Exam 2: Walenga 2 Flashcards
Hemostasis: the process by which blood remains ____ and free from clots, yet permits changes in the blood vessel and ______ formation to plug defects in injured vessels to prevent blood loss
Hemostasis is a balance of ____ and _____
Hemostasis: the process by which blood remains liquid and free from clots, yet permits changes in the blood vessel and rapid clot formation to plug defects in injured vessels to prevent blood loss
Hemostasis is a balance of blood clotting and its prevention
Hemostasis:
The vasculature and the _______, that line the luminal surface of all vessels, play an integral role in normal hemostasis and in pathological disorders.
Platelets become activated with __ or ___
Platelets initiate blood clotting via __ and __
The coagulation enzymatic system becomes activated ________, using the platelet surface to localize the process.
Coagulation activation results in _____ generation
Coagulation activation results in ____ formation
The fibrinolytic system removes the blood clot after it has fulfilled its purpose
Hemostasis:
The vasculature and the endothelial cells that line the luminal surface of all vessels play an integral role in normal hemostasis and in pathological disorders
Platelets become activated with damage to the vasculature or other enviornmental factors
Platelets initiate blood clotting via adhesion and aggregation
The coagulation enzymatic system becomes activated after platelet activation, using the platelet surface to localize the process
Coagulation activation results in thrombin generation, leading to fibrin formation
The fibrinolytic system removes the blood clot after it has fufilled its purpose
There are good clots and bad clots:
Good clots maintain ______
When clots are too slow in the making, __ results
When clots are made in excess, they become ___ clots, causing unwanted ____ and cardiovascular disorders
There are good clots and bad clots
Good clots maintain normal hemostasis
When clots are too slow in the making, bleeding results
When clots are made in excess, they become bad clots, causing unwanted thrombosis and cardiovascular disorders
PLATELET disorders cause what type of bleeding
Give examples
Platelet disorders cause mucocutaneous bleeding
Examples: petechaie, purpura, ecchymoses (bruises)
What is the reference range for platelet count?
What is it called when your platelet count is less than 100,000 /uL?
Reference range for platelet count, 150k-400k / uL
If your platelet count is less than 100k than you have Thrombocytopenia
Bleeding risk occurs with less thatn 50k
Thrombocytopenia is the most common cause of clinically significant bleeding
___________ is the most common cause of clinically significant bleeding
Thrombocytopenia is the most common cause of clinically significant bleeding
Platelet count number:
Low platelet count is called “_____”
This can be due to two reasons:
- Decreased production
- Increased destruction (more common)
Explain
Platelet Count Number:
Low platelet count is called “thrombocytopenia”
This can be due to:
- Decreased production (low thrombopoeitin due to bone marrow disorders, drugs)
- Increased destruction (more common):
* hyper spleen activity, mechanical like dialysis, immune and non immune like DIC)
Explain the term ‘Giant Platelet Syndrome”
Giant platelet syndrome:
several inherited syndromes associated with abnormally large Platelets and thrombocytopenia
Examples:
Bernard Souiller
Gray Platelet
May-H
Platelet Dysfunction Disorders:
Typically platelet count is normal but platelet ____ is impaired (adhesion, aggregation, activation)
Inherited types are _____ common
- ______ is the most common inherited platelet dysfunciton disorder
Aquired types are _____ common (especially from drugs)
Platelet Dysfunction Disorders:
Typically platelet count is normal but platelet function is impaired
Inherited types are less common
- most common inherited is von Willebrand Disease (vWD)
Aquired is more common (especially from drugs)
What are the Disorders of Platelet Adhesion:
Inherited
1.
2.
Acquired:
1.
2.
Disorders of Platelet Adhesion:
Inherited:
- vWD (VWF level, VWF activity)
- BS syndrome (GP II/IX/X dysfunction)
Acquired:
- Uremia (renal failure)
- Acquired vWD
What is the most important disorder of platelet aggregation?
Disorder of platelet aggregation:
Glanzman thromblasthenia
(disorder of GP IIb/IIIa receptor dysfunction)
remember that receptor binds to fibrinogen
What is an example of a Disorder of Platelet Secretion aka a Storage Pool Disease
Disorder of Platelet Secretion aka Storage Pool Disease
Inherited alpha granule defeciency aka “Gray Platelet syndrome”
What is the most common cause of platelet function disorders?
Explain the mechanism of action of aspirin
Drug Induced Platelet dysfunction is the msot common cause of platelet funciton disorders
Aspirin inhibits platelet function by blocking the enzyme cyclooxygenase, inhibiting thromboxane from being produced
Note: aspirin is the most common cause of platelet function defects leading to bleeding
________ are the most common cause of platelet dysfunction
_______ is a nonreversible inhibitor of cyclooxygenase
_______ are reversible
DRUGS are the most common cause of platelet dysfunction
Asipirin is a nonreversible inhibitor of cyclooxygenase
NSAIDS are reversible
Chronic liver disorders mess with platelet function because they decrease the level of ________
Chronic liver disorders decrease thrombopoietin
Glanzman Thrombobasthenia: _____ defect, causing a defect in _____
Bernard Souller Disease: ______ defect, causing a defect in _____
VonWillebrand Disease: ______ defect, causing a defect in _____
Storage Pool Disease: _______ defeceincy of ___
Glanzman Thrombobasthenia: GP IIb/IIIa receptor defect aka the receptor that binds to fibrinogen, aggregation defect
Bernard Souller Disease: GP IIb/IX/X receptor defect, causing defect in adhesion (defect ini vWD)
vWD: GP II/IX/X defect, adhesion problems
Storage Pool Disease: Dense or alpha granule defeciency of release reaction
What type of bleeding results from a Coagulation Disorder?
ANATOMIC bleeding results from a coagulation disorder (joint bleeding, deep tissue bleeding)
remember, mucosal bleeding results from platelet disorder
Explain the factor that is defecient in the following diseases:
Hemophilia A
Hemophilia B
Rosenthal Syndrome
vWBDisease
Hemophilia A: Factor VIII, x linked recessive
Hem B: Factor IX, x linked recessive
Rosenthal/Hemophilia C: Factor XI, autosomal recessive
vWD: von Willebrand Factor autosomal dominant
Coagulation Factor Disorders:
Most common quantitative inherited disorders:
Hemophilia A (______ defecient, ____ recessive, most common)
Hemophilia B (____ defecient, ______ recessive, less common)
Explain how in Hemophilia B, the severity of bleeding depends on the amount of factor present
Hemophilia A (factor VIII deficiency, x linked recessive, most common)
Hemophilia B (Factor IX deficiency, x linked recessive less common)
- severity of bleeding depends on the amount of factor
- < 1% SEVERE, spontaneous bleeding
- 1-5% moderate, diagnosed at childhood
Hemophilia C
- Also called ________
- Autosomal recessive
- Mild to moderate bleeding symptoms
- Frequency and severity of bleeding _____ correlate with factor ___ levels
Hemophilia C (FXI defeciency)
- Also called Rosenthal Syndrome
- Autosomal Recessive
- Mild to moderate bleeding symtoms
- Frequency and severity of bleeding DOES NOT correlate with FXI levels
How do you test for hemophilia C?
Prolonged APPT, FXI assay
Thrombocytopenia is technically an individual with a platelet count of less than _______
Bleeding risk for patient with count of
Spontaneous bleeding can occur at count of ___
______ is most common cause of clinical significant bleeding
Thrombocytopenia = platelet count less than 100,000 / uL
Bleeding risk for patient with count less thatn 50,000
Spontaneous bleeding can occur at count of 10,000
Thrombocytopenia is most common cause of clinical significant bleeding
Explain what how the Platelet Aggregation Assay Works:
Platelet aggregation assay:
Prepare the PRP (centrifuge blood but keep platelets in plasma)
Then add an agonist (epi, collagen, ADP)
Then you measure platelet aggregation
Which coagulation factor will be messed up with liver disease BUT normal for someone with a vitamin K defeciency
Factor V problems are exclusive to liver disease
can determine if something is liver problem vs vitamin k problem by measuring factor v
Vitamin K defeciency:
- can be acquired due to diet or drugs
What gets affected within the cascade?
Now that vitamin K is defecient what is the concenquence?
Vitamin K defeciency:
FII, FVII, FIX, FX (factors 2, 7, 9, and 10) and protein S and protein C are all affected by vitamin K
If you do not have vitamin K, the second gamma carboxylase group will not be added, therefore ionized Calcium and phospholipid cannot bind— messes up the coagulation cascade
Prothrombin Test (PT Test)
Screening Test
Assesses the function of the coagulation factors of which pathway?
Monitors _____ therapy
PT Test:
screening test to assess function of coagulation factors in the EXTRINSIC and common pathway
Monitors warfarin therapy
remember: extrinsic pathway if TF activating FVII
APPT Test:
Screening test to assess the function of the coagulation factors in the ______ pathways
Monitors _____ therapy
APTT Test:
Screening test to assess the function of the coagulation factors in the INTRINSIC and common pathways
Monitors heparin therapy
Lab Diagnosis of Bleeding Disorders:
If you have abnormal PT what could it be?
If you have abnormal APTT, what could it be?
If you have abnormal BOTH PT, and APTT?
If you have normal both PT and APTT?
Abnormal PT: liver disease, vitamin K, FVII defeciency
Abnormal APTT: FVIII inhibitor, FVIII, IX, XI defeciency
Abnormal PT and APTT: DIC, lupus, liver disease, factor V, factor X defeciency
Normal PT and APTT: thrombocytopenia, , vWD, Factor XIII
Which factor is not detected by either PT or APTT and needs its own assay to quantitate?
FACTOR 13 (FXIII)
Fibrinolytic System:
The function of the fibrinolytic system is to _____
_______ (enzyme) is highly controlled so that it is not overexpressed
___________ of the fibrinolytic system can cause bleeding
Fibrinolytic System:
Function of fibrinolytic system is to breakdown clots
Plasmin is highly controlled so that it is not overexpressed
Excessive activation of the fibrinolytic system can cause bleeding
Hyperfibrinolytic Mechanisms:
Plasmin breaks down ____ reducing its amount available to make clots
This increases _____ product formation , acting as an anticoagulant
- can be caused by ________
- or be caused by ________
The result is bleeding due to early degradation of formed clots
Hyperfibrinolytic Mechanisms:
Plasmin breaks down fibrinogen
This increases FDP product formation, acting as an anticoagulant
- can be caused by excess activators (TPA)
- or be caused by defeciency in inhibitors/breaks on the system (PAI1)
The result is bleeding due to early degradation of formed clots
What are the lab tests that evaluate fibrinolytic activity?
Lab tests that evaluate fibrinolytic activity?
FDP, D-dimer
VWF is required for platelet ______
Serves as the bridge between collagen and platelets
_______, the platelet plug that closes the damaged vessel, is dependent on vWF
VWF is required for platelet adhesion
Serves as the bridge between collagen and platelets
Primary hemostasis, the platelet plug that closes the damaged vessel, is dependent on vWF
What enzyme cleaves vWF?
What coagulation factor is tightly linked to vWF?
ADAMS13 is the enzyme that cleaves vWF
Factor VIII is transported in blood by vWF
FVIII is unstable without vWF
What is the most common inherited bleeding disorder?
Most common inherited bleeding disorder is vWD
It is either dysfunctional or absent vWF
Messes up platelet adhesion
Explain the following VWD subtypes
Type 1
Type 2
Type 3
von Willebrand Disease:
Type 1: quantitative defeciency, most common
Type 2: structural abnormalities (note 2B is a gain of function mutation)
Type 3: absent vWF
What is the assay that will detect VWF?
Platelet Aggregation Results:
Ristocetin (RIPA) detects vWF only
It will be messed up in vWD, and BS
Type 1 Classical VWD:
What hallmark test results will you see in type 1 vWD?
Type 1 vWD:
Abnormal APTT
Abnormal Bleeding Time Test
Abnormal RIPA platelet aggregation
DIC is a syndrome not a disease itself
What are some causes of DIC?
DIC is a syndrome not a disease itself
Causes:
OB issues (abruptio placentae)
Cancer
Sepsis
DIC is a “_______” coagulopathy
It is a simultaneous activation of _____ and ____
DIC is considered a _____ disorder that causes bleeding from consumption of hemostatic factors
DIC is a consumptive coagulopathy
It is a simultaneous activation of BOTH clotting cascade and fibrinolytic mechanisms
DIC is considered a thrombotic disorder that causes bleeding from consumption of hemostatic factors
DIC
What are some hallmark clinical indications/symptoms?
How do you treat DIC?
Hallmark clinical indications:
petechia/purpura, mucosal bleeding, blood in stool, bleeding from venipuncture site
Treat DIC via removing underlying cause
DIC:
Although no single test can confirm DIC, what is a HUGE lab indication of DIC?
Testing of multiple coagulation factors are performed
Huge lab indication of DIC: presence of schistocytes on blood film (pieces of RBCS)
