CH. 10 - Platelet Production, Structure, and Function

Megakaryocytes

Platelets arise from unique bone marrow cells called?

GATA-1

Megakaryocyte progenitors arise from the common myeloid progenitor under the influence of this transcription gene product.

Endomitosis

• A partially characterized form of mitosis unique to megakaryocytes in which DNA replication and cytoplasmic maturation are normal but cells lose their capacity to divide.

• It is a form of mitosis that lacks telophase and cytokinesis

Terminal differentiation

A series of stages in which microscopists become able to recognize unique Wright-stained morphology in bone marrow aspirate films.

MK-I stage / megakaryoblast

This is called the least differentiated megakaryocyte precursor

DMS

A series of membrane-lined channels that invade from the plasma membrane and grow inward to subdivide the entire cytoplasm

MK-II stage

The promegakaryocyte reaches its full ploidy level by the end of what stage?

MK-III stage

In this stage, the megakaryocyte is easily recognized at 103 magnification on the basis of its 30- to 50-mm diameter

2000-4000

During thrombocytopoiesis, a single megakaryocyte may shed how many platelets?

TPO growth factor

It is a 70,000 Dalton molecule that possesses 23% homology with the red blood cell-producing hormone erythropoietin

MPL

It is a viral oncogene associated with murine myeloproliferative leukemia

IL-6 and IL-11

These cytokines act in the presence of TPO to enhance endomitosis

IL-3

This cytokine acts in synergy with TPO to induce the early differentiation of stem cells

Reticulated platelets

Also known as stress platelets, they appear in compensation for thrombocytopenia

Cholesterol

It stabilizes the membrane, maintains fluidity, and helps control the transmembranous passage of materials through the selectively permeable plasma membrane

Surface-Connected Canalicular System (SCCS)

• This enables the platelet to store additional quantities of the same hemostatic proteins found on the glycocalyx

• It is the route for endocytosis and for secretion of a-granule contents upon platelet activation.

Dense Tubular System (DTS)

• It is a condensed remnant of the rough endoplasmic reticulum.

• It sequesters Ca2+ and bears a number of enzymes that support platelet activation including phospholipase A2, cyclooxygenase, and thromboxane synthetase.

Actin

It is contractile in platelets (as in muscle) and anchors the plasma membrane glycoproteins and proteoglycans

FcyIIA (CD32)

A low-affinity receptor for the immunoglobulin Fc portion that plays a role in a dangerous condition called heparin-induced thrombocytopenia

P-selectin (CD62)

It is an integrin that facilitates platelet binding to endothelial cells, leukocytes, and one another.

ADAMTS13

The interaction between platelet and VWF remains localized by a liver-secreted plasma enzyme

Blood vessel injury

This exposes tissue factor expressed on subendothelial smooth muscle cells and fibroblasts

Microparticles

These are membrane-derived vesicles that form in response to an activating stimulus that increases the platelet intracellular concentration of calcium

1. Vascular System

2. Platelets (Thrombocytes)

3. Blood Coagulation Factors

4. Fibrinolysis and ultimate tissue repair

4 Major Components of Hemostasis

Vasoconstriction

It is a reflex in which blood vessels narrow to increase blood pressure.

Epinephrin and serotonin

These hormones promote vasoconstriction

Endothelium

• It regulates the permeability of the inner vessel wall and provides the principal stimulus to thrombosis following injury to a blood vessel.

• Involved in the clotting process by producing or storing clotting components.

Prostacyclin

It strongly inhibits platelet aggregation and adhesion

Endothelins

They act as modulators of vasomotor tone, cell proliferation, and hormone production

Endothelin-1

It is the only family member produced in endothelial cells and is also produced in vascular smooth muscle cells

Endothelin-2

It is produced predominantly within the kidney and intestine, with smaller amounts produced in the myocardium, placenta, and uterus.

Endothelin-3

• It has been found in high concentrations in the brain and may regulate important functions, such as proliferation and development in neurons and astrocytes

• It also is found throughout the gastrointestinal tract and in the lung and kidney

Endothelial Dysfunction

It plays an important role in the initiation, progression, and clinical complications of various forms of inflammatory and degenerative vascular diseases

First phase of Endothelial Dysfunction

Rapid vasoconstriction for up to 30 minutes reduces blood flow and promotes contact activation of platelets and coagulation factors

Second phase of Endothelial Dysfunction

Platelets adhere immediately to the exposed subendothelial connective tissue, particularly collagen.

Third phase of Endothelial Dysfunction

Coagulation is initiated through both the intrinsic and extrinsic systems

Fourth phase of Endothelial Dysfunction

• Fibrinolysis occurs following the release of tissue plasminogen activators (t-PAs) from the vascular wall.

• Fibrinolytic removal of excess hemostatic material is necessary to reestablish vascular integrity.

• Circulating functional platelets

• Adrenocorticosteroids

• Ascorbic Acid

Essential Factors for Vascular Integrity

Veins

They may rupture with a slight increase in hydrostatic pressure

Megakaryocytopoiesis

Proceeds initially through a phase characterized by mitotic division of a progenitor cell, followed by a wave of nuclear endoreduplication.

Endoreduplication

It is the process in which chromosomal material (DNA) and the other events of mitosis occur without subsequent division of the cytoplasmic membrane into identical daughter cells

Thrombopoietin

It is the hormone thought to stimulate the production and maturation of megakaryocytes, which in turn produce platelets, has recently been purified and cloned

TRUE

Platelets have no nucleus. TRUE OR FALSE

FALSE

Nuclei are still visible in megakaryocytes. TRUE OR FALSE

Inactive or unstimulated platelet

It circulates as a thin, smooth-surfaced disc

Glycocalyx or fluffy coat

• It surrounds the cellular membrane of the platelet externally

• Composed of plasma proteins and carbohydrate molecules that are related to the coagulation, complement, and fibrinolytic systems

Microfilaments and Microtubules

• Located directly beneath the cell membrane of platelet

• Provide structure of the platelet to maintain its discoid shape

• Maintains the position of the organelles

Alpha

Most abundant type of granules in a mature platelet

Dense or delta

Type of granules that contain serotonin, adenosine diphosphate (ADP), adenosine triphosphate (ATP), and calcium.

Lysosomes

They store hydrolase enzymes

Contractile proteins

• Actomyosin (thrombosthenin),

• Myosin

• Filamin

1000-2000

An average megakaryocyte produces about how many platelets?

2 days

Platelets initially enter the spleen & remains for how many days?

5 days

Marrow transit time / maturation period of megakaryocyte

G-proteins

Type of proteins that control cellular activation for all cells at the inner membrane surface

LD-CFU-Meg

REVIEW QUESTION:

The megakaryocyte progenitor that undergoes endomitosis is:

Thrombopoietin

REVIEW QUESTION:

The growth factor that is produced in the kidney and induces growth and differentiation of committed megakaryocyte progenitors is:

Dense tubular system

REVIEW QUESTION:

What platelet organelle sequesters ionic calcium and binds a series of enzymes of the eicosanoid pathway?

GP IIb/IIIa

REVIEW QUESTION:

What platelet membrane receptor binds fibrinogen and supports platelet aggregation?

Phosphatidylserine

REVIEW QUESTION:

What platelet membrane phospholipid flips from the inner surface to the plasma surface on activation and serves as the assembly point for coagulation factors?

Prostacyclin

REVIEW QUESTION:

What is the name of the eicosanoid metabolite produced from endothelial cells that suppresses platelet activity?

Serotonin

REVIEW QUESTION:

Which of the following molecules is stored in platelet dense granules?

VWF

REVIEW QUESTION:

What plasma protein is essential for platelet adhesion?

Increased platelet production in response to need

REVIEW QUESTION:

Reticulated platelets can be enumerated in peripheral blood to detect:

Are largely composed of platelets and von Willebrand factor

REVIEW QUESTION:

White clots:

The surface connected canalicular system

REVIEW QUESTION:

Upon activation, platelets secrete their a-granule contents via:

Bud off of platelets after their exposure to strong agonists

REVIEW QUESTION:

Microparticles:

Thiazole orange

This nucleic acid dye binds the RNA of the endoplasmic reticulum

50 to 80

How many α-granules are there in each platelet?

2 to 7

How many dense granules are there per platelet?

GP IV

It is a key collagen receptor that binds thrombospondin

Thrombin

It cleaves two STRs, PAR1and PAR4.

TXA2

TPα and TPβ bind?

Platelet aggregation

Platelet-to-platelet binding referred to as?

Red clot

This type of clot is essential to wound repair, but may also be characteristic of inappropriate coagulation.

White clot

This type of clot is composed primarily of platelets and Von Willebrand factor (VWF).

Arachidonic acid

5,8,11,14-eicosatetraenoic acid is commonly called?

Cyclooxygenase

It converts arachidonic acid to prostaglandin H2 to produce TXA2

IP3-DAG pathway

This is the second G-protein dependent platelet activation pathway.