Apex- Coags Flashcards
4 steps after vascular injury occurs to prevent hemorrhage
- vascular spasm
- formation of the platelet plug (primary hemostasis)
- coagulation and fibrin formation (secondary hemostasis)
- Fibrinolysis when clot is no longer needed
What are the 3 layers of the arteries and veins
which is the thickest in the arteries vs veins ?
Function of collagen
clot strength
procoagulant/pro clot
Function of vWF
platelet adhesion
pro-coagulant/pro clot
Function of fibronectin
Cell adhesion
pro-coagulant/pro clot
function of Protein C & S
Protein C - degrades factor 5a & 8a (pro-coagulants)
Protein S is a co-factor for protein C
anticoagulant/anti-clot
Function of prothrombin
degrades factors 9a, 10a, 11a, 12a
anticoagulant/anti-clot
What is plasminogen?
a precursor to plasmin (breakds down fibrin)
fibrinolytic
3 fibrinolytics
plasminogen, tPa & Urokinase
what 2 substances activate plasmin?
what happens when plasmin is activated?
tPA & urokinase
plasmin breaks down fibrin
What inactivates tPA & urokinase?
alpha-antiplasmin
The 3 substances that result in vascular smooth muscle constriction
& 2 that result in VSM relaxation
constriction:
thromoxane A2, ADP, Serotonin
relaxation:
nitric oxide & prostayclin
Platlets contain the following components EXCEPT:
A. Actin
B. Deoxyribonucleic acid
C. Adenosinde Diphosphate
D. Calcium
B.
platlets dont have a nucleus and therefore dont contain DNA and cant undergo cell division
What produces platelets?
The bone marrow (megakaryocytes)
Nomal platelet value
Lifespan
150,000-300,000
8-12 days (1-2 weeks)
the sp[leen can sequester up to how much of the circulating plateleets for later use?
1/3
2 main functions of platelets
- they are a structural component to the clot
- they are vehicles that provide many substrates required for clot formation*
T/F- platelets are cleared by the liver
false- they are cleared by macrophases in the reticuloendothelial system and spleen
Key receptors on the platelet that can be targeted for antiplatelet therapy (5)
mneumonic
Thrombin
Thromboxane A2
ADP
GpIb
GPIIb-IIIa complex
TTAGG (TEG) switch A to E and double the ends
-thrombin
-thromboxane A2 - VSM cx
-ADP- VSM cx
-GpIb - attaches activated platelet to vWF
-Giib-IIIa complex - links platlets together to form a plug
How are serotonin and platelets associated?
Serotonin is located on the inside of platelets and activates nearby platelets
Which substance is responsible for adhering the platlet to the damaged vessel?
A. Thromboxane A2
B. ADP
C. Tissue Factor
D. VWf
D. VWf
*VWF = PLATELET ADHESION!!!
What should you associate platelet adhesion with vs platelet activation and aggregation?
platelet adhesion → VWf
platelet activation and aggregation → ADP & Thromboxane A2
What is the first, most immediate thing that happens following vascular injury
spasm
the vessel (tunica media) contracts to reduce blood flow to the affected area
What is primary hemostasis?
what 3 steps can it be divided into?
formation of the platelet plug
- adhesion- vascular injury results in exposed collagen and the platelets adhere to it with the hellp of VWF
- Activation- platelets contract and release compounds that attract other platelets to the site of injury and promote cloting
- Aggregation- platelet plug forms (process stops here for small injuries - for larger injuries the coagulation process is required to strengthen the clot)
T/F- after the platelet plug is formed, that’s all that is required for small injuries
True - for larger injuries, the coagulation process is required to strengthen the clot
under normal circumstances, about how long does it take to form a platelet plug once vascular injury occurs
~ 5 mins
What is the main purpose of the coagulation cascade?
to produce fibrin
Vitamin K- dependent factors
2, 7, 9, 10
PNS = 3, 7, 9 , 10
Intrinsic pathway
what measures it
12, 11, 9, 8
(count backwards from 12, skipping 10)
PTT (longer than the extrinsic which is measured by PT)
Extrinsic pathway factors
what is used to measure it
what drug inhibits it
3 + 7 (tissue factor + stable factor)
= 10 (x marks the spot)
PT (shorter)
Warfarin (TF = Trigger finger = war = warfarin)
What makes up the final common pathway
10 - marks the spot
5 (labile factor)
x
2 (prothombin)
x
1 (fibrinogen)
or just remember $ denominations: $10, $5, $2, $1
What is the FIRST coagulation factor activated in the extrinsic pathway?
A. Fibrinogen
B. Stuart Prower factor
C. Tissue Factor
D. Labile factor
what # are all of these factors and where do they fall
C. Tissue Factor (3)
*extravascular injury causes blood to be exposed to extravasc. Tissue
Fibrinogen = 1 (FCP)
Stuart-Power factor = 10 (FCP)
Labile factor = 5 (FCP)
Which pathway is the fastest
Extrinsic
*short and fast :
3,7
PT/INR
what event activates the extrinsic pathway
vascular injury / vessel wall comes into contact with blood
factors 3 and 7 (tissue factor and stable factor)
Mneumonic for Clotting Cascade
Foolish People Try Climbing Long (Fucking) Slopes After Christmas, Some People Have Fallen
Fibrinogen (1)
Prothrombin (2)
Tissue Factor (3)
Calcium (4)
Labile Factor (5)
(no six)
Stable factor (7 - stable seven)
Antihemophelic factor (8)
Christmas facotr (9)
Stuart Power Factor (10)
Plasma thromboplamin Antedecent (11)
Hagman Factor (12)
Fibrin Stablizing Factor (13)
The extrinsic pathway is (slow/fast) requiring ~ how many seconds/minutes?
15 seconds
*normal PT 14-16
Which factor has the shortest half life of all coagulation factors
clinical significance?
Factor 7 (4-6 hours)
think normal pt = 14-16seconds
4 and 6s
It’s going to be the first factor to become deficient in patients with liver disease , vitamin K deficiency, and those on warfarin
What is going to be the first factor that becomes deficient in someone with liver disease and why?
what 2 other conditions would this also be seen with?
factor 7 bc it has the shortest half life (4-6hrs)
vitamin K deficiency and those on warfarin
Which pathway is activated by blood trauma
Intrinsic Pathway
(extrinsic is activated by TISSUE trauma, tissue factor)
T/F- the intrinsic pathway is slower than the extrinsic
what is it measured by
what is it inhibited by?
True
PTT and ACT
heparin
What is also known as the Contact Activation Pathway
The intrinsic pathway
How long does it take for the intrinsic pathway to form a clot?
up to 6 minutes
A deficiency in factor 8 causes what type of hemophilia?
Hemophilia A (A.8)
What does the final common pathway begin with?
When prothrombin activator (prothrombinase) changes prothrombin (2) to thrombin (2a)
What activates the FCP?
the intrinsic or extrinsic pathways
extrinsic from tissue trauma which liberates TF from the subendothelium
intrinsic from blood trauma/collagen exposure activating factor 11 (Hagmans)
What does thrombin do?
converts fibrinogin to fibrin
(more specifically a fibrinogen monomer that when combined with calcium makes fibrin fibers)
then factor 13a cross-links those fibrin fibers
What must be present to convert fibrinogen monomer to fibrin fibers?
calcium (factor 4)
Identify the true statements regarding fibrinolysis (select 2)
A. D-dimer measures fibrin split products
B. Plasminogen is synthesized in the endothelium
C. tPA inhibitor inhibits the conversion of tibrinogen to fibrin
D. Alpha-2 antiplasmin inhibits the action of plasmin on fibrin
A & D
-plasminogen is synthesized in the liver (not the endothelium)
-It’s converted to plasmin by tPA, and plasmin converts fibrin to fibrin degregation products which are measured by D-Dimer
-Alpha-2 antiplasmin inhibits the action of plasmin on fibrin
-tPA inhibitor inhibits the conversion of plasminogen to plasmin (not fibrinogen to fibrin)
True or false: tPA inhibitor inhibits the conversion of fibronogen to fibrin
False- it inhibits the converion of plasminogen to plasmin
Since the clot is only a temporary fix while the vessel repairs itself, the body needs a way to breakdown the clot after it is no longer needed. What is this process called?
Fibrinolysis
What does plasmin do?
where is it synthesized?
It degrades fibrin into fibrin degradation products (measured by D-dimer)
liver
What does D-dimer measure?
the breakdown of clots (fibrin) (fibrin degragation products)
plasmin breaks down fibrin
What two things turn off fibrinolysis when the clot is dissolved and fibrinolysis is no longer needed
tPA inhibitor - inhibits conversion of plasminogen to plasmin
Alpha-2 antiplasmin- inhibits the action of plasmin on fibrin
Major and minor mechanisms by which plasminogen is converted to plasmin to break down fibrin
major = tPA (the injured tissue releases tissue plasminogen activating facotr over a period of days)
minor = urokinase - produced by the kidneys and released into circulation
T/F- urokinase is produced by the liver
what does it do?
False - produced by the kidneys
helps convert plasminogen to plasmin in order to break down a clot
Match each phase of the contemporary model of coagulation with it’s key event: Amplification, Propagation, Initiation
-The TF/7a reaction activates the FCP
-Platelets are activated
-A large quantity of thrombin is produced
Phase 1 = Initiation = TF/7a reaction activates FCP
Phase 2 = amplification = platelets are activated
Phase 3 = Propagation = a large quantity of thrombin is produced
Which is the BEST predictor of bleeding during surgery:
A. PT/INR
B. H&P
C. Thromboelastogram
D. Bleeding time
B. H&P
Which pathway(s) does aPTT assess?
Normal value?
Intrinsic and FCP
25-35 seconds
What does PT stand for, what pathway(s) does it assess
normal value
Prothrombin Time
Extrinsic and FCP
12-14 seconds
What does INR stand for? What does it do?
Target for those on warfarin therapy
International Normalized Ratio
it standardizes the PT results
*Target is 2-3x the control
Does the platelet count monitor the quantity or quality of platelets
Normal value
quantity - it does not measure how well the platlets function
150,000- 300,000 mm^3
What does bleeding time monitor?
Platlet function
*rarely used in clinical practice (i wonder why)
What guides heparin dosing?
normal value?
value before going on CPB?
Activated clotting time (ACT)
90-120 seconds
> 400 seconds
T/F- aPTT measures the therapeutic response to unfractionated heparin & LMWH
False -not LMWH
Factors must be reduceb by more than what % before a change in aPTT is observed
what about PT?
more than 30% for both
INR is a ratio of what?
why is it important?
ratio between the patients PT and the standard mean PT
without standardization, different labs might report different PT results, so it would be impossible to compare results from different labs (dont get this)
Normal INR for healthy patients
vs those on coumadin
~1 for healthy patients
2-3x control for those on warfarin
When should ACT levels be checked
before giving heparin, 3 mins after giving it, and every 30 mintues thereafter
Why not just check PTT intraop instead of ACT?
ACT tends to be more acurate than PTT when large doses of heparin are administered
T/F- a normal platelet count signifies normal platelet function
false- it’s a quantitative measure, not a qualatative measure
Platelet counts less than what increase surgical bleeding risk vs spontaneous bleeding risk
<50,000 - surgical bleeding risk
< 20,000 - spontaenous bleeding risk
Normal value of Bleeding time
What 2 things prolong bleeding time?
2-10 mins
Aspirin and NSAIDs
D-dimer normal value
what if it’s increased?
differential diagnosis should include what 3 things?
< 500mg/mL
there is likely a thrombus in the body
DVT/PE/DIC
T/F: INR directly measures the therapeutic response to Warfarin
False! - PT
What lab test measures fibrinolysis?
D-Dimer
Primary Fibrinolysis
What are the 5 components of the TEG?
- R-time = time it takes to begin forming a clot
- K-time = time it takes until clot has formed a fixed strength
- Alpha angle = speed of fibrin accumulation
- Maximum amplitude = measures clot strength
- A60 = Height of amplitude 60 mins after maximum amplitude
TEG: Definition, normal value, problem with, treat with:
R-Time
-Time to begin forming a clot
-6-8 minutes
-coag factors
- FFP
TEG: Definition, normal value, problem with, treat with:
K-Time
Meaures time until a clot has acheived a fixed strength
3-7 minutes
problem with fibrinogen
tx with Cryo
TEG: Definition, normal value, problem with, treat with:
Alpha angle
Speed of fibrin accumulation
50-60 degrees
problem with fibrinogen
Give Cryo
TEG: Definition, normal value, problem with, treat with:
Maximum amplitude (MA)
-Highest verticle amplitude on the TEG (measures clot strength)
- 50-60mm
- problem with platlets
- tx with platelets OR DDAVP
TEG: Definition, normal value, problem with, treat with:
Amplitude at 60mins after max amplitude (A60)
Highest verticle amplitude 60 mins after the max
MA - 5
Problem with excess fibrinolysis
Tx with TXA or amicar
Label
Coagulation factors → Fibrinogen → Fibrinogen → Platelets → Fibrinolysis
FFP → Cryo → Cryo → Platelets/DDAVP → Amicar/TXA
How does Heparin work?
It binds to Antithrombin III , in hibiting the conversion of fibrinogen to fibrin, preventing fibrin from particpating in clot formation
*increases AT3’s anticoagulation effect 1,000 fold
inhibits the intrnsic and FCPs
the Heparin-AT complex neutralizes what factor in particular + 4 more
does it naturally inhibit platelet function?
Thrombin (2a)
+ 9a, 10a, 11a, 12a
Yes it inhibits platlet function
Standard cardiac dosing of heparin
VTE prophylaxis
Unstable angina/Acute MI dose
300-500units/kg
5,000units SC BID/TID
5,000units IV then infusion of 1,000units/hr
Side effects of heparin (2)
Hemorrhage and HIT
How do you reverse heparin?
With protamine 1mg for every 100units given
What is endogenous heparin produced by (3)
What is exogenous heparin derived from (2)
Basophils, mast cells, and the liver
bovine lung and GI mucousa
Failed heparinization should prompt consideration of what?
Antithrombin deficiency
T/F: antithrombin is a naturally occuring anticoagulant that circulates in the plasma
True
Is Heparin safe in pregnancy? Why or why not?
Yes bc its a large, water-soluble molecule with a small volume of distribution
3,000-30,000 daltons
How is heparin metabolized?
by heparinase
How is heparin eliminated?
- degraded by macrophages
- renally excreted
theruaputic aPTT for someone on heparin for VTE prophylaxis is how many times the normal range?
normal range?
1.5-2.5x normal range
normal range = 25-32 seconds
so…. 37.5-48 to 48-80
A deficiency in what 3 things can affect ACT?
fibrinogen (1), factor (7), factor (12)
T/F: ACT is affected by hypothermia and thrombocytopenia
True
T/F: if someone has been on a heparin gtt for days leading up to heart surgery and you have difficulty getting a therapeutic ACT, they probably have AT 3 deficiency
False- they probably have chewed through all the circulating AT and now the heparin doesnt have any to work on
*decreased antithrombin concentration
3 contraindications to Hepain
Neurosurgical procedures
HIT
Regional anesthesia (see guidelines)
T/F: when given aline, protamine is an anticoagulant
True
What causes the hypotension seen with protamine?
Histamine release
What causes pulmonary hypertension seen with protamine?
The heparin/protamine complex releases TxA2 and serotonin -> pulm htn
pt’s with what 4 conditions would you be nervous about a protamine allergy occuring?
- previous exposure to protamine (whether surgery or NPH insulin)
- fish allergy
- vasectomy
- multiple drug allergies
Warfarin inhibits factors:
A. 3 & 10
B. 2, 7, 9, 10
C. 2, 7, 9, 10, and protein C
D. 2, 7, 9, 10, and protein C & S
D
How does Warfarin work?
It inhibits vitamin K, imparing the synthesis of factors 2, 7, 9, 10 & Proteins C & S
How can warfarin be reversed:
1 slow way vs 3 fast ways
quickly with FFP (1-2 units), recombiant factor 7a, or prothrombin complex concentrate
slowly with vitamin K (10-20mg) for non-emergent procedures
What is vitamin K and what does it require for absorption?
fat soluble vitamin
-requires the presence of fat and bile for absoprtion
T/F - vitamin K deficiency produces coagulopathy
True
Why shouldn’t you give someone vitamin K supplementation to fix coagulopathy in someone with liver disease
bc vitamin k supplementation requires a functional liver to work
How long will administration of vitamin K take to restore the concentration of vitamin K depdenting clotting factors?
4-8 hours
So Vitamin K can be given IV - but why isn’t this a great idea?
what if you have to?
bc it’s associated with life-threatening anaphylaxis
if you have to, dont exceed 1mg/min
So Vitamin K can be given IV - but why isn’t this a great idea?
what if you have to?
bc it’s associated with life-threatening anaphylaxis
if you have to, dont exceed 1mg/min
What do you know about vitamin K epoxide reductase complex 1? (VKOR c1)
it converts inactive vitamin K to active vitamin K
& is inhibited by warfarin
Why does warfarin take several days (36-72 hrs) to achieve a therapeutic concentration?
bc the body will stop producing vitamin-k dependent factors, but it has to use the factors that have already been made and are circulating prior to administration
Why does antibiotic administration increase risk of coagulopathy?
bc antibiotic theroapy kills of GI flora and reduces the bacterial synthesis of vitamin K
What is phytonadione?
dose?
Another name for exogenously administered vitamin K
10-20mg PO, IM, or IV
TF- vitamin K reverses warfarin and heparin
False- not heparin
4 classes of antiplatlet drugs
- ADP receptor Inhibitors
- GpIIb/IIIa Receptor antagonists
- COX inhibitors (non-specific)
- COX 2 inhibitors
- Clopidogrel, Ticagrelor, Prasurgel, Ticlopidine
- Abciximab, Eptifibatide, Tirofiban
- Asprin, NSAIDs
- Celecoxib, Rofecoxib
2 Thrombin inhibitors and how long to hold prior to surgery
- Argatroban : 4-6 hrs
- Bilvalirudin: 2-3 hrs
How long to hold heparin prior to surgery
what about LMWH?
6 hours
1-2 days
The 3 LMWHs
suffix
Enoxaparin, Dalteparin, Tinza**parin **
parin
How do LMWH’s work?
irreversabily inhibits factor 10a
What Class of anticoagulant is fondaparinux ?
how long to hold prior to surgery
Factor 10 inhibitor
hold 4 days (fonda/four)
How long to hold aspirin vs nsaids prior to surgery
Asprin 7 days (life of platelet)
NSAIDS 1-2 days
Drugs in the ADP receptor inhibitor category (4)
anti-platlets
how long to hold each prior to surgery
- Clopidogril (Plavix) : 5-7 days
- Ticagrelor: 5-7 days
- Prasurgel: 7-10 days
- Ticlopidine: 14 days
start with clopids- plavis 5-7 then ticlopidine is double that
then 2nd is same and prasurgel is in between (Dr. singer freaking out about being on that agent and needing to wait longer)
GpIIb/IIIa Receptor Antagonists (3) and how long to hold each before surgery
- Abciximab - 3 days (ABC, 1,2,3!)
- Tirofiban - 1 day
- Eptifibatide -1 day
2 plasminogen activators and how long to hold before surgery
Fibrinolytics = plasminogen activators
tPA - 1 hour
Streptokinase - 2 hours
plasminogen > plasmin
How do COX inhibitors work?
difference b/t asprin and NSAIDS
what about tylenol and cox-2 specifics
they prevent platelet aggregation by blocking cox-1
blocking cox 1 stops the conversion of arachondic acid to prostaglandins and ultimately thromboxane A2
asprin irreversibly inhibits cox-1 for life of platelet; NSAIDS revers.
tyelnol and cox-2 specicif dont affect plaelet function
How do Amicar and TXA work?
they are plasminogen activation inhibitors
What inhibits plasmin, kallikrein, thrombin ,and protein C?
Aprotinin
How does Demopressin (DDAVP) stop bleding?
stimulates factor 8 and vWF release
What stops vs accelerates the conversion of plasminogen to plasmin?
what does plasmin do?
stops conversion: TXA and amicar (antifibrinlytics)
accelerates conversion: tPA, urokinase, streptokinase (fibrinolytics)
it breaks down fibrin to fibrin degregation products (measured by d-dime
Why do we give TXA - how does it work?
it helps decrease bleeding by preserving the fibrin clot
prevents the conversion of plasminogen to plasmin
plasmin breaks down the clot, so itprevents clot breakdown
what is a synthetic derivative of lysine (an amino acid)
TXA
it binds to the lysine binding sites on plasminogen which prevents its conversion to plasmin
A patient scheduled for coronary revascularization is diagosed with type 3 von Willebrand disease. What is the BEST treatment for this patient:
A. DDAVP
B. Platelets
C. Cryo
D. vWF/factor 8 concentrate
D.
What is the most common inherited disorder of platelet function
von Willebrand disease
T/F: someone with von willebrand disease will have normal platelet levels
True!
It is a qualatative platlet disorder- the count is normal but they do not function properly.
And they dont function properly bc they need VWF to anchor themsleves to the vessel wall at the site of vascular injury (adhesion) - with low levels of VWF, they cant adhere and therefore dont function as they are supposed to
What does von willebrand factor do? (2)
it anchors platlets to the vascualr wall at the site of injury (ADHESION)
- carries inactivated factor 8 in the plasma
is VWF factor 8?
no, but it carries inactivated factor 8 in the plasma, so if its deficient, clotting will be impacted
Lab abnormalities with VWD? (2)
increased PTT and bleeding time
Someone’s trying to figure out why someone has a really high PTT but normal Pt/INR … what could it be?
VWD - check a bleeding time? maybe? lol
How does Demopressin (DDAVP) work?
It stimulates the release of vWF (helps platlet adhesion) & increases factor 8 activity (helps clotting)
What is vWF synthesized by?
the vascular endothelium and megakaryocytes
What are the 3 classifications of VWD?
Type 1- mild to moderate reduction in amounto f vWF produced
Type 2- the vWF produced doesn’t work well
Type 3- severe reduction in vWF produced
if you see VWD on somoenes chart what 3 things should you think
- Ask them about excessive bleeding/bruising
- What’s their PTT?
- What TYPE of VWD do they have (dictates how we treat it)
if type 1- demopressin 0.3mcg/kg IV
type 2 and 3 - FFP or Cryo
If your patient is ordered DDAVP- what are you thinking?
Do they have VWD? And if so, check and make sure it’s type 1 because type 3 doesn’t respond to demopressin bc they dont make vWF at all and DDAVP liberates whatever vWF someone has
How long is bleeding time improved for after giving DDAVP?
12-24 hrs
What does Cryo contain (5)
What about FFP?
Fibrinogen
Fibronectin
VWF
Factors 8 & 13
All the cloting factors
What is the first-line treatment in type 3 VWD?
why?
Purified 8-vWF concentrate
reduces risk of transfusion related infection
T/F: FFP and cryo can be used for all types of VWD
true- but demopression should be used for type 1 and vWF-8 concentrate for type 3 to reduce the risk of transfusion related infection
Cryo is useful in treating which type of vWB?
types 1, 2, 3 (all of them)
Which coagulopathies present with a prolonged PTT and normal PT? (select 2):
A. Hemophilia A
B. Hemophilia B
C. Factor 10 deficency
D. Factor 2 deficiency
A & B
Hemophilia A is factor 8 deficiency
Hemophilia B is factor 9 deficency
PT measures extrinsic pathway (factors 3 & 7)
PTT measures intrinsic pathway (12, 11, 9, 8)
Factor 2 & 10 are apart of FCP and will prolong both PT and PTT!
Since hemophilia A&B affect only the intrinsic and not extrinsic, theese coagulopathies prolong the PTT only.
Hemophilia A vs B
A = factor 8 deficinecy (A/8)
B= factor 9 deficiency (christmas factor/christmas disease)
What is christmas disease AKA?
hemophilia B - factor 9 deficiency
T/F- hemophilia A is more common in females
False- males
Which is usually more severe- Hemophilia A or B?
A
Treatment options for hemophilia A
What 2 things can be used for both?
Vs Hemophilia B
A:
FFP (all factors)
Cryo (1,8,13, fibronectin and vwf)
Factor 8 concentrate
DDAVP - liberates VWF and increases factor 8 activity
FFP & Recombiant factor 7 (risk of MI/stroke/PE/DVT)
B:
FFP (all factors)
Factor 9 concentrate (“prothrombin complex”) - but high risk of thrombembolic events
What can be given as a last ditch effort for bleeding without an identifiable cause (off-label)
dose
recombiant factor 7
20-40mcg/kg
What can be given as a last ditch effort for bleeding without an identifiable cause (off-label)
dose
recombiant factor 7
20-40mcg/kg
Pt’s with hemophilia A should receive what before surgery
what’s the half life and how long should it be continued after surgery?
Factor 8
8hrs; continue 2-6 weeks after surgery
What might be used to minimize bleeding with dental procedures in pt’s with hemophila A?
anti-fibrinolytics (TXA/Amicar)
What should you make sure you have with any patient undergoing surgery with a bleeding disorder?
Type & Cross
How do you know the severity of someones hemophilia?
the degree of PTT prolongation
(normal 25-32)
A septic patient undergoing ex. lap has developed bleeding from the wound and around his IV sites. He has a platelet count of 40,000, fibrinogen of 95mg/dL, and an elevated D-dimer. What is the best treatment for this patient?
A. Heparin infusion
B. TXA
C. FFP
D. Albumin
C. FFP
-The patient is in DIC- clotting and fibrinolysis that leads to simultaneous hemorrhage and systemic thrombis
-Definitive treatment is reversal of the cause which is sepsis in this case but in the meantime, treatment is supportive
some may consider it “feeding the beast” but failure to replace platelets, FFP, and cryo will lead to diffuse coagulopathy and hemorrhage
Explain what happens with DIC
So some underlying disorder signals systemic activation of coagulation
-generalized increase in thrombin creates microvascular clots that can impair tissue perfusion leading to tissue hypoxia and acidosis
-widespread fibrin depostion leads to widespread consumption of coagulation factors, fibrinogen, and platelets –> hemorrhage
end point - bleeding will win- replace FFP, platelets
What physical signs would suggest DIC (4)
bruising , petechiae, mucosal bleeding, bleeding at IV puncture sites
Key lab findings with DIC (3)
Prolonged PT and PTT
Increased D-Dimer
Decreased fibrinogen and antithrombin
3 high risk categories for DIC
and the highest risk in each category (1/3/3)
- Sepsis
- OB complications
- Malignancy
- Gram negative bacilli
- Pre-eclampsia, abruption, AFE
- adenocarcinoma, leukemia, lymphoma
Highest risk of DIC in someone with sepsis
Gram - bacilli
Antithrombin inactivates what which ultimately leads to what?
inactivates 9a, 10a, 11a, 12a
ultimatley leads to thrombin (2a) inhibition
Treatment for AT deficiency
AT concentrate or FFP
T/F: HIT causes clot formation throughout the body
True
Type 1 HIT vs type 2 HIT
Type 1- resolves spontaneously with minimal issue
Type 2- causes a hypercoagulable state that can result in amputation and death
Proteins C & S work as a team to inhibit which factors?
what happens if your deficitn in these factors
5a & 8a
5a and 8a (clotting factors) wont be inhibited and will lead to a hypercoagulable state , increasing risk of thrombosis
What is factor 5 leiden mutation?
it produces a hypercoagulable state bc the mutation of factor 5 (labile factor) resists the balancing anticoagulant effect of protein C
T/F: pt’s with factor 5 Leiden are on lifelong anticoagulation
false- only if pt has had recurrent thrombotic events
How does HIT cause clot formation throughout the body? Thought it was thrombocytopenia???
It’s an immune response agaisnt heparin after it binds to platelet factor 4 (PF4).
-IgG antibodies activate platelets resulting in uncontrolled clot formation
-the platelet count actually falls because the platelets are being consumed faster than they are produced
HIT Type 1 or 2:
occurs after large heparin dose vs any heparin dose
type 1- after large heparin dose
type 2- after any
HIT Type 1 vs type 2:
Onset 1-4 days after administration vs 5-14 days after
Type 1 = 1-4 days after (think less problematic, easer caught)
Type 2 = 5-14 days after (more problematic one hides first)
Platelet coutn in type 1 vs type 2 HIT
type 1 < 100,000
type 2 < 50,000
T/F: type 1 HIT can resolve spontaneously even if heparin is continued
True
Tx for type 2 HIT
d/c heparin and anticoagulate with a direct thrombin inhibitor
bivalrudin, argatroban, hirudin
What are the 4 main thrombotic disorders
- Antithrombin deficency
- HIT
- Protein C & S deficiency
- Factor 5 Leiden mutation
What four factors are inactivated by antirhombin ?
9a, 10a, 11a, 12a
T/F: antithrombin deficiency leads to thromboembolism
True
not enough ANTI-thrombin > too much thrombin
T/F: antithrombin deficiency leads to thromboembolism
True
not enough ANTI-thrombin > too much thrombin
What 5 factors can trigger a sickle cell crisis that you will need to aim to prevent during the periop period?
- dehydration
- pain
- hypothermia
- hypoxemia
- acidosis
What is the most common manifestation of sickle cell disease
what does treatment include?
2 other complications that can occur
Vaso-occlusive crisis
hydration and analgesics
acute chest syndrome and sequestration crisis
T/F- pts with sickle cell trait do not advance to crisis
TRUE - EXCEPT if they become severely hypoxemic
what condition results from valine being substituted for glutamic acid on the beta globulin chain
sickle cell (alters RBC geometry)
Why would someone with Sickle cell be on hydroxyurea?
it reduces the incidence and severity of vasoocclusive crisis
What is the #1 cause of mortality in sickle cell patients
Acute Chest Syndrome
caused by thrombosis, embolism and infection
T/F: Acute chest syndome is more common in adults with SCD
false! more common in children
T/F: acute chest syndome is common during the postop period in someone with SCD
true
causes: hypoventilation, narcotics, splinting, and pain
How is acute chest syndrome diagnosied in someone with SCD?
new lung infiltrates on CXR plus one of hte following:
CP, cough, dyspnea, wheezing
What is vaso-occlusive crisis with SCD?
sickled cells impair tissue perfusion and cause ischemic injury
What is Sequestration crisis
what can it lead to
occurs when the spleen removes RBCs from circulation at a faster rate than the bone marrow can produce them
leads to anemia and hemodynamic instability
Significance of Parovirus B19 in SCD?
usually leads to bone marrow suppression and aplastic crisis
*RBCs with hgbS have a short half-life, so even a small amount of bone marrow suppression can cause anemia
Parovirus B19 is usually the culprit but can be caused by any viral infx
SCD pt prophylaxis for pneumococcal disease
pneumococcal vaccine and daily PCN (up to 5yo)
Common co-existing diseases in the SCD population
Asthma - 50%!
Pulmonary HTN 10%
Homozygous vs Heterozygous SCD?
Homozygous = SCD (0.5-1% of AAs population)
Heterozygus = SC Trait (10% of AA population)
What condition can advance a patient with sickle cell trait into criss?
severe hypoxemia
Which condition places a patient at the GREATEST risk of developing DIC?
A. Placental abruption
B. Adenocarcinoma
C. Preeclampsia
D. Gram-negative sepsis
D.
Severe liver failure will reduce the synethesis of which coagulation factors (select 2):
8, 3, 1, 4
1, 8
liver produces all factors except for 3 & 4
liver produces factor 8 (antihemophilic factor) but does not synthesize vWF (produced in vascular wall endothelium
A deficiency in which mediators favor hypercoagulability (select 2)
A. Antithrombin
B. Protein S
C. Alpha-antiplasmin
D. Fibronectin
A & B
lack of antithrombin = too much thrombin
protein S is an anticoagulant co-factor - lack of it = pro coagulant
Which mediator promotes vasoconstriction in response to vascular injury?
A. Prostacyclin
B. Nitric oxide
C. VWF
D. Thromboxane A2
D
TXA2 also activates platelets to begin forming the platelet plug
-VWF contributes to platelet adhesion
-NO and prostacyclin cause smooth muscle relaxation (vasodilation)
A 80kg pt with type 1 VWD is schedule for a right hip arthroplasty; how much demopressin should be administered prior to surgery?
24mcg
(0.3mcg/kg)
4 common lab results in DIC and why
- low platelets (consumption
- low fibrinogen (consumption
- high PT/PTT (low suply or procoagulants)
- high D-dimer (increased clot breakdown)
Match the following with values:
Aspirin, Heparin, Warfarin
Normal PT & Nomrmal PTT
Elevated PT and normal PT
Normal PT and high PTT
Asprin - both normal
heparin- normal PT
warfarin- normal PTT
preop INR is 2.1- pt doesnt take anticoags ; which is MOST likely the explanation:
A. increased production of CCK
B. hyperinsulinemmia
C. blockage of the pancreatic duct
D. decreased bile synthesis
D.
Vitamin K = fat soluble vitamin that play s an integral role in the coag cascade
bile salts are required for the GI tract to absorb vitamin K
why would a biliary duct obstruction result in an incerased INR ?
bc bile is needed for the GI tract to absorb vitamin K
liver cant synthesize 2, 7, 9 ,10 without vitamin K
(Warfarin inhibits vitamin k, also resulting in a prolonged INR)
When administered IV, what is the MINIMUM amount of time 20mg of phytoadione should be infused over?
20 mg over 20 minutes (1mg/min)
*Risk of anaphylaxis
When administered IV, what is the MINIMUM amount of time 20mg of phytoadione should be infused over?
20 mg over 20 minutes (1mg/min)
*Risk of anaphylaxis
A patient with afiib and PUD is on warfarin; co-administering which of the following drugs will increase the risk of hemorrhage (select 2)
-Nizatidine
-Rantidine
-Cimetidine
-Famotidine
-Rantidine
-Cimetidine
theyinhibit the same P450 enzymes as warfarin, enhancing warfarins anticoagulant effects , increasing the risk of hemorrhage (CYPA34)
