**2. Platelets**

These cell fragments are morphologically small scale but functionally vital under life threatening conditions (1). They originate from megakaryocytes located mainly in the bone marrow, found in circulating blood and stored in spleen (2). Platelets don't contain a nuclei and during their inactive state they have a discoid morphology with a diameter of 2-4 micrometer (3, 4). But whenever they are active they can change their morphology very rapidly to an irregular branched spread form (5). Currently platelets are being used at wide spread clinic treatments from cosmetic needs to supporting insufficient heart (6, 7).

## **2.1. Development of Platelets**

It is not exactly explained how platelets originate from megakaryocytes. There are several models to explain formation of platelets.

Megakaryocytes seem to locate as triple form. With their VEGF secretion capacity they hold vessel endothelial cells close to themselves (8). The most scientifically accepted three models are mentioned as,


bone marrow and on these branches there are uprising small bodies where by the help of blood shear force platelets enter directly to circulating blood stream. It was suggested that the concept of platelet like bodies arise from pseudopods of Megakaryocytes, the forming platelets were named as "proplatelet" (10).

Platelets 5

These small cell fragments have complex properties; 2 cytoplasmic regions can be seen in

1. **Hyalomere:** The light blue homogeneous region of the peripheral cytoplasm is called Hyalomere. Hyalomere includes cytoplasmic filaments and circumferential microtubule bundle under the cell membrane. These elements of the cytoskeleton provide the

2. **Granulomere (Chromomere):** This is the central region and tight area. It is ranging in color from blue to purple-staining. Granulomere includes small Golgi complex, smooth endoplasmic reticulum, lysosome, scattered granules surrounded by a membrane and a

Platelets have a simple appearance but carry very complex functional properties. By dividing this simple cell fragment to four regions helps for a better understanding of the

This region is composed from unit membrane with open canalicular system. Three parts

This is a glycocalix membrane with 10-20 nm thickness and thicker than the other blood cells, rich from glycoproteins that are mainly receptors for cell-cell and cell-vessel

Platelet unit membrane has some similarities and appearance with other unit membranes of cells, it is composed from bilipid layer rich of phospholipids (12), it can distribute molecules according to phsico-chemical properties for passing the membrane. The membrane has anionic and cationic pumps. Platelet unit membrane is an important

Just located under the unit membrane a layer composed of microflament network. This network is anatomically and functionally related to membrane glycoproteins and

This is cytoplasm corresponding part of the cellular fragment, platelet. It is in soluble or gel phase according to changes of polymerization of the filaments; actin and

Just under the submembrane zone there are microtubules forming a peripheral ring which helps platelet to maintain its discoid shape in inactive form. When activated**,** the microtubules surround the organelles and with the contribution of other filaments (13)**,** the organelles are tightly contracted. During silent form only 30-40 % of actin filaments are polymerized, when platelets are activated the polymerized amount

movement and the protection of the platelets' shapes.

variety of mitochondria (4).

functions of platelets.

1. Peripheral Zone:

are defined as;

a. Exterior outer layer:

interactions(1, 8).

c. Submembrane Zone:

microtubules(1).

increases(1).

2. Sol-Jel Zone:

b. Platelet Unit Membrane:

catalyst for liquid phase coagulation.

cytoplasmic filament system.

platelets

**Figure 1.** Megakaryocyte branches with Platelet Buds (PB) are seen. Proplatelets are released as Dumbell shaped bodies. This image is referenced from Hartwig and Italiano 2003 (Thanks for the kind permission of John Wiley and Sons to use this image) (11) .

Kinetics of platelets; they have a life span as 7-10 days and in 1 liter human blood it is estimated that there are 150-400X109 platelets so for a balanced number they are formed 15X109 -40X109 daily. Megakaryocytes located in the bone marrow sinusoids form a barrier to other bone marrow cells, it forms a physical barrier preventing direct contact to blood circulation. But there are canallicular openings in megakaryocyte membrane which permits cell migration to other cells to enter blood stream; this is named as "Emperipolesis" (8).

These small cell fragments have complex properties; 2 cytoplasmic regions can be seen in platelets


Platelets have a simple appearance but carry very complex functional properties. By dividing this simple cell fragment to four regions helps for a better understanding of the functions of platelets.

1. Peripheral Zone:

4 Blood Cell – An Overview of Studies in Hematology

forming platelets were named as "proplatelet" (10).

bone marrow and on these branches there are uprising small bodies where by the help of blood shear force platelets enter directly to circulating blood stream. It was suggested that the concept of platelet like bodies arise from pseudopods of Megakaryocytes, the

**Figure 1.** Megakaryocyte branches with Platelet Buds (PB) are seen. Proplatelets are released as Dumbell shaped bodies. This image is referenced from Hartwig and Italiano 2003 (Thanks for the

Kinetics of platelets; they have a life span as 7-10 days and in 1 liter human blood it is estimated that there are 150-400X109 platelets so for a balanced number they are formed 15X109 -40X109 daily. Megakaryocytes located in the bone marrow sinusoids form a barrier to other bone marrow cells, it forms a physical barrier preventing direct contact to blood circulation. But there are canallicular openings in megakaryocyte membrane which permits cell migration to other cells to enter blood stream; this is named as "Emperipolesis" (8).

kind permission of John Wiley and Sons to use this image) (11) .

This region is composed from unit membrane with open canalicular system. Three parts are defined as;

a. Exterior outer layer:

This is a glycocalix membrane with 10-20 nm thickness and thicker than the other blood cells, rich from glycoproteins that are mainly receptors for cell-cell and cell-vessel interactions(1, 8).

b. Platelet Unit Membrane:

Platelet unit membrane has some similarities and appearance with other unit membranes of cells, it is composed from bilipid layer rich of phospholipids (12), it can distribute molecules according to phsico-chemical properties for passing the membrane. The membrane has anionic and cationic pumps. Platelet unit membrane is an important catalyst for liquid phase coagulation.

c. Submembrane Zone:

Just located under the unit membrane a layer composed of microflament network. This network is anatomically and functionally related to membrane glycoproteins and cytoplasmic filament system.

2. Sol-Jel Zone:

This is cytoplasm corresponding part of the cellular fragment, platelet. It is in soluble or gel phase according to changes of polymerization of the filaments; actin and microtubules(1).

Just under the submembrane zone there are microtubules forming a peripheral ring which helps platelet to maintain its discoid shape in inactive form. When activated**,** the microtubules surround the organelles and with the contribution of other filaments (13)**,** the organelles are tightly contracted. During silent form only 30-40 % of actin filaments are polymerized, when platelets are activated the polymerized amount increases(1).

	- 3. Organel Zone:

This is the zone where granule's, peroxisome's, lysosome's and mitochondria's are localized. There are enzymes, adenine nucleotids, calcium, serotonin and many other proteins in this region (1).

Platelets 7

Thrombospondin

 beta thromboglobulinler Factors V, XI, XIII fibrinogen

von Willebrand factor

high molecular weight complexes kininogen

**Table 1.** Some main components of alpha granules.

are briefly given in Table 2 (10, 14, 19, 20).

pyrophosphate Nucleotides ATP, GTP, ADP, GDP

**Table 2.** Some main components of dense granules.

participant for homeostasis (14).

vascular endothelial growth factor

mitogenic growth factors (platelet-derived growth factor)

These are smaller granules with 150 nm diameter (24), because of the calcium and phosphate content there image seems dense under electron microscopic (EM) observation (21, 25). Each platelet contains 3-8 of these granules (14). The components of dense granules

In activated platelet these granules fuse with plasma membrane and expel their ingredients to their environment which causes other platelets to aggregate and a local vasoconstriction (especially by serotonin) in the involved vessels. Also the ADP content is a very important

The importance of the components of dense granules for homeostasis is recognized when the diseases of the deficiency of dense granules was defined as Hermansky-Pudlak

 P-selectin platelet factor 4

fibronectin vitronectin

chemokines

TGF-beta

Ca Mg P

 LAMP 2 Serotonin GPIb, GPIIb/IIIa P-Selectin Histamine Epinephrine

**4. Dense granules** 

 Membrane proteins CD63 (granulophysin)

4. Membrane Zone

There is a distinguishing feature of platelets that their plasma membrane contains wide spread invaginations that forms a network inside platelet. Finally with pore openings the inner network is directly in contact with outer zone. This system is named as "open canallicular system" (OCS) and with this system an extensive amount of surface area stays as potential in silent state. With this system also platelet gains a large area for molecular trafficking. A second canal system is composed from endoplasmic reticulum networks and named as "Dense Tubular System" (DTS). Here in DTS many enzymes and calcium ions that are important for activation are located. DTS is not directly connected to outer membrane (1, 14) but has close connections with OCS. These two systems actively exchange molecules (1).

The granulles have diameters ranging between 200 to 500 nm and they are found as spherical or oval structures (15). There are 3 types of granules in platelets, Alfa Granules, Dense granules, lysosomes. Alpha granules are most prominent in terms of material content and majority. These granules include inflammatory molecules, cytokines, cell-activating molecules, proteins, Growth Factors, adhesion molecules, integrins and other proteins These granules are filled by megakaryocytes (3).
