic pathway
IXaand calcium convert factor X to Xa (intrinsic pathway)
Factor Xa begins the final common pathway
Slide 12
Describe the intrinsic pathway hemostasis initiation
Upon contact with a negatively charged surface, factor XII becomes activated
Factor XIIa converts XI to XIa
(IXa + VIIIa +plt-membrane phospholipid + Ca++) converts factor X to Xa
Xa initiates the final common pathway
Slide 14
Describe intrinsic pathway propogation
Activated Thrombin (IIa) activates factors V, VII, VIII and XI to amplify extrinsic thrombin generation
This process activates the platelets, leading to propagation of the FCP(final common pathway)
Slide 14
Describe the common pathway
Factor X becomes Xa and binds with Va to form “prothrombinase complex”
Prothrombinase complex rapidly converts prothrombin (II) into thrombin (IIa)
Thrombin attaches to the platelets and converts fibrinogen (I) to fibrin (Ia)
Fibrin molecules crosslink to form a mesh that stabilizes the clot
Thrombin cleaves fibrinopeptides A & B from fibrinogen to generate fibrin monomers, which polymerize into fibrin strands to form basic clot
Finally, factor XIIIa crosslinks the fibrin strands to stabilize and make an insoluble clot, resistant to fibrinolytic degradation
slide 15 and 16
Vascular injury exposes ____, initiating ____ pathway. ____ pathway further amplifies thrombin and fibrin generation. Platelets adhere to ____, become activated and ____ additional platelets
TF
extrensic
intrinsic
collagen
recruit
Slide 16
What is the key step to regulating hemostasis?
Thrombin generation
Slide 15
What does the common pathway depict?
Thrombin generation and firbin formation
*both intrinsic and extrinsic tenase-complexes facilitate the formation of the prothrominase complexes
Slide 17
What is the function of prothrombinase complex?
Converts PT (II) into thrombin (IIa)
Slide 17
What are the 4 major Coagulation counter mechanisms?
Fibrinolysis
tissue factor pathway inhibitor (TFPI)
protein C system
Serine Protease inhibitors (SERPINs)
Slide 19
Describe fibrinolysis
endovascular TPA & urokinase convert plasminogen to plasmin
Plasmin breaks down clots enzymatically, and degrades factors V & VIII
Slide 19
Describe TFPI
forms complex w/Xa that inhibits TF/7a complex, along with Xa; Downregulating the extrinsic pathway
Slide 19
Describe the protein C system
inhibits factors 2 (II), 5a (Va) & 8a (VIIIa)
Slide 19
What are the SERPINs?
Antithrombin (AT) inhibits thrombin, factors 9a (IXa), 10a (Xa), 11a (XIa), 12a (XIIa)
Heparin binds to AT, causing a conformational change that accelerates AT activity
Heparin cofactor II inhibits thrombin alone
Slide 19
Preoperative assessment factors for coagulation
1) identify and correct hemostatic disorders
2) bleeding hx is more effective predictor of bleeding
3) inquire: frequent epistaxis, bleeding gums, easy bruising?
4) hx of excess bleeding with procedures or blood transfusion?
5) family hx
6) use of blood thinners (ASA, NSAID, Vit E, Ginko, Ginger, Garlic supp
7) coexisting disease (renal, liver, thyroid, bone marrow)
Slide 20
If a bleeding disorder is suspected in the preop assessment, what are the standard first-line labs?
PT, aPTT
Slide 20
Common bleeding disorders
Von Willebrand’s
Hemophilia
Drug-induced bleeding
Liver disease
Chronic renal disease
Disseminated Intravascular Coagulation
Trauma-induced coagulopathy
Slide 21
What is the most common inherited bleeding disorder? What percent of the population is affected?
Von Willebrand’s- effects 1% of the population
Slide 22
Describe the MOA of a deficiency in vWF
Deficiency in vWF, causing defective plt adhesion/aggregation
vWF plays critical role in plt adhesion & prevents degradation of factor 8 (VIII)
Slide 22
In vWF, are routine labs helpful?
how will labs look?
Which tests are more beneficial?
No
normal: platelets and PT, prolonged: aPTT d/t deficiency in factor 8
better tests: vWF level, vWF plt-binding activity, factor 8 level, plt function assay
Slide 22
What treatment is vWF responsive to?
DDAVP in mild cases (it increases vWF)
Slide 22
for patients with vWF, intraoperative bleeding may require administration of what?
vWF, and factor 8 concentrates
Slide 22
What are the 2 types of Hemophilia?
is this inherited or not?
A: factor 8 (VIII) deficiency; occurs in 1 in 5,000
B: factor 9 (IX) deficiency; occurs in 1 in 30,000
2/3 of cases are inherited, 1/3 present as new mutation w/o family hx
Slide 23
How does hemophlia commonly present?
in childhood as spontaneous hemorrhage involving joints and muscles
Slide 23
Labs in hemophilia
Normal PT, plts, bleeding time
PTT is prolonged
Slide 23
In patients with bleeding disorders, especially hemophilia, who should be consulted?
Hematology
Slide 23
What may be indicated pre-operatively for patients with hemophilia?
DDAVP and factors 8 and/or 9
Slide 23
What is the most significant cause of intraoperative bleeding?
Anticoagulant medications
Heparin
Warfarin
Direct Oral Anticoags (DOAC
Beta lactam ABx
Nitroprusside
NTG
NO
SSRI
Slide 24
What are common supplements that increase the risk of bleeding?
Cayenne, Garlic, Ginger, Ginkgo Biloba, grapseed oil, st johns wart, Turmeric, Vitamin E
Good Grief Girls, St. John’s Grape’s Turned Very Crimson
Slide 24
When should common herbal supplements be stopped prior to surgery?
Slide 24
The ____ is the primary source of which factors?
- Liver
- 1,2,5,7, 9, 10, 11, 12 (I, II, V, VII, IX, X, XI, XII)
along with proteins C & S, and antithrombin
Slide 25
How can liver disease lead to hemostatic issues?
Impaired synthesis of coagulation factors
Quantitative and qualitative platelet dysfunction
Impaired clearance of clotting and fibrinolytic proteins
Slide 25
Lab findings in liver disease
-Prolonged PT and PTT
***lab values only reflect the lack of pro-coagulation factors, NOT accounting for concurrent lack of anti-coagulation factors
TEG and ROTEM are valuable guidelines
Slide 25
Chronic liver patents often display a ________ ________ as well as ________ amount of ________ production
What should we still consider with these patients?
rebalanced hemostasis, sufficient, thrmobin
although rebalanced, they are very susceptible to disruption in coagulation
Slide 25
CKD patients have baseline ______ d/t what 2 things?
Anemia!
-lack of erythropoietin
-platelet dysfunction
Slide 26
Picture of a TEG
Slide 35
Absolute and relative contraindications for thrombolytics
Slide 42
Neuraxial anesthesia on anti-coags
Slide 45
Which labs are required to monitor for each drug and possible reversal for each
Pic
Slide 47
