Thrombopoiesis

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Thrombopoiesis is the formation of platelets in the Bone marrow. Thrombopoietin is the main regulator of thrombopoiesis. Thrombopoietin affects most aspects of the production of platelets. This includes self-renewal and expansion of hematopoietic stem cells, stimulating the increase of megakaryocyte progenitor cells, and supporting these cells so they mature to become platelet-producing cells. [2] The process of Thrombopoiesis is caused by the breakdown of proplatelets (mature megakaryocyte membrane pseudopodial projections). During the process almost all of the membranes, organelles, granules, and soluble macromolecules in the cytoplasm are being consumed. Apoptosis also plays a role in the final stages of thrombopoiesis by letting proplatelet processes to occur from the cytoskeleton of actin. [3]

Contents

Platelets

Platelets are formed by megakaryocytes and are present in the bloodstream for 5-7 days. Platelets are regulators of hemostasis and thrombosis. Platelets become active in the blood following vascular injury. Vascular injury causes platelets to stick to the cellular matrix that is exposed under the endothelium, form a platelet plug, and then form a thrombus. Platelets are essential in the formation of an occlusive thrombus and are the main target of preventing the formation of an arterial thrombus. Platelets are also important in innate immunity and regulating tumor growth and vessel leakage. [4]

Megakaryocytes

The megakaryoblast is a platelet precursor that undergoes endomitosis to form megakaryocytes that have 8 to 64 nuclei. Megakaryocytes shed platelets into the bloodstream. β1-tubulin microtubules, which are found in megakaryocytes, facilitate this process of shedding platelets into the bloodstream. [5] Megakaryocytes are precursor cells that are highly specialized. Megakaryocytes give rise to 1,000 to 3,000 platelets. Megakaryocytes function in the process of Thrombopoiesis by producing platelets and releasing platelets into the bloodstream. [6] Megakaryocyte development is regulated mainly by thrombopoietin. IL-3, IL-6, and IL-11 also play a role in the development of megakaryocytes by working closely with thrombopoietin. [7]

Thrombopoietin

Thrombopoietin is the main regulator in the process of thrombopoiesis. In the liver and renal tubular epithelial cells, thrombopoietin is constantly being produced. Platelets and platelet precursors clear and destroy the thrombopoietin that is produced so the concentration of plasma thrombopoietin levels and platelet and platelet precursor mass are inversely proportional. If there is less platelet mass present, less thrombopoietin is cleared, which causes an increase in free plasma thrombopoietin that stimulates thrombopoiesis. [5]

Related Research Articles

Haematopoiesis The formation of blood cellular components

Haematopoiesis is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult person, approximately 1011–1012 new blood cells are produced daily in order to maintain steady state levels in the peripheral circulation.

Blood cell Cell produced by hematopoiesis

A blood cell, also called a hematopoietic cell, hemocyte, or hematocyte, is a cell produced through hematopoiesis and found mainly in the blood. Major types of blood cells include red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes). Together, these three kinds of blood cells add up to a total 45% of the blood tissue by volume, with the remaining 55% of the volume composed of plasma, the liquid component of blood.

Thrombus

A thrombus, colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of cross-linked fibrin protein. The substance making up a thrombus is sometimes called cruor. A thrombus is a healthy response to injury intended to prevent bleeding, but can be harmful in thrombosis, when clots obstruct blood flow through healthy blood vessels.

Platelet Component of blood aiding in coagulation

Platelets, also called thrombocytes, are a component of blood whose function is to react to bleeding from blood vessel injury by clumping, thereby initiating a blood clot. Platelets have no cell nucleus; they are fragments of cytoplasm that are derived from the megakaryocytes of the bone marrow, which then enter the circulation. Circulating unactivated platelets are biconvex discoid (lens-shaped) structures, 2–3 µm in greatest diameter. Activated platelets have cell membrane projections covering their surface. Platelets are found only in mammals, whereas in other vertebrates, thrombocytes circulate as intact mononuclear cells.

Coagulation Process by which blood changes from a liquid to a gel, forming a blood clot

Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism of coagulation involves activation, adhesion and aggregation of platelets, as well as deposition and maturation of fibrin.

Immune thrombocytopenic purpura

Immune thrombocytopenic purpura (ITP), also known as idiopathic thrombocytopenic purpura or immune thrombocytopenia, is a type of thrombocytopenic purpura defined as an isolated low platelet count with a normal bone marrow in the absence of other causes of low platelets. It causes a characteristic red or purple bruise-like rash and an increased tendency to bleed. Two distinct clinical syndromes manifest as an acute condition in children and a chronic condition in adults. The acute form often follows an infection and spontaneously resolves within two months. Chronic immune thrombocytopenia persists longer than six months with a specific cause being unknown.

Paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease of the blood characterized by destruction of red blood cells by the complement system, a part of the body's innate immune system. This destructive process occurs due to the presence of defective surface protein DAF on the red blood cell, which normally functions to inhibit such immune reactions. Since the complement cascade attacks the red blood cells within the blood vessels of the circulatory system, the red blood cell destruction (hemolysis) is considered an intravascular hemolytic anemia. Other key features of the disease, such as the high incidence of blood clot formation, are incompletely understood.

Megakaryocyte

A megakaryocyte is a large bone marrow cell with a lobated nucleus responsible for the production of blood thrombocytes (platelets), which are necessary for normal blood clotting. In humans, megakaryocytes usually account for 1 out of 10,000 bone marrow cells, but can increase in number nearly 10-fold during the course of certain diseases. Owing to variations in combining forms and spelling, synonyms include megalokaryocyte and megacaryocyte.

Thrombopoietin

Thrombopoietin (THPO) also known as megakaryocyte growth and development factor (MGDF) is a protein that in humans is encoded by the THPO gene.

Primary myelofibrosis (PMF) is a rare bone marrow blood cancer. It is classified by the World Health Organization (WHO) as a type of myeloproliferative neoplasm, a group of cancers in which there is abnormal growth of cells in the bone marrow. This overproduction is most often associated with a somatic mutation in the JAK2, CALR, or MPL gene markers. In PMF, the healthy marrow is replaced by scar tissue (fibrosis), resulting in a lack of production of normal blood cells. Symptoms include anemia, increased infection and an enlarged spleen (splenomegaly).

P-selectin Cell adhesion molecule (CAM) on the surfaces of activated endothelial cells, which line the inner surface of blood vessels, and activated platelets

P-selectin is a protein that in humans is encoded by the SELP gene.

GPVI

Glycoprotein VI (platelet), also known as GPVI, is a glycoprotein receptor for collagen which is expressed in platelets. In humans, glycoprotein VI is encoded by the GPVI gene. GPVI was first cloned in 2000 by several groups including that of Martine Jandrot-Perrus from INSERM.

Microvesicles Type of extracellular vesicle

Microvesicles are a type of extracellular vesicle (EV) that are released from the cell membrane. In multicellular organisms, microvesicles and other EVs are found both in tissues and in many types of body fluids. Delimited by a phospholipid bilayer, microvesicles can be as small as the smallest EVs or as large as 1000 nm. They are considered to be larger, on average, than intracellularly-generated EVs known as exosomes. Microvesicles play a role in intercellular communication and can transport molecules such as mRNA, miRNA, and proteins between cells.

Thrombopoietin receptor

The thrombopoietin receptor also known as the myeloproliferative leukemia protein or CD110 is a protein that in humans is encoded by the MPL oncogene.

SH2B3

SH2B adapter protein 3 (SH2B3), also known as lymphocyte adapter protein (LNK), is a protein that in humans is encoded by the SH2B3 gene on chromosome 12.

CFU-GEMM

CFU-GEMM is a colony forming unit that generates myeloid cells. CFU-GEMM cells are the oligopotential progenitor cells for myeloid cells; they are thus also called common myeloid progenitor cells or myeloid stem cells. "GEMM" stands for granulocyte, erythrocyte, monocyte, megakaryocyte.

Congenital amegakaryocytic thrombocytopenia

Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare inherited disorder.

Kenneth Kaushansky, M.D., Master of the American College of Physicians (MACP) is an American medical doctor, hematologist, former editor of the medical journal Blood, and has served as the Dean of the Stony Brook University School of Medicine since July 2010. Prior to moving to Stony Brook, he was the Helen M. Ranney Professor, and Chair of the Department of Medicine at University of California, San Diego School of Medicine.

Thromboregulation is the series of mechanisms in how a primary clot is regulated. These mechanisms include, competitive inhibition or negative feedback. It includes primary hemostasis, which is the process of how blood platelets adhere to the endothelium of an injured blood vessel. Platelet aggregation is fundamental to repair vascular damage and the initiation of the blood thrombus formation. The elimination of clots is also part of thromboregulation. Failure in platelet clot regulation may cause hemorrhage or thrombosis. Substances called thromboregulators control every part of these events.

The platelet plug, also known as the hemostatic plug or platelet thrombus, is an aggregation of platelets formed during the earlier stage of hemostasis in response to blood vessel wall injury. After platelets are recruited and begin to accumulate around the breakage, their “sticky” nature allows them to adhere to each other. This forms a platelet plug, which prevents more blood from leaving the body as well as any outside contaminants from getting in. The plug provides a temporary blockage of the break in the vasculature. As such, platelet plug formation occurs after vasoconstriction of the blood vessels but before the creation of the fibrin mesh clot, which is the more permanent solution to the injury. The result of the platelet plug formation is the coagulation of blood. It can also be referred to as primary hemostasis.

References

  1. Betts JG, Young KA, Wise JA, Johnson E, Poe B, Kruse DH, Korol O, Johnson JE, Womble M, DeSaix P. "Ch. 1 Introduction - Anatomy and Physiology". OpenStax. openstax.org. Retrieved 2020-11-12.
  2. Kaushansky K (December 2005). "The molecular mechanisms that control thrombopoiesis". The Journal of Clinical Investigation. 115 (12): 3339–47. doi:10.1172/JCI26674. PMID   16322778.
  3. Kaushansky K (February 2008). "Historical review: megakaryopoiesis and thrombopoiesis". Blood. 111 (3): 981–6. doi:10.1182/blood-2007-05-088500. PMID   18223171.
  4. Holinstat M (June 2017). "Normal platelet function". Cancer Metastasis Reviews. 36 (2): 195–198. doi:10.1007/s10555-017-9677-x. PMC   5709181 . PMID   28667366.
  5. 1 2 Boes KM, Durham AC (February 2017). "Bone Marrow, Blood Cells, and the Lymphoid/Lymphatic System.". Pathologic Basis of Veterinary Disease. pp. 724–804.e2. doi:10.1016/B978-0-323-35775-3.00013-8. PMC   7158316 .
  6. Kaushansky K (February 2008). "Historical review: megakaryopoiesis and thrombopoiesis". Blood (3 ed.). Elsevier Inc. 111 (3): 981–6. doi:10.1182/blood-2007-05-088500. PMID   18223171.
  7. Italiano JE, Shivdasani RA (June 2003). "Megakaryocytes and beyond: the birth of platelets". Journal of Thrombosis and Haemostasis. 1 (6): 1174–82. doi:10.1046/j.1538-7836.2003.00290.x. PMID   12871316.