Developmental Haemostasis
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Developmental Haemostasis
The haemostatic (blood clotting) system involves the interaction of proteins in the blood, the blood vessel wall and the flow of blood to control bleeding and blood clotting. Developmental Haemostasis is a term that represents the maturation of the haemostatic system from birth to adulthood. There are differences in the concentration, structure and activity of many proteins involved in blood clotting. These changes play an important role in physiological development and are important in providing appropriate diagnosis and treatment of bleeding and clotting disorders (e.g. thrombosis). The age-specific differences in the blood clotting system may contribute to the fact that children are less prone to developing thrombosis compared to adults. Differences in structure of haemostatic proteins Studies have shown that there are structural differences in some of the major blood clotting proteins in newborns and children when compared to adults.Karlaftis V, Attard C, Monagle P, Ignjatovic ...
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Blood Clotting
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. Coagulation begins almost instantly after an injury to the endothelium lining a blood vessel. Exposure of blood to the subendothelial space initiates two processes: changes in platelets, and the exposure of subendothelial tissue factor to plasma factor VII, which ultimately leads to cross-linked fibrin formation. Platelets immediately form a plug at the site of injury; this is called ''primary hemostasis. Secondary hemostasis'' occurs simultaneously: additional coagulation (clotting) factors beyond factor VII ( listed below) respond in a cascade to form fibrin strands, which strengthen the platelet plug. Disorders of ...
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Heparin
Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the treatment of heart attacks and unstable angina. It is given intravenously or by injection under the skin. Other uses for its anticoagulant properties include inside blood specimen test tubes and kidney dialysis machines. Common side effects include bleeding, pain at the injection site, and low blood platelets. Serious side effects include heparin-induced thrombocytopenia. Greater care is needed in those with poor kidney function. Heparin is contraindicated for suspected cases of vaccine-induced pro-thrombotic immune thrombocytopenia (VIPIT) secondary to SARS-CoV-2 vaccination, as heparin may further increase the risk of bleeding in an anti-PF4/heparin complex autoimmune manner, in favor of alternative anticoagulant medications (such as arg ...
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Anticoagulant
Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where they help keep the bite area unclotted long enough for the animal to obtain some blood. As a class of medications, anticoagulants are used in therapy for thrombotic disorders. Oral anticoagulants (OACs) are taken by many people in pill or tablet form, and various intravenous anticoagulant dosage forms are used in hospitals. Some anticoagulants are used in medical equipment, such as sample tubes, blood transfusion bags, heart–lung machines, and dialysis equipment. One of the first anticoagulants, warfarin, was initially approved as a rodenticide. Anticoagulants are closely related to antiplatelet drugs and thrombolytic drugs by manipulating the various pathways of blood coagulation. Specifically, antiplatelet drugs inhibit platelet agg ...
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Reference Range
In medicine and health-related fields, a reference range or reference interval is the range or the interval of values that is deemed normal for a physiological measurement in healthy persons (for example, the amount of creatinine in the blood, or the partial pressure of oxygen). It is a basis for comparison for a physician or other health professional to interpret a set of test results for a particular patient. Some important reference ranges in medicine are reference ranges for blood tests and reference ranges for urine tests. The standard definition of a reference range (usually referred to if not otherwise specified) originates in what is most prevalent in a reference group taken from the general (i.e. total) population. This is the general reference range. However, there are also ''optimal health ranges'' (ranges that appear to have the optimal health impact) and ranges for particular conditions or statuses (such as pregnancy reference ranges for hormone levels). Values withi ...
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White Blood Cell
White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from multipotent cells in the bone marrow known as hematopoietic stem cells. Leukocytes are found throughout the body, including the blood and lymphatic system. All white blood cells have cell nucleus, nuclei, which distinguishes them from the other blood cells, the anucleated red blood cells (RBCs) and platelets. The different white blood cells are usually classified by cell division, cell lineage (myelocyte, myeloid cells or lymphocyte, lymphoid cells). White blood cells are part of the body's immune system. They help the body fight infection and other diseases. Types of white blood cells are granulocytes (neutrophils, eosinophils, and basophils), and agranulocytes (monocytes, and lymphocytes (T cells and B cells)). Myeloid cells ...
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Platelet
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) 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 or lung, which then enter the circulation. Platelets are found only in mammals, whereas in other vertebrates (e.g. birds, amphibians), thrombocytes circulate as intact mononuclear cells. One major function of platelets is to contribute to hemostasis: the process of stopping bleeding at the site of interrupted endothelium. They gather at the site and, unless the interruption is physically too large, they plug the hole. First, platelets attach to substances outside the interrupted endothelium: ''adhesion''. Second, they change shape, turn on receptors and secrete chemical messengers: ''activatio ...
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Alpha-2-Macroglobulin
α2-Macroglobulin (α2M), or alpha-2-macroglobulin, is a large (720 KDa) plasma protein found in the blood. It is mainly produced by the liver, and also locally synthesized by macrophages, fibroblasts, and adrenocortical cells. In humans it is encoded by the ''A2M'' gene. α2-Macroglobulin acts as an antiprotease and is able to inactivate an enormous variety of proteinases. It functions as an inhibitor of fibrinolysis by inhibiting plasmin and kallikrein. It functions as an inhibitor of coagulation by inhibiting thrombin. α2-macroglobulin may act as a carrier protein because it also binds to numerous growth factors and cytokines, such as platelet-derived growth factor, basic fibroblast growth factor, TGF-β, insulin, and IL-1β. No specific deficiency with associated disease has been recognized, and no disease state is attributed to low concentrations of α2-macroglobulin. The concentration of α2-macroglobulin rises 10-fold or more in the nephrotic syndrome when other lower mo ...
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Isoform
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have unique functions. A set of protein isoforms may be formed from alternative splicings, variable promoter usage, or other post-transcriptional modifications of a single gene; post-translational modifications are generally not considered. (For that, see Proteoforms.) Through RNA splicing mechanisms, mRNA has the ability to select different protein-coding segments ( exons) of a gene, or even different parts of exons from RNA to form different mRNA sequences. Each unique sequence produces a specific form of a protein. The discovery of isoforms could explain the discrepancy between the small number of protein coding regions genes revealed by the human genome project and the large diversity of proteins seen in an organism: different ...
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Antithrombin
Antithrombin (AT) is a small glycoprotein that inactivates several enzymes of the coagulation system. It is a 432-amino-acid protein produced by the liver. It contains three disulfide bonds and a total of four possible glycosylation sites. α-Antithrombin is the dominant form of antithrombin found in blood plasma and has an oligosaccharide occupying each of its four glycosylation sites. A single glycosylation site remains consistently un-occupied in the minor form of antithrombin, β-antithrombin. Its activity is increased manyfold by the anticoagulant drug heparin, which enhances the binding of antithrombin to factor IIa (prothrombin) and factor Xa. Nomenclature Antithrombin is also termed antithrombin III (AT III). The designations antithrombin I through to antithrombin IV originate in early studies carried out in the 1950s by Seegers, Johnson and Fell. Antithrombin I (AT I) refers to the absorption of thrombin onto fibrin after thrombin has activated fibrinogen. Antithro ...
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Haemostasis
In biology, hemostasis American and British English spelling differences#ae and oe, or haemostasis is a process to prevent and stop bleeding, meaning to keep blood within a damaged blood vessel (the opposite of hemostasis is Bleeding, hemorrhage). It is the first stage of wound healing. This involves coagulation, which changes blood from a liquid to a gel. Intact blood vessels are central to moderating blood's tendency to form thrombus, clots. The endothelium, endothelial cells of intact vessels prevent blood clotting with a heparin-like molecule and thrombomodulin, and prevent platelet aggregation with nitric oxide and prostacyclin. When endothelium of a blood vessel is damaged, the endothelial cells stop secretion of coagulation and aggregation inhibitors and instead secrete von Willebrand factor, which initiate the maintenance of hemostasis after injury. Hemostasis involves three major steps: * vasoconstriction * temporary blockage of a hole in a damaged blood vessel by a platelet ...
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Protein C
Protein C, also known as autoprothrombin IIA and blood coagulation factor XIX, is a zymogen, that is, an inactive enzyme. The activated form plays an important role in regulating anticoagulation, inflammation, and apoptosis, cell death and maintaining the vascular permeability, permeability of blood vessel walls in humans and other animals. Activated protein C (APC) performs these operations primarily by proteolysis, proteolytically inactivating proteins Factor V, Factor Va and Factor VIII, Factor VIIIa. APC is classified as a serine protease since it contains a residue (chemistry), residue of serine in its active site. In humans, protein C is encoded by the ''PROC'' gene, which is found on chromosome 2 (human), chromosome 2. The zymogenic form of protein C is a vitamin K-dependent glycoprotein that circulates in blood plasma. Its structure is that of a two-chain polypeptide consisting of a light chain and a heavy chain connected by a disulfide bond. The protein C zymog ...
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Fibrin
Fibrin (also called Factor Ia) is a fibrous, non-globular protein involved in the clotting of blood. It is formed by the action of the protease thrombin on fibrinogen, which causes it to polymerize. The polymerized fibrin, together with platelets, forms a hemostatic plug or clot over a wound site. When the lining of a blood vessel is broken, platelets are attracted, forming a platelet plug. These platelets have thrombin receptors on their surfaces that bind serum thrombin molecules, which in turn convert soluble fibrinogen in the serum into fibrin at the wound site. Fibrin forms long strands of tough insoluble protein that are bound to the platelets. Factor XIII completes the cross-linking of fibrin so that it hardens and contracts. The cross-linked fibrin forms a mesh atop the platelet plug that completes the clot. Fibrin was discovered by Marcello Malpighi in 1666. Role in disease Excessive generation of fibrin due to activation of the coagulation cascade leads to thrombos ...
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