unit 4 hem sum

platelets

thrombocytes, anucleate fragments of cytoplasm from megakaryocytes, derived from precursor cells (megakararyocytes) in BM, in pb for 7-10 days, aged or nonviable platelets removed by spleen or liver

platelets function

hemostasis, wound healing, vascular endothelial cell integrity

megakaryocytes

proliferate (megakaryopoiesis) and mature (thrombopoiesis) in bm and released becoming platelets, rare in BM (0.1% of nucleated cells)

BM produces how many platelets per day

1 × 10 ^11, can increase 10-20 fold in times of increased demand

megakaryopoiesis

begins with CMP, megakaryoblast 1st morph platelet id, actively prolif progenitor cell pool, postmitotic nonprolif megakaryocytes pool

CMP development

megakaryoblast, promegakaryocyte, megakaryocyte, thrombocyte

megakaryopoiesis- transit

progenitor to platelet release from bm to circulation= 4-7 days

megakaryopoiesis- regulation

thrombopoietin TPO influences all stages, produced in liver at constant rate, binds to receptor on BM megakaryocytes and progenitors, circulate in platelets (internalized and degraded), not available to stimulate progenitor cells

high platelets in pb

more TPO bound, less free TPO, less platelet production, if low in pb less TPO bound, more free TPO more platelet production

megakarayocyte development divided into 4 stages based on

quantity and characteristics of cytoplasm, size, lobulation, and chromatin pattern of nucleus

megakarayocyte development divided into 4 stages

stage 1 megakaryoblast, 2 promegakaryocyte, 3 granular megakaryocyte, 4 mature megakaryocyte

megakarayocyte development cytoplasm

high volume, basophilic nongranular to granular acidophilic, specific granules (alpha, dense)

megakarayocyte development nucleus

becomes lobulated, coarse chromatin, no visible nucleoli

megakarayocyte

40-100 um, abundant acidophilic granular cytoplasm, multilobed nucleus

megakarayocyte development endomitosis

dna doubles without nuclear/cell division, polyploid, 4N to 64N

8N

can start maturing

dense tubular system DTS

closed internal membrane system, later involved with plt activation

demarcation membrane system DMS

internal, highly branched, interconnected system of channels, maintains open communication with extracellular space

as DMS becomes more extensive

MK cytoplasm compartmentalizes to form proplatelets that form the plts (1k-3k), nucleus remains in BM, engulfed by macrophages

plt pools in constant eq

70% pb, 30% sequestered in spleen

plt on wright stained pb smear

small, lavender-blue-colorless bodies, reddish-purple granules, 2-3 um, if immature= reticulated plt, lack nuc material, contain remnants of golgi complex, ribosomes, small amount of RNA

plt satellitosis

plts appear decreased when adhereing to neutrophils, in vitro, EDTA not heparin or sodium citrate

giant plts

megathrombocytes, >5umM, myeloproiferative disorders, recovery from severe thrombocytopenia

plt evaluation- concentration

2 pools in constant eq, 70% pb (150-450 × 10 3), 30% sequestered in spleen

plt evaluation- estimated plt count from PB smear

normal count= 8-20 plt/100x or 1 plt for every 20 rbcs

plt evaluation- MPV

6.8-10.2 fL, inverse correlation to plt count

plt evaluation- PDW

variation in plt size, analogous (similar) RDW, 9-15 fL

hemostasis tasks

stop bleeding after injury, form primary plug, provide surface for fibrin generation and 2ndary hemostasis, tissue and vessel repair

immune response of plts

synthesize cytokines, chemokines, inflamm mediators, NET formation, and lymph trafficking activation and differentiation

hemostasis purpose

maintain blood fluid state within intact vessles, form a localized clot (blood coag) to prevent blood loss, clot breaksdown after repair (fibrinolysis)

primary hemostasis

plts interact with injured vessel wall forming the fragile easily dislodged plt plug, initially halts loss of blood

secondary hemostasis

reinforcement of plt plug by fibrin formation

bv structure

lumen (central cavity), inner layer (endothelium, basement membrane), middle layer (smooth muscle), outer layer (connective tissue)

vasoconstriction

narrow bv to reduce blood loss, bring plts and coag proteins near the injury, triggered by neural signals (serotonin and thromboxane A2)

intact endothelium aka nonthrombogenic

inhibition of ptl activation (antiplt), inhib of coag, activation of fibrinolysis

antiplt

nitric oxide NO, prostacyclin PGI2 elevated plt cAMP inhib activation, ADPase

anticoag

thrombomodulin and protein C, heparan sulfate and antithrombin, TFPI

profibrinolytic

tPA= tissue plasminogen activator

intact endothelium aka nonthrombogenic components

PGI2, NO, ADPase (CD39), heparan sulfate HS, antithrombin AT, thrombomodulin TM and protein C, TFPI, tPA

endothelium injury aka thrombogenic

activation of plt adhesion aggregation and vasoconstriction (pro plt), activate coag, inhib fibrinolysis

promote plts

vWF release and collagen exposure, plt activating factor PAF, endothelin vasoconstric

procoag

tissue factor exposure/expression

antifibrinolytic

PAI= 1

non hemostatic endothelial cells function

blood/tissue barrier, presentation of blood borne ags, produce vessel-supporting extracellular matix

vessel-supporting extracellular matix

collagen for strength, elastin for stretch and recoil, laminin and fibronectin for cell attachment

platelet ultra structure 4 zones

organelle- mitochondrion, lysosome, glycogen

peripheral

structural- actin (G and F), myosin

membran system

plt structure- peripheral zone

glycocalyx (surface coat) and plasma membrane, surface receptors that detect and respond to vessel injury, activated membrane provides a surface for coag

plt structure- structural zone

cytoskeleton of microtubules and actin, maintains resting discoid shape, produces shape change and pseudopods during activation, supports clot contraction

plt structure- organelle zone

granule released during activation, dense granules- ADP, calcium, serotonin promoting activation aggregation and vasoconstriction, a-granules- vWF fibrinogen factor V PF4 support adhesion coag and repair

plt structure- membrane systems

open canalicular OCS- same as DMS in megakaryocyte, conected to plt surface, route for granule release, shape change

dense tubular DTS- closed internal network, stores Ca2, produces thromboxane A2 TXA2

primary plug formation

adhesion, activation and shape change (constriction), secretion, aggregation

agonists

bind plt receptors to trigger activation, callagen, thrombin, ADP, TXA2

collagen

exposed by vessel injuyry, promotes adhesion and activation

thrombin

produced during coag, powerful plt activator

ADP

released from plt dense granules, promotes GPIIb/IIIa activation, recruits and activates plts

TXA2 thromboxane A2

promotes plt activation recruitment and vasoconstriction, asprin irreveribly inhib COX-1 preventing TXA2 production

TXA2 thromboxane A2 synthesis

by activated plts

membrane phospholipids > arachidonic acid > COX-1 > prostaglandin intermediate > TXA2 production

adhesion

collagen binds vWF binding to plt GPIIb/IX/V tethering the plt, plt GPVI and GPIa/lla bind collagen strengthening adhesion and promoting activation

vWF stored in

endothelial weibel-palade bodies and plt alpha granules

GPIIb/IX/V, GPVI, GPla/lla

plt receptor for vWF, collagen receptor triggers activation, collagen receptor strengthens adhesion

activation and shape change

DTS releases Ca2 into plt cytoplasm, actin/mysin cytoskeleton contracts (disc to spiny sphere, pseudopods, increases surface area, granules move toward plt center), plt GPIIb/IIIa change to active form

calcium

supports shape change secretion and GPllb/lla activation

secretion

granules fuse with OCS or plt membrane, alpha and dense granule release, ADO and TXA2 recruit and activate additional plt

aggregation

activate plt GPllb/lla bind fibrinogen bridging on adjacent plts, additional plts join

stages of plt activation

resting disc shaped, partially activated and fully spiny sphere, aggregate of actives, plt adherence to exposed subendothelium, and intact endoth cells

physical controls of activation and aggregation

endothelial cell barrier limits contact with agonists, flowing blood dilutes agonists

chem and protein controls of activation and aggregation

short agonist T1/2, and EC production of NO, PGI2 (increase cAMP), ADPase, antithrombin

plt structural controls of activation and aggregation

reg intracellular Ca, inability of resting GPllb/llla to bing fibrinogen, limited duration of agonist receptor activity