{"id":5301,"date":"2021-05-15T00:21:52","date_gmt":"2021-05-14T22:21:52","guid":{"rendered":"https:\/\/meddists.com\/learn\/clinical\/hematology\/hemoglobinopathies\/"},"modified":"2021-10-11T22:10:50","modified_gmt":"2021-10-11T20:10:50","slug":"hemoglobinopathies","status":"publish","type":"page","link":"https:\/\/meddists.com\/learn\/clinical\/internal-medicine\/hematology\/hemoglobinopathies\/","title":{"rendered":"Hemoglobinopathies"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\">Hemoglobinopathies are genetic disorders of the globin genes leading to a qualitative or quantitative abnormality of globin synthesis.<\/p>\n\n\n<span class=\"block-heading\" id=\"header_1\">\n<h3 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Hemoglobin<\/h3>\n<\/span><span class=\"block-content\" id=\"contents_1\">\n\n\n<p class=\"wp-block-paragraph\">Hemoglobin consists of heme (<em>iron <\/em>+ <em>protoporphyrin<\/em>) + globin.<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li><strong>Primitive hemopoiesis<\/strong>: 2 pairs of zetta-epsilon (Hb-Gower1) or alpha-epsilon (Hb-Gower2) or zetta-gamma (Hb-Portland)<\/li><li><strong>Fetal<\/strong>: 2 pairs of alpha-gamma (Hb-F)<\/li><li><strong>Adult<\/strong>: 2 pairs of alpha-beta (Hb-A) or the much less common alpha-delta (Hb-A2)<\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_2\">\n<h3 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Classification<\/h3>\n<\/span><span class=\"block-content\" id=\"contents_2\">\n\n\n<ul class=\"wp-block-list\"><li>Abnormal hemoglobin synthesis (qualitative)<ul><li>Sickle-cell anemia<\/li><li>Hemoglobin C\/D\/E<\/li><\/ul><\/li><li>Reduced rate of synthesis of alpha or beta chains (quantitative)<ul><li>Thalassemias (alpha, beta, intermedia)<\/li><\/ul><\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_3\">\n<h3 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Sickle-cell anemia<\/h3>\n<\/span><span class=\"block-content\" id=\"contents_3\">\n\n\n<p class=\"wp-block-paragraph\">Sickle-cell anemia is a group of autosomal recessive disorders characterized by a defective beta-globin chain, leading to the formation of sickle-cells.<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>Caused by the substitution of valine for glutamic acid in the beta chain, forming hemoglobin S.<\/li><li>Hemoglobin S forms crystals in low-oxygen environments, polymerizing into long strands that distort the shape of the RBCs into a sickle shape.<\/li><li>The homozygous form is the most common severe form and is often symptomatic, while the heterozygous form is most often asymptomstic.<\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_4\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Clinical presentation<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_4\">\n\n\n<p class=\"wp-block-paragraph\">Sickle cells can clump up and cause thrombosis and infarction leading to symptomatic cases divided into <strong>painful<\/strong> and <strong>visceral<\/strong> <strong>vaso-occlusive crises<\/strong>.<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li><strong>Painful vaso-occlusive crises<\/strong> are more frequent, typically involving the digits and extremities first (hand-foot syndrome, or painful dactylitis), and occur spontaneously or triggered by certain infections, cold temperature, exercise. They typically cause deep bone pain caused by the infarctions in the bones.<\/li><li><strong>Visceral vaso-occlusive crises<\/strong> involve organ infarctions and dysfunction and pooling of blood with severe anemia. <ul><li>Any organ can be affected and damaged. <\/li><li>Hepatic and splenic involvements may lead to severe illness, hepatosplenomegaly, and severe abdominal pain requiring splenectomy.<\/li><li>Liver microinfarcts can lead to chronic damage with frequent events of cholelithiasis.<\/li><li>Kidney infarcts often affect the medulla and cause papillary necrosis.<\/li><li>A large splenic infarct can cause auto-splenectomy.<\/li><li>A severe presentation of a visceral event often leading to death is <strong>acute sickle chest syndrome<\/strong> seen with dyspnea, decreased PO2, and chest pain.<\/li><li>The most severe presentation is CNS infarcts.<\/li><li>Retinopathy and priapism (painful erection) are common complications.<\/li><\/ul><\/li><li>Typically, the vaso-occlusive crises are followed by <strong>hemolytic crises<\/strong> in which hemoglobin levels are reduced and the reticulocyte count is increased.<\/li><li>The sickle cells have a shorter lifespan compared to regular RBCs, and in cases of parvovirus infections, <strong>aplastic crises<\/strong> can occur. <\/li><li>Infections are common in the infarcted sites (pneumonia, UTIs, osteomyelitis, and septicemia).<\/li><li><strong>Sickle cell trait<\/strong> is relatively benign apart from the occasional hematuria resulting from minor kidney infarcts.<\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_5\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Diagnosis<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_5\">\n\n\n<ul class=\"wp-block-list\"><li>Complete blood workup (reduced Hgb: 60-90g\/L)<\/li><li>Dithionite tube test (deoxygenation of hemoglobin from sickling cells)<\/li><li>Blood smear (demonstrating sickle cells and <strong>Howell-Jolly bodies<\/strong> &#8211; remnants of RBC nuclei that are normally removed by the spleen typically seen in sickle-cell disease and asplenic patients)<\/li><li>Chromatography or electrophoresis (in homozygous form, no Hb-A is detected).<\/li><li>DNA tests (PCR)<\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_6\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Treatment<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_6\">\n\n\n<ul class=\"wp-block-list\"><li>Prophylactic measures include proper hydration, hygiene and nutrition, avoid infections and cooling, pneumococcal, meningococcal, and H. influenza vaccinations<\/li><li>Folic acid supplementation (5mg\/wk)<\/li><li>Hydroxycarbamide (hydroxyurea) can increase Hb F levels<\/li><li>Stem cell transplantation<\/li><li>During crisis:<ul><li>Rest, warmth, rehydration, and analgesia<\/li><li>Transfusion in severe anemia<\/li><\/ul><\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_7\">\n<h3 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Hemoglobin C\/D\/E<\/h3>\n<\/span><span class=\"block-content\" id=\"contents_7\">\n\n\n<p class=\"wp-block-paragraph\">In these hemoglobin diseases, there are different substitutions leading to defects in the beta-globin; the result is typically mild hemolytic anemia (Hb-C\/D), and mild microcytic hypochromic anemia (Hb-E).<\/p>\n\n\n<\/span><span class=\"block-heading\" id=\"header_8\">\n<h3 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Thalassemia<\/h3>\n<\/span><span class=\"block-content\" id=\"contents_8\">\n\n\n<p class=\"wp-block-paragraph\">Thalassemia is a group of disorders resulting in reduced synthesis of alpha or beta chains.<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>They are largely divided into <strong>alpha-thalassemia<\/strong> and <strong>beta-thalassemia<\/strong> depending on the defective globin chain.<\/li><li>Alpha-thalassemia is more common in the far East, where beta-thalassemia is more common in the Mediterranean region.<\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_9\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Alpha thalassemia<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_9\">\n\n\n<p class=\"wp-block-paragraph\">The alpha-globin chain is encoded by 4 genes (2 from each parent). Most defects are deletions. The severity of the condition depends on the number of defective genes:<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li><strong>Alpha-thalassemia traits<\/strong> are when one or two genes are defective. This typically appears without anemia. Most cases are asymptomatic, but some cases are associated with mental retardation.<\/li><li><strong>Hemoglobin H disease<\/strong> occurs when three genes are defective. This typically appears as moderate microcytic hypochromic anemia. Hb-H (4 beta chains) can be seen in adults, while Hb-Barts (4 gamma chains) can be seen during fetal life.<\/li><li>Deletion of all 4 alpha chains leads to death in utero (<strong>hydrops fetalis<\/strong>), as alpha chains are essential to life. <\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_10\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Beta thalassemia<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_10\">\n\n\n<p class=\"wp-block-paragraph\">The beta-globin chain is encoded by 2 genes (1 from each parent). Most defects are mutations. It is classified as <strong>beta-thalassemia major<\/strong> and <strong>minor<\/strong>.<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li><strong>Beta-thalassemia minor<\/strong> (or trait) occurs when one gene is defective; it is more common and is typically asymptomatic apart from the occasional mild anemia.<\/li><li><strong>Beta-thalassemia major<\/strong> occurs when both genes are defective (2 carrier parents). There are few or no beta chains produced, leading to an excess of alpha chains which cause ineffective erythropoiesis and hemolysis.<ul><li>As a result, gamma chains are formed instead, leading to the formation of fetal Hb-F (alpha-gamma), which is then the most abundant hemoglobin type.<\/li><li>It becomes evident after birth, once the body stops producing Hb-F and attempts to switch onto Hb-A.<\/li><li>It is transfusion-dependent, exposing the patient to increased risks of infection (hepatitis in particular) and iron overload.<\/li><li>Clinical presentations include:<ul><li>Growth retardation<\/li><li>Hepatosplenomegaly (due to extramedullary hematopoiesis)<\/li><li>Bone expansion (due to bone marrow hyperplasia), even in the calvaria of the skull, typically seen as &#8220;hair-on-end&#8221; on X-ray.<\/li><li>Increased susceptibility to infections (hepatitis from the transfusions)<\/li><li>Liver damage (caused by excess iron from frequent transfusions and hepatitis infections), leading to hepatocellular carcinoma.<\/li><li>Osteoporosis<\/li><\/ul><\/li><\/ul><\/li><li><strong>Beta-thalassemia intermedia<\/strong> is thalassemia of moderate severity requiring occasional transfusions. It can come with some clinical presentations seen in beta-thalassemia major.<\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_11\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Diagnosis<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_11\">\n\n\n<ul class=\"wp-block-list\"><li>Blood smear (demonstrates hypochromic microcytic anemia in both alpha and beta-thalassemia).<\/li><li>Chromatography and electrophoresis (in severe cases, no Hb-A is detected; in beta-thalassemia major, mostly Hb-F is detected).<\/li><li>DNA tests (PCR)<\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_12\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Treatment<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_12\">\n\n\n<ul class=\"wp-block-list\"><li>Transfusion in severe cases + iron chelation<\/li><li>Stem-cell transplantation<\/li><\/ul>\n<\/span><div id=\"the_titles\" style=\"display:none;\"><h3 class=\"wp-block-heading\" class=\"wp-block-heading\">Hemoglobin<\/h3><h3 class=\"wp-block-heading\" class=\"wp-block-heading\">Classification<\/h3><h3 class=\"wp-block-heading\" class=\"wp-block-heading\">Sickle-cell anemia<\/h3><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Clinical presentation<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Diagnosis<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Treatment<\/h4><h3 class=\"wp-block-heading\" class=\"wp-block-heading\">Hemoglobin C\/D\/E<\/h3><h3 class=\"wp-block-heading\" class=\"wp-block-heading\">Thalassemia<\/h3><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Alpha thalassemia<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Beta thalassemia<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Diagnosis<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Treatment<\/h4><\/div>","protected":false},"excerpt":{"rendered":"<p>Hemoglobinopathies are genetic disorders of the globin genes leading to a qualitative or quantitative abnormality of globin synthesis. Hemoglobin Hemoglobin consists of heme (iron + protoporphyrin) + globin. Primitive hemopoiesis: 2 pairs of zetta-epsilon (Hb-Gower1) or alpha-epsilon (Hb-Gower2) or zetta-gamma (Hb-Portland) Fetal: 2 pairs of alpha-gamma (Hb-F) Adult: 2 pairs of alpha-beta (Hb-A) or the [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":4472,"menu_order":4,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-5301","page","type-page","status-publish","hentry"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.9 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Hemoglobinopathies &#8211; Meddists<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/meddists.com\/learn\/clinical\/internal-medicine\/hematology\/hemoglobinopathies\/\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"5 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/meddists.com\\\/learn\\\/clinical\\\/internal-medicine\\\/hematology\\\/hemoglobinopathies\\\/\",\"url\":\"https:\\\/\\\/meddists.com\\\/learn\\\/clinical\\\/internal-medicine\\\/hematology\\\/hemoglobinopathies\\\/\",\"name\":\"Hemoglobinopathies &#8211; 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