Coagulation

Question 1

Mechanisms that limit size of the clot

Answer 1

• vasodilation: washing out ADP and TxA2
• anti-thrombin: inactivating thrombin
• tissue factor pathway inhibitor: neutralizing TF
• Protein C & S: inhibit factors III, V, VIII

Question 2

Protein C & S inhibit which factors?

Answer 2

III, V, VIII

Question 3

Mechanisms that breakdown the clot (fibrinolysis)

Answer 3

• plasminogen

- plasmin

Question 4

Plasminogen

Answer 4

• proenzyme
• synthesized in the liver
• incorporated into clot dormant until activated

Question 5

Plasmin

Answer 5

• proteolytic enzyme

- degrades fibrin into fibrin degradation products

Question 6

Plasmin activation involves what substances?

Answer 6

• tPA

- Urokinase

Question 7

When is tPA released?

Answer 7

• released by injured tissue over a period of days (major mechanism)

Question 8

Where is Urokinase produced?

Answer 8

• produced by the kidneys and released into circulation (minor mechanism)

Question 9

What are the mechanisms that turn off Fibrinolysis

Answer 9

• tPA inhibitor

- alpha-2 antiplasmin

Question 10

What is the action of tPA?

Answer 10

inhibits conversion of plasminogen to plasmin

Question 11

What is the action of alpha-2 antiplasmin?

Answer 11

inhibits the action of plasmin on fibrin

Question 12

Contemporary Cell-Based coagulation cascade consists of what 3 phases?

Answer 12

• initiation: TF/VIIa rxn activates factor X (common pathway) - makes small amt of thrombin (IIa)
• amplification: activates plts, V, and XI
• propagation: produces enough thrombin to activate fibrin

Question 13

Activated Partial Thromboplastin Time (aPTT)

Answer 13

• assesses intrinsic and common pathways
• 25-32 sec
• measures time it takes to form a clot using phospholipid, calcium, & an activator

Question 14

International Normalized Ration (PT/INR)

Answer 14

• assesses extrinsic and common pathways
• 12-14
• measures time it takes to form clot w/ TF and Ca+

Question 15

INR

Answer 15

• Normal: 1

- target for warfarin: 2-3 x control

Question 16

Plt Count

Answer 16

• monitors # of plts (not how well they fxn)
• 150,000 - 300,000
• < 50,000 inc. surgical bleed risk
• < 20,000 inc. spontaneous bleed risk

Question 17

Bleeding Time

Answer 17

• monitors plt fxn
• 2-10 min
• ASA and NSAIDs prolong bleeding time
• not commonly used in practice

Question 18

Activated Clotting Time (ACT)

Answer 18

• guides heparin dosing
• 90-120
• ACT >400 sec before CPB
• measured before heparin, 3 min. after its given, & every 30 min thereater

Question 19

TEG - R Time

Answer 19

• time to begin forming clot
• problem: coagulation factors
• tx: FFP

Question 20

TEG - K Time

Answer 20

• time until clot has achieved fixed strength
• problem: fibrinogen
• tx: cryo

Question 21

TEG - Alpha Angle

Answer 21

• speed of fibrin
• problem: fibrinogen
• tx: cryo

Question 22

TEG - Max Amplitude (MA)

Answer 22

• highest vertical amplitude on TEG
• measures clot strength
• problem: plts
  t- tx: plts +/- DDAVP

Question 23

Amplitude at min. after max aimplitude (A60)

Answer 23

• height of vertical amplitude 60 min. after max amplitude
• problem: excess fibrinolysis
• tx: Tranexamic, aminocaproic acid

Question 24

Endogenous heparin is produced by…

Answer 24

• basophils
• mast cells
• liver

Question 25

Exogenous heparin is produced by...

Answer 25

- bovine and porcine GI mucosa

Question 26

Heparin MOA

Answer 26

- inhibits intrinsic and final common pathways - Antithrombin III: natural anticoagulant in the plasma - Heparin binds to antithrombin and accelerates it 1000 fold - AT complex neutralizes thrombin and factors X, XII, XI, & IX - inhibits plt fxn - failed heparin should consider AT deficiency

Question 27

Heparin Pharmacokinetics

Answer 27

- metabolized by heparinase - elimination: degradation by macrophages & renal excretion - doesn't cross the placenta & is safe in pregnancy

Question 28

aPTT therapeutic normal

Answer 28

- 1.5-2.5x normal (25-35 sec)

Question 29

ACT is affected by...

Answer 29

- hypothermia - thrombocytopenia - deficiency of fibrinogen, factor VII, or factor XII

Question 30

Heparin side effects

Answer 30

- hemorrhage - Heparin Induced Thrombocytopenia (HIT) - allergic rxn - Hypotension - dec. ATIII Concentration

Question 31

Heparin contraindications

Answer 31

- neurological procedures - Heparin induced thrombocytopenia - regional anesthesia

Question 32

Protamine

Answer 32

- derived from salmon sperm | - 1mg per every 100 u

Question 33

Another name for vitamin k

Answer 33

Phytonadione

Question 34

IV administration of vitamin k is associated with?

Answer 34

- life threatening anaphylaxis | - if given IV, rate should not exceed 1 mg/min

Question 35

Cryoprecipitate contains which factors?

Answer 35

VIII, XIII, fibrinogen, & vWF

Question 36

Which coagulopathies prolong PTT but no PT?

Answer 36

Hemophilia A | Hemophilia B

Question 37

What lab values are increased and decreased in DIC?

Answer 37

PT/PTT: inc D-dimer: inc Plts: dec fibrinogen: dec

Question 38

3 conditions associated with high risk of DIC

Answer 38

- sepsis (highest risk = gram - bacilli) - OB complications (highest risk = preeclampsia, placental abruption, amniotic fluid embolism) - malignancy (highest risk = adenocarcinoma, leukemia, lymphoma)

Question 39

What are the supportive treatments for DIC?

Answer 39

- Hypovolemia: tx w/ IV fluids - coagulopathy: replace consumed blood components w/ FFP, plts, cryoprecipitate - severe microvascular thrombosis: IV heparin or LMWH

Question 40

Antithrombin deficiency

Answer 40

- antithrombin captures factors XII, XI, X, and IX which ultimately leads to thrombin (IIa) inhibition - heparin works by inc anticoagulant effect of AT by 1000 fold - pts w/ AT deficiency are unresponsive to Heparin - repeated heparin administration can consume the body's supply of AT & produce an acquired form of AT deficiency - tx: AT concentrate and FFP

Question 41

Triggers of sickle cell anemia

Answer 41

- pain - hypothermia - hypoxemia - acidosis - dehydration