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Hematology > Primary hemostasis > Flashcards

Primary hemostasis Flashcards

1
Q

Hemostasis definition

A

process by which the body spontaneoulsy stops bleeding and maintains blood in the fluid state within the vascular compartment

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2
Q

bleeding that doesnt stop

A

hemorrhage

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3
Q

too mcuh coagulation

A

thrombosis

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4
Q

Primary hemostasis

A

Injury

Vascular Phase

Platelet Adhesion

Platelet Aggregation

Temporary Plug

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5
Q

Secondary hemostasis

A

Coagulation cascade

Fibrin Clot Forms

Healing

Fibrinolysis

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6
Q

Major systems

A
  • Vascular
  • platelets
  • coagulation
  • Fibrinolytic
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7
Q

Minor systems

A
  • Kinin
  • Serine Protease
  • Complement
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8
Q

Blood vessel

A

smooth, continuous endothelial lining
- “nonwettable”
- facilitates blood flow

Under normal conditions, hemostasis is prevented by
- endothelium as a physical barrier
- Endothelial secretions of platelet inhibitors Prostacyclin PGI2, and Nitric Oxide NO

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9
Q

Blood vessel layer composition

Inside–> Out

A

Tunica Intima
Tunica media
Tunica adventitia

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10
Q

Tunica intima

A
  • Broad flat endothelial cells
  • supports migration of cells
  • subendothelium = collagen, connective tissue and fibroblasts
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11
Q

Tunica media

A
  • Elastic tissue and smooth muscle
  • Vasoconstriction
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12
Q

Tunica adventitia

A
  • connective tissue
  • support
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13
Q

Smooth muscle constricts

A

vasoconstriction

Diverts blood flow around damaged vasculature

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14
Q

When a blood vessel is breached

A
  • sub-membranous collagen is exposed
  • platelet and coagulation factors are able to be activated = contact activation
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15
Q

Blood vessel secretes

A

cytokines

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16
Q

ADP releases from

A

Endothelium
- promotes platelet aggregation (Platelet plug)

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17
Q

Tissue thromboplastin (Tissue Factor/ Factor III) is released from

A

vessel wall

  • initiates fibrin formation through extrinsic cascade (initiates secondary hemostasis)
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18
Q

PLT count normal

A

150,000-400,000 uL

30% are sequestered in spleen as functional reserve

Aged or non-viable platelets are removed by the spleen and liver

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19
Q

Peripheral platelet zone

A

Function: adhesion and aggregation

  • Open Canilicular system - helps in releasing granules
  • Glycoproteins on surface = Glycocalyx - contains blood group and tissue compatibility antigens
  • Surface provides help with fibrin clot formation: Factor V and VIII

Membrane is former demarcation of membrane parent

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20
Q

Phospholipids

Peripheral Zone

A
  • Makes platelet sticky
  • Platelet Factor 3 - PF3 –> allows assembly of vitamin K dependent coagulation (secondary hemostasis)
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20
Q

Phospholipids

Peripheral Zone

A
  • Makes platelet sticky
  • Platelet Factor 3 - PF3 –> allows assembly of vitamin K dependent coagulation (secondary hemostasis)
21
Q

Adhesion receptors

A

GP1b –> Von Willebrand Factor (wWF)

Fibronectin

22
Q

Aggregation receptors

A

GPIIb/IIIa (normally inaccessible)
- binds fibrinogen
- ADP
- Thrombin
- Epinephrine
- Collagen
- Thromoboxane A2 (TXA2
- Serotonin

23
Q

Sol-Gel Zone

A

Function: Help support membrane

Cytoskeleton contains microfilaments and microtubules

Contractile proteins: Actin, myosin, actomyosin, and “thrombosthenin”

Capable of contracting within seconds

24
Q

Organelle Zone of platelet

A

Function: metabolic reserve

Contains storage granules

Aid in protaglandin/Thromboxane A2 Synthesis

Dense tubular system

Mitochondroa
- 10-60/platelet
- Has glycogen (storage form of glucose)

25
Q

Alpha granules

A

most numerous (up to 200/plt)

  • PLT specific proteins
  • Plasma proteins
26
Q

PLT specific proteins

A

Stay on membrane post secretion

27
Q

Platelet factor 4

A

inhibits heparin

28
Q

beta-thromboglobulin and platelet derived growth factor

A

promotes vessel smooth muscle vessel

29
Q

thrombospondin

A

promotes PLT-PLT interaction

30
Q

plasma proteins

A

become soluble post secretion
- Albumin
- vWF
- Fibrinogen
- Plasminogen
- a2 antiplasmin

31
Q

vWF

A

promotes adhesion

32
Q

Fibrimogen, Factor V, Factor III, high molecular weight kiniogen

A

coagulation

33
Q

Plasminogen

A

fibrinolysis

34
Q

alpha2 antiplasmin

A

inhibits fibrinolysis

35
Q

Dense granules

A
  • 2-10/plt
  • nonmetabolic ATP
  • nonmetabolic ADP - promtotes aggregation
  • calcium - regulates PLT activation/aggregation
  • serotonin - vasoconstriction
36
Q

Lysosomes

A

Proteases
- breaks down protein/peptide

Hydrolyases
- uses water to break a chemical bond

Bactericidial enzymes

37
Q

Platelet plug formation

A

Adhesion
Shape change
aggregation
Secretion Release

38
Q

Platelet plug - adhesion

A

Reversible process where platelets stick to foreign surfaces

Subendothelium is exposed due to injuty
- composed of adhesive molecules: collagen, vWF and others

vWF attaches to platelet membrane GPIb = adhesion

39
Q

Platelet plug - shape change

A

PLT becomes activated and changes from circle disc to “spiny” sphere-pseudopods Thromboplastin) to be accessible

40
Q

Platelet Plug - aggregation 1st wave

(GPIIb/IIIa-Fibrinogen-GP IIb/IIIA)

A

Energy dependent process - requires ATP

Fibrinogen binds to the now usuable GPIIb/IIIa receptors

Bridges of fibrinogen and Ca2+ form between GPIIb/IIIa recepors on adjacent platelets = aggregation

41
Q

Platelet plug - 2nd wave

A

Secretiojn requires a strong stimulus
- thrombin (from coagulation) is great candidate

Platelets secrete their granules - promotes Thromboxane A2 synthesis

Irreversible form, this point

Result = Viscous metamorphosis-transformation of irreversibly aggregated platelets into a mass of degenerative platelet material without membranes

42
Q

Thromboxane A2 (TXA2)

A
  • Recruits more platelets (amplification) and activates them in helping to promote aggregation
  • Once TXA2 is used up, it becomes the inactive form TXB2
43
Q

Effects of Aspirin

A
  • inhibits enzyme cyclo-oxygenase
  • this inhibits endoperoxide and Thromboxsane A2 synthesis
  • When thromboxane A2 synthesis is blocked, this prevents aggregation
44
Q

Platelet plug only provides temporary hold, so we need to reinforce it with fibrin

A

secondary hemostasis

45
Q

Platelet aggregeometry

A

PLT rich plasma and exogenous aggregating agents are added in a cuvette

As platelets aggregate and clump, more light is transmitted = decreasing optical density (absorbance)

% transmittance is recorded creating a pattern

46
Q

Plt count and peripheral smear

A
  • PLT decrease in number in platelet count and visually on smear
  • Giant platelets
  • RBC fragments present from fibrin cutting in circulation
47
Q

Clot retraction

A

After clot formaiton, the blood clot retracts (shrinks) and serum begins to seperate from the clot
- contractile proteins in platelet are responsiblr for clot retraction

Decreased/abnormal retraction can be due to
- thrombocytopenia
- Glanzmann’s Thrombasthenia

48
Q

Platelet Function Assays

A

Screens for platelets ability to adhere to collagen and aggregate together.

Whole blood is added to cartridges containing collagen and either ADP or epinephrine

Used as a screen for von Willebrand Disease, drug-related platelet inhibition and hereditary platelet defects. Also produces abnormal results with vascular disorders

49
Q

Platelet markers

A

Provides proof of platelet activation
virtually absent in normal plasma

Ex:
- Beta Thromboglobulin
- Platelet Factor 4
- Thrombospondin
- Platelet Derived Growth Factor

50
Q

Ultimate goal of coagulation cascade

A

Convert main substrate: fibrinogen (aka Factor I) into fibrin

51
Q

All factors are synthesized in the liver except

A

vWF

PLT contents (alpha granules) are believed to have orig. from the plasma and not truly synthesized in the platelet.

Hematology (36 decks)

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