Введение
Низкое количество тромбоцитов, вызванное гепарином, связано с риском тромбоза.
Low platelet count due to heparin, associated with a risk of thrombosis
Гепарин-индуцированная тромбоцитопения (ГИТ) – это развитие тромбоцитопении (низкого количества тромбоцитов) вследствие применения различных форм гепарина, антикоагулянта. ГИТ предрасполагает к тромбозу (аномальному образованию кровяных сгустков внутри кровеносного сосуда). При выявлении тромбоза состояние называется гепарин-индуцированной тромбоцитопенией и тромбозом (ГИТТ). ГИТ вызывается образованием аномальных антител, которые активируют тромбоциты, высвобождающие микрочастицы, активирующие тромбин, что приводит к тромбозу. Если у пациента, получающего гепарин, развивается новый или ухудшающийся тромбоз, или если снижается количество тромбоцитов, ГИТ может быть подтверждена специфическими анализами крови. Лечение ГИТ требует прекращения терапии гепарином, защиты от тромбоза и выбора препарата, который не будет дополнительно снижать количество тромбоцитов. Для этой цели доступны различные альтернативы, в основном используются данапароид, фондапаринукс, аргатробан и бивалирудин. Хотя гепарин был открыт в 1930-х годах, о ГИТ не сообщалось до 1960-х годов.
Heparin induced thrombocytopenia (HIT) is the development of thrombocytopenia (a low platelet count), due to the administration of various forms of heparin, an anticoagulant. HIT predisposes to thrombosis (the abnormal formation of blood clots inside a blood vessel). When thrombosis is identified the condition is called heparin induced thrombocytopenia and thrombosis (HITT). HIT is caused by the formation of abnormal antibodies that activate platelets, which release microparticles that activate thrombin, leading to thrombosis. If someone receiving heparin develops new or worsening thrombosis, or if the platelet count falls, HIT can be confirmed with specific blood tests. The treatment of HIT requires stopping heparin treatment, and both protection from thrombosis and choice of an agent that will not reduce the platelet count any further. Several alternatives are available for this purpose; mainly used are danaparoid, fondaparinux, argatroban, and bivalirudin. While heparin was discovered in the 1930s, HIT was not reported until the 1960s.
Признаки и симптомы
Гепарин может использоваться как для профилактики, так и для лечения тромбоза. Он существует в двух основных формах: "нефракционированный" гепарин, который может быть введен под кожу (подкожно) или внутривенно, и "низкомолекулярный" гепарин, который обычно вводится подкожно. Наиболее часто используемые низкомолекулярные гепарины – эноксапарин, далтепарин, надропарин и тинзапарин. При ГИТ (гепарин-индуцированной тромбоцитопении) количество тромбоцитов в крови снижается ниже нормы, состояние называется тромбоцитопенией. Однако, как правило, снижение недостаточно выражено, чтобы привести к повышенному риску кровотечений. Поэтому у большинства пациентов с ГИТ симптомы не проявляются. Обычно снижение количества тромбоцитов происходит через 5–14 дней после начала терапии гепарином; если пациент получал гепарин в течение предыдущих трех месяцев, снижение может произойти раньше, иногда в течение суток. У пациентов, получающих гепарин внутривенно, при начале инфузии может развиться комплекс симптомов ("системная реакция"). Он включает лихорадку, озноб, повышение артериального давления, тахикардию, одышку и боль в груди. Это происходит примерно у четверти пациентов с ГИТ. У других может появиться кожная сыпь в виде красных пятен. Антитела IgG образуют комплекс с гепарином и PF4 в кровотоке. Затем Fc-фрагмент антитела связывается с FcγIIa-рецептором – белком на поверхности тромбоцитов. Это приводит к активации тромбоцитов и образованию микрочастиц тромбоцитов, которые инициируют образование тромбов; в результате количество тромбоцитов снижается, вызывая тромбоцитопению. Однако не у всех пациентов со снижением количества тромбоцитов на фоне терапии гепарином развивается ГИТ. Вероятность ГИТ определяется сроками снижения тромбоцитов, степенью тромбоцитопении, возникновением нового тромбоза и наличием альтернативных объяснений. Для оценки вероятности ГИТ часто используется шкала "4T", предложенная в 2003 году. Анализ надежности шкалы 4T показал, что низкий балл имеет отрицательную прогностическую ценность 0,998, средний балл – положительную прогностическую ценность 0,14, а высокий балл – 0,64; следовательно, средний и высокий баллы требуют дальнейшего обследования.
Heparin may be used for both prevention and the treatment of thrombosis. It exists in two main forms: an "unfractionated" form that can be injected under the skin (subcutaneously) or through an intravenous infusion, and a "low molecular weight" form that is generally given subcutaneously. Commonly used low molecular weight heparins are enoxaparin, dalteparin, nadroparin and tinzaparin. In HIT, the platelet count in the blood falls below the normal range, a condition called thrombocytopenia. However, it is generally not low enough to lead to an increased risk of bleeding. Most people with HIT, therefore, do not experience any symptoms. Typically, the platelet count falls 5–14 days after heparin is first given; if someone has received heparin in the previous three months, the fall in platelet count may occur sooner, sometimes within a day. In those receiving heparin through an intravenous infusion, a complex of symptoms ("systemic reaction") may occur when the infusion is started. These include fever, chills, high blood pressure, a fast heart rate, shortness of breath, and chest pain. This happens in about a quarter of people with HIT. Others may develop a skin rash consisting of red spots. The IgG antibodies form a complex with heparin and PF4 in the bloodstream. The tail of the antibody then binds to the FcγIIa receptor, a protein on the surface of the platelet. This results in platelet activation and the formation of platelet microparticles, which initiate the formation of blood clots; the platelet count falls as a result, leading to thrombocytopenia. However, not all people with a falling platelet count while receiving heparin turn out to have HIT. The timing, severity of the thrombocytopenia, the occurrence of new thrombosis, and the presence of alternative explanations, all determine the likelihood that HIT is present. A commonly used score to predict the likelihood of HIT is the "4 Ts" score introduced in 2003. In an analysis of the reliability of the 4T score, a low score had a negative predictive value of 0.998, while an intermediate score had a positive predictive value of 0.14 and a high score a positive predictive value of 0.64; intermediate and high scores, therefore, warrant further investigation. Element The 4T score for heparin induced thrombocytopenia Thrombocytopenia 2 points if the fall in platelet count is >50% of the previous value, AND the lowest count (nadir) is 20–100 × 109/liter1 point if the fall is 30–50% or the nadir is 10–19 × 109/literNo points if the fall is less than 30% or the nadir is <10 × 109/liter. Timing 2 points if the fall is between days 5–10 after commencement of treatment1 point if the fall is after day 10. If someone has been exposed to heparin within the last 30 days and then has a drop in platelet count within a day of reexposure, 2 points are given. If the previous exposure was 30–100 days ago, 1 pointIf the fall is early but there has been no previous heparin exposure, no points. Thrombosis 2 points in new proven thrombosis, skin necrosis (see below), or systemic reaction1 point if progressive or recurrent thrombosis, silent thrombosis or red skin lesionsNo points if there are no symptoms. Alternative cause possible 2 points if no other cause1 point if there is a possible alternative causeNo points if there is a definite alternative cause. The first screening test in someone suspected of having HIT is aimed at detecting antibodies against heparin PF4 complexes. This may be with a laboratory test of the enzyme linked immunosorbent assay type. This ELISA test, however, detects all circulating antibodies that bind heparin PF4 complexes, and may also falsely identify antibodies that do not cause HIT. Therefore, those with a positive ELISA are tested further with a functional assay. This test uses platelets and serum from the patient; the platelets are washed and mixed with serum and heparin. The sample is then tested for the release of serotonin, a marker of platelet activation. If this serotonin release assay (SRA) shows high serotonin release, the diagnosis of HIT is confirmed. The SRA test is difficult to perform and is usually only done in regional laboratories. Lepirudin production stopped on May 31, 2012.
**Элемент: Шкала 4T для гепарин-индуцированной тромбоцитопении**
Heparin may be used for both prevention and the treatment of thrombosis. It exists in two main forms: an "unfractionated" form that can be injected under the skin (subcutaneously) or through an intravenous infusion, and a "low molecular weight" form that is generally given subcutaneously. Commonly used low molecular weight heparins are enoxaparin, dalteparin, nadroparin and tinzaparin. In HIT, the platelet count in the blood falls below the normal range, a condition called thrombocytopenia. However, it is generally not low enough to lead to an increased risk of bleeding. Most people with HIT, therefore, do not experience any symptoms. Typically, the platelet count falls 5–14 days after heparin is first given; if someone has received heparin in the previous three months, the fall in platelet count may occur sooner, sometimes within a day. In those receiving heparin through an intravenous infusion, a complex of symptoms ("systemic reaction") may occur when the infusion is started. These include fever, chills, high blood pressure, a fast heart rate, shortness of breath, and chest pain. This happens in about a quarter of people with HIT. Others may develop a skin rash consisting of red spots. The IgG antibodies form a complex with heparin and PF4 in the bloodstream. The tail of the antibody then binds to the FcγIIa receptor, a protein on the surface of the platelet. This results in platelet activation and the formation of platelet microparticles, which initiate the formation of blood clots; the platelet count falls as a result, leading to thrombocytopenia. However, not all people with a falling platelet count while receiving heparin turn out to have HIT. The timing, severity of the thrombocytopenia, the occurrence of new thrombosis, and the presence of alternative explanations, all determine the likelihood that HIT is present. A commonly used score to predict the likelihood of HIT is the "4 Ts" score introduced in 2003. In an analysis of the reliability of the 4T score, a low score had a negative predictive value of 0.998, while an intermediate score had a positive predictive value of 0.14 and a high score a positive predictive value of 0.64; intermediate and high scores, therefore, warrant further investigation. Element The 4T score for heparin induced thrombocytopenia Thrombocytopenia 2 points if the fall in platelet count is >50% of the previous value, AND the lowest count (nadir) is 20–100 × 109/liter1 point if the fall is 30–50% or the nadir is 10–19 × 109/literNo points if the fall is less than 30% or the nadir is <10 × 109/liter. Timing 2 points if the fall is between days 5–10 after commencement of treatment1 point if the fall is after day 10. If someone has been exposed to heparin within the last 30 days and then has a drop in platelet count within a day of reexposure, 2 points are given. If the previous exposure was 30–100 days ago, 1 pointIf the fall is early but there has been no previous heparin exposure, no points. Thrombosis 2 points in new proven thrombosis, skin necrosis (see below), or systemic reaction1 point if progressive or recurrent thrombosis, silent thrombosis or red skin lesionsNo points if there are no symptoms. Alternative cause possible 2 points if no other cause1 point if there is a possible alternative causeNo points if there is a definite alternative cause. The first screening test in someone suspected of having HIT is aimed at detecting antibodies against heparin PF4 complexes. This may be with a laboratory test of the enzyme linked immunosorbent assay type. This ELISA test, however, detects all circulating antibodies that bind heparin PF4 complexes, and may also falsely identify antibodies that do not cause HIT. Therefore, those with a positive ELISA are tested further with a functional assay. This test uses platelets and serum from the patient; the platelets are washed and mixed with serum and heparin. The sample is then tested for the release of serotonin, a marker of platelet activation. If this serotonin release assay (SRA) shows high serotonin release, the diagnosis of HIT is confirmed. The SRA test is difficult to perform and is usually only done in regional laboratories. Lepirudin production stopped on May 31, 2012.
**Тромбоцитопения:**
Heparin may be used for both prevention and the treatment of thrombosis. It exists in two main forms: an "unfractionated" form that can be injected under the skin (subcutaneously) or through an intravenous infusion, and a "low molecular weight" form that is generally given subcutaneously. Commonly used low molecular weight heparins are enoxaparin, dalteparin, nadroparin and tinzaparin. In HIT, the platelet count in the blood falls below the normal range, a condition called thrombocytopenia. However, it is generally not low enough to lead to an increased risk of bleeding. Most people with HIT, therefore, do not experience any symptoms. Typically, the platelet count falls 5–14 days after heparin is first given; if someone has received heparin in the previous three months, the fall in platelet count may occur sooner, sometimes within a day. In those receiving heparin through an intravenous infusion, a complex of symptoms ("systemic reaction") may occur when the infusion is started. These include fever, chills, high blood pressure, a fast heart rate, shortness of breath, and chest pain. This happens in about a quarter of people with HIT. Others may develop a skin rash consisting of red spots. The IgG antibodies form a complex with heparin and PF4 in the bloodstream. The tail of the antibody then binds to the FcγIIa receptor, a protein on the surface of the platelet. This results in platelet activation and the formation of platelet microparticles, which initiate the formation of blood clots; the platelet count falls as a result, leading to thrombocytopenia. However, not all people with a falling platelet count while receiving heparin turn out to have HIT. The timing, severity of the thrombocytopenia, the occurrence of new thrombosis, and the presence of alternative explanations, all determine the likelihood that HIT is present. A commonly used score to predict the likelihood of HIT is the "4 Ts" score introduced in 2003. In an analysis of the reliability of the 4T score, a low score had a negative predictive value of 0.998, while an intermediate score had a positive predictive value of 0.14 and a high score a positive predictive value of 0.64; intermediate and high scores, therefore, warrant further investigation. Element The 4T score for heparin induced thrombocytopenia Thrombocytopenia 2 points if the fall in platelet count is >50% of the previous value, AND the lowest count (nadir) is 20–100 × 109/liter1 point if the fall is 30–50% or the nadir is 10–19 × 109/literNo points if the fall is less than 30% or the nadir is <10 × 109/liter. Timing 2 points if the fall is between days 5–10 after commencement of treatment1 point if the fall is after day 10. If someone has been exposed to heparin within the last 30 days and then has a drop in platelet count within a day of reexposure, 2 points are given. If the previous exposure was 30–100 days ago, 1 pointIf the fall is early but there has been no previous heparin exposure, no points. Thrombosis 2 points in new proven thrombosis, skin necrosis (see below), or systemic reaction1 point if progressive or recurrent thrombosis, silent thrombosis or red skin lesionsNo points if there are no symptoms. Alternative cause possible 2 points if no other cause1 point if there is a possible alternative causeNo points if there is a definite alternative cause. The first screening test in someone suspected of having HIT is aimed at detecting antibodies against heparin PF4 complexes. This may be with a laboratory test of the enzyme linked immunosorbent assay type. This ELISA test, however, detects all circulating antibodies that bind heparin PF4 complexes, and may also falsely identify antibodies that do not cause HIT. Therefore, those with a positive ELISA are tested further with a functional assay. This test uses platelets and serum from the patient; the platelets are washed and mixed with serum and heparin. The sample is then tested for the release of serotonin, a marker of platelet activation. If this serotonin release assay (SRA) shows high serotonin release, the diagnosis of HIT is confirmed. The SRA test is difficult to perform and is usually only done in regional laboratories. Lepirudin production stopped on May 31, 2012.
* 2 балла – снижение количества тромбоцитов более чем на 50% от исходного значения, И минимальное количество тромбоцитов (надир) составляет 20–100 × 109/л.
* 1 балл – снижение на 30–50% или надир 10–19 × 109/л.
* 0 баллов – снижение менее 30% или надир < 10 × 109/л.
Heparin may be used for both prevention and the treatment of thrombosis. It exists in two main forms: an "unfractionated" form that can be injected under the skin (subcutaneously) or through an intravenous infusion, and a "low molecular weight" form that is generally given subcutaneously. Commonly used low molecular weight heparins are enoxaparin, dalteparin, nadroparin and tinzaparin. In HIT, the platelet count in the blood falls below the normal range, a condition called thrombocytopenia. However, it is generally not low enough to lead to an increased risk of bleeding. Most people with HIT, therefore, do not experience any symptoms. Typically, the platelet count falls 5–14 days after heparin is first given; if someone has received heparin in the previous three months, the fall in platelet count may occur sooner, sometimes within a day. In those receiving heparin through an intravenous infusion, a complex of symptoms ("systemic reaction") may occur when the infusion is started. These include fever, chills, high blood pressure, a fast heart rate, shortness of breath, and chest pain. This happens in about a quarter of people with HIT. Others may develop a skin rash consisting of red spots. The IgG antibodies form a complex with heparin and PF4 in the bloodstream. The tail of the antibody then binds to the FcγIIa receptor, a protein on the surface of the platelet. This results in platelet activation and the formation of platelet microparticles, which initiate the formation of blood clots; the platelet count falls as a result, leading to thrombocytopenia. However, not all people with a falling platelet count while receiving heparin turn out to have HIT. The timing, severity of the thrombocytopenia, the occurrence of new thrombosis, and the presence of alternative explanations, all determine the likelihood that HIT is present. A commonly used score to predict the likelihood of HIT is the "4 Ts" score introduced in 2003. In an analysis of the reliability of the 4T score, a low score had a negative predictive value of 0.998, while an intermediate score had a positive predictive value of 0.14 and a high score a positive predictive value of 0.64; intermediate and high scores, therefore, warrant further investigation. Element The 4T score for heparin induced thrombocytopenia Thrombocytopenia 2 points if the fall in platelet count is >50% of the previous value, AND the lowest count (nadir) is 20–100 × 109/liter1 point if the fall is 30–50% or the nadir is 10–19 × 109/literNo points if the fall is less than 30% or the nadir is <10 × 109/liter. Timing 2 points if the fall is between days 5–10 after commencement of treatment1 point if the fall is after day 10. If someone has been exposed to heparin within the last 30 days and then has a drop in platelet count within a day of reexposure, 2 points are given. If the previous exposure was 30–100 days ago, 1 pointIf the fall is early but there has been no previous heparin exposure, no points. Thrombosis 2 points in new proven thrombosis, skin necrosis (see below), or systemic reaction1 point if progressive or recurrent thrombosis, silent thrombosis or red skin lesionsNo points if there are no symptoms. Alternative cause possible 2 points if no other cause1 point if there is a possible alternative causeNo points if there is a definite alternative cause. The first screening test in someone suspected of having HIT is aimed at detecting antibodies against heparin PF4 complexes. This may be with a laboratory test of the enzyme linked immunosorbent assay type. This ELISA test, however, detects all circulating antibodies that bind heparin PF4 complexes, and may also falsely identify antibodies that do not cause HIT. Therefore, those with a positive ELISA are tested further with a functional assay. This test uses platelets and serum from the patient; the platelets are washed and mixed with serum and heparin. The sample is then tested for the release of serotonin, a marker of platelet activation. If this serotonin release assay (SRA) shows high serotonin release, the diagnosis of HIT is confirmed. The SRA test is difficult to perform and is usually only done in regional laboratories. Lepirudin production stopped on May 31, 2012.
**Время:**
Heparin may be used for both prevention and the treatment of thrombosis. It exists in two main forms: an "unfractionated" form that can be injected under the skin (subcutaneously) or through an intravenous infusion, and a "low molecular weight" form that is generally given subcutaneously. Commonly used low molecular weight heparins are enoxaparin, dalteparin, nadroparin and tinzaparin. In HIT, the platelet count in the blood falls below the normal range, a condition called thrombocytopenia. However, it is generally not low enough to lead to an increased risk of bleeding. Most people with HIT, therefore, do not experience any symptoms. Typically, the platelet count falls 5–14 days after heparin is first given; if someone has received heparin in the previous three months, the fall in platelet count may occur sooner, sometimes within a day. In those receiving heparin through an intravenous infusion, a complex of symptoms ("systemic reaction") may occur when the infusion is started. These include fever, chills, high blood pressure, a fast heart rate, shortness of breath, and chest pain. This happens in about a quarter of people with HIT. Others may develop a skin rash consisting of red spots. The IgG antibodies form a complex with heparin and PF4 in the bloodstream. The tail of the antibody then binds to the FcγIIa receptor, a protein on the surface of the platelet. This results in platelet activation and the formation of platelet microparticles, which initiate the formation of blood clots; the platelet count falls as a result, leading to thrombocytopenia. However, not all people with a falling platelet count while receiving heparin turn out to have HIT. The timing, severity of the thrombocytopenia, the occurrence of new thrombosis, and the presence of alternative explanations, all determine the likelihood that HIT is present. A commonly used score to predict the likelihood of HIT is the "4 Ts" score introduced in 2003. In an analysis of the reliability of the 4T score, a low score had a negative predictive value of 0.998, while an intermediate score had a positive predictive value of 0.14 and a high score a positive predictive value of 0.64; intermediate and high scores, therefore, warrant further investigation. Element The 4T score for heparin induced thrombocytopenia Thrombocytopenia 2 points if the fall in platelet count is >50% of the previous value, AND the lowest count (nadir) is 20–100 × 109/liter1 point if the fall is 30–50% or the nadir is 10–19 × 109/literNo points if the fall is less than 30% or the nadir is <10 × 109/liter. Timing 2 points if the fall is between days 5–10 after commencement of treatment1 point if the fall is after day 10. If someone has been exposed to heparin within the last 30 days and then has a drop in platelet count within a day of reexposure, 2 points are given. If the previous exposure was 30–100 days ago, 1 pointIf the fall is early but there has been no previous heparin exposure, no points. Thrombosis 2 points in new proven thrombosis, skin necrosis (see below), or systemic reaction1 point if progressive or recurrent thrombosis, silent thrombosis or red skin lesionsNo points if there are no symptoms. Alternative cause possible 2 points if no other cause1 point if there is a possible alternative causeNo points if there is a definite alternative cause. The first screening test in someone suspected of having HIT is aimed at detecting antibodies against heparin PF4 complexes. This may be with a laboratory test of the enzyme linked immunosorbent assay type. This ELISA test, however, detects all circulating antibodies that bind heparin PF4 complexes, and may also falsely identify antibodies that do not cause HIT. Therefore, those with a positive ELISA are tested further with a functional assay. This test uses platelets and serum from the patient; the platelets are washed and mixed with serum and heparin. The sample is then tested for the release of serotonin, a marker of platelet activation. If this serotonin release assay (SRA) shows high serotonin release, the diagnosis of HIT is confirmed. The SRA test is difficult to perform and is usually only done in regional laboratories. Lepirudin production stopped on May 31, 2012.
* 2 балла – снижение происходит между 5-м и 10-м днем после начала лечения.
* 1 балл – снижение происходит после 10-го дня.
* 2 балла – если пациент подвергался воздействию гепарина в течение последних 30 дней, а затем у него наблюдается снижение количества тромбоцитов в течение суток после повторного введения.
* 1 балл – если предыдущее воздействие гепарина было 30–100 дней назад.
* 0 баллов – если снижение произошло рано, но ранее пациент не получал гепарин.
Heparin may be used for both prevention and the treatment of thrombosis. It exists in two main forms: an "unfractionated" form that can be injected under the skin (subcutaneously) or through an intravenous infusion, and a "low molecular weight" form that is generally given subcutaneously. Commonly used low molecular weight heparins are enoxaparin, dalteparin, nadroparin and tinzaparin. In HIT, the platelet count in the blood falls below the normal range, a condition called thrombocytopenia. However, it is generally not low enough to lead to an increased risk of bleeding. Most people with HIT, therefore, do not experience any symptoms. Typically, the platelet count falls 5–14 days after heparin is first given; if someone has received heparin in the previous three months, the fall in platelet count may occur sooner, sometimes within a day. In those receiving heparin through an intravenous infusion, a complex of symptoms ("systemic reaction") may occur when the infusion is started. These include fever, chills, high blood pressure, a fast heart rate, shortness of breath, and chest pain. This happens in about a quarter of people with HIT. Others may develop a skin rash consisting of red spots. The IgG antibodies form a complex with heparin and PF4 in the bloodstream. The tail of the antibody then binds to the FcγIIa receptor, a protein on the surface of the platelet. This results in platelet activation and the formation of platelet microparticles, which initiate the formation of blood clots; the platelet count falls as a result, leading to thrombocytopenia. However, not all people with a falling platelet count while receiving heparin turn out to have HIT. The timing, severity of the thrombocytopenia, the occurrence of new thrombosis, and the presence of alternative explanations, all determine the likelihood that HIT is present. A commonly used score to predict the likelihood of HIT is the "4 Ts" score introduced in 2003. In an analysis of the reliability of the 4T score, a low score had a negative predictive value of 0.998, while an intermediate score had a positive predictive value of 0.14 and a high score a positive predictive value of 0.64; intermediate and high scores, therefore, warrant further investigation. Element The 4T score for heparin induced thrombocytopenia Thrombocytopenia 2 points if the fall in platelet count is >50% of the previous value, AND the lowest count (nadir) is 20–100 × 109/liter1 point if the fall is 30–50% or the nadir is 10–19 × 109/literNo points if the fall is less than 30% or the nadir is <10 × 109/liter. Timing 2 points if the fall is between days 5–10 after commencement of treatment1 point if the fall is after day 10. If someone has been exposed to heparin within the last 30 days and then has a drop in platelet count within a day of reexposure, 2 points are given. If the previous exposure was 30–100 days ago, 1 pointIf the fall is early but there has been no previous heparin exposure, no points. Thrombosis 2 points in new proven thrombosis, skin necrosis (see below), or systemic reaction1 point if progressive or recurrent thrombosis, silent thrombosis or red skin lesionsNo points if there are no symptoms. Alternative cause possible 2 points if no other cause1 point if there is a possible alternative causeNo points if there is a definite alternative cause. The first screening test in someone suspected of having HIT is aimed at detecting antibodies against heparin PF4 complexes. This may be with a laboratory test of the enzyme linked immunosorbent assay type. This ELISA test, however, detects all circulating antibodies that bind heparin PF4 complexes, and may also falsely identify antibodies that do not cause HIT. Therefore, those with a positive ELISA are tested further with a functional assay. This test uses platelets and serum from the patient; the platelets are washed and mixed with serum and heparin. The sample is then tested for the release of serotonin, a marker of platelet activation. If this serotonin release assay (SRA) shows high serotonin release, the diagnosis of HIT is confirmed. The SRA test is difficult to perform and is usually only done in regional laboratories. Lepirudin production stopped on May 31, 2012.
**Тромбоз:**
Heparin may be used for both prevention and the treatment of thrombosis. It exists in two main forms: an "unfractionated" form that can be injected under the skin (subcutaneously) or through an intravenous infusion, and a "low molecular weight" form that is generally given subcutaneously. Commonly used low molecular weight heparins are enoxaparin, dalteparin, nadroparin and tinzaparin. In HIT, the platelet count in the blood falls below the normal range, a condition called thrombocytopenia. However, it is generally not low enough to lead to an increased risk of bleeding. Most people with HIT, therefore, do not experience any symptoms. Typically, the platelet count falls 5–14 days after heparin is first given; if someone has received heparin in the previous three months, the fall in platelet count may occur sooner, sometimes within a day. In those receiving heparin through an intravenous infusion, a complex of symptoms ("systemic reaction") may occur when the infusion is started. These include fever, chills, high blood pressure, a fast heart rate, shortness of breath, and chest pain. This happens in about a quarter of people with HIT. Others may develop a skin rash consisting of red spots. The IgG antibodies form a complex with heparin and PF4 in the bloodstream. The tail of the antibody then binds to the FcγIIa receptor, a protein on the surface of the platelet. This results in platelet activation and the formation of platelet microparticles, which initiate the formation of blood clots; the platelet count falls as a result, leading to thrombocytopenia. However, not all people with a falling platelet count while receiving heparin turn out to have HIT. The timing, severity of the thrombocytopenia, the occurrence of new thrombosis, and the presence of alternative explanations, all determine the likelihood that HIT is present. A commonly used score to predict the likelihood of HIT is the "4 Ts" score introduced in 2003. In an analysis of the reliability of the 4T score, a low score had a negative predictive value of 0.998, while an intermediate score had a positive predictive value of 0.14 and a high score a positive predictive value of 0.64; intermediate and high scores, therefore, warrant further investigation. Element The 4T score for heparin induced thrombocytopenia Thrombocytopenia 2 points if the fall in platelet count is >50% of the previous value, AND the lowest count (nadir) is 20–100 × 109/liter1 point if the fall is 30–50% or the nadir is 10–19 × 109/literNo points if the fall is less than 30% or the nadir is <10 × 109/liter. Timing 2 points if the fall is between days 5–10 after commencement of treatment1 point if the fall is after day 10. If someone has been exposed to heparin within the last 30 days and then has a drop in platelet count within a day of reexposure, 2 points are given. If the previous exposure was 30–100 days ago, 1 pointIf the fall is early but there has been no previous heparin exposure, no points. Thrombosis 2 points in new proven thrombosis, skin necrosis (see below), or systemic reaction1 point if progressive or recurrent thrombosis, silent thrombosis or red skin lesionsNo points if there are no symptoms. Alternative cause possible 2 points if no other cause1 point if there is a possible alternative causeNo points if there is a definite alternative cause. The first screening test in someone suspected of having HIT is aimed at detecting antibodies against heparin PF4 complexes. This may be with a laboratory test of the enzyme linked immunosorbent assay type. This ELISA test, however, detects all circulating antibodies that bind heparin PF4 complexes, and may also falsely identify antibodies that do not cause HIT. Therefore, those with a positive ELISA are tested further with a functional assay. This test uses platelets and serum from the patient; the platelets are washed and mixed with serum and heparin. The sample is then tested for the release of serotonin, a marker of platelet activation. If this serotonin release assay (SRA) shows high serotonin release, the diagnosis of HIT is confirmed. The SRA test is difficult to perform and is usually only done in regional laboratories. Lepirudin production stopped on May 31, 2012.
* 2 балла – новый подтвержденный тромбоз, некроз кожи (см. ниже) или системная реакция.
* 1 балл – прогрессирующий или рецидивирующий тромбоз, бессимптомный тромбоз или кожные поражения покраснения.
* 0 баллов – отсутствие симптомов.
Heparin may be used for both prevention and the treatment of thrombosis. It exists in two main forms: an "unfractionated" form that can be injected under the skin (subcutaneously) or through an intravenous infusion, and a "low molecular weight" form that is generally given subcutaneously. Commonly used low molecular weight heparins are enoxaparin, dalteparin, nadroparin and tinzaparin. In HIT, the platelet count in the blood falls below the normal range, a condition called thrombocytopenia. However, it is generally not low enough to lead to an increased risk of bleeding. Most people with HIT, therefore, do not experience any symptoms. Typically, the platelet count falls 5–14 days after heparin is first given; if someone has received heparin in the previous three months, the fall in platelet count may occur sooner, sometimes within a day. In those receiving heparin through an intravenous infusion, a complex of symptoms ("systemic reaction") may occur when the infusion is started. These include fever, chills, high blood pressure, a fast heart rate, shortness of breath, and chest pain. This happens in about a quarter of people with HIT. Others may develop a skin rash consisting of red spots. The IgG antibodies form a complex with heparin and PF4 in the bloodstream. The tail of the antibody then binds to the FcγIIa receptor, a protein on the surface of the platelet. This results in platelet activation and the formation of platelet microparticles, which initiate the formation of blood clots; the platelet count falls as a result, leading to thrombocytopenia. However, not all people with a falling platelet count while receiving heparin turn out to have HIT. The timing, severity of the thrombocytopenia, the occurrence of new thrombosis, and the presence of alternative explanations, all determine the likelihood that HIT is present. A commonly used score to predict the likelihood of HIT is the "4 Ts" score introduced in 2003. In an analysis of the reliability of the 4T score, a low score had a negative predictive value of 0.998, while an intermediate score had a positive predictive value of 0.14 and a high score a positive predictive value of 0.64; intermediate and high scores, therefore, warrant further investigation. Element The 4T score for heparin induced thrombocytopenia Thrombocytopenia 2 points if the fall in platelet count is >50% of the previous value, AND the lowest count (nadir) is 20–100 × 109/liter1 point if the fall is 30–50% or the nadir is 10–19 × 109/literNo points if the fall is less than 30% or the nadir is <10 × 109/liter. Timing 2 points if the fall is between days 5–10 after commencement of treatment1 point if the fall is after day 10. If someone has been exposed to heparin within the last 30 days and then has a drop in platelet count within a day of reexposure, 2 points are given. If the previous exposure was 30–100 days ago, 1 pointIf the fall is early but there has been no previous heparin exposure, no points. Thrombosis 2 points in new proven thrombosis, skin necrosis (see below), or systemic reaction1 point if progressive or recurrent thrombosis, silent thrombosis or red skin lesionsNo points if there are no symptoms. Alternative cause possible 2 points if no other cause1 point if there is a possible alternative causeNo points if there is a definite alternative cause. The first screening test in someone suspected of having HIT is aimed at detecting antibodies against heparin PF4 complexes. This may be with a laboratory test of the enzyme linked immunosorbent assay type. This ELISA test, however, detects all circulating antibodies that bind heparin PF4 complexes, and may also falsely identify antibodies that do not cause HIT. Therefore, those with a positive ELISA are tested further with a functional assay. This test uses platelets and serum from the patient; the platelets are washed and mixed with serum and heparin. The sample is then tested for the release of serotonin, a marker of platelet activation. If this serotonin release assay (SRA) shows high serotonin release, the diagnosis of HIT is confirmed. The SRA test is difficult to perform and is usually only done in regional laboratories. Lepirudin production stopped on May 31, 2012.
**Альтернативная причина:**
Heparin may be used for both prevention and the treatment of thrombosis. It exists in two main forms: an "unfractionated" form that can be injected under the skin (subcutaneously) or through an intravenous infusion, and a "low molecular weight" form that is generally given subcutaneously. Commonly used low molecular weight heparins are enoxaparin, dalteparin, nadroparin and tinzaparin. In HIT, the platelet count in the blood falls below the normal range, a condition called thrombocytopenia. However, it is generally not low enough to lead to an increased risk of bleeding. Most people with HIT, therefore, do not experience any symptoms. Typically, the platelet count falls 5–14 days after heparin is first given; if someone has received heparin in the previous three months, the fall in platelet count may occur sooner, sometimes within a day. In those receiving heparin through an intravenous infusion, a complex of symptoms ("systemic reaction") may occur when the infusion is started. These include fever, chills, high blood pressure, a fast heart rate, shortness of breath, and chest pain. This happens in about a quarter of people with HIT. Others may develop a skin rash consisting of red spots. The IgG antibodies form a complex with heparin and PF4 in the bloodstream. The tail of the antibody then binds to the FcγIIa receptor, a protein on the surface of the platelet. This results in platelet activation and the formation of platelet microparticles, which initiate the formation of blood clots; the platelet count falls as a result, leading to thrombocytopenia. However, not all people with a falling platelet count while receiving heparin turn out to have HIT. The timing, severity of the thrombocytopenia, the occurrence of new thrombosis, and the presence of alternative explanations, all determine the likelihood that HIT is present. A commonly used score to predict the likelihood of HIT is the "4 Ts" score introduced in 2003. In an analysis of the reliability of the 4T score, a low score had a negative predictive value of 0.998, while an intermediate score had a positive predictive value of 0.14 and a high score a positive predictive value of 0.64; intermediate and high scores, therefore, warrant further investigation. Element The 4T score for heparin induced thrombocytopenia Thrombocytopenia 2 points if the fall in platelet count is >50% of the previous value, AND the lowest count (nadir) is 20–100 × 109/liter1 point if the fall is 30–50% or the nadir is 10–19 × 109/literNo points if the fall is less than 30% or the nadir is <10 × 109/liter. Timing 2 points if the fall is between days 5–10 after commencement of treatment1 point if the fall is after day 10. If someone has been exposed to heparin within the last 30 days and then has a drop in platelet count within a day of reexposure, 2 points are given. If the previous exposure was 30–100 days ago, 1 pointIf the fall is early but there has been no previous heparin exposure, no points. Thrombosis 2 points in new proven thrombosis, skin necrosis (see below), or systemic reaction1 point if progressive or recurrent thrombosis, silent thrombosis or red skin lesionsNo points if there are no symptoms. Alternative cause possible 2 points if no other cause1 point if there is a possible alternative causeNo points if there is a definite alternative cause. The first screening test in someone suspected of having HIT is aimed at detecting antibodies against heparin PF4 complexes. This may be with a laboratory test of the enzyme linked immunosorbent assay type. This ELISA test, however, detects all circulating antibodies that bind heparin PF4 complexes, and may also falsely identify antibodies that do not cause HIT. Therefore, those with a positive ELISA are tested further with a functional assay. This test uses platelets and serum from the patient; the platelets are washed and mixed with serum and heparin. The sample is then tested for the release of serotonin, a marker of platelet activation. If this serotonin release assay (SRA) shows high serotonin release, the diagnosis of HIT is confirmed. The SRA test is difficult to perform and is usually only done in regional laboratories. Lepirudin production stopped on May 31, 2012.
* 2 балла – отсутствие других возможных причин.
* 1 балл – наличие возможной альтернативной причины.
* 0 баллов – наличие установленной альтернативной причины.
Heparin may be used for both prevention and the treatment of thrombosis. It exists in two main forms: an "unfractionated" form that can be injected under the skin (subcutaneously) or through an intravenous infusion, and a "low molecular weight" form that is generally given subcutaneously. Commonly used low molecular weight heparins are enoxaparin, dalteparin, nadroparin and tinzaparin. In HIT, the platelet count in the blood falls below the normal range, a condition called thrombocytopenia. However, it is generally not low enough to lead to an increased risk of bleeding. Most people with HIT, therefore, do not experience any symptoms. Typically, the platelet count falls 5–14 days after heparin is first given; if someone has received heparin in the previous three months, the fall in platelet count may occur sooner, sometimes within a day. In those receiving heparin through an intravenous infusion, a complex of symptoms ("systemic reaction") may occur when the infusion is started. These include fever, chills, high blood pressure, a fast heart rate, shortness of breath, and chest pain. This happens in about a quarter of people with HIT. Others may develop a skin rash consisting of red spots. The IgG antibodies form a complex with heparin and PF4 in the bloodstream. The tail of the antibody then binds to the FcγIIa receptor, a protein on the surface of the platelet. This results in platelet activation and the formation of platelet microparticles, which initiate the formation of blood clots; the platelet count falls as a result, leading to thrombocytopenia. However, not all people with a falling platelet count while receiving heparin turn out to have HIT. The timing, severity of the thrombocytopenia, the occurrence of new thrombosis, and the presence of alternative explanations, all determine the likelihood that HIT is present. A commonly used score to predict the likelihood of HIT is the "4 Ts" score introduced in 2003. In an analysis of the reliability of the 4T score, a low score had a negative predictive value of 0.998, while an intermediate score had a positive predictive value of 0.14 and a high score a positive predictive value of 0.64; intermediate and high scores, therefore, warrant further investigation. Element The 4T score for heparin induced thrombocytopenia Thrombocytopenia 2 points if the fall in platelet count is >50% of the previous value, AND the lowest count (nadir) is 20–100 × 109/liter1 point if the fall is 30–50% or the nadir is 10–19 × 109/literNo points if the fall is less than 30% or the nadir is <10 × 109/liter. Timing 2 points if the fall is between days 5–10 after commencement of treatment1 point if the fall is after day 10. If someone has been exposed to heparin within the last 30 days and then has a drop in platelet count within a day of reexposure, 2 points are given. If the previous exposure was 30–100 days ago, 1 pointIf the fall is early but there has been no previous heparin exposure, no points. Thrombosis 2 points in new proven thrombosis, skin necrosis (see below), or systemic reaction1 point if progressive or recurrent thrombosis, silent thrombosis or red skin lesionsNo points if there are no symptoms. Alternative cause possible 2 points if no other cause1 point if there is a possible alternative causeNo points if there is a definite alternative cause. The first screening test in someone suspected of having HIT is aimed at detecting antibodies against heparin PF4 complexes. This may be with a laboratory test of the enzyme linked immunosorbent assay type. This ELISA test, however, detects all circulating antibodies that bind heparin PF4 complexes, and may also falsely identify antibodies that do not cause HIT. Therefore, those with a positive ELISA are tested further with a functional assay. This test uses platelets and serum from the patient; the platelets are washed and mixed with serum and heparin. The sample is then tested for the release of serotonin, a marker of platelet activation. If this serotonin release assay (SRA) shows high serotonin release, the diagnosis of HIT is confirmed. The SRA test is difficult to perform and is usually only done in regional laboratories. Lepirudin production stopped on May 31, 2012.
Первым скрининговым тестом у пациентов с подозрением на ГИТ является определение антител к комплексам гепарина и PF4. Это может быть выполнено с помощью иммуноферментного анализа (ELISA). Однако ELISA выявляет все циркулирующие антитела, связывающиеся с комплексами гепарина и PF4, и может давать ложноположительные результаты, обнаруживая антитела, не вызывающие ГИТ. Поэтому пациенты с положительным результатом ELISA подвергаются дальнейшему обследованию с помощью функционального анализа. В этом анализе используются тромбоциты и сыворотка пациента; тромбоциты промываются и смешиваются с сывороткой и гепарином. Затем образец исследуется на высвобождение серотонина – маркера активации тромбоцитов. Если тест на высвобождение серотонина (SRA) показывает повышенное высвобождение серотонина, диагноз ГИТ подтверждается. Тест SRA сложен в исполнении и обычно проводится только в специализированных лабораториях. Производство лепирудина было прекращено 31 мая 2012 года.
Heparin may be used for both prevention and the treatment of thrombosis. It exists in two main forms: an "unfractionated" form that can be injected under the skin (subcutaneously) or through an intravenous infusion, and a "low molecular weight" form that is generally given subcutaneously. Commonly used low molecular weight heparins are enoxaparin, dalteparin, nadroparin and tinzaparin. In HIT, the platelet count in the blood falls below the normal range, a condition called thrombocytopenia. However, it is generally not low enough to lead to an increased risk of bleeding. Most people with HIT, therefore, do not experience any symptoms. Typically, the platelet count falls 5–14 days after heparin is first given; if someone has received heparin in the previous three months, the fall in platelet count may occur sooner, sometimes within a day. In those receiving heparin through an intravenous infusion, a complex of symptoms ("systemic reaction") may occur when the infusion is started. These include fever, chills, high blood pressure, a fast heart rate, shortness of breath, and chest pain. This happens in about a quarter of people with HIT. Others may develop a skin rash consisting of red spots. The IgG antibodies form a complex with heparin and PF4 in the bloodstream. The tail of the antibody then binds to the FcγIIa receptor, a protein on the surface of the platelet. This results in platelet activation and the formation of platelet microparticles, which initiate the formation of blood clots; the platelet count falls as a result, leading to thrombocytopenia. However, not all people with a falling platelet count while receiving heparin turn out to have HIT. The timing, severity of the thrombocytopenia, the occurrence of new thrombosis, and the presence of alternative explanations, all determine the likelihood that HIT is present. A commonly used score to predict the likelihood of HIT is the "4 Ts" score introduced in 2003. In an analysis of the reliability of the 4T score, a low score had a negative predictive value of 0.998, while an intermediate score had a positive predictive value of 0.14 and a high score a positive predictive value of 0.64; intermediate and high scores, therefore, warrant further investigation. Element The 4T score for heparin induced thrombocytopenia Thrombocytopenia 2 points if the fall in platelet count is >50% of the previous value, AND the lowest count (nadir) is 20–100 × 109/liter1 point if the fall is 30–50% or the nadir is 10–19 × 109/literNo points if the fall is less than 30% or the nadir is <10 × 109/liter. Timing 2 points if the fall is between days 5–10 after commencement of treatment1 point if the fall is after day 10. If someone has been exposed to heparin within the last 30 days and then has a drop in platelet count within a day of reexposure, 2 points are given. If the previous exposure was 30–100 days ago, 1 pointIf the fall is early but there has been no previous heparin exposure, no points. Thrombosis 2 points in new proven thrombosis, skin necrosis (see below), or systemic reaction1 point if progressive or recurrent thrombosis, silent thrombosis or red skin lesionsNo points if there are no symptoms. Alternative cause possible 2 points if no other cause1 point if there is a possible alternative causeNo points if there is a definite alternative cause. The first screening test in someone suspected of having HIT is aimed at detecting antibodies against heparin PF4 complexes. This may be with a laboratory test of the enzyme linked immunosorbent assay type. This ELISA test, however, detects all circulating antibodies that bind heparin PF4 complexes, and may also falsely identify antibodies that do not cause HIT. Therefore, those with a positive ELISA are tested further with a functional assay. This test uses platelets and serum from the patient; the platelets are washed and mixed with serum and heparin. The sample is then tested for the release of serotonin, a marker of platelet activation. If this serotonin release assay (SRA) shows high serotonin release, the diagnosis of HIT is confirmed. The SRA test is difficult to perform and is usually only done in regional laboratories. Lepirudin production stopped on May 31, 2012.
Эпидемиология
У до 8% пациентов, получающих гепарин, существует риск развития антител к ГИТ, но только у 1–5% пациентов, получающих гепарин, ГИТ прогрессирует до развития ГИТ с тромбоцитопенией, а у трети из них впоследствии может развиться артериальный или венозный тромбоз. Точное число случаев ГИТ в общей популяции неизвестно. Известно, что женщины, получающие гепарин после недавней хирургической операции, особенно кардиоторакальной, подвержены более высокому риску, в то время как риск очень низок у женщин непосредственно перед и после родов. Некоторые исследования показали, что ГИТ встречается реже у пациентов, получающих гепарин с низкой молекулярной массой. О связи этого явления с тромбоцитопенией впервые сообщили в 1969 году; до этого момента подсчет тромбоцитов не проводился в рутинном порядке. Первоначально существовали различные теории относительно точной причины снижения уровня тромбоцитов при ГИТ. Постепенно накапливались данные об истинном лежащем в основе механизме. Лечение первоначально ограничивалось аспирином и варфарином, но в 1990-х годах появились препараты, способные обеспечить антикоагуляцию без риска рецидива ГИТ. Это редкое нежелательное явление (1:1 миллиона – 1:100 000), возникающее после вакцинации против COVID-19 (особенно после вакцинации аденовирусными векторными вакцинами). Оно также известно как синдром тромбоза с тромбоцитопенией или СТТ.
Up to 8% of patients receiving heparin are at risk to develop HIT antibodies, but only 1–5% on heparin will progress to develop HIT with thrombocytopenia and subsequently one third of them may develop arterial or venous thrombosis. The exact number of cases of HIT in the general population is unknown. What is known is that women receiving heparin after a recent surgical procedure, particularly cardiothoracic surgery, have a higher risk, while the risk is very low in women just before and after giving birth. Some studies have shown that HIT is less common in those receiving low molecular weight heparin. The fact that this phenomenon occurred together with thrombocytopenia was reported in 1969; prior to this time, platelet counts were not routinely performed. Initially, various theories existed about the exact cause of the low platelets in HIT. Gradually, evidence accumulated on the exact underlying mechanism. Treatment was initially limited to aspirin and warfarin, but the 1990s saw the introduction of a number of agents that could provide anticoagulation without a risk of recurrent HIT. It is a rare adverse event (1:1 million to 1:100,000) resulting from COVID 19 vaccines (particularly adenoviral vector vaccines). This is also known as thrombosis with thrombocytopenia syndrome or TTS.