7. Hematologic Disorders Flashcards
Hemostasis
Primary hemostasis
Platelet ____
Secondary hemostasis
____ cascade
____ formation
aggregation/plug
coagulation
fibrin
Platelets
____ cell fragments from ____
150-400 million/mL of blood
Average life around ____ days
anuclear
megakaryocytes
7-10
Platelet aggregation and formation of platelet plug
____
____
____
adhesion
activation
aggregation
Primary Hemostasis
Endothelial damage
____ exposure- vWF, TF, laminin, fibronectin
Platelet Adhesion
____ binds Von Willebrand Factor
____ produced by endothelial cells, catches platelets
GP1b deficiency- ____
collagen
GP Ib-IX-V
vWF
bernard-soulier
Platelet activation
Caused by adhesion to ECM
Leads to degranulation and conformational change
Degranulation
____ granules- vWF, fibrinogen, FV, FXIII
____ granules- ADP, serotonin
Phospholipid membrane metabolism
Arachidonic acid release eventually leads to ____-> platelet activation and ____
____ and ____- platelet recruitment and activation
alpha
dense
thromboxane A2
aggregation
ADP
thromboxane A2
Formation of Thromboxane
This is basically the breakdown of phospholipids.
• •
•
You have ____ which makes arachidonic acid.
Then you have these cox 1 and cox 2 that break down arachidonic acid into ____ and all these diff prostaglandins can cause through thromboxane synthase release of thromboxane A2 which activates the ____.
Also ____ which is important in inflammation.
____ which is kind of a protective prostaglandin within your gut if you remember that.
So this is the breakdown of phospholipid membranes and its important because some meds impact this and impact platelet activation and aggregation which is the whole point of why you’re taking these medications
phospholipase A2
prostaglandins
platelets
prostacyclines
PGE2
Platelet Activation
So again this is kind of a picture format of this.
• The platelet adheres to the ____. It becomes activated, the release of these
granules, the alpha and dense granules, that release ____ and serotonin which act on itself creating a ____ feedback mechanism that further activates platelets in the area and causes platelet aggregation.
• If you’ll note, the ADP interacts with the ____ receptor which we’ll talk about down the road as well.
endothelium
ADP
positive
P2Y12
Primary Hemostasis
Platelet Aggregation
____ integrin on platelets is the receptor for fibrinogen
Platelet Plug
TF activation
GPIIb/IIIa deficiency- ____
GPIIb/IIIa
glanzman thrombasthenia
We have endothelial cell damage, these platelets are flying by, the ____ factor basically catches these platelets causing conformational change and causing platelet activations, a release of ____ and ____ through these different granules that then feed back and cause further activation and aggregation of platelets becoming a ____. Hopefully that’s a simplified way of the whole platelet plug process.
vWF
ADP
TXA2
platelet plug
Secondary hemostasis
- Fibrin clot
Secondary hemostasis once you have this ____.
This should look somewhat familiar to you, you know your intrinsic and extrinsic pathway of the coagulation cascade, all these different factors.
Basically 1 through 13. All cause in the end, the formation of ____ which then causes fibrinogen to turn into ____. fibrin is basically these strands that hold the platelet plug together and mature and help you stop bleeding.
we’ll talk about different medications and deficiencies of some of these factors that can cause bleeding.
if you know basic physiology, you can figure most of this stuff out like how medications work, why people take medications, when to stop the medications and what happens when you stop.
platelet plug
thrombin
fibrin
Fibrin clot
Fibrinogen cleaved to ____
Fibrin is ____ and crosslinks platelets
Forms a hemostatic ____ and blood clot
fibrin
insoluble
platelet plug
Lab tests
PT/INR
Tests ____ pathway
Factor ____
PTT
Tests ____ pathway
Factor ____
Bleeding time
Measures ____ function
extrinsic
I, II, V, VII, X
intrinsic
I, II, V, VIII, IX, X, XI, XII
platelet
Von Willebrand’s Disease
The most ____ hereditary coagulation abnormality
1/100 of general population
Deficiency of von Willebrand factor
vWF binds to other proteins (____/collagen)
vWF binds ____
Symptoms
____, easy bruising, nosebleeds, ____ bleeding, heavy menstrual periods
common
factor VIII
platelets
bleeding
gingival
Von Willebrand Disease
Type 1- ____ defect (85%) Failure to secrete, or cleared more quickly
Many ____ or mild symptoms
Type 2- ____ defect (15%) Type 3- ____ of production (rare)
quantitative
asymptomatic
qualitative
absence
Von Willebrand Disease
Diagnosis- Labs
____
measures amount of vWF (____)
____ activity- vWF activity Measures how well vWF works (____)
vWF multimer study
Evaluates ____
Factor VIII levels ____
____ PTT
vWF:Ag
quantitative
ristocetin cofactor
qualitative
structure
decreased
elevated
Von Willebrand Disease
Treatment-
____ (IV or IN)- minor trauma
Stimulates vWF release from ____ bodies in endothelial cells
____- major trauma
____ vWF
Cryoprecipitate
____, vWF, ____, XIII, ____
Transfusions
dDAVP
weibel palade
factor VIII
recombinant
fibrinogen
VIII
fibronectin
Hemophilia
Hemophilia A
____ deficiency (____)
~____% of hemophilia cases
30% caused by new mutations
Hemophilia B
Factor ____ deficiency (____) ~20% of hemophilia cases
Hemophilia C
Factor ____ deficiency (____)
factor VIII
x-linked recessive
80
IX
X-linked recessive
XI
autosomal
Hemophilia
Signs/Symptoms Variable Internal \_\_\_\_ Hemarthrosis, Muscle/soft tissue, Retroperitoneal Petechiae characteristically \_\_\_\_
Complications
____ damage
Transfusion reactions
____ hemorrhage
bleeding
absent
joint
intracranial
Hemophilia labs
Bleeding Time
____
Prothrombin/INR
____
PTT
____
Factor ____ and ____ assays to confirm diagnosis
normal
normal
prolonged
VIII
IX
Again hemophilia’s basically with factor ____ and factor ____ which is within your clotting cascade.
8
9
Hemophilia
Treatment
Recombinant factor ____ Recombinant factor ____
Plasma derived ____ or FIX ____ Acid / Aminocaproic Acid
____
____
VIII IX FVIII tranexamic DDAVP cryoprecipitate
Aminocaproic Acid/Tranexamic Acid
Amicar and TXA Amicar- Derivative of \_\_\_\_ TXA- synthetic analog of \_\_\_\_ Lysine inhibits \_\_\_\_, such as proteolytic enzymes like \_\_\_\_ Swish for \_\_\_\_ minutes, spit or swallow
lysine lysine enzymes plasmin 1-2
Liver
Regulates ____
Makes ____ and proteins
Removes ____ and drugs Makes bile for ____ digestion
blood glucose
amino acids
toxins
fat
Causes of Liver Failure
Viral
____
Metabolic
____
____
Hereditary
____
NAFLD- non alcoholic fatty liver disease
hepatitis A-E
EtOH
drugs
autoimmune
Coagulation Cascade
So liver failure - all of these factors are made in your liver except for factor ____.
So someone with fulminant liver disease, someone on the transplant list, it can be very dangerous to take a bunch of teeth out.
• People have died from having their teeth out. There’s a case in Portland Oregon
where OS took out a bunch of teeth and this person bled to death.
8
Acquired
Medication induced \_\_\_\_ \_\_\_\_ \_\_\_\_ inhibitor \_\_\_\_ inhibitor Anti-\_\_\_\_
warfarin heparin direct thrombin factor Xa platelets
Warfarin
Decreases thrombosis Mechanism of Action Inhibits \_\_\_\_ Antagonizes the recycling of \_\_\_\_ II,VII,IX,X,protein C and S Half-life about \_\_\_\_ hours
vitamin K epoxide reductase
vitamin K1
35
Warfarin
Indications- Prevent thrombosis
____ (PE)/Deep Vein Thrombosis (DVT) treatment and prophylaxis
____
____ heart valves
____ states (Factor V Leiden, APLS, etc.)
pulmonary embolus
atrial fibrillation
artificial
hypercoagulable
Virchow’s Triad
- ____ Injury
- ____
- Stasis of ____
Hopefully this is something that you’ve seen before.
Why people get thrombosis or blood clots, typically you have these 3 things in conjuction.
Endothelial injury or trauma of some sort, stasis of blood flow, and a hypercoagulable state.
Injury is self-explanatory, stasis of blood flow people after surgery like big GI surgeries are laying in bed for a long time as they recover. They’re more prone to getting DVTs. People sitting on a long plane ride, people have heard of getting DVTs (lol do we have DVTs
from chronic studying ̄_(ツ)_/ ̄ ) he recommends we get up & walk)
Hypercoagulability - people with cancer or pregnant, there’s a lot of different reasons to
be hypercoagulable. Genetic problems like factor 5 leiden.
endothelial
hypercoagulability
blood flow
Factor V Leiden
this is one of the most common heriditary hypercoagulable disorders, particularly with people of european descent.
• •
A mutated factor 5 does not get deactivated by the activated protein C. So activated protein C typically deactivates ____.
when you deactivate factor 5 obviously you’re not forming ____ and then you don’t form ____. If you’re not deactivating it because its mutated then you continue to form thrombin and you’re ____ because you’re forming too many clots basically.
factor 5
thrombin
blood clots
hypercoaguable
Warfarin
Monitored by ____
Normal INR is ____
Risk of ____ when 1st started
– ____ inactivate clotting factors
PT/INR
1
thrombosis
protein C/S
What to do if your patient is taking warfarin?
CHEST Guidelines
In patients who require temporary interruption of a VKA before surgery, we recommend stopping VKAs approximately ____ days before surgery instead of stopping ____ a shorter time before surgery (Grade 1C).
recommend resuming VKAs approximately ____h after surgery (evening of or next morning) and when there is adequate hemostasis instead of later resumption of ____
In patients who require a ____ dental procedure, we suggest continuing VKAs with coadministration of an oral prohemostatic agent or stopping VKAs 2 to 3 days before the procedure instead of ____ strategies
Check INR ____hrs prior to procedure!!!
VKAs
5
12 to 24
12 to 24
VKAs
minor
alternative
24-48
Warfarin
Reversal Agents
____ (IV or Oral)
Fresh Frozen Plasma (FFP) Contains all ____
Has an INR of ____
4-factor prothrombin complex concentrate
Beriplex, Octaplex, Kcentra, Cofact
Factor ____,VII, ____, X, ____ and S
vitamin K
factors
1.6
II
IX
protein C
Heparin
Naturally occurring anticoagulant in ____ and mast cells.
Prevents ____ formation and propagation
Mechanism of Action
Binds and activates ____
Activated ATIII inactivates ____ and some factors, especially factor Xa
basophils
clot
antithrombin III
thrombin
Secondary Hemostasis
Heparin
Indications
____ treatment and prophylaxis
____ Fibrillation
____ (acute coronary syndrome)/NSTEMI (non ST- elevation myocardial infarction)
____ bypass / ECMO (extracorporeal membrane oxygenation)
____/dialysis
DVT atrial ACS cardiopulmonary hemofiltration
Heparin
Unfractionated heparin (UFH) vs. Low molecular weight heparin (LMWH)
UFH - half life ____ minutes, monitored by PTT
Given ____ or SC
LMWH (dalteparin, enoxaparin)
Half life ~____ hours, not monitored by ____
Given ____ or SC
90
IV
4
PTT
IV
Heparin - CHEST Guidelines
Perioperative therapeutic IV UFH
Suggest stopping UFH ____ h before surgery instead of closer to surgery.
Perioperative therapeutic SC LMWH
Suggest administering the last preoperative dose of LMWH approximately ____ h before surgery instead of 12 h before surgery.
high-bleeding-risk surgery, we suggest resuming therapeutic-dose LMWH ____ h after surgery instead of resuming LMWH within 24 h after surgery
4-6
24
48-72
Heparin
Reversal with ____
Binds to heparin and LMWH
Adverse effects of heparin
____
____
protamine sulfate
heparin induced thrombocytopenia, thrombosis
hyperkalemia
Direct Thrombin Inhibitor
Dabigatran (Pradaxa)
Half-life ____ hours
Reversible with ____ (Praxbind)
Argatroban
For ____
Bivalirudin/Lepirudin/Desirudin (Iprivask)
Pradaxa has reversal agent (Praxbind)- idarucizumab
12-14
idarucizumab
heparin induced thrombocytopenia (HIT)
Factor Xa Inhibitor
____ (Xarelto)
____ (Eliquis)
____ (Savaysa)
No specific ____ agents
rivaroxaban
apixaban
edoxaban
reversal
Discontinuation of medications
Should be decided by ____ physician
Dabigatran (Pradaxa), Rivaroxaban (Xarelto), Apixaban (Eliquis), Edoxaban (Savaysa)
Typically stop ____ days prior
Restart after hemostasis ____ days after procedure, or ____ days if high bleeding risk procedure
prescribing
2-3
1-2
2-3
Antiplatelets
\_\_\_\_ Clopidogrel (Plavix) \_\_\_\_ (Ticlid) \_\_\_\_ (Effient) Ticagrelor (Brilinta) \_\_\_\_ (Kengreal)
aspirin
ticlopidine
prasugrel
cangrelor
Indications for antiplatelets
Acute ____ syndrome Prevention of ____ thrombosis
____ prevention
coronary
stent
stroke
Antiplatelets
Aspirin
Aspirin basically inhibits ____.
End result of the degradation of phospholipids is ____.
cox 1 or cox2
thromboxane A2
Platelet Activation
Phospholipid membrane metabolism
Arachidonic acid release eventually leads to ____-> platelet activation and aggregation
____- platelet recruitment and activation
thromboxane A2
ADP and thromboxane A2
Formation of Thromboxane
Aspirin blocks all of that and blocks the whole cascade
NSAIDS all work on these similar proteins that help with pain and inflammation and prolong ____ because of the decreased thromboxane A2 then decrease platelet ____ and aggregation
bleeding
activation
Antiplatelets
Irreversibly binds P2Y12
____ (Plavix)
____ (Effient)
Reversibly binds P2Y12
____ (Brilinta)
____ (Kengreal)
clopidogrel
prasugrel
ticagrelor
cangrelor
Plavix decreases platelet activation
If you’re blocking this receptor you’re blocking platelet ____ and platelet aggregation disrupting ____. Hopefully you now understand why people take these and how they work.
activation
blood clots
Perioperative management of antiplatelets
American College of Chest Physicians
In patients who are receiving ASA for the secondary prevention of cardiovascular disease and are having minor ____ or dermatologic procedures or cataract surgery, we suggest ____ ASA around the time of the procedure instead of stopping ASA 7 to 10 days before the procedure
In patients at modrate to high risk for cardiovascular events who are receiving ASA therapy and require noncardiac surgery, we suggest ____ ASA around the time of surgery instead of stopping ASA 7 to 10 days before surgery (Grade 2C).In patients at low risk for cardiovascular events who are receiving ASA therapy, we suggest stopping ASA ____ days before surgery instead of continuation of ASA
dental
continuining
contiuning
7-10
Discontinuation of medications
Should be decided by prescribing ____!
physician
