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Hematology > Lecture 5- do not > Flashcards

Lecture 5- do not Flashcards

1
Q

what are platelets

A

Complex, Anucleate cell fragments that are 2-4 um

-in a wrights stain they appear Circular to irregular in shape
‒ Cytoplasm light blue to colourless
‒ ‘Granular’ looking
■ Granules are abundant
■ Red to violet in colour
■ Only slightly visible using light microscopy
-flat or discoid shape or bi convex

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2
Q

Platelet Morphology

A

Complex, granular structure
-have alpha granules, mitochondrion , open canicular system
‒ Involved in clotting of blood and tissue repair

-Platelets circulate in an inactivated or resting state
-become activated by tissue injury
-Activation includes shape change, adhesion, aggregation & secretion (granule release)

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3
Q

Platelet precursors arise
from which stem cells?

A

MHCs - common myeloid progenitor

BM megakaryocytopoiesis - sit right beside because the venous sinusoid
-cytokines help to go from one stage to next

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4
Q

Megakaryocytic Progenitors

A

Proliferation Phase
● BFU-Meg clones hundreds of daughter cells (mitosis) (least mature) - job is proliferation

● CFU-Meg clones a dozen daughter cells (mitosis) - more intermediate forms

● LD-CFU-Meg undergoes the first stage of Endomitosis (most mature) most ready to produce the precursors for the BM

-need flow cytometry to test cant tell by just looking

a Megakaryocytic erythrocyte Progenitors with CFU GEMM acts on BFU Meg using TPO, Meg - CSF and IL 3

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5
Q

Endomitosis

A

DNA is duplicated without cell division (replicates nucleaus cytoplasm) (do not see separation of parents from daughters causing larger cells) no cytokinesis
● Unique to Megakaryocyte linage
● MKs become ‘polyploid’
‒ Contain multiple copies of DNA within a single cell
‒ Most have a ploidy of 16N(range 4N - 64N)
● MKs are the largest normally occurring cells in the marrow (20-90µm)
‒ More DNA= larger cell or more cytoplasm synthesized= more
PLTs

-how does the cytoplasm become more abundant - the higher the N the more ptls being produced

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6
Q

what is Terminal Differentiation of Megakaryocytic Progenitors

A

Series of stages where MK differentiation becomes recognizable in BM using LD CFU MEG
● Broken into three morphological stages:
1. MK-I or Megakaryoblast- round nucleus, , Endomitosis only , basophilic cytoplasm with granules

  1. MK-II or Promegakaryocyte- indented nucleus, condensed chromatin,, Endomitosis ENDS, cytoplasm is abundant, basophilic and granular
  2. MK-III or Megakaryocyte -LARGEST (undergoes proplatelet process and platelet shedding)- multilobed nucleus, condensed chromatin, NO MITOSIS OR ENDOMITOSIS, azurophilic and granular cytoplasm

● MK-I can look like any blast
● MK-II & -III identified in BM

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7
Q

how are platelets formed

A

-Massive amounts of DNA produce equally massive amounts of cytoplasm and proteins

-plasma membrane ‘invades’ the cytoplasm in a series of channels –
this is the Demarcation System or DMS - divide the megakaryocyte cytoplasm

-Form basis for fragmentation into single PLTs

  • After the cytoplasm is released as platelets, the MK nucleus that
    remains is reabsorbed by Macrophages in the bone marrow

-PLATELET SHEDDING
-MKs sit adjacent to BM venous sinusoids
-DMS dilates & tubules called ‘proplatelet processes’ (pseudopodia) develop

-Across processes constrictions form, ready to fragment

-These pierce through or squeeze between endothelial cells and break off or shed into the central vein of BM and then into peripheral circulation

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8
Q

Control of Thrombopoiesis
Thrombopoietin or TPO

A

Glycoprotein hormone produced by kidney and liver, that circulates in plasma
‒ Also produced by smooth muscle cells, and stromal cells

Binds to megakaryocytes and circulating platelets via MPL membrane receptor
-PLTs and MKs degrade TPO, taking it out of circulation or removing stimulus for PLT production (primary platelet count control mechanism)

● decrease PLTs = INCREASE circulating TPO
‒ stimulates platelet production

TPO Induces:
● Stem cells to differentiate into MK progenitors
● MK progenitors to differentiate into MK
● Proliferation and maturation of MK
● Platelet release (PLT shedding) from MK

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9
Q

Thrombopoietin INDUCES

A

-Stem cells to differentiate into MK progenitors
● MK progenitors to differentiate into MK
● Proliferation and maturation of MK
● Platelet release (PLT shedding) from MK

acts In synergy with various cytokines (e.g., Interleukins, IL-3, IL-6 & IL-11)

increases platelet production

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10
Q

WHAT IS THE Platelet Plasma Membrane LIKE

A

●Phospholipid bilayer
● Receptors on the membranesurface
● Thick surface or glycocalyx - also absorbs plasma proteins
● The outer membrane also extends inside – similar to the
DMS of MK
● Surface is negatively charged ‒ Repels other PLTs so they
don’t stick together spontaneously

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11
Q

what are the Platelet Plasma Membrane: Receptors like

A

▪ Promotes PLT adhesion and aggregation

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12
Q

what are some Platelet Plasma Inner Organelles

A

Surface-Connected Canalicular System (SCCS)
‒ Inner extension of plasma membrane that binds
coagulation factors and provides a route for secretion of α-granule
contents

● Dense Tubular System (DTS)
‒ Supports PLT activation, provides cytoskeleton

● Microfilaments & Microtubules
‒ Maintain PLT (discoid) shape
‒ Allow for shape change (via membrane contraction and pseudopod extension)

● Granules
‒ α- and dense granules –
‒ Also contain few lysosomes (similar content to Neutrophils)

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13
Q

what are α-Granules all about

A

●50-80 per PLT
● Some proteins absorbed from plasma
● Some made in MK
● Released through SCCS during PLT activation
‒ α-granule membrane fuses with SCCS and contents are released
‒ E.g., Coagulation factors
(Fibrinogen, Factor V and VWF)

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14
Q

what are Dense Granules

A

2 – 7 per PLT (endocytosed)
● Migrate to PLT plasma membrane to release contents directly into the plasma when PLT is activated

-contains ADP - non metabolic and support platelet aggregation by binding to P2Y and ADP receptors

-Serotonin - Vasoconstrictor

CA and MG - divalent cations support platelet activation and coagulation

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15
Q

Platelet Function - first line of defense during blood lose -

A

PLTs circulate in a resting or inactivated state
● PLTs attach to injured vessel
● Upon activation, PLTs:
‒ Adhere, Aggregate & Secrete
● Part of PRIMARY HEMOSTASIS or Blood Clotting
● Platelet ‘Plug’ formation is the start of clot formation

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16
Q

Resting to Activated Platelet how does that happen in 3 steps

A

Initially discoid (resting)
● Change shape
‒ When activated become- Round with long, finger-like projections (pseudopods) and lamelipodia
‒ Sticky and adhere to one another and to blood vessel surfaces to form a PLT plug

Adhesion
‒ Receptors to Collagen or VWF
● Aggregation
‒ PLT to PLT receptors
● Secretion
‒ From granules through SCCS or directly to membrane

17
Q

what happens when Platelet Activated - secondary hemostasis

A

Release molecules that cause fibrinogen to be converted to fibrin
* Fibrin molecules combine:
‒ Form a long, sticky fibrous mesh
‒ Traps other platelets, RBCs & WBCs
* Summon more platelets to the damaged vessel
* Activate other clotting factors

Fibrin clot (or red clot) formation
‒ Series of plasma protein interactions on PLT surface
‒ PLT phospholipid surface is essential to solid clot formation

18
Q

what is Primary Hemostasis

A

Injury or trauma to blood vessel endothelium
● Blood vessels contract to seal wound & reduce blood flow in
general area
● Collagen exposed
● Damaged endothelial cells release adhesion molecules
& VWF
● Platelets adhere to Collagen &/or VWF

19
Q

what is Platelet Adhesion

all occurs simultaneously

A

Occurs via receptors specific to Collagen or VWF
● GP Ib/IX/V –
‒ Binds VWF & Thrombin
-vwf acts as bridge

● GP Ia/IIa & GP VI –
‒ Bind Collagen

● Firm but Reversible binding
● PLT loses disc shape and spreads

extending of the pseudopodia

20
Q

what is Platelet Aggregation

A

PLT to PLT binding to build up the plug
● PLT microenvironment supports binding via activation of GPIIb/IIIa
receptor
● Fibrinogen with Ca2+ and VWF bind GPIIb/IIIa of adjacent PLTs
● PLT shape continues to spread and form pseudopods
‒ Forms large clump(s) that cover greater surface area
● Irreversible – shape

some granules contain the plt proteins and in the system and also in the endothelial cells

21
Q

what is Platelet Secretion

A

Secretion of α- & dense granules
‒ Via SCCS or directly to PLT plasma
membrane, respectively
● Occurs simultaneously with adhesion and aggregation
● Amplification of aggregation by
releasing more Fibrinogen & Ca2+

alpha granules are also coag proteins

22
Q

what is primary and secondary hemostasis

A

●Primary – Platelet plug
(or white clot) is insufficient to repair most damaged vessels
-plts and vWf

● A solid clot requires Secondary
Hemostasis – Fibrin clot (or red clot) formation
‒ Series of plasma protein interactions on PLT surface
‒ PLT phospholipid surface is essential to solid clot formation

23
Q

how many PLT are in PB

A

● R.I. 150 – 450 x 10^9 /L decreases as you get older
● Live an average of 8-12 days
● 2/3 of total platelet numbers circulate in PB
● 1/3 are sequestered in splenic pool ‒ Released when sudden depletion of PLTs occurs
-acts as a reserve for after surgery or injury
-if the spleen is inflamed there will be low plt due to increased sequestration

-megakaryocytic precursors made in the red pulp MPV corresponds to larger platelet diameter

24
Q

Thrombocytopenia

A

● < 150 x 10^9 /L
● Caused by:
‒ decreased Production
■ E.g., Acute Leukemias, BM failure like aplastic anemia (can
manifests as bruising in patient) or Myelodysplasia
‒ Splenic sequestration
‒ increase Peripheral destruction
■ Antibodies to PLTs
■ , MAHA, hemolytic anemias- DIC & TTP)

25
Q

Thrombocytosis

A

● > 450 X 10^9/L
● Causes include:
‒ Reactive
■ E.g., Injury, surgery, stress, pregnancy, or immune response
‒ Pathological
■ E.g., Chronic Leukemia or Chronic bleeding

26
Q

Abnormal PLT Morphology
‘Giant’ platelets
Agranular platelets
Elongated platelets

A

● ‘Giant’ platelets- same size or larger then RBC
‒ Great variation in size – 20um
‒ Result of abnormal megakaryopoiesis

● Agranular platelets
‒ Appear light gray due to lack of protein within granules

● Elongated platelets - like a dumbbell two platelets at each end
‒ Reticulated PLTs – released early – larger proplatelet processes
(cylindrical and beaded seen in citrated whole blood)

27
Q

Most common cause of
PLT clumping in PBF:

A

● Poor venipuncture technique with CBC sample
‒ Slow or difficult draws
‒ Improper or delayed mixing

● We can also see similar
results with EDTA induced PLT clumping

● Platelets start to aggregate or ‘clump’
‒ Leads to falsely decreased PLT count on CBC
● ‘Clumps’ can also be counted as WBC by analyzers
‒ Falsely high WBC count on CBC

28
Q

‘Platelet Satellitism’

A

● In vitro phenomenon known as
‘Platelet Satellitism’
‒ Rare and only seen in certain patients
● Caused by patient’s PLT response to EDTA in ETS tube
‒ EDTA causes PLTs to adhere to Neutrophil surface
● Find out after examining CBC & PBF
‒ Pseudothrombocytopenia on CBC
‒ PLTs surrounding Neuts on PBS

29
Q

How to resolve?

Poor venipuncture

EDTA-induced PLT clumping or PLT Satellitism

A

● Poor venipuncture
‒ Reject sample and recollect in new lavender-top EDTA tube
‒ Troubleshoot technique

● EDTA-induced PLT clumping or PLT Satellitism
‒ Reject sample and recollect using Sodium Citrate anticoagulant
■ Draw a light blue-top tube (liquid anticoagulant)
■ Adjust the CBC results for the dilution factor

30
Q

real pr thrmbon pseudopedia

A

ttur thrmbo - pt with low plt

pseudo thyr - lab error

check with a smear if you dont see large clumps look for platelet clumps in the smear

Hematology (12 decks)

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