310 exam 1

A complex physiologic process that keeps circulating blood in a fluid state:

Hemostasis

The hemostatic system:

All of the above

Procoagulant:

initiates clotting if required

Anticoagulant:

prevents undesirable clotting

Fibrinolytic:

clot breakdown

1˚ hemostasis

vascular system & platelets

2˚ hemostasis

coagulation system

mucocutaneous bleeding (petechiae, purpura, & echymosis) is a clinical manifestation of ___ hemostasis

1˚

anatomical bleeding and thrombosis (due to control protein deficiency) are clinical manifestations of ___ hemostasis

2˚

Which of the following are not involved in 1˚ hemostasis PLT function studies?

• Bleeding time (PFA-100)

• PBS eval & PLT count

• PLT aggregometry

• vWF analysis

• ROTEM (magnetic)

• PT/INR

ROTEM & PT/INR

Which of the following are not involved in 2˚ hemostasis lab investigations?

• Bleeding time (PFA-100)

• PLT aggregometry

• ROTEM (magnetic)

• PT/INR

• Reflex testing

PLT function studies (PLT aggregometry) & Bleeding time (PFA-100)

What is the first response to damage in 1˚ hemostasis?

Blood vessel vasoconstriction

What produces a smooth, natural anti-coag lining when intact to facilitate blood flow?

Blood vessels

The larger the blood vessel, the _____ involvement of the hemostatic system to seal the breach

more

Correlate the correct vessel to the type of bleeding:

1. Capillaries, venules, and arterioles

2. Veins

3. Arteries

1.petechiae, 2.ecchymosis, 3.blowout hemorrhage

Capillaries generally require what for breach-sealing?

Generally direct sealing

Venules and arterioles generally require what for breach-sealing?

Mostly fused platelets

Veins and arteries generally require what for breach-sealing?

Vascular contraction & Hemostatic factor activation & Fused platelets

The BV layers from blood side to tissue side:

tunica intima, tunica media, tunica adventitia

The tunica intima layer consists of?

endothelial cells, sub-endothelium, basement membrane, collagen

The tunica media layer consists of?

elastic fibers of smooth muscle for vasoconstriction

The tunica adventitia layer consists of?

connective tissue and nerves for structural support

What three things maintain the integrity of a BV wall?

endothelial cells, connective tissue of the sub-endothelium, and platelets

Anticoagulant properties of an intact endothelium:

endothelium cells secrete prostacyclin (PGI2), nitric oxide (NO), heparin sulfate, tissue factor pathway inhibitor (TFPI), and tissue plasminogen activator (TPA). ECs also express endothelial protein C receptor (EPCR) and thrombomodulin

Procoagulant properties of an injured endothelium:

vasoconstriction, exposed collagen and tissue factor (TF), released vWF and plasminogen activator inhibitor (PAI)

vWF has the capability to connect to what 4 things?

FVIII, platelets, fibrinogen, and collagen

Platelets or thrombocytes are derived from cytoplasmic fragmentation of?

megakaryocytes (MK)

What differentiates megakaryocytes from osteoblasts?

megakaryocytes are multi-nucleated and fused

MK development and maturation follows the following sequence under the influence of cytokines such as:

IL-3, IL-6, IL-11, TPO: CMP, BFU-Meg, CFU-Meg, MK-I, MK-II, MK-III

MK development and maturation follows what type of division?

endomitosis & endoreduplication

Endomitosis occurs only at what stage(s)?

MK-I & MK-II

What facilitates subdivision of the MK cytoplasm during thrombocytopoiesis?

demarcation membrane system (DMS)

During thrombopoiesis, MK-III cells start shedding what?

proplatelets

Release of proplatelets occur at what stage of megakaryocyte development?

MK-III

What are anucleated cytoplasmic fragments (derived from MKs) with an average diameter of 2-4 µm and MPV 8-10 fL?

platelets

___% of platelets are in circulation while ___% are sequestered in the spleen

70; 30

The spleen will sequester more platelets if it is?

hyperactive

In order to perform a hemostatic task optimally, PLT must have normal function and count must be at least?

100,000

A patient with at least _______ normally functioning platelets can undergo most surgeries without major bleedings

50,000

Glycocalyx, platelet membrane, and open canalicular system (OCS) are all in what zone?

peripheral zone

circumferential microtubules and microfilaments are in what zone?

sol-gel zone

alpha & dense granules, mitochondria, dense tubular system (DTS), and peroxisomes are all in what zone?

organelle zone

ADP, ATP, calcium, and serotonin are examples of?

dense granules

plasminogen, α₂-Antiplasmin, albumin, high molecular weight kininogen (HMWK), fibrinogen, vWF, and FVIII are examples of?

alpha granules: plasma proteins

thrombospondin, platelet factor 4, beta-thromboglobulin, and platelet-derived growth factor (PDGF) are examples of?

alpha granules: platelet-specific proteins

This glycoprotein receptor is for PLT adhesion to the subendothelium

GPIb/IX/V

This receptor is for PLT adhesion to each other (aggregation)

GPIIb/IIIa

P2Y1, PAR1, α2A, GPVI, and GPIb/IX/V

are all receptors for?

agonists

GPIb/IX/V is the receptor for?

vWF

GPIIb/IIIa is the receptor for?

fibrinogen

GPVI is the receptor for?

collagen

A patient with GPIb/IX/V deficiency will experience thrombosis upon exposure to the antibiotic ristocetin

False

Platelet plug formation span several responses which proceed sequentially and rapidly:

shape change, platelet adhesion, granular secretion, platelet aggregation

Platelet adhesion requires?

vWF, GPIb/IX/V, collagen fibers

arterioles have _____ ______ ______. so PLTs can directly bind to collagen easily

lower sheer force

arteries have _____ ______ ______. so PLTs require vWF and collagen binding through GPVI

higher sheer force

When platelets are exposed to agonists (like collagen, ADP, thrombin, and TXA2), they …?

change shape to spheres with pseudopodia

What is a critical step in triggering the secondary wave of aggregation?

ADP from dense granules is released to amplify PLT secretion and aggregation

Platelet aggregation requires?

calcium, fibrinogen, and GPIIb/IIIa

For the release reaction of ADP secretion to occur, …?

the stimulus must be strong enough

To stabilize an injury, the platelet plug requires activation of what?

2˚ hemostasis and formation of fibrin

What tests should be performed if the patient presents with bleeding history but the PLT count if normal?

PLT function studies

Bleeding time reference interval

2.5 - 9.5 mins

The bleeding time (BT) test …

is a screening test which evaluates 1˚ hemostasis issues but is prone to variations

Aspirin, NSAIDs, and antihistamines _____ BT

prolong

the screening test PFA-100 uses …?

citrated whole blood

the mechanism for PFA-100 is based on?

optical aggregometry

BT: in vivo

PFA-100: in vitro

True

What is the gold standard in PLT function studies?

Platelet aggregation (using PLT aggregometer)

How does light transmission platelet aggregometry (LTA) work?

As the agonists are added to PLT-rich plasma in constant agitation, higher % transmittance means higher aggregation rate

An LTA result of 30% is…?

Abnormal

A biphasic aggregation trace pattern is produced by which agonist?

ADP

A primary wave followed by disaggregation trace pattern is produced by what level of ADP?

very low concentration

A single broad wave of aggregation trace pattern is produced by what level of ADP?

high concentration

A biphasic aggregation trace pattern is produced by which two agonists (not ADP)?

epinephrine & thrombin

A lag phase followed by a single broad wave of aggregation trace pattern is produced by what agonist?

collagen

The LTA pattern for severe fibrinogen deficiency is?

No curve because no aggregation

The LTA pattern for storage pool disease is?

Single wave

The LTA pattern for GPIb/IX/V deficiency is?

Reduced aggregation

The LTA pattern for GPIIb/IIIa deficiency is?

No curve because no aggregation

The LTA pattern for vWF deficiency is?

Reduced aggregation

The LTA pattern for regular aspirin consumption is?

Reduced aggregation, no secondary wave

Adding healthy plasma to a patient sample that produces a reduced LTA trace pattern will…?

Normalize vWF deficiency but have no effect on GPIb/IX/V deficiency

thrombocytopenia is defined by?

PLT count below 150 × 10^3/µL

Which of the following coagulation proteins is a “co-factor”?

FVIII

Which of the following coagulation factors is a serine protease?

FX

This coagulation method test takes advantage of the protease activity of a coagulation factor to measure its activity

Chromogenic

Do the following have “anti-coagulant” properties?

• PGI2 (prostacylcin)

• NO (nitric oxide)

• heparan sulfate

Yes, they are produced by intact endothelium cells

Which endothelium-derived factor is “thrombogenic”?

vWF

beta–thromboglobulin

alpha: platelet specific protein

fibrinogen

alpha: plasma protein

calcium

dense

plasminogen

alpha: plasma protein

In a patient who is deficient in PAR1 receptor, PLT response to which agonist will be impaired?

thrombin

In a patient who is deficient in P2Y₁ receptor, PLT response to which agonist will be impaired?

ADP

In a patient who is deficient in alpha2-adregnergic receptor, PLT response to which agonist will be impaired?

arachidonic acid

In a patient who is deficient in GPVI receptor, PLT response to which agonist will be impaired?

collagen

which of the following has thrombogenic qualities?

TF

ROTEM:

magnetic detection

chromogenic

protease activity detection