Lupus Anticoagulant
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Lupus Anticoagulant
Lupus anticoagulant is an immunoglobulin that binds to phospholipids and proteins associated with the cell membrane. Its name is a partial misnomer, as it is actually a prothrombotic antibody ''in vivo''. Lupus anticoagulant in living systems causes a decrease in clotting time. The name derives from their properties ''in vitro'', as these antibodies increase coagulation times in laboratory tests such as the activated partial thromboplastin time (aPTT). Investigators speculate that the antibodies interfere with phospholipids used to induce in vitro coagulation. In vivo, the antibodies are thought to interact with platelet membrane phospholipids, increasing adhesion and aggregation of platelets, which accounts for the in vivo prothrombotic characteristics. The condition was first described by hematologist C. Lockard Conley in 1952. Terminology Both words in the term "lupus anticoagulant" can be misleading: * Most patients with a lupus anticoagulant do not actually have lupus erythem ...
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Immunoglobulin
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the pathogen, called an antigen. Each tip of the "Y" of an antibody contains a paratope (analogous to a lock) that is specific for one particular epitope (analogous to a key) on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can ''tag'' a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly (for example, by blocking a part of a virus that is essential for its invasion). To allow the immune system to recognize millions of different antigens, the antigen-binding sites at both tips of the antibody come in an equally wide variety. In contrast, the remainder of the antibody is relatively constant. It only occurs in a few vari ...
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Preeclampsia
Pre-eclampsia is a disorder of pregnancy characterized by the onset of high blood pressure and often a significant amount of protein in the urine. When it arises, the condition begins after 20 weeks of pregnancy. In severe cases of the disease there may be red blood cell breakdown, a low blood platelet count, impaired liver function, kidney dysfunction, swelling, shortness of breath due to fluid in the lungs, or visual disturbances. Pre-eclampsia increases the risk of undesirable outcomes for both the mother and the fetus. If left untreated, it may result in seizures at which point it is known as eclampsia. Risk factors for pre-eclampsia include obesity, prior hypertension, older age, and diabetes mellitus. It is also more frequent in a woman's first pregnancy and if she is carrying twins. The underlying mechanism involves abnormal formation of blood vessels in the placenta amongst other factors. Most cases are diagnosed before delivery. Commonly, pre-eclampsia continues i ...
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Anticoagulants
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 aggre ...
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Sensitivity And Specificity
''Sensitivity'' and ''specificity'' mathematically describe the accuracy of a test which reports the presence or absence of a condition. Individuals for which the condition is satisfied are considered "positive" and those for which it is not are considered "negative". *Sensitivity (true positive rate) refers to the probability of a positive test, conditioned on truly being positive. *Specificity (true negative rate) refers to the probability of a negative test, conditioned on truly being negative. If the true condition can not be known, a " gold standard test" is assumed to be correct. In a diagnostic test, sensitivity is a measure of how well a test can identify true positives and specificity is a measure of how well a test can identify true negatives. For all testing, both diagnostic and screening, there is usually a trade-off between sensitivity and specificity, such that higher sensitivities will mean lower specificities and vice versa. If the goal is to return the ratio at w ...
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Kaolin Clotting Time
Kaolin clotting time (KCT) is a sensitive test to detect lupus anticoagulants. There is evidence that suggests it is the most sensitive test for detecting lupus anticoagulants. It can also detect factor VIII inhibitors but is sensitive to unfractionated heparin as well. The KCT on whole blood is known as the "Activated Clotting Time" (ACT) and is widely used in various instruments during surgery such as cardiac bypass to monitor heparin. History KCT was first described by Dr. Joel Margolis in 1958. Later on it was found to be very sensitive to lupus anticoagulants but was only reliable when test plasmas were mixed with normal plasma in various proportions. It became the preferred method for lupus anticoagulant testing after Dr Wilhelm Lubbe showed it to be a good marker for recurrent fetal loss. Principle KCT is similar to the activated partial thromboplastin time test, except it does not use exogenous phospholipid. Thus, a confirmatory test that uses excess phospholipid is nee ...
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Dilute Russell's Viper Venom Time
Dilute Russell's viper venom time (dRVVT) is a laboratory test often used for detection of lupus anticoagulant (LA). History Russell's viper venom (RVV) was known to clot blood many years ago. It was widely used as a styptic to clot minor wounds when razor blades were more commonly used for shaving (e.g. “Stypven”, Burroughs-Wellcome Pharma). RVV came to be useful in laboratory tests for blood clotting factors V, X, prothrombin and phospholipid. It was first used in clotting tests for lupus anticoagulant (LA) in an individual case in 1975. The “dilute Russells Viper Venom time (dRVVT)” test was then applied in 1985 to diagnose LA in a large number of patients and it became more widely used for this purpose. This multi-step method involved adding individual solutions of dilute phospholipid, RVV and calcium chloride to a test plasma and then measuring how long it took for the mixture to clot. In 1989, researchers at Westmead Hospital developed a simpler assay by combining ...
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Phospholipid
Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typically have omega-3 fatty acids EPA and DHA integrated as part of the phospholipid molecule. The phosphate group can be modified with simple organic molecules such as choline, ethanolamine or serine. Phospholipids are a key component of all cell membranes. They can form lipid bilayers because of their amphiphilic characteristic. In eukaryotes, cell membranes also contain another class of lipid, sterol, interspersed among the phospholipids. The combination provides fluidity in two dimensions combined with mechanical strength against rupture. Purified phospholipids are produced commercially and have found applications in nanotechnology and materials science. The first phospholipid identified in 1847 as such in biological tissues was lecith ...
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Mixing Test
Mixing studies are tests performed on blood plasma of patients or test subjects to distinguish factor deficiencies from factor inhibitors, such as lupus anticoagulant, or specific factor inhibitors, such as antibodies directed against factor VIII. The basic purpose of these tests is to determine the cause of prolongation of Prothrombin Time (PT), Partial Thromboplastin Time, or sometimes of thrombin time (TT). Mixing studies take advantage of the fact that factor levels that are 50 percent of normal should give a normal Prothrombin time (PT) or Partial thromboplastin time (PTT) result. Factor deficient plasmas (Adsorbed Plasma & Aged Plasma, etc.) are used in mixing studies. Plasma with known factor deficiencies are commercially available but are very expensive, so they are often prepared in the laboratory and can then be used for mixing experiments. Test method Fresh normal plasma has all the blood coagulation factors with normal levels. Plasma from patients on oral anticoagulant ...
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False Positive
A false positive is an error in binary classification in which a test result incorrectly indicates the presence of a condition (such as a disease when the disease is not present), while a false negative is the opposite error, where the test result incorrectly indicates the absence of a condition when it is actually present. These are the two kinds of errors in a binary test, in contrast to the two kinds of correct result (a and a ). They are also known in medicine as a false positive (or false negative) diagnosis, and in statistical classification as a false positive (or false negative) error. In statistical hypothesis testing the analogous concepts are known as type I and type II errors, where a positive result corresponds to rejecting the null hypothesis, and a negative result corresponds to not rejecting the null hypothesis. The terms are often used interchangeably, but there are differences in detail and interpretation due to the differences between medical testing and statist ...
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Prothrombin Time
The prothrombin time (PT) – along with its derived measures of prothrombin ratio (PR) and international normalized ratio (INR) – is an assay for evaluating the ''extrinsic'' pathway and common pathway of coagulation. This blood test is also called ''protime INR'' and ''PT/INR''. They are used to determine the clotting tendency of blood, in such things as the measure of warfarin dosage, liver damage, and vitamin K status. PT measures the following coagulation factors: I (fibrinogen), II (prothrombin), V (proaccelerin), VII (proconvertin), and X (Stuart–Prower factor). PT is often used in conjunction with the activated partial thromboplastin time (aPTT) which measures the ''intrinsic'' pathway and common pathway of coagulation. Laboratory measurement The reference range for prothrombin time depends on the analytical method used, but is usually around 12–13 seconds (results should always be interpreted using the reference range from the laboratory that performed ...
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Coagulation
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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Differential Diagnosis
In healthcare, a differential diagnosis (abbreviated DDx) is a method of analysis of a patient's history and physical examination to arrive at the correct diagnosis. It involves distinguishing a particular disease or condition from others that present with similar clinical features. Differential diagnostic procedures are used by clinicians to diagnose the specific disease in a patient, or, at least, to consider any imminently life-threatening conditions. Often, each individual option of a possible disease is called a differential diagnosis (e.g., acute bronchitis could be a differential diagnosis in the evaluation of a cough, even if the final diagnosis is common cold). More generally, a differential diagnostic procedure is a systematic diagnostic method used to identify the presence of a disease entity where multiple alternatives are possible. This method may employ algorithms, akin to the process of elimination, or at least a process of obtaining information that shrinks the "p ...
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