Learning Objectives Discuss the roles played by platelets in the blood. Key Takeaways Key Points Platelets, also called thrombocytes, are derived from megakaryocytes, which are derived from stem cells in the bone marrow. Platelets circulate in the blood and are involved in hemostasis, leading to the formation of blood clots and blood coagulation. Platelets lack a nucleus, but do contain some organelles, such as mitochondria and endoplasmic reticulum fragments.
If the number of platelets in the blood is too low, excessive bleeding can occur. However, if the number of platelets is too high, blood clots can form thrombosis , which may obstruct blood vessels. Platelets are a natural source of growth factors involved in wound healing, coagulatants, and inflammatory mediators. Key Terms extracellular matrix : All the connective tissues and fibers that are not part of a cell, but rather provide support.
It plays an important role in the formation of blood clots. Platelet Formation Platelets are membrane-bound cell fragments derived from megakaryocytes, which are produced during thrombopoiesis. Learning Objectives Describe the process of platelet formation. Key Takeaways Key Points Megakaryocytes are produced from stem cells in the bone marrow by a process called thrombopoiesis.
Megaryocytes create platelets by releasing protoplatelets that break up into numerous smaller, functional platelets. Thrombopoiesis is stimulated and regulated by the hormone thrombopoietin. Platelets have an average life span of five to ten days. Old platelets are destroyed by phagocytosis. The spleen holds a reservoir of additional platelets. Abnormal numbers of platelets result from problems in thrombopoiesis. However, as in the human conditions, normal platelets, when transfused into WASp KO mice, circulate normally indicating that a simple anti-platelet antibody mediated clearance is not the mechanism.
In mice, splenectomy has been shown to be without effect on the clearance rate. In efforts to identify the mechanism of removal, WASp Null platelets were transfused into mice lacking specific phagocytic receptors.
A survey on macrophage receptors failed to reveal any in which the WASp null platelets had enhanced circulatory lifetimes. However, WASp KO platelets were found to circulate normally in Asgr null mice, a finding once again posits the Asgr as a central molecule involved in the recognition and removal of damaged platelets. The surface of WASp KO platelets is, however, not desialylated and lectin binding studies have instead revealed hypersialylation.
This sialylation occurs specifically in the 2,6 linkage, not the normal 2,3 linkage. Critically, the Asgr also receptor recognizes this unique sialic linkage, leading to binding and platelet removal. The carrier of this sialic acid turns out to be surface bound Ig and sialylation of its Fc N-linked glycan shifts recognition of the Fc domain from macrophages to the hepatocytes.
Interestingly, the source of the 2,6 sialyltranferase ST6Gal1 is liver hepatocytes, which make and secrete this enzyme into blood. This blood enzyme is an acute phase reactant protein, upregulated in liver in response to bacterial sepsis, cancer, or inflammation. In this case, platelet ingestion itself, feedbacks to upregulate ST6Gal1 mRNA transcription and translation and this increases by fold the blood levels of this enzyme. Because WASp is a protein that interacts with the actin cytoskeleton, it is likely that internal cytoskeletal changes in its absence result in an altered topology of platelet receptors or the expression of the neo-epitope.
In general, platelet function in the absence of WASp is near normal although as the precision of assays increase, some differences have now been recognized. Active platelets lack small focal actin assembly sites in the absence of WASp, although spreading and filopodial formation are normal. In resting platelets, failure to express WASp alters the stability of microtubules, increasing their acetylation and slowing their turnover. How these internal changes alter the surface remains for future studies.
The basic processes involved in megakaryocyte commitment, maturation and platelet formation are well described although many precise details remain to be clarified. Proplatelet and platelet production requires a massive enlargement in MK size that is driven by high levels of mRNA transcription from their amplified polyploid nuclei followed by mRNA translation into platelet essential components.
This includes the production of an abundant internal network of membranes called the demarcation membrane system DMS that dramatically increases the apparent membrane to surface ratio during proplatelet formation, platelet specific granules, and the synthesis of large amounts of the cytoskeletal machinery that is used to form and fill assembling platelets.
As MKs mature, they develop an extensive network of internal membranes called the DMS that are enriched phosphatidylinositol 4,5 bisphosphate and the vWf receptor [ 22 ] and are used as the primary membrane source for proplatelet elongation.
To form the DMS, the plasma membrane of megakaryocytes enfolds at specific sites and a perinuclear pre-DMS is generated. Next, the pre-DMS is expanded into its mature form by material added from golgi-derived vesicles and endoplasmic reticulum-mediated lipid transfer. This structural description is in accordance with the studies on platelet glycosyltransferases, which arrive early in the forming DMS and eventually make their way to the megakaryocyte and platelet surfaces [ 24 ].
Only a small number of proteins have been identified thus far to participate in the DMS formation process based on alterations in its structure in certain knockout animals. The OCS, like the DMS, is a unique anastomosing network of internal membrane tubes that is connected to the plasma membrane at multiple points. To release platelets, megakaryocytes in the marrow space move to and nestle the marrow sinusoids where they project their proplatelet protrusions into the blood flow [ 25 , 26 ].
Whether all proplatelets are directed to grow specifically into the sinusoids or if only some of the proplatelets elaborated by a MK find their way into the sinusoids is unknown, although living MKs in marrow have been observed to have many proplatelet projections, some of which project into the marrow space while others project into the sinusoids [ 27 ].
Studies have demonstrated that proplatelet fragments considerably larger than platelets are released by MKs into blood [ 26 , 27 ] and that proplatelets can be both found, and can mature into platelets, in blood [ 28 ]. The state of our current knowledge of the mechanics of proplatelet production has come primarily from studies on MKs in culture. This work has clarified the essential role of microtubules, which were recognized early as the most prominent structure found within the MK projections [ 29 ] and that proplatelet and platelet production were adversely affected by MT poisons [ 30 ].
More recent studies using gene deleted MKs have begun to reveal the precise roles of specific proteins in proplatelet and platelet production and these are highlighted below. Signals that initiate proplatelet formation, if present, remain undefined and it remains possible that the program to make platelets starts when the synthesis of cytoskeletal proteins for this process reaches a critical mass.
From a mechanical view, centrosome dissolution precedes proplatelet extension, and the release of MTs from these multiple nucleating sites correlates best with the start of proplatelet elaboration. Released MTs first collect as bundles in the MK cortex where they are driven apart by their associated motor protein, dynein.
These MT-dynein reactions deform the membrane outward and generate the structural motor of the proplatelet, which is a MT bundle that folds over in the proplatelet tip and runs back into the shafts. Each bundle is composed of many MTs that are continuously growing and shrinking from their ends. Six types of behaviors characterize the elaboration of proplatelets: elongation, branching, pausing, fusions, fragmentations, and retractions.
These rates correlate well with the sliding rates of MTs within the bundles. This implies that there are regions within the bundles where MTs are crosslinked to increase resistance or they are pushing against resistive structures. Branching is a modified form of extension derived from tension asymmetry where a portion of the MT bundle detaches from the mother bundle and elongates rapidly forming a new tear shaped structure and proplatelet shaft.
Retraction, where the sliding could either reverse or all crosslinking derived tension releases, could serve to subfragment the proplatelets.
In addition to playing a crucial role in proplatelet elongation, the microtubules lining the shafts of proplatelets serve a secondary function — tracks for the transport of membrane, organelles, and granules into proplatelets and assembling platelets at proplatelet ends [ 32 ].
Individual organelles are sent from the cell body into the proplatelets, where they move bidirectionally until they are captured at proplatelet ends. Immunofluorescence and electron microscopy studies indicate that organelles are in direct contact with microtubules, and actin poisons do not diminish organelle motion. Therefore, movement appears to involve microtubule-based forces. Bidirectional organelle movement is conveyed in part by the bipolar organization of microtubules within the proplatelet, as kinesin-coated beads move bidirectionally over the microtubule arrays of permeabilized proplatelets.
Of the two major microtubule motors — kinesin and dynein — only the plus-end-directed kinesin is situated in a pattern similar to organelles and granules, and is likely responsible for transporting these elements along microtubules. It appears that a twofold mechanism of organelle and granule movement occurs in platelet assembly. Although microtubules and associated motor and regulatory proteins power proplatelet motility, elimination of certain actin cytoskeletal-associated proteins have now been demonstrated to modulate this process.
In this condition, your bone marrow makes too many platelets. People with this condition may have platelet counts of more than 1 million, which can lead to bleeding.
Other symptoms can include blood clots that form and block blood supply to the brain or the heart. Doctors don't fully know what causes this type of thrombocythemia, but changes in bone marrow cells called mutations can lead to some cases. Secondary thrombocytosis.
This is another condition caused by too many platelets. Secondary thrombocytosis is more common. It's not caused by a bone marrow problem. Instead, another disease or condition stimulates the bone marrow to make more platelets. Causes include infection, inflammation, some types of cancer, and reactions to medicines. Symptoms are usually not serious. The platelet count goes back to normal when the other condition gets better.
Platelet dysfunction. Platelet function tests may also be performed if there are symptoms of or potential for excessive bleeding, and to also monitor anti-platelet medications.
If the body doesn't have enough platelets in circulation, you may develop a condition called thrombocytopenia. Other examples of conditions that may cause thrombocytopenia include having a mechanical heart valve, heparin antibodies, chronic alcohol abuse, liver disease, severe sepsis, and toxic exposures. A platelet count below 20, per microliter is a life-threatening risk as spontaneous bleeding may occur and be hard to stop. At that level, you may be given a platelet transfusion.
If the body has too many platelets in circulation, you may develop a condition called thrombocytosis. In addition, a temporary increase in the platelet count can happen after major surgery or trauma. Platelets are tiny cells with a highly important function in the body—to stop bleeding. There is a wide range of normal in terms of platelet count, but it's important to be aware of the extremes, too, especially if you're considering surgery or undergoing another procedure that may require bleeding and clotting.
If you have very low or very high levels of platelets, make sure you're communicating with your healthcare provider about a safe plan of action. Treatment is only necessary if thrombocytopenia is causing health problems. Treatment may include blood transfusion, which is a temporary fix; spleen removal; and medications that may include steroids and immunoglobulins.
Many people who experience high blood platelets, or thombocytosis, do not require treatment but may be monitored regularly by their healthcare provider. If symptoms are problematic, treatment may include daily low-dose aspirin to prevent blood clots, medications that reduce platelet production, and treating the underlying cause of the condition.
Under a microscope, blood platelets look like small plates when inactive. When activated, they look like an octopus as they grow small tentacles. Sign up for our Health Tip of the Day newsletter, and receive daily tips that will help you live your healthiest life. University of Rochester Medical Center. Health Encyclopedia. What Are Platelets?
Merck Manual Professional Version. Thrombocytopenia: Other Causes. Revised February Natioinal Heart, Lung, and Blood Institute.
Thrombocythemia and Thrombocytosis.
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