Platelets Flashcards
Platelets are produced directly from…
Megakaryocyte cytoplasm
Hormone responsible for megakaryopoiesis
Thrombopoietin
70,000 daltons
Thombopoietin is produced by which organ
Liver
Refers to the form of mitosis that lacks telophase and cytokinesis
Endomitosis
formation of giant multinucleated or polyploidy cells
Megakaryopoiesis: Least mature specific progenitor
Burst forming unit-Meg / BFU-Meg
Megakaryopoiesis: most mature specific progenitor
Light density colony forming unit - Meg / LD-CFU-Meg
Megakaryopoiesis: Least mature precursor
MK-I / Megakaryoblast
Megakaryopoiesis: Most mature precursor
MK-III / Megakaryocyte
Endomitosis starts at_________________ (specific progenitor)
LD-CFU-Meg
Endomitosis end at ________________ (precursor)
MK-II / Promegakaryocyte
Thrombopoietin (TPO) is also known as…
MPL ligand
Stimulating hormonal factors that controls the production and release of platelets
TPO/MPL ligand and IL-11
Each megakaryocyte produces ________ (#) platelets
2,000-4,000 (Rodaks)
1,000-4,000 (Steinenger)
Thrombocytes’ lifespan
8-11 days or 9-12 days
Platelets are phagocytized by the…
Liver
Spleen
Other mononuclear phagocytic system
Major source of energy of platelets
Glucose / dextrose
Platelet composition
60% protein
30% lipid
8% carbohydrates
Mineral
Water
Nucleotides
Platelet’s maturation time:
5 days
Platelet structure that is responsible for adhesion and aggregation
Peripheral zone
Coagulation factors composed in Glycocalyx
Factor V, Factor VIII, Fibrinogen
Platelet structure responsible for change in shape, extension of pseudopods, and secretion of granules
Sol-gel zone
Which among the Sol-gel components is majorly responsible for the platelet disc shape
Microtubules
Microtubules disassemble when treated with…
Colchicine
Rope-like polymers
Intermediate filaments of the Sol-gel zone
connect the actin to tubules = maintain shape
Alpha granules
Platelet factor IV, platelet derived growth factor, thrombospondin, VWF, fibrinogen, fibrinectin, Factor V
Dense / Delta granules
CAPASM
Calcium, ADP, Pyrophosphate, ATP, Serotonin, Magnesium
Lysosomes / Lysosomal type granules
Acid hydrolases, ACP, hydrolytic enzymes
Which composition in organelle zone has “clearing” responsibilities
Lysosomes
Membranous system that is derived from Rough ER
Dense tubular system / DTS
DTS sequesters/hold _________ for _______________ and ________________
Calcium
Platelet activation process
Prostaglandin synthesis
Control center for platelet activation
DTS system
System that acts as a canal for the release of alpha-granules
Surface connecting canalicular system (SCCS) or Open canalicular system (OCS)
Sponge like portion of the cell
SCCS / OCS
provides an expanded reactive surface to which plasma clotting factors are selectively adsorbed
Route for endocytosis
SCCS / OCS
Type of platelet that is associated with increased risk of cardiovascular disease
Reticulated platelets
Platelets become round when in ____________ and cylindrical and beaded when in ___________
EDTA
Citrated blood
Pro platelet process occur in MK- ______
III
Megakaryocyte progenitors arise from _______ under the influence of transcription gene product: ___________, regulated by: _____________.
CMP
GATA-1
Cofactor FOG1
Megakaryocyte differentiation is suppressed by ________
transcription gene product: MYB
Which transcription factor mediates the switch from mitosis to endomitosis?
RUNX1
suppress Rho/ROCK signaling pathway = suppresses the assembly of actin cytoskeleton
Morphological vague clue of megakaryoblast
Plasma membrane blebs
Blunt projections from the margin that resemble platelets
Procoagulant-laden alpha-granules, dense granules (bodies), and demarcation system (DMS) begin to develop during the ___________ stage
Megakaryoblast / MK-I
Nuclear lobularity first becomes apparent during the _______________ stage.
MK-II / Promegakaryocyre
Most abundant precursor stage
MK-III / Megakaryocyte
Megakaryocyte characteristics/features
30-50um
Intensely indented and lobulated nucleus
Degree of lobulation is imprecisely proportional to ploidy
Chromatin is variably condensed w/ light and dark patches
Azurophilic cytoplasm, granular
Ploidy levels are measured using
Mepacrine
a nucleic acid dye in megakaryocyte flow cytometry
MRNA for TPO is found in….
Liver
Kidney
Stromal cells
Smooth muscle cells
Liver - has the most copies = main site
Cytokines act in synergy with TPO to induce early differentiation of stem cells
IL-3
Cytokine that enhance endomitosis, megakaryocyte maturation, and thrombocytopeiesis
IL-6 and IL-11
Normal peripheral blood platelet count
150-400x10^9/L
Excess hemostasis = ___________________
Inadequate hemostasis = __________________
Clot extension, thrombosis
Poor wound healing and prone to bleeding
Key component in intravascular hemostasis
Platelets and biochemical (procoagulants)
Primary or Secondary hemostasis: Involves vascular intima
Primary hemostasis
Primary or secondary hemostasis: activated by large injuries to blood vessels and surrounding tissues
Secondary hemostasis
Primary or secondary hemostasis: Rapid, short lived
Primary hemostasis
Primary hemostasis is initiated by…
Exposure of platelets to the subendothelial connective tissue components blood vessels
Factors essential for vascular integrity or resistance to vessel disruption
CFP-3As:
Circulating functional platelets
Adrenocorticosteroids
Ascorbic acid
Anticoagulant used for collection tubes for hemostasis testing
Buffered sodium citrate
Example of drug to avoid prior hemostasis testing
Aspirin
Needle gauge:
Adult w/ good veins: ______
Child/adult w/ small/fragile/hardened veins: ________
Transfer from syringe to tube:______
20-21
23
19
Tourniquet application of >1min
Activate endothelial cells
Elevate conc. Of vWF and fibrinogen
Falsely shortening clot-based tests
Specimen storage at 1-6deg C causes
Precipitation of VWF multimers
Activation of coagulation factor 7/11
Activation of plts
Destruction of plt integrity
Specimen storage at >25deg C causes
Coagulation of factor 5/8 to deteriorate
Ratio if blood to anticoagulant
9:1
Specimen processing for hemostasis should be done at _________ (*temp *)
37deg C
Drugs like aspirin and other NSAIDS INHIBIT __________________
Cyclooxygenase pathway
Plt Func Test: 1 week abstinence
Bleeding time test: 24hrs prior to test
Specimen processing validity:
PT: _______
APTT: ______
24hrs
4hrs
Platelet rich plasma obtained by centrifuging ______________ from 3.2% sodium citrate at ___________________________
Whole blood
50g x for 30mins
Platelet poor plasma obtained by centrifuging ______________ from 3.2% sodium citrate at ___________________________
Whole blood
1500g x for 15mins
PRP samples are used for __________________ (type of tests)
Platelet aggregometry or platelet function test
PPP is for clot-based coagulation tests (PT/APTT)
Blood collection volume is less than specified minimum
PT falsely prolonged
Recollect
Visible hemolysis PT is….
Falsely shortened
Recollect
If sample undergo heparin therapy, solution:
Use rgt known to be in to heparin sensitive
Or w heparin neutralizer such as polybrene
Electromechanical detection fibrin clot formation uses ________________
Instrument: _______________
Wire loop/hook
Fibrometer
Detection of fibrin clot formation through Photo-optical detection depends on the _________________________
Increase in light scattering
Semi automated photo-optical detection instruments
Electra 750 and 750A
Fibrintimer series
FP 910 Coagulation analyzer
Other semi automated instruments:
Fibrometer
-Start 4
-Cascade M and M-4 -BFT-II
-KC1 -KC4
Automated photo-optical detection instruments
Ortho Koagulab 16s and 40A,
Coag-A-Mate X2 and XC,
MLA Electra 700
Other Automated instruments:
ACL TOP,
STA-R Evolution,
STA Compact, and Compact CT
Sysmex CA-530, CA-560, CA-620, CA-660, CA1500, CA-7000, BCS XP, CoaLAB
Clotted samples will cause results to be _______________
Falsely shortened clotting times
Due to premature activation of coagulation factors and plts that generate Factor VIIa and thrombin
(same with Hemolyzed samples)
Samples that are expected to have liver dysfunction
Icterus/Bilirubinemia and abnormal clot formation
Prolonged clotting times because of inadequate factor production
Measurement that measures the uniformity of platelet size
Platelet distribution width
Serve as validity chech and monitor false results
PdW normal value
<20%
Conditions w/ INC PDW
Aplastic and megaloblastic anemia
CML
Antileukemic chemotherapy
Measurement that measures the average volume of platelets
Mean Platelet Volume
Analogous to erythrocytic MCV
MPV should be based on EDTA specimens that are between _______________ hours old
1-4
Healthy patients have inverse relationship between ________________ and ___________
Count
Size
INC count = DEC MPV (vice versa)
Conditions w/ INC MPV
ITP
After splenectomy
Sickle cell anemia
Prostacyclin’s action:
Inhibit PLT activation
Vasodilator (synthesized through eicosanoid pathway)
ATP’s action in intact endothelial cells:
Stimulates vasodilation
Endothelial surface receptor of thrombin
Thrombomodulin
Binds and inactivates thrombin, enhances anticoagulant and fibrinolytic action of protein c in plasma
Heparan sulfate’s action in endothelial cells:
Coats the surface and weakly enhances anti-thrombim III
Converts plasminogen to plasmin
Tissue plasminogem activator (tPA)
Storage site of vwf in:
- endothelium:
- PLTs or Megakaryocyte:
Wiebel palade
Alpha granules
“Carpet” on which activated platelets assemble
VWF
Teh vasculau “relaxing” factor
Nitric oxide
Heparan sulfate is a…..
Blood plasma serine protease that enhances the activity of antithrombin
The alteration in cellular shape is triggered by an ____________^^^^^
Increase level of cytoplasmic calcium
During platelet (adhesion, activation, aggregation) occurs the morphological and functional change in platelets
Activation
During platelet (activation, aggregation, secretion):
Cyclooxygenase metabolizes _______________ to form _______________ that is then converted to _______________ which is a ____________ and a ____________ that causes _________ and __________
Arachidonic acid
Prostagalndin endoperoxidase
Thromboxane A2
Vasoconstrictor
Platelelet stimulator
Platelet Aggregation
Secretion
Necessary cofactor for platelet aggregation
Fibrinogen
(Adhesion, aggregation, secretion) seals the endothelial gaps
Adhesion
Requires VWF
(Adhesion, aggregation, adhesion) essential to coagulation
Secretion
Proteins that controls the cellular activation for all cells in the inner membrane surface
G proteins
Three stages of coagulation mechanism
Generation of prothrombinase complex
Conversion of prothrombin to thrombin
Conversion of fibrinogen to fibrin
Extrinsic pathway is initiated by the entry of ______________________
Tissue thromboplastin (tissue factor)
Fibrinogen is mainly synthesized in ______________
Liver
Largest and most concentrated clotting factor
Fibrinogen
Fibrinogen is the primary substrate of __________
Thrombon
Prothrombin half life
3 days
70% consumption during clotting
In the presence of ______________, prothrombin is converted to ____________ by the enzymatic action of _________________ from both extrinsic and intrinsic sources
Ionized calcium
Thrombin
Thromboplastin
In the presence of ___________, prothrombin is converted to ___________ by the enzymatic action of ________________ from both extrinsic and intrinsic sources
Ionized calcium
Thrombin
Thromboplastin
Thrombin is consumed during ___________________
The conversion of fibrinogen to fibrin
Main enzyme of coagulation pathway
Thrombin (Factor IIa)
Thrombin bound to __________ activate ___________ to suppress _________
Thrombomodulin
Protein C pathway
Coagulation
Tjrombin activates ________ to suppress ___________
TAFI
Fibrinolysis
Factor V half life
16hrs
Action of Factor VII
Activation of thromboplastin
Acceleration of conversion of prothrombin to thrombin
Vitamin K deficiency and Vitamin K antagonists reduce Factor _____
VII
Factor ______ falsely decreased in presence of Lupus anticoagulant (LA)
VIII
Factor VIII is produced by __________ and _______________ in lungs
Hepatocytes
Microvascular endothelial cells
Alpha subunit of Factor XIII is produced by ___________, beta subunit by ___________
Megakaryocyte and monocyte
Liver
Factors that are acute phase reactants
Fibrinogen
Prothrombin
Factor VIII
INC during inflammation (trauma, pregnancy, infection, stress)
Fibrinogen group factors (Thrombin sensitive group)
Factor I, V, VIII, XIII
Prothrombin group factors (Vit. k dependent group)
Factor VII IX X II
Contact group factors
Factor XII XI HMWK PK
Major inhibitor of blood coagulation
Protein C
Protein C stimulates fibrinolysis by……
Inactivating plasminogen activator inhibitors
Cofactor of protein C
Protein S
40% is free and active
60% is bound to complement c4 binding protein and is inactive
Major inhibitor of thrombin
Antithrombin C
Enhanced by heparin = Heparin cofactor II
Also called as lipoprotein associated coagulation inhibitor (LACI) , inhibits the VIIa-tissue factor complex
Extrinsic pathway inhibitor (EPI)
Principle inactivator of factor XIIa and plasma kallekrein
C1-inhibitor
Weak inhibitor of thrombin and factor Xa and XIa
Alpha 1 antitrypsin
Primary purpose of fibrinolysis
Digest fibrin clots
Fibrinolysis occurs when _________ is converted to ____________
Plasminogen
Plasmin
dissolved fibrin or fibrinogen into smaller fragments = (FDP) Fibrin Degradation product or (FSP) Fibrin split product
Plasminogen is produced by the ______
Liver
It is a single-chain protein possessing 5 glycosylated loops termed “kringles”
Plasmimogen
Fibrin-bound plasminogen is converted to __________________ when cleaved between _____________ and ___________
Two-chain active plasmin
Arginin at position 561
Valine at position 562
Primary or Secondary Fibrinolysis: excessive amount of plasminogen activator from damaged cells or malignant cells
Primary fibrinolysis
Ex. Surgery, trauma, malignancy
Primary or secondary fibrinolysis: DEC fibrinogen and DEC plt count
Secondary hemostasis
Primary hemostasis has Normal PLT count
Marker of thrombosis and fibrinolysis
D-dimer
Disseminated intravascular coagulation, rule out venous thromboembolism, and pulmonary embolism
Primary inhibitor of plasmin
Alpha 2 antiplasmin
Urokinase
- secreted by: ________
- circulates in ___________ at a ______ng/mL
- converts _________ to plasmin
- therapeutically used to: _________
Urinary tract epithelial cells, monocytes and macrophages
Plasma
2-4ng/mL
Dissolve thrombi
Playelet stimulating agents
Adp
Collagen
Thrombin
Epinephrine
