hema - platelets Flashcards
___ are directly produced from the megakaryocyte cytoplasm
platelets
As the megakaryocyte _____, clusters of granules aggregates to form _____
matures ; platelets
platelet development occurs via ______
endomitosis
NUCLEAR DIVISION WITHOUT CYTOPLASMIC DIVISION
endomitosis
A single megakaryoblast nucleus may contain ___ to ___ times the normal number of chromosomes
2 to 64
______ is densely staining, dispersed early and more compact at later stages
nuclear chromatin
______ are small at all development stages
nucleoli
Each Megakaryocyte produces ____ to _____ platelets
2,000 to 4,000
Most megakaryocytes at any stage of maturation and their precursors (megakaryoblasts) normally are found ONLY IN THE _______, not in the ______
BONE MARROW ; peripheral blood
Normal bone marrow contains approximately ______ megakaryocyte ( ____ megakaryocytes per 10x power field)
15 million ; 5-10
Megakaryocyte proliferation is largely regulated by ______
THROMBOPOIETIN
Additional growth factors including _____, _____, ____ support megakaryocytic development in the presence of thrombopoietin
kit-ligand, IL-3, IL-11
Serum thrombopoietin levels are inversely proportional to platelet count, however levels are increased in ________
liver disease and inflammation
Maturation sequence of megakaryoblast takes about ____ days
5
the more nuclear lobes the megakaryocyte possess, the _____ the cytoplasmic mass & therefore the more ____ produced.
larger ; platelets
Conversely megakaryocytes w/ lower _____ values produce larger platelets that are denser & more functionally active.
ploidy
increased production of platelets may be accomplished by means of 3 possible mechanisms:
- the no. of megakaryocytes in the BM may increase
- the size of the megakaryocytes may increase
- there may be a decrease in the maturation time of the megakaryocyte
major platelet production takes place in the _____, where the megakaryocytes make up less than 1% of the _______.
bone marrow ; nucleated cells of the marrow
thrombocytopoiesis occurs in _____
bone marrow
thrombocytopoiesis life span
5-9 days
platelet size
1-4 um or 2-4 um
platelet cytoplasm
light blue-purple and very granular
granular and located centrally
chromomere
surrounds the chromomere, nongranular and clear to light blue
hyalomere
Platelets are removed by ____ in the liver and spleen or by active use in _____
macrophage ; daily coagulation mechanisms
Circulating platelets are distributed between the spleen and blood.. ____ in spleen and ____ in blood
1/3 are always in the spleen and 2/3 are in peripheral blood
What is the platelet value in splenectomy?
platelet count is higher w/o a slpeen (undergone splenectomy)
What is the platelet value in splenomegaly?
platelet count is lower in splenomegaly
first stage of platelet maturation
megakaryoblast
the second stage of platelet maturation
promegakaryocyte
the third stage of platelet maturation
granular megakaryocyte
the fourth stage of platelet maturation
mature megakaryocyte
size of megakaryoblast
20-50 um (earliest recognizable)
size of promegakaryocyte
20-60 um
size of granular megakaryocyte
30-90 um
size of mature megakaryocyte
40-120um (largest cell in the bone marrow)
M: Round oval, or may be kidney shaped
C: Fine
Nucleoli: Multiple nucleoli
Nuclei: –
color: Deeply basophilic (blue)
Usually darker than myeloblast
Amount: small - moderate
Granules: Nongranular or rare
N/C: 10:1 (high)
Megakaryoblast (Stage I)
M: Irregular in shape maybe horseshoe shaped
C: Coarse
Nucleoli: Multiple nucleoli
Nuclei: –
color: Less basophilic
Amount: more abundant
Granules: Granules begin to form in the golgi region
N/C: 4:1-7:1 (high)
Promegakaryocyte (Stage II)
M: Smaller size
C: Coarser than stage II
Nucleoli: No nucleoli visible
Nuclei: Multiple nuclei visible
color: pinkish
amount: abundant
granules: Very fine & diffusely granular
N/C: 2:1-1:1 (low)
Granular Megakaryocyte (Stage III)
M: multilobulated
C: Coarse and linear
Nucleoli: No nucleoli visible
Nuclei: Multiple nuclei present or nucleus is multilobulated
Color: Totally pink
Amount: abundant
Granules: Coarse clumps of granules aggregating into little bundles, which bud off from the periphery to become platelets
N/C: Less than 1:1 (low)
Mature Megakaryocyte (Stage IV)
ULTRASTRUCTURE OF PLATELET
- peripheral zone
- sol-gel zone
- organelle zone
consists 30 or more glycoproteins, phospholipids & platelet VIII:vWF
plasma membrane
receptor for von Willebrand’s factor (vWF)
Glycoprotein lb
receptor for fibrinogen
Glycoprotein llb/llla
receptor for thrombin
Glycoprotein Va
lies directly beneath the platelet membrane
sol-gel zone
sol-gel zone is composed of _____ & ______
microfilaments & microtubules
maintain platelet shape & a contractile system
cytoskeleton
contain the proteins actin & myosin w/c, upon stimulation of the platelet, will interact to actomyosin (thrombosthenin)
Microfilaments
contractile protein important in clot retraction
actomyosin (thrombosthenin)
composed of the protein tubulin, w/c maintains the platelet’s disc shape.
microtubules
composed of the mitochondria, alpha granules, dense bodies & lysosomal type granule.
Organelle Zone
are the most numerous & contain a no. of substances including platelet factor 4, ß- thromboglobulin, platelet derived growth factor (PDGF), thrombospodin, von Willebrand factor, fibrinogen, fibrinectin & platelet albumin.
alpha granules
Ca, ADP, Serotonin (5-hydroxytryptamine) of organelle zone
dense granules
for energy production
mitochondria
What are the 2 membranous systems?
dense tubular system
open canalicular system
- serves as the site of Arachidonic acid metabolism
- Also functions as a Calcium-sequestering pump that maintains platelet cytoplasmic Ca levels
- It also synthesizes prostaglandin.
- The surface connecting system, as an invagination of the plasma membrane, acts as a canal for the release of the granule constituents & cytoplasm to the exterior of the platelet.
- It also involved in platelet phagocytosis.
Dense tubular system
- release of granules
- Provides direct communication between intracellular and extracellular compartments
Open canalicular system
- originates from MK ER
- composed of channels located near OCS
Dense Tubular System
Dense Tubular System is a site of
- Ca2+ storage
- several enzymes, ATPases, Cyclooxygenase (PG synthesis)
Ca2+ storage is important for ____
triggering contraction of actinomysin
platelet function: hemostasis and thrombosis
adhesion
activation
spreading
secretion
aggregation
procoagulant activity
clot retraction
tissue repair
platelet function: maintenance/regulation of vascular tone
uptake of serotonin when resting
release of serotonin, thromboxane, prostaglandins upon activation
platelet function: inflammation
atherosclerosis
allergic asthma
renal disease
chemotaxis
platelet function: host defense
phagocytosis/internalisation of viruses and bacteria
killing of bacteria
release of platelet microbicidal proteins
superoxide production
platelet function: tumour biology
tumour growth
tumour killing
tumour metastasis
what substances promote coagulation
HMWK, Fibrinogen, Factor V, Factor VIII :vWF
the source of the substances: HMWK, Fibrinogen, Factor V, Factor VIII :vWF
alpha granules
principal/function of HMWK
Contact activation of intrinsic coagulation pathway
principal/function of fibrinogen
Converted to fibrin clot
principal/function of Factor V
cofactor in fibrin clot formation
principal/function of HMWK Factor VIII :vWF
Assists platelet adhesion to subendoethelium to provide coagulation surface
what substances promote aggregation
ADP, Calcium, Platelet Factor 4, Thrombospondin
sour of substances ADP and Calcium
Dense Bodies
source of substances Platelet Factor 4 and Thrombospondin
Alpha granules
principal/function of ADP, Calcium, Platelet Factor 4, Thrombospondin
promote platelet aggregation
what substances promote vasoconstriction
serotonin, Thromboxane A2 precursors
source of serotonin
dense bodies
source of thromoxane A2 precursors
membrane phospholipids
principal/function of serotonin, Thromboxane A2 precursors
Promotes vasoconstriction at injury site
what substance promote vascular repair
Platelet-derived growth factor
Beta thromboglobulin
source of Platelet-derived growth factor and Beta thromboglobulin
Alpha granules
principal/function of platelet-derived growth factor
Promotes smooth muscle growth for vessel repair
principal/function of beta thromboglobulin
Chemotactic for fibroblasts to help in vessel repair
other systems affected
Plasminogen, α2- antiplasmin, C1 esterase inhibitor
source of Plasminogen, α2- antiplasmin, C1 esterase inhibitor
alpha granules
principal/function of Plasminogen
Precursor to plasmin, which induces clot lysis
principal/function of α2- antiplasmin
Plasmin inhibitor; inhibits clot lysis
principal/function of C1 esterase inhibitor
Complement system inhibitor
_________ must be sufficient for them to play their supportive role in hemostasis. When evaluating a bleeding problem that may be traceable to platelets, the counting of platelets is an important & logical starting point.
platelet numbers
platelet count may be done simply by _______ on a peripheral blood film or by using various ___________.
estimating the no. of platelets ; manual or automated techniques
a general reference range is ______
150-400x10^9/L
there are approx. ________ in normal peripheral blood.
10-40 RBCs/platelet
an oil immersion field containing 100 RBCs should have between _______, whereas a filed containing 200 RBCs should have between _______
3-10 platelets ; 5-20 platelets
review of peripheral films is advantageous in ___________.
detecting causes of artifactually low counts secondary to platelet clumping caused by anticoagulant-dependent platelet agglutinins or clots from poorly collected specimens
Giant platelets seen in some___________ will also be appreciated by this mtd.
congenital platelet defects & certain myeloproliferative disorders
The accepted normal range of the platelet count is generally between _________ of blood, although values much lower than this can be quite adequate for ______.
150 to 400 X 10^9/L ; hemostasis
Many clinicians will refrain from platelet repletion in a stable patient until counts drop below _______
10 to 20 X 10^9/L.
Initial evaluation of the platelet count must take into consideration any ___________
pseudothrombocytopenia.
often due to cold-reacting platelet agglutinins or platelet binding to neutrophils (platelet satellitism).
Pseudothrombocytopenia
In Pseudothrombocytopenia, The agglutinins are often seen in patients with __________ and usually only bind platelets when calcium is _______, such as in an ______ blood collection tube.
high immunoglobulin levels or infections ; chelated ; EDTA
A pseudothrombocytopenia associated with the ________ has also been reported.
glycoprotein IIb/IIIa antagonist drug abciximab
________ is an indication of platelet size.
mean platelet volume (MPV)
Normal MPV ranges are approximately _________
8 to 10 fL
The MPV can be an indication of _________, because platelets newly released from the bone marrow are _____ and tend to ______ with age in the circulation.
platelet turnover ; larger ; decrease in size
In patients with rapid turnover, the platelets will, in general, be _____ because of the ________.
larger ; larger size of newly produced platelets
True ________ usually have uniformly large platelets; often the platelets are at least ______ the normal size and may be as large as ______.
congenital macrothrombocytopenias ; twice ; erythrocytes
Newer techniques based on messenger RNA detection in platelets (reticulated platelets) may also be helpful to indicate the rate of _________.
thrombopoiesis
