Coags Flashcards
what is normal hemostasis
a balance between clot generation, thrombus formation, and counter-regulatory mechanisms that inhibit uncontrolled thrombogenesis or premature thrombus degradation
what are the 3 goals of hemostasis
- to limit blood loss from vascular injury
- maintain intravascular blood flow
- promtoe revascularization after thrombosis
what are the 2 stages of hemostasis
primary hemostasis and secondary hemostasis
what is primary hemostasis
immediate platelet deposition at hte endovascualr injury site
* leads to the intial platelet plug
only adequate for minor injury
what is secondary hemostasis
clotting actors activated
stabilized clot formed and secured with crosslinked fibrin
what is a characteristic of vascular endothelial cells
they have antiplatelet, anticoagulant, and profibrinolytic effects that inhibit clot formation
anti-clotting mechanisms of the endothelial cell
is the enothelial cell negative or positively charged
negatively charged to repel platelets
anti-clotting mechanisms of the endothelial cell
what is produced by the endothelial cell
prodcue platelet inhibtors such as prostacylin and nitric oxide
what is released by vascular endothelial cells and what does it do
excrete adenosine diposphotase, which degreades adenosine diphosphate (ADP) a platelet activator
what anticoagulant is increased through the endothelial cells
increase protein C, an anticoagulant,
the endothelial cell produces tissue factor pathway inhibitor (TFPI) which inhibits what
factor Xa and TF-VIIa complex
what is synthesized by the endothelial cells
tissue plasminogen activator (t-PA)
platelets play a critical role in hemostasis, where are they derived from
bone- marrow megakarocytes
what is the lifespan of non-activated platelets
nonactivated platelets circulate as discoid anuclear cells with a lifespan of 8 to 12 years
approximately 10% of platelets are consumeed to support vascular integrity how many platelets are formed daily
1.2-1.5 x 10^11 formed daily
damage to the endothelium exposed the underlying
extracellular matrix (ECM)
the extracellular matrix contains
collagen, vWF, and other platelet adhesive glycoproteins
upon exposure to ECM platelets undergo what 3 phases of alteration
bonus: what stage of hemostasis is this
adhesion, activation, aggregation
when does adhesion occur
when exposed to ECM proteins
activation of platelets happens when the platelets are stimulated and interacts with
collagen and tissue factor (TF) causing the release of granular contents
platelets contain 2 type of storage granules what are they
alpha granules and dense bodies
alpha granules contain what
fibrinogen, factors V and VIII, vWF, plt-derived growth factor and more
what do the dense bodies contain
ADP, ATP, calcium, serotonin, histmaine, and epinphrine
aggregation occurs when
the granular contents are released, which recruits and activates additional platelets, propagating plasma-mediated coagulation
activated glycoprotein 2B/3A on the platelet surface bind what
fibrinogen, promoting fibrin crosslinking
each stage of the cascade requires assembly of the membrane activation tenase complexes
what is each complex composed of
a substrate (inactive precursor)
an ezyme (activated coagulation factor)
a cofactor (accelerator or catalyst)
calcium
Clotting Factors
Factor I is also called
fibrinogen
Factor II is also called
prothrombin
Factor III is also called
tissue thomboplastin
Factor IV is also called
calcium ions
Factor V is also called
labile factor
Factor VII is also called
stable factor
Factor VIII is also called
antihemophilic factor
Factor IX is also called
christmas factor, plasma thomboplastic component (PTC)
Factor X is also called
stuart-prower factor
Factor XI is also called
plasma thromboplastin antecedent (PTA)
Factor XII is also called
hageman factor
Factor XIII is also called
fibrin stabilizing factor
extrinisc pathway is the intiation of
plasma mediated hemostasis
what begins the extrinsic pathway
endothelial injury, exposing TF to plasma
what is the extrinisc pathway
TF forms an active complex VIIa (TF/VIIa complex)
TF/VIIa complex binds to and activates factor X converting it to Xa
TF/VIIa complex also activates IX to IXa in the the intrinsic pathway
what is needed to convert Factor X to Xa
IXa and calcium
what begins the final common pathway
factor Xa
what begins the intrinsic pathway
XIIa
most thrombotic events follow ______ pathway; however lab-coag studies rely on ____ pathway to activate the cascade
extrinsic ; intrinsic
the intrinsic pathway plays a ____ role in the initiation of hemostasis, and is more an ______ _______ system to progoate thombin generation intiated by the extrinisic pathway
minor; amplification system
upon contact with a ______ charged surface, factor ______ is activated
negatively charged ; factor XII
factor XIIa converts
XI to XIa
what converts factor X to Xa
XIa + VIIIa + platelet membrane phospholipid + Calcium
activated thrombin IIa activates which factors to amplify extrinisc thombin generation
V, VIII, XII
this process activates platelets leading to the propogation of the FCP
Factor X becomes Xa and binds with what to form prothrombinase complex
Va
p
prothrombinase complex rapidly converts
prothrombin (II) into thrombin (IIa)
thrombin attaches to platelets and converts
fibrinogen (I) to fibrin (Ia)
fibrin molecules _____ to form a mesh that stabilizes the clot
crosslink
whats happening
Vascular injury exposes TF, initiating extrinsic pathway. Intrinsic pathway further amplifies thrombin & fibrin generation. Platelets adhere to collagen, become activated, and recruit additional platelets.
thrombin cleaves fibrinopeptides A & B from fibringogen to generate fibrin monomers, which does what
polymerize into fibrin strands to form basic clot
what factor cross links the fibrin strands to stabilize and make the clot insoluble, resitant to fibrinolytic degradation
XIIIa
T/F only the intrinsic tenase complex factilitates the fromation of prothrominase complexes
false both intrinsic and extrinsic tenase complexes factilitate the formation of prothrombinase complexes
fibrinolysis
endocvascular TPA and urokinase
convert plasminogen to plasmin
what does plasmin break down clots ____, and degrades which factors
ezymatically; degrading Factors V and VIII
TFPI forms complex with which factor and inhibits what
forms complex with Xa that inhibits TF/7a complex, along with Xa
downregulating the extrinisic pathway
protein C system inhibits which factors
Factor II, Va, VIIIa
serine protease inhibitors (SERPINs)
AT3- inhibits thrombin, Factors 9a, 10a, 11a, 12a
heparin - binds to AT causing a conformational change that accelerates AT
Heparin Co-factor II - inhibits thombin alone
if you suspect bleeding disorder preop what are the first line lab
PT, aPTT
what Rx meds/ herbal supplements increase bleeding risk
ASA, NSAIDs, Vitamin E, Ginko, Ginger, Garlic supplements
what coexisting disease are at risk for bleeding
renal, liver, thryoid, and bone marrow disorders
list the common bleeding disorders (7)
Von Willebrand’s
Hemophilia
Drug-induced bleeding
Liver disease
Chronic renal disease
Disseminated Intravascular Coagulation
Trauma-induced coagulopathy
1.
von Willebrand’s Disease
deficiency in vWF, causing defective platelet adhesion/aggregation
vWF plats a critical role in
platelet adhesion and prevents degradation of factor VIII (8)
why might routine coagulation labs not be helpful with von willebrand’s disease? what would be a better test to order
platelets and PT will be normal
aPTT may be prolonged depending on level of factor 8
better test: vWF level, vWF platelet bidning activity, Factor 8 level, platelet function assay
mild vWD often responsive to
DDAVP which increases vWF
intraop bleeding may require administration of Factor 8/vWF concentrates
difference between Hemophilia A and Hemophilia B
A- factor 8 deficiency
B- factor 9 deficiency
2/3 genetically inherited; 1/3 new mutation without family hx
when does hemophilia present itself
in childhood as spontanoeus hemorrahe involving joints and muscles
labs of hemophiliac
normal PT, plts, bleeding time
PTT normally prolonged
Preop considerations in hemophilia
hematologist preop
DDAVP, Factor 8 and/or 9 may be indicated before surgey
drug induced bleeding
Heparin
Warfarin
Direct Oral Anticoags (DOACs)
Beta-Lactam Abx
Nitroprusside
NTG
NO
SSRIs
the liver is the primary source of which factors
5,7,9,10,11,12 as well as protein C & S, and antithombin
liver disease leads to complex, multifactorial hemostatic issues such as
impaired synthesis of coagulation factors
quantitiative and qualitivat platelet dysfunction
impaired clearance of clotting and fibrinolytic proteins
coags of pt with liver disease
prolonged PT and possible prolonged PTT
TEG & ROTEM are valuable guides
CKD have a baseline anemia due to
lack of erythopoietin
platelet dysfunction due to uremic environment
what can shorten bleeding times in CKD patietns
dialysis and correction of anemia
treatment of platelet dysfunction in CKD includes
cryo
DDAVP
conjugated estrogen (give preop x 5days)
what is Disseminated Intravascular Coagulation
pathological hemostatic response to TF/7a complex causing excessive activation of the extrinisc pathway which overwhelms the anticoagulant mechanism and generates intravasculat thrombin
T/F in DIC: Coagulation factors & platelets become depleted during widespread microvascular thrombotic activity, causing multi-organ dysfunction
true!
what can precipitate DIC
trauma, amniotic fluid emobolus, malignancy, sepsis, or incompatible blood transfusion
labs of DIC
decreased platelets, prolonged PT/PTT/ thrombin time, increased soluble fibirn and fibrin degradation products
management of DIC
treat cause, give appropriate blood products
what is trauma-induced coagulopathy
independent acute coagulopathy seen in trauma patietns; thought to be related to activated protein C decreasing thombin generation
coagulopathies occur to what 3 things
acidosis, hypothermia, and/or hemodilution
whats the common cause of trauma related death
uncontrolled hemorrhage
in trauma induced coagulopathies what is the driving factor for protein C activation
hypoperfusion
endothelial glycocalyx, which contains proteoglycans degrades resulting in
auto-heparinization
most common prothrombotic states are caused by a mutation where
factor V or Prothrombin
Factor V Leiden Mutation leads to
activated protein C resistance
prothrombin mutation causes
increased PT concentration, leading to hypercoagulation
thrombophilia
inherited or aquired prediposition for thrombotic events
generally manifests as venous thrombosis
highly susceptible to virchows triad
antiphospholipid syndrome
autoimmune disorder with antibodies against the phospholipid binding proteins in the coag system
characterized by recurrent thrombosis and pregnancy loss
often require life long anticoags
in patients with thrombotic state disorders what can increase the risk of thrombosis in these patients
oral contraceptives, pregnancy, immobility, infection, surgery, trauma
what is HIT (heparin-induced thrombocytopenia) and when does it occur after initiating heparin therapy
mild-moderate thrombocytopenia associated with heparin
occurs 5-14 days after heparin therapy
HIT results in
platelet count reduction as well as activation of the remaining platelets and potential thrombosis
risk factors for HIT
women, patietnt receiving high heparin doses such as with cardiopulmonary bypass
UFH greater risk than LMWH
if HIT is suspected what should you do
DC heaprin convert to direct anticoagulant
wafarin CI bc it decreases protein C and protein S synthesis
HIT is diagnosed with what
how long do the antibodies last in circualtion
diagnosed with HIT antibody test
antibodies cleared from circulation in 3 months
PT assess integrity of extrinsic and common pathways and can reflect deficiences in what factors
1,2,5,7,10
used to monitor vitamin K antagonist warfarin (2,7,10 are v.K dependent)
aPTT assess the integrity of intrinsic and common pathways and can reflect deficencies in which factors
Factor 8 and 9
may be used to measure effect of heparin
which lab am I?
I measure the seconds until clot forms after mixing plasma w/phospholipid, Ca², and an activator of the intrinsic pathway
Activated Partial Thromboplastin Time (aPTT)
What lab am I?
I measure the time until a clot forms after plasma is mixed w/TF
prothrombin time (PT)
antifactor Xa activity assay provides assessment of which antiacoagulant effect
heparin’s anticoagulant effect
can also be used to assess effect of LMWH, fondaparinux, factor Xa inhbitors
normal plt count
greater than 100K/microliter
activated clotting time (ACT) measures which pathways?
what is the normal ACT value
addresses the intrinsic and common pathways
normal = 107 +/- 13 seconds
measures responsiveness to heparin
1 mg of protamine will inhibit how much heparin (in mg)
increasing protamine will cause the clot time to decrease until protamine concentration > heparin concentration
1mg
TEG :)
on the TXWes Reference Guide for alpha angle < 53 it has give cryo -/+ platelets
3 main classes of antiplatelet drugs
Cyclooxygenase Inhibitors
P2Y12 receptor antagonists
Platelet GIIb/IIIa R antagonists
moa of Cyclooxygenase Inhibitors
Block COX 1 from forming TxA₂, which is important in plt aggregation
ASA: anti-plt effects x 7-10 days after d/c
NSAIDS: anti-plt effect x 3 days
P2Y12 receptor antagonists MOA
Inhibit P2Y12-R→preventing GIIb/IIIa expression
Clopidogrel: anti-plt effects x 7 days after d/c
Ticlopidine: anti-plt effects x 14-21 days after d/c
Ticagrelor & Cangrelor: Short-acting, <24h activity
Platelet GIIb/IIIa receptor antagonists MOA
prevent vWF & fibrinogen from binding to GIIb/IIIa-R
Abciximab, Eptifibatide, Tirofiban
anticoagulant drug
Vitamin K antagonist (wafarin)
- inhibit synthesis of factors 2,7,9,10, protein C & S
- DOC for valvular Afib & valve-replacements
- Long half life (40h), can take 3-4 days to reach therapeutic INR (2-3)
- Usually requires heparin until therapeutic effect achieved
- Frequent lab monitoring required (PT/INR)
- Reversable w/Vitamin K
UFH
Short 1/2 life, given IV
Fully reversable w/Protamine
Close monitoring required
1.
LMWH
Longer 1/2 life, dosed BID SQ
No coag testing needed
Protamine only partially effective
Fondaparinux
Much longer HL (17-21h), dosed once/day
Protamine not effective
direct thrombin inhibtors MOA
bind/block thrombin in both soluble and fibrin bound states
direct thrombin inhibitors
Hirudin: naturally found in leeches
Argatroban: synthetic, reversibly binds to thrombin. HL 45 min.
Monitored intraop w/PTT or ACT
Bivalirudin: synthetic, shortest HL of DTI’s
DOC for renal or liver impairment
Dabigatran (Pradaxa): 1st DOAC
DTI approved for CVA prevention and non-valvular A-fib
direct oral anticoagulants
Direct Thrombin Inhibitor-Dabigatran (Pradaxa)
**Direct Xa Inhibitors: **Rivaroxaban (Xarelto), Apixaban (Eliquis), Edoxaban (Savaysa)
Predictable PK/PD
Fewer drug interactions
Dosed daily w/o lab monitoring
Efficacy similar to Warfarin, but much shorter HL
Fewer embolic events, intracranial hemorrhages, and lower mortality than warfarin
thrombolytics
used to dissolve blood clots
Most are Serine Proteases that convert plasminogen to plasmin, which breaks down fibrinogen to fibrin
how long is surgery CI with use of thrombolytic therapy
10 days
the 2 categories of thrombolytics are
Fibrin-Specific: Altepase (tPA), Reteplase, Tenecteplase
Non-Fibrin-Specific: Streptokinase * not widely used d/t allergic reactions
absolute contraindications to thrombolytics (6)
vascular lesions
uncontrolled HTN (>185/>110)
recent cranial surgery or trauma
brain tumor
ischemic stroke <3 months prior
active bleeding
relative contraindications to thrombolytics
ischemic stroke > 3 months
active peptic ulcer
current use of anticoagulant
pregnacy
prolonged/traumatic CPR < 3 weeks prior
major surgery < 3 weeks prior
procoagulants are used to mitigate blood loss; which 2 classes are there
Antifibrinolytics:
Lysine analogues: Epsilon-amino-caproic acid (EACA) & Tranexamic Acid (TXA)
SERPIN: Aprotinin (removed from market d/t renal & cardio toxicity)
Factor Replacements
Recombinant VIIa (RfVIIa): ↑’s thrombin generation via intrinsic & extrinsic paths
Prothrombin Complex Concentrate (PCC): contain vitamin-K factors
Fibrinogen Concentrate: derived from pooled plasma.
Cryoprecipitate & FFP
lysine analogues MOA
bind and inhibit plasminogen from binding to fibrin impairing fibrinolysis
post coronary stent placement guidelines:
Bare-metal stents→ delay elective surgery 6 weeks after placement
Drug-eluding stents→ delay elective surgery 6 months after placement
preop ASA guidelines
mod/high rx pts- current recommendation is to continue ASA
low rx pts- stop 7-10 days prior to surgery
preop heparin guidelines
UFH should be d/c’d 4-6h prior to surgery & resumed (no bolus) ≥12h postop
LWMH should be d/c’d 24h prior to surgery & resumed 24h postop
wafarin preop guidelines
**low rx pts **should d/c 5 days prior to surgery & restart 12-24h postop
high rx pts should stop 5 days prior & bridge w/UFH or LMWH
neuraxial anesthesia and anticaogs
top 6 rows most common
emergent reversal for wafarin
Prothrombin complex concntrates: DOC for emergent coumadin reversal (short 1/2 life)
concurrent Vitamin K required to restore carboxylation of Vitamin K dependent factors by the liver for more sustained correction
emergent reversal of direct thrombin inhibitors
no reversal, however most direct thrombin inhibitors have a relativelt short half life
The DOAC Dabigatran (Pradaxa) does have an antidote –Idarucizumab
Factor Xa inhibitors emergent reversal
Andexanet, a derivative of factor Xa
anotha one..
know this one!
how long should garlic be DC’d before surgery
7-10 days
T/F st.johns wort will increase bleeding times
false, increased clotting risk
what herbal supplements increased bleeding time (7)
cayenne
garlic
ginger
ginkgo bibloa
grapseed oil
tumeric
vitamin E
heparin MOA
binds to antithrombin and directly inhibits soluble thrombin and Xa
direct thrombin inhibitors
bind/block thrombin in both soluble and fibrin bound states
NSAIDs/ASA neuraxial guidelines
no restrictions for catheter placement or removal
BID Heparin SQ and neuraxial considerations
no restrictions for catheter placement or removal
TID SQ Heparin and neuraxial anesthesia
at least 4 hours between last dose and catheter placement and removal
at least 2 hours after catheter placement and resuming drug, and removal of catheter and next dose
Lovenox QD and neuraxial
