Exam 2: Walenga 2

Question 1

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 _____

Answer 1

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

Question 2

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

Answer 2

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

Question 3

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

Answer 3

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

Question 4

PLATELET disorders cause what type of bleeding

Give examples

Answer 4

Platelet disorders cause mucocutaneous bleeding

Examples: petechaie, purpura, ecchymoses (bruises)

Question 5

What is the reference range for platelet count?

What is it called when your platelet count is less than 100,000 /uL?

Answer 5

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

Question 6

___________ is the most common cause of clinically significant bleeding

Answer 6

Thrombocytopenia is the most common cause of clinically significant bleeding

Question 7

Platelet count number:

Low platelet count is called “_____”

This can be due to two reasons:

1. Decreased production
2. Increased destruction (more common)

Explain

Answer 7

Platelet Count Number:

Low platelet count is called “thrombocytopenia”

This can be due to:

1. Decreased production (low thrombopoeitin due to bone marrow disorders, drugs)
2. Increased destruction (more common):
   * hyper spleen activity, mechanical like dialysis, immune and non immune like DIC)

Question 8

Explain the term ‘Giant Platelet Syndrome”

Answer 8

Giant platelet syndrome:

several inherited syndromes associated with abnormally large Platelets and thrombocytopenia

Examples:

Bernard Souiller

Gray Platelet

May-H

Question 9

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)

Answer 9

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)

Question 10

What are the Disorders of Platelet Adhesion:

Inherited

1.

2.

Acquired:

1.

2.

Answer 10

Disorders of Platelet Adhesion:

Inherited:

1. vWD (VWF level, VWF activity)
2. BS syndrome (GP II/IX/X dysfunction)

Acquired:

1. Uremia (renal failure)
2. Acquired vWD

Question 11

What is the most important disorder of platelet aggregation?

Answer 11

Disorder of platelet aggregation:

Glanzman thromblasthenia

(disorder of GP IIb/IIIa receptor dysfunction)

remember that receptor binds to fibrinogen

Question 12

What is an example of a Disorder of Platelet Secretion aka a Storage Pool Disease

Answer 12

Disorder of Platelet Secretion aka Storage Pool Disease

Inherited alpha granule defeciency aka “Gray Platelet syndrome”

Question 13

What is the most common cause of platelet function disorders?

Explain the mechanism of action of aspirin

Answer 13

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

Question 14

________ are the most common cause of platelet dysfunction

_______ is a nonreversible inhibitor of cyclooxygenase

_______ are reversible

Answer 14

DRUGS are the most common cause of platelet dysfunction

Asipirin is a nonreversible inhibitor of cyclooxygenase

NSAIDS are reversible

Question 15

Chronic liver disorders mess with platelet function because they decrease the level of ________

Answer 15

Chronic liver disorders decrease thrombopoietin

Question 16

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 ___

Answer 16

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

Question 17

What type of bleeding results from a Coagulation Disorder?

Answer 17

ANATOMIC bleeding results from a coagulation disorder (joint bleeding, deep tissue bleeding)

remember, mucosal bleeding results from platelet disorder

Question 18

Explain the factor that is defecient in the following diseases:

Hemophilia A

Hemophilia B

Rosenthal Syndrome

vWBDisease

Answer 18

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

Question 19

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

Answer 19

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

Question 20

Hemophilia C

• Also called ________
• Autosomal recessive
• Mild to moderate bleeding symptoms
• Frequency and severity of bleeding _____ correlate with factor ___ levels

Answer 20

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

Question 21

How do you test for hemophilia C?

Answer 21

Prolonged APPT, FXI assay

Question 22

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

Answer 22

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

Question 23

Explain what how the Platelet Aggregation Assay Works:

Answer 23

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

Question 24

Which coagulation factor will be messed up with liver disease BUT normal for someone with a vitamin K defeciency

Answer 24

Factor V problems are exclusive to liver disease

can determine if something is liver problem vs vitamin k problem by measuring factor v

Question 25

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?

Answer 25

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

Question 26

Prothrombin Test (PT Test) Screening Test Assesses the function of the coagulation factors of which pathway? Monitors _____ therapy

Answer 26

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

Question 27

APPT Test: Screening test to assess the function of the coagulation factors in the ______ pathways Monitors _____ therapy

Answer 27

APTT Test: Screening test to assess the function of the coagulation factors in the **INTRINSIC and common** pathways Monitors **heparin** therapy

Question 28

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?

Answer 28

_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

Question 29

Which factor is not detected by either PT or APTT and needs its own assay to quantitate?

Answer 29

FACTOR 13 (FXIII)

Question 30

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

Answer 30

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

Question 31

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

Answer 31

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

Question 32

What are the lab tests that evaluate fibrinolytic activity?

Answer 32

Lab tests that evaluate fibrinolytic activity? FDP, D-dimer

Question 33

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

Answer 33

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

Question 34

What enzyme cleaves vWF? What coagulation factor is tightly linked to vWF?

Answer 34

ADAMS13 is the enzyme that cleaves vWF Factor VIII is transported in blood by vWF FVIII is unstable without vWF

Question 35

What is the most common inherited bleeding disorder?

Answer 35

Most common inherited bleeding disorder is vWD It is either dysfunctional or absent vWF Messes up platelet adhesion

Question 36

Explain the following VWD subtypes Type 1 Type 2 Type 3

Answer 36

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

Question 37

What is the assay that will detect VWF?

Answer 37

Platelet Aggregation Results: Ristocetin (RIPA) detects vWF only It will be messed up in vWD, and BS

Question 38

Type 1 Classical VWD: What hallmark test results will you see in type 1 vWD?

Answer 38

Type 1 vWD: Abnormal APTT Abnormal Bleeding Time Test Abnormal RIPA platelet aggregation

Question 39

DIC is a syndrome not a disease itself What are some causes of DIC?

Answer 39

DIC is a syndrome not a disease itself Causes: OB issues (abruptio placentae) Cancer Sepsis

Question 40

DIC is a "\_\_\_\_\_\_\_" coagulopathy It is a simultaneous activation of _____ and \_\_\_\_ DIC is considered a _____ disorder that causes bleeding from consumption of hemostatic factors

Answer 40

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

Question 41

DIC What are some hallmark clinical indications/symptoms? How do you treat DIC?

Answer 41

Hallmark clinical indications: petechia/purpura, mucosal bleeding, blood in stool, bleeding from venipuncture site Treat DIC via removing underlying cause

Question 42

DIC: Although no single test can confirm DIC, what is a HUGE lab indication of DIC?

Answer 42

Testing of multiple coagulation factors are performed Huge lab indication of DIC: presence of schistocytes on blood film (pieces of RBCS)