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Platelet-transfusion Refractoriness
Platelet transfusion refractoriness is the repeated failure to achieve the desired level of blood platelets in a patient following a platelet blood transfusion, transfusion. The cause of refractoriness may be either immune system, immune or non-immune. Among immune-related refractoriness, antibodies against Human leukocyte antigen, HLA antigens are the primary cause. Non-immune causes include splenomegaly (enlargement of the spleen), fever, and sepsis. Cause Platelet refractoriness can be due to immune causes or non-immune causes. Non-immune causes account for over 80% of cases of platelet refractoriness, and sepsis is one of the most common non-immune causes. Human leukocyte antigen, HLA alloimmunization is the commonest immune cause of platelet refractoriness. Non-immune causes Patient-related * Sepsis * Fever * Disseminated intravascular coagulation * Splenomegaly * Treatment of infection, antibiotics (vancomycin), antifungals (amphotericin B) * Graft-versus-host disease * H ...
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Blood Platelet
Platelets or thrombocytes () are a part of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a blood clot. Platelets have no cell nucleus; they are fragments of cytoplasm from megakaryocytes which reside in bone marrow or lung tissue, and 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 where the lining of vessels (endothelium) has been interrupted. Platelets 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: ''activation''. Third, they connect to each other through r ...
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Graft-versus-host Disease
Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants. White blood cells of the donor's immune system which remain within the donated tissue (the graft) recognize the recipient (the host) as foreign (non-self). The white blood cells present within the transplanted tissue then attack the recipient's body's cells, which leads to GvHD. This should not be confused with a transplant rejection, which occurs when the immune system of the transplant recipient rejects the transplanted tissue; GvHD occurs when the donor's immune system's white blood cells reject the recipient. The underlying principle ( alloimmunity) is the same, but the details and course may differ. GvHD can also occur after a blood transfusion, known as ''Transfusion-associated graft-versus-host disease'' or TA-GvHD if the blood products used have not been gamma irradiated or treated ...
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Transfusion Reactions
Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but modern medical practice commonly uses only components of the blood, such as red blood cells, plasma, platelets, and other clotting factors. White blood cells are transfused only in very rare circumstances, since granulocyte transfusion has limited applications. Whole blood has come back into use in the trauma setting. Red blood cells (RBC) contain hemoglobin and supply the cells of the body with oxygen. White blood cells are not commonly used during transfusions, but they are part of the immune system and also fight infections. Plasma is the "yellowish" liquid part of blood, which acts as a buffer and contains proteins and other important substances needed for the body's overall health. Platelets are involved in blood clotting, preven ...
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Eculizumab
Eculizumab, sold under the brand name Soliris among others, is a recombinant humanized monoclonal antibody used to treat paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, generalized myasthenia gravis, and neuromyelitis optica. In people with paroxysmal nocturnal hemoglobinuria, it reduces both the destruction of red blood cells and need for blood transfusion, but does not appear to affect the risk of death. Eculizumab was the first medication approved for each of its uses, and its approval was granted based on small trials. It is given by intravenous infusion. It is a humanized monoclonal antibody functioning as a terminal complement inhibitor. It binds to the complement C5 protein and inhibits activation of the complement system, a part of the body's immune system. This binding prevents the breakdown of red blood cells in the bloodstream (intravascular hemolysis) in people with paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome ...
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Thrombopoietin Receptor Agonists
Thrombopoietin mimetics are drugs that considerably increase platelet production by stimulating the receptor for the hormone thrombopoietin; Romiplostim and Eltrombopag are examples. Thrombopoietin mimetics are a type of thrombopoietic agents. There has been a development of a registry of pregnant Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ... patients that were treated with these drugs. References {{Cytokine receptor modulators Thrombopoietin receptor agonists ...
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Sepsis
Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and symptoms include fever, tachycardia, increased heart rate, hyperventilation, increased breathing rate, and mental confusion, confusion. There may also be symptoms related to a specific infection, such as a cough with pneumonia, or dysuria, painful urination with a pyelonephritis, kidney infection. The very young, old, and people with a immunodeficiency, weakened immune system may not have any symptoms specific to their infection, and their hypothermia, body temperature may be low or normal instead of constituting a fever. Severe sepsis may cause organ dysfunction and significantly reduced blood flow. The presence of Hypotension, low blood pressure, high blood Lactic acid, lactate, or Oliguria, low urine output may suggest poor blood flow. Se ...
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Body Surface Area
In physiology and medicine, the body surface area (BSA) is the measured or calculated surface area of a human body. For many clinical purposes, BSA is a better indicator of metabolic mass than body weight because it is less affected by abnormal adipose mass. Nevertheless, there have been several important critiques of the use of BSA in determining the dosage of medications with a narrow therapeutic index, such as chemotherapy. Typically there is a 4–10 fold variation in drug clearance between individuals due to differing the activity of drug elimination processes related to genetic and environmental factors. This can lead to significant overdosing and underdosing (and increased risk of disease recurrence). It is also thought to be a distorting factor in Phase I and II trials that may result in potentially helpful medications being prematurely rejected. The trend to personalized medicine is one approach to counter this weakness. Uses Examples of uses of the BSA: * Renal clea ...
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Immune Complex
An immune complex, sometimes called an antigen-antibody complex or antigen-bound antibody, is a molecule formed from the binding of multiple antigens to antibodies. The bound antigen and antibody act as a unitary object, effectively an antigen of its own with a specific epitope. After an antigen-antibody reaction, the immune complexes can be subject to any of a number of responses, including complement deposition, opsonization, phagocytosis, or processing by proteases. Red blood cells carrying CR1-receptors on their surface may bind C3b-coated immune complexes and transport them to phagocytes, mostly in liver and spleen, and return to the general circulation. The ratio of antigen to antibody determines size and shape of immune complex. This, in turn, determines the effect of the immune complex. Many innate immune cells have FcRs, which are membrane-bound receptors that bind the constant regions of antibodies. Most FcRs on innate immune cells have low affinity for a singular a ...
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Hepatic Veno-occlusive Disease
Hepatic veno-occlusive disease (VOD) or veno-occlusive disease with immunodeficiency is a potentially life-threatening condition in which some of the small veins in the liver are obstructed. It is a complication of high-dose chemotherapy given before a bone marrow transplant or excessive exposure to hepatotoxic pyrrolizidine alkaloids. It is classically marked by weight gain due to fluid retention, increased liver size, and raised levels of bilirubin in the blood. The name sinusoidal obstruction syndrome (SOS) is preferred if hepatic veno-occlusive disease happens as a result of chemotherapy or bone marrow transplantation. Apart from chemotherapy, hepatic veno-occlusive disease may also occur after ingestion of certain plant alkaloids such as pyrrolizidine alkaloids (in some herbal teas), and has been described as part of a rare hereditary disease called ''hepatic venoocclusive disease with immunodeficiency'' (which results from mutations in the gene coding for a protein called ...
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Splenomegaly
Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant (LUQ) of the human abdomen. Splenomegaly is one of the four cardinal signs of ''hypersplenism'' which include: some reduction in number of circulating blood cells affecting granulocytes, erythrocytes or platelets in any combination; a compensatory proliferative response in the bone marrow; and the potential for correction of these abnormalities by splenectomy. Splenomegaly is usually associated with increased workload (such as in hemolytic anemias), which suggests that it is a response to hyperfunction. It is therefore not surprising that splenomegaly is associated with any disease process that involves abnormal red blood cells being destroyed in the spleen. Other common causes include congestion due to portal hypertension and infiltration by leukemias and lymphomas. Thus, the finding of an enlarged spleen, along with caput medusae, is an important sign of portal hypertension ...
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Blood Transfusion
Blood transfusion is the process of transferring blood products into a person's Circulatory system, circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but modern medical practice commonly uses only components of the blood, such as red blood cells, blood plasma, plasma, platelets, and other clotting factors. White blood cells are transfused only in very rare circumstances, since granulocyte transfusion has limited applications. Whole blood has come back into use in the Major trauma, trauma setting. Red blood cells (RBC) contain hemoglobin and supply the Cell (biology), cells of the body with oxygen. White blood cells are not commonly used during transfusions, but they are part of the immune system and also fight infections. Plasma is the "yellowish" liquid part of blood, which acts as a buffer and contains proteins and other important substances needed for the body's overall ...
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Disseminated Intravascular Coagulation
Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout the body, blocking Microvessel, small blood vessels. Symptoms may include chest pain, shortness of breath, leg pain, problems speaking, or problems moving parts of the body. As clotting factors and platelets are used up, bleeding may occur. This may include hematuria, blood in the urine, GI bleed, blood in the stool, or bleeding into the skin. Complications may include organ failure. Relatively common causes include sepsis, surgery, major trauma, cancer, and complications of pregnancy. Less common causes include snake bites, frostbite, and burns. There are two main types: acute (rapid onset) and chronic (slow onset). Diagnosis is typically based on blood tests. Findings may include thrombocytopenia, low platelets, low fibrinogen, high International normalized ratio, INR, or high D-dimer. Treatment is mainly directed towards the underlying condition. Other measures may include givin ...
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