Hemostasis & Coag

Question 1

Hemostasis

general

Answer 1

Innate, stepwise processes within the body that occurs following vessel injury → clot formation and cessation of bleeding

Question 2

hemostasis

steps
Primary and secondary

Answer 2

Primary hemostasis
Platelet adhesion, activation, and aggregation to the damaged vascular endothelium, forming a plug (weak) that stops the bleeding temporarily

Secondary hemostasis
Activation of the coagulation cascade resulting in the formation of a more stable plug (strong fibrin clot)

Question 3

Vasoconstriction

general

Answer 3

The blood vessel transiently constricts tolimit blood flow to the area

Vessel wall injury and constriction:
1. Site of injury
2. Constriction caused by endothelin release
3. Exposed collagen fibers

Question 4

what drives vasoconstriction

Answer 4

What drives vasoconstriction?
* Neural stimulation reflex:innate contraction of the vascularsmooth muscles upon injury
* Endothelin:a vasoconstrictorsecreted from the damaged endothelial cells
* Thromboxane A2: a vasoconstrictor released fromactivated platelets

Question 5

Primary Hemostasis

Answer 5

Following an endothelialcell injury, the following processes occur with theplateletsto form a temporary platelet plug:
Adhesion
Activation
Aggregation
Secretion

Question 6

Primary Hemostasis

Platelet Adhesion

Answer 6

Platelets adhere to the site of injury with exposure to subendothelial components

What drives adhesion?
Platelet Gplb receptors tightly bind von Willebrand factor (vWF) which is released from injured endothelial cells
Other adhesion interactions with collagen, glycoprotein receptors, and tyrosine kinase receptors leading to adherent “activated” platelets

Question 7

primary hemostasis

von Willebrand factor

Answer 7

glycoprotein that serves as the initial stationary foundation for clot formation

Question 8

primary hemostasis

platelet activation

Answer 8

Activatedplateletsenhance further platelet adhesion and aggregation, and stimulatesecretion

Question 9

Primary Hemostasis - Platelet Activation

Platelet activators

potent and weak

Answer 9

Potent platelet activators:
Thrombin: produced in the coagulation cascade
Collagen: interacts withplatelets at the site of injury

Weaker platelet activators:
ADP: acts in an autocrine fashion → released byplateletsto help activate otherplatelets
Epinephrine

Question 10

Primary Hemostasis - Platelet Activation

Activatedplatelets will..

Answer 10

Undergo shape change to become an elongated pseudopod → new shape is extremely adherent
Activate theirGpIIb/IIIareceptors
Release their granules (alpha and dense)

Question 11

Primary Hemostasis -

Platelet Aggregation

Answer 11

GpIIb/IIIareceptorspresent on the activated plateletsbegin binding to fibrinogen
Fibrinogen
Symmetricalmolecule
Canbind2plateletssimultaneously forming bridges betweenplatelets → platelet aggregation and formation of aprimary hemostatic plug

Question 12

Primary Hemostasis - Platelet Secretion

Answer 12

Activated platelets release their granules (alpha and dense)

Question 13

Primary Hemostasis - Platelet Secretion

Functions of secreted substances from granules of platelets

Answer 13

Recruit and activate additionalplatelets
Stimulate expression of GpIIb/IIIa onplatelets→ enhancedaggregation
Promotevasoconstriction
Stimulate the process of vascular repair via fibroblast/smooth muscle cellrecruitment
Contribute to initiation of thecoagulation cascade

Question 14

Question 15

Secondary Hemostasis – Coagulation Cascade

general

Answer 15

Series of reactions that ultimately generates a strong, cross-linkedfibrinclot

A number ofcoagulation factors undergo sequential activation by 1 of the 2 pathways

Question 16

Secondary Hemostasis – Coagulation Cascade

Extrinsic pathway

Answer 16

Extrinsic pathway: primarily responsible forinitiationof the cascade; activated by tissue factor (factor 3) released by injured endothelial cells

ends with factor 10.

Question 17

Secondary Hemostasis – Coagulation Cascade

intrinsic

Answer 17

Intrinsic pathway: primarily involved inamplificationof the cascade; activated by negatively charged collagen in the subendothelial matrix

starts with 12 ends with 10

Question 18

Secondary Hemostasis – Coagulation Cascade

Common pathway:

Answer 18

Common pathway:
The extrinsic and intrinsic pathways join together to form the final common pathway when factor X is activated
Formation of thefibrinclot occurs at the end of the common pathway

starts with 10
ends with factor 13 which is fibrin clot

Question 19

Question 20

where do the Factors come from?

Answer 20

The liver is responsible for the formation of most factors (hepatocytes)
Factors XIII, XII, XI, X, IX, VII, V, II, and I

Exceptions:
Factor III and VIII originate from endothelial cells
Factor IV (calcium ion) is freely available in plasma

there is no factor 6

Question 21

as zymogens

Answer 21

inactive form of factors for coagulation

Become activated → act as a catalyst to cleave the next zymogen
Zymogen to enzyme activation was denoted with the letter a – Example: XII → XIIa

Question 22

which factors belong to which pathways

Answer 22

Pathway Factors
Extrinsic pathway: III and VII
Intrinsic pathway: XII, XI, IX, and VIII
Common pathway: X, V, II, I, and XIII

Question 23

vitamin K

general

Answer 23

Lipid cofactor that is required for normal blood clotting

Primarily synthesized in the colon as a byproduct of bacteria
Activated by epoxide reductase in theliver

Question 24

Vitamin K-dependent factors:

Answer 24

Factors II, VII, IX, X
Undergo carboxylation to become functional

Question 25

# Inhibition of Coagulation general

Answer 25

The body produces several substances that inhibit platelet binding, aggregation, and secretion = **natural anticoagulants**

Question 26

# natural anticoagulants Tissue factor pathway inhibitor (TFPI)

Answer 26

Inhibits the activation of factor X Located primarily on the surface of microvascular endothelial cells

Question 27

# natural anticoagulants Antithrombin III

Answer 27

Natural circulating anticoagulant produced by the liver Inhibits activated forms of factors II, IX, and X

Question 28

# natural anticoagulants Proteins C and Protein S

Answer 28

C: Vitamin K-dependent factors produced by the liver Protein C cleaves and inactivates factors V and VIII S: Vitamin K-dependent factors produced by the liver Augments the activity of protein C

Question 29

Fibrinolytic Phase

Answer 29

The fibrinolytic system functions to remove the clot after the vasculature is repaired Prevents excessive fibrin deposition This process is accomplished primarily by plasmin

Question 30

# Fibrinolytic Phase Plasmin

Answer 30

Plasmin Cleaves fibrin fibers (fibrinolysis) to form fibrin-degradation products Cleaves other clotting factors (V, VIII, IX and X) Plasminogen is activated →converted to plasmin by: Tissue plasminogen activator (tPA) Urine plasminogen activator (uPA)aka urokinase Both are secreted by endothelial cells

Question 31

# Coagulation Studies general

Answer 31

Group of hematologic studies that reflect the function of blood vessels, platelets, and coagulation factors Uses of coagulation studies Evaluation of abnormal bleeding or thrombosis Pre-operative testing Management of anticoagulation therapy Assist in resuscitation management during massive transfusions

Question 32

Prothrombin Time (PT)

Answer 32

Time taken for the plasma  to clot when exposed to tissue factor Measures function of the extrinsic and common pathways Normal range: ~11–13 seconds

Question 33

# prothrombin time elevated in:

Answer 33

Warfarin therapy Vitamin K deficiency Deficiency of factors II, V, VII, and X Liver disease  Disseminated intravascular coagulation (DIC)

Question 34

# prothrombin time (PT) International Normalized Ratio (INR)

Answer 34

International Normalized Ratio (INR) A ratio comparing the patient’s PT to a reference PT Measures function of the **extrinsic and common pathways** Normal range: approximately 0.8–1.1

Question 35

Activated Partial Thromboplastin Time (aPTT) 

Answer 35

Time taken for the plasma to clot when exposed to a negatively charged substance (which activates the intrinsic pathway) Measures function of both the **intrinsic and common pathways** Normal range: ~25–40 sec

Question 36

# Activated Partial Thromboplastin Time (aPTT)  elevated in

Answer 36

Elevated in: Heparin therapy  Hemophilia (abnormal factor VIII or IX) von Willebrand disease (vWD) Liver disease Disseminated intravascular coagulation (DIC)

Question 37

Bleeding time (BT)

Answer 37

Measures the time for bleeding to stop after a lancet incision Indirect measure of platelet function Normal range: 2–7 minutes prolonged in: Thrombocytopenia Disseminated intravascular coagulation (DIC) von Willebrand disease (vWD) Renal failure NSAID and/or aspirin use

Question 38

# Laboratory Evaluation of Coagulation Fibrinogen

Answer 38

Precursor to fibrin Abnormally low levels can increase bleeding risk Bleeding tends to occur when levels < 100 mg/dL Normal range: 200–400 mg/dL

Question 39

# Laboratory Evaluation of Coagulation D-dimer

Answer 39

Primary fibrin-degradation product Released upon cleavage of cross-linked fibrin by plasmin **Indicates recent or ongoing coagulation and fibrinolysis** Normal range: < 500 ng/mL Elevated in: DVT/PE Stroke Disseminated intravascular coagulation (DIC) Covid-19 infection