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Human iron metabolism
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Diagram showing a generalized view of cellular iron homeostasis in humans. Iron import can occur via endocytosis of transferrin receptor 1 or via ferrous iron importers DMT1 and ZIP14, which require the activity of iron reductases such as STEAP2, SDR-2 and Dcytb. Intracellular iron can be stored in ferritin, used for protein biosynthesis, generate reactive oxygen species (ROS) and regulate transcription via iron-responsive element-binding proteins (IRP1/2). Export occurs through ferroportin, often aided by hephaestin (Hp) and/or ceruloplasmin (Cp), and repressed by hepcidin.
Human iron metabolism is the set of chemical reactions that maintain human homeostasis of iron at both the systemic and cellular level. The control of this necessary but potentially toxic metal is an important part of many aspects of human health and disease. Hematologists have been especially interested in systemic iron metabolism because iron is essential for red blood cells, where most of the human body's iron is contained. Understanding iron metabolism is also important for understanding diseases of iron overload, such as hereditary hemochromatosis, and iron deficiency, such as iron deficiency anemia.
Contents
[hide]
1 Importance of iron regulation
1.1 Cellular respiration
1.2 Oxygen transport
1.3 Toxicity
1.4 Bacterial protection
2 Body iron stores
3 Mechanisms of iron regulation
3.1 Systemic iron regulation
3.1.1 Dietary iron uptake
3.1.2 Iron recycling and loss
3.2 Cellular iron regulation
3.2.1 Iron import
3.2.2 The labile iron pool
3.2.3 The storage iron pool
3.2.4 Iron export
3.2.5 Translational control of cellular iron
4 Iron-related pathology
4.1 Iron deficiency
4.2 Iron overload
5 References
6 Further reading
7 External links
Importance of iron regulation[edit]
Structure of Heme b; "Fe" is the chemical symbol of iron, "II" indicates its oxidation state.
Iron is an essential bioelement for most forms of life, from bacteria to mammals. Its importance lies in its ability to mediate electron transfer. In the ferrous state, iron acts as an electron donor, while in the ferric state it acts as an acceptor. Thus, iron plays a vital role in the catalysis of enzymatic reactions that involve electron transfer (reduction and oxidation, redox). Proteins can contain iron as part of different cofactors, such as iron-sulfur clusters (Fe-S) and heme groups, both of which are assembled in mitochondria.
Cellular respiration[edit]
Main article: Cellular respiration
Human cells require iron in order to obtain energy as ATP from a multi-step process known as cellular respiration, more specifically from oxidative phosphorylation at the mitochondrial cristae. Iron is present in the iron-sulfur clusters and heme groups of the electron transport chain proteins that generate a proton gradient that allows ATP synthase to synthesize ATP (chemiosmosis).
Heme groups are part of hemoglobin, a protein found in red blood cells that serves to transport oxygen from the lungs to the tissues. Heme groups are also present in myoglobin to store and diffuse oxygen in muscle cells.
Oxygen transport[edit]
See also: Hemoglobin and myoglobin
The human body needs iron for oxygen transport. Oxygen (O2) is required for the functioning and survival of nearly all cell types. Oxygen is transported from the lungs to the rest of the body bound to the heme group of hemoglobin in erythrocytes. In muscles cells, iron binds myoglobin, which regulates its release.
Toxicity[edit]
Iron is also potentially toxic. Its ability to donate and accept electrons means that it can catalyze the conversion of hydrogen peroxide into free radicals. Free radicals can cause damage to a wide variety of cellular structures, and ultimately kill the cell.[1]
Iron bound to proteins or cofactors such as heme is safe. Also, there are virtually no truly free iron ions in the cell, since they readily form complexes with organic molecules. However, some of the intracellular iron is bound to low-affinity complexes, and is termed labile iron or "free" iron. Iron in such complexes can cause damage as described above.[2]
To prevent that kind of damage, all life forms that use iron bind the iron atoms to proteins. This binding allows cells to benefit from iron while also limiting its ability to do harm.[1][3] Typical intracellular labile iron concentrations in bacteria are 10-20 micromolar,[4] though they can be 10-fold higher in anaerobic environment,[5] where free radicals and reactive oxygen species are scarcer. In mammalian cells, intracellular labile iron concentrations are typically smaller than 1 micromolar, less than 5 percent of total cellular iron.[2]
Bacterial protection[edit]
Electron micrograph of E. coli. Most bacteria that cause human disease require iron to live and to multiply.
In response to a systemic bacterial infection, the immune system initiates a process known as iron withholding. If bacteria are to survive, then they must obtain iron from their environment. Disease-causing bacteria do this in many ways, including releasing iron-binding molecules called siderophores and then reabsorbing them to recover iron, or scavenging iron from hemoglobin and transferrin. The harder they have to work to get iron, the greater a metabolic price they must pay. That means that iron-deprived bacteria reproduce more slowly. So our control of iron levels appears to be an important defense against most bacterial infections; there are some exceptions however. TB causing bacterium can reside within macrophages which are an iron rich environment and Borrelia burgdorferi utilises manganese in place of iron. People with increased amounts of iron, like people with hemochromatosis, are more susceptible to some bacterial infection.[6]
Although this mechanism is an elegant response to short-term bacterial infection, it can cause problems when inflammation goes on for longer. Since the liver produces hepcidin in response to inflammatory cytokines, hepcidin levels can increase as the result of non-bacterial sources of inflammation, like viral infection, cancer, auto-immune diseases or other chronic diseases. When this occurs, the sequestration of iron appears to be the major cause of the syndrome of anemia of chronic disease, in which not enough iron is available to produce enough hemoglobin-containing red blood cells.[3]
Body iron stores[edit]
Illustration of blood cell production in the bone marrow. In iron deficiency, the bone marrow produces fewer blood cells, and as the deficiency gets worse, the cells become smaller.
Most well-nourished people in industrialized countries have 4 to 5 grams of iron in their bodies (∼38 mg iron/kg body weight for women and ∼50 mg iron/kg body for men).[7] Of this, about 6997250000000000000♠2.5 g is contained in the hemoglobin needed to carry oxygen through the blood, and most of the rest (approximately 2 grams in adult men, and somewhat less in women of childbearing age) is contained in ferritin complexes that are present in all cells, but most common in bone marrow, liver, and spleen. The liver's stores of ferritin are the primary physiologic source of reserve iron in the body. The reserves of iron in industrialized countries tend to be lower in children and women of child-bearing age than in men and in the elderly. Women who must use their stores to compensate for iron lost through menstruation, pregnancy or lactation have lower non-hemoglobin body stores, which may consist of 6996500000000000000♠500 mg, or even less.
Of the body's total iron content, about 6996399999999999999♠400 mg is devoted to cellular proteins that use iron for important cellular processes like storing oxygen (myoglobin) or performing energy-producing redox reactions (cytochromes). A relatively small amount (3–4 mg) circulates through the plasma, bound to transferrin.[8] Because of its toxicity, free soluble iron is kept in low concentration in the body.
Iron deficiency first affects the storage iron in the body, and depletion of these stores is thought to be relatively non-symptomatic, although some vague and non-specific symptoms have been associated with it. Since iron is primarily required for hemoglobin, iron deficiency anemia is the primary clinical manifestation of iron deficiency. Iron-deficient people will suffer or die from organ damage well before cells run out of the iron needed for intracellular processes like electron transport.
Macrophages of the reticuloendothelial system store iron as part of the process of breaking down and processing hemoglobin from engulfed red blood cells. Iron is also stored as a pigment called hemosiderin which is an ill-defined deposit of protein and iron, created by macrophages where excess iron is present, either locally or systemically for example among people with iron overload due to frequent blood cell destruction and transfusions. If the systemic iron overload is corrected, over time the hemosiderin is slowly resorbed by macrophages.
Mechanisms of iron regulation[edit]
Human iron homeostasis is regulated at two different levels. Systemic iron levels are balanced by the controlled absorption of dietary iron by enterocytes, the cells that line the interior of the intestines, and the uncontrolled loss of iron from epithelial sloughing, sweat, injuries and blood loss. In addition, systemic iron is continuously recycled. Cellular iron levels are controlled differently by different cell types due to the expression of particular iron regulatory and transport proteins.
Systemic iron regulation[edit]
Humans use 6995199999999999999♠20 mg of iron each day for the production of new red blood cells, much of which is recycled from old red blood cells.
Dietary iron uptake[edit]
The absorption of dietary iron is a variable and dynamic process. The amount of iron absorbed compared to the amount ingested is typically low, but may range from 5% to as much as 35% depending on circumstances and type of iron. The efficiency with which iron is absorbed varies depending on the source. Generally the best-absorbed forms of iron come from animal products. Absorption of dietary iron in iron salt form (as in most supplements) varies somewhat according to the body’s need for iron, and is usually between 10% and 20% of iron intake. Absorption of iron from animal products, and some plant products, is in the form of heme iron, and is more efficient, allowing absorption of from 15% to 35% of intake. Heme iron in animals is from blood and heme-containing proteins in meat and mitochondria, whereas in plants, heme iron is present in mitochondria in all cells that use oxygen for respiration.
Like most mineral nutrients, the majority of the iron absorbed from digested food or supplements is absorbed in the duodenum by enterocytes of the duodenal lining. These cells have special molecules that allow them to move iron into the body. To be absorbed, dietary iron can be absorbed as part of a protein such as heme protein or iron must be in its ferrous Fe2+ form. A ferric reductase enzyme on the enterocytes’ brush border, duodenal cytochrome B (Dcytb), reduces ferric Fe3+ to Fe2+.[9] A protein called divalent metal transporter 1 (DMT1), which can transport several divalent metals across the plasma membrane, then transports iron across the enterocyte’s cell membrane into the cell.
These intestinal lining cells can then either store the iron as ferritin, which is accomplished by Fe3+ binding to apoferritin (in which case the iron will leave the body when the cell dies and is sloughed off into feces), or the cell can release it into the body via the only known iron exporter in mammals, ferroportin. Hephaestin, a ferroxidase that can oxidize Fe2+ to Fe3+ and is found mainly in the small intestine, helps ferroportin transfer iron across the basolateral end of the intestine cells. In contrast, ferroportin is post-translationally repressed by hepcidin, a 25-amino acid peptide hormone. The body regulates iron levels by regulating each of these steps. For instance, enterocytes synthesize more Dcytb, DMT1 and ferroportin in response to iron deficiency anemia.[10] Iron absorption from diet is enhanced in the presence of vitamin C and diminished by excess calcium, zinc, or manganese.[11][citation needed]
The human body’s rate of iron absorption appears to respond to a variety of interdependent factors, including total iron stores, the extent to which the bone marrow is producing new red blood cells, the concentration of hemoglobin in the blood, and the oxygen content of the blood. The body also absorbs less iron during times of inflammation, in order to deprive bacteria of iron. Recent discoveries demonstrate that hepcidin regulation of ferroportin is responsible for the syndrome of anemia of chronic disease.
Iron recycling and loss[edit]
Most of the iron in the body is hoarded and recycled by the reticuloendothelial system, which breaks down aged red blood cells. In contrast to iron uptake and recycling, there is no physiologic regulatory mechanism for excreting iron. People lose a small but steady amount by gastrointestinal blood loss, sweating and by shedding cells of the skin and the mucosal lining of the gastrointestinal tract. The total amount of loss for healthy people in the developed world amounts to an estimated average of 6994100000000000000♠1 mg a day for men, and 1.5–2 mg a day for women with regular menstrual periods.[citation needed] People with gastrointestinal parasitic infections, more commonly found in developing countries, often lose more.[1] Those who cannot regulate absorption well enough get disorders of iron overload. In these diseases, the toxicity of iron starts overwhelming the body's ability to bind and store it.[12]
Cellular iron regulation[edit]
Iron import[edit]
Most cell types take up iron primarily through receptor-mediated endocytosis via transferrin receptor 1 (TFR1), transferrin receptor 2 (TFR2) and GAPDH. TFR1 has a 30-fold higher affinity for transferrin-bound iron than TFR2 and thus is the main player in this process.[13][14] The higher order multifunctional glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) also acts as a transferrin receptor.[15][16] Transferrin-bound ferric iron is recognized by these transferrin receptors, triggering a conformational change that causes endocytosis. Iron then enters the cytoplasm from the endosome via importer DMT1 after being reduced to its ferrous state by a STEAP family reductase.[17]
Alternatively, iron can enter the cell directly via plasma membrane divalent cation importers such as DMT1 and ZIP14 (Zrt-Irt-like protein 14).[18] Again, iron enters the cytoplasm in the ferrous state after being reduced in the extracellular space by a reductase such as STEAP2, STEAP3 (in erythrocytes), Dcytb (in enterocytes) and SDR2.[17]
The labile iron pool[edit]
In the cytoplasm, ferrous iron is found in a soluble, chelatable state which constitutes the labile iron pool (~0.001 mM).[19] In this pool, iron is thought to be bound to low-mass compounds such as peptides, carboxylates and phosphates, although some might be in a free, hydrated form (aqua ions).[19] Alternatively, iron ions might be bound to specialized proteins known as metallochaperones.[20] Specifically, poly-r(C)-binding proteins (PCBPs) appear to mediate transfer of free iron to ferritin (for storage) and non-heme iron enzymes (for use in catalysis).[18][21] The labile iron pool is potentially toxic due to iron's ability to generate reactive oxygen species. Iron from this pool can be taken up by mitochondria via mitoferrin to synthesize Fe-S clusters and heme groups.[17]
The storage iron pool[edit]
Iron can be stored in ferritin as ferric iron due to the ferroxidase activity of the ferritin heavy chain.[22] Dysfunctional ferritin may accumulate as hemosiderin, which can be problematic in cases of iron overload.[23] The ferritin storage iron pool is much larger than the labile iron pool, ranging in concentration from 0.7 mM to 3.6 mM.[19]
Iron export[edit]
Iron export occurs in a variety of cell types, including neurons, erythrocytes, macrophages and enterocytes. The latter two are especially important since systemic iron levels depend upon them. There is only one known iron exporter, ferroportin.[24] It transports ferrous iron out of the cell, generally aided by ceruloplasmin and/or hephaestin (mostly in enterocytes), which oxidize iron to its ferric state so it can bind ferritin in the extracellular medium.[17] Hepcidin causes the internalization of ferroportin, decreasing iron export. Besides, hepcidin seems to downregulate both TFR1 and DMT1 through an unknown mechanism.[25] Another player assisting ferroportin in effecting cellular iron export is GAPDH.[26] A specific post translationally modified isoform of GAPDH is recruited to the surface of iron loaded cells where it recruits apo-transferrin in close proximity to ferroportin so as to rapidly chelate the iron extruded.[27]
The expression of hepcidin, which only occurs in certain cell types such as hepatocytes, is tightly controlled at the transcriptional level and it represents the link between cellular and systemic iron homeostasis due to hepcidin's role as "gatekeeper" of iron release from enterocytes into the rest of the body.[17] Erythroblasts produce erythroferrone, a hormone which inhibits hepcidin and so increases the availability of iron needed for hemoglobin synthesis.[28]
Translational control of cellular iron[edit]
Although some control exists at the transcriptional level, the regulation of cellular iron levels is ultimately controlled at the translational level by iron-responsive element-binding proteins IRP1 and especially IRP2.[29] When iron levels are low, these proteins are able to bind to iron-responsive elements (IREs). IREs are stem loop structures in the untranslated regions (UTRs) of mRNA.[17]
Both ferritin and ferroportin contain an IRE in their 5' UTRs, so that under iron deficiency their translation is repressed by IRP2, preventing the unnecessary synthesis of storage protein and the detrimental export of iron. In contrast, TFR1 and some DMT1 variants contain 3' UTR IREs, which bind IRP2 under iron deficiency, stabilizing the mRNA, which guarantees the synthesis of iron importers.[17]
Iron-related pathology[edit]
Main article: Iron metabolism disorder
Iron deficiency[edit]
Main article: Iron deficiency
Iron is an important topic in prenatal care because women can sometimes become iron-deficient from the increased iron demands of pregnancy.
Functional or actual iron deficiency can result from a variety of causes. These causes can be grouped into several categories:
Increased demand for iron, which the diet cannot accommodate.
Increased loss of iron (usually through loss of blood).
Nutritional deficiency. This can result due to a lack of dietary iron or consumption of foods that inhibit iron absorption, including calcium, phytates and tannins. Black tea steeped for long has high tannins.
Inability to absorb iron: A common cause of iron deficiency is the widespread use of acid reducing medications, the strongest of which are proton pump inhibitors (PPIs) such as omeprazole.[citation needed]
Damage to the intestinal lining. Examples of causes of this kind of damage include surgery involving the duodenum, or diseases like Crohn's or celiac sprue which severely reduce the surface area available for absorption.
Inflammation leading to hepcidin-induced restriction on iron release from enterocytes (see above).
Iron overload[edit]
Main article: Iron overload
The body is able to substantially reduce the amount of iron it absorbs across the mucosa. It does not seem to be able to entirely shut down the iron transport process. Also, in situations where excess iron damages the intestinal lining itself (for instance, when children eat a large quantity of iron tablets produced for adult consumption), even more iron can enter the bloodstream and cause a potentially deadly syndrome of iron overload. Large amounts of free iron in the circulation will cause damage to critical cells in the liver, the heart and other metabolically active organs.
Iron toxicity results when the amount of circulating iron exceeds the amount of transferrin available to bind it, but the body is able to vigorously regulate its iron uptake. Thus, iron toxicity from ingestion is usually the result of extraordinary circumstances like iron tablet over-consumption[1][30] rather than variations in diet. The type of acute toxicity from iron ingestion causes severe mucosal damage in the gastrointestinal tract, among other problems.
Chronic iron toxicity is usually the result of more chronic iron overload syndromes associated with genetic diseases, repeated transfusions or other causes. In such cases the iron stores of an adult may reach 50 grams (10 times normal total body iron) or more. Classic examples of genetic iron overload includes hereditary hemochromatosis (HH) and the more severe disease juvenile hemochromatosis (JH) caused by mutations in either the gene RGMc gene, a member of a three gene repulsive guidance molecule family,[31] (also called hemojuvelin (HJV), and HFE2), Hemojuvelin, or the HAMP gene that encodes (an iron regulatory peptide). The exact mechanisms of most of the various forms of adult hemochromatosis, which make up most of the genetic iron overload disorders, remain unsolved. So while researchers have been able to identify genetic mutations causing several adult variants of hemochromatosis, they now must turn their attention to the normal function of these mutated genes.
References[edit]
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Further reading[edit]
Andrews S, Norton I, Salunkhe AS, Goodluck H, Aly WS, Mourad-Agha H, Cornelis P (2013). "Chapter 7, Control of Iron Metabolism in Bacteria". In Banci L. Metallomics and the Cell. Metal Ions in Life Sciences. 12. Springer. doi:10.1007/978-94-007-5561-1_7. ISBN 978-94-007-5560-4. electronic-book ISBN 978-94-007-5561-1 ISSN 1559-0836 electronic-ISSN 1868-0402
Andrews NC (May 2004). "Anemia of inflammation: the cytokine-hepcidin link". The Journal of Clinical Investigation. 113 (9): 1251–3. doi:10.1172/JCI21441. PMC 398435  . PMID 15124013.
Camaschella C (Dec 2005). "Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders". Blood. 106 (12): 3710–7. doi:10.1182/blood-2005-05-1857. PMID 16030190.
Frazer DM, Anderson GJ (Oct 2005). "Iron imports. I. Intestinal iron absorption and its regulation". American Journal of Physiology. Gastrointestinal and Liver Physiology. 289 (4): G631–5. doi:10.1152/ajpgi.00220.2005. PMID 16160078.
Insel P, Ross D, McMahon K, Bernstein M (2011). "Iron". Nutrition (4th ed.). Sudbury, Massachusetts: Jones and Bartlett Publishers. pp. 510–514. ISBN 978-0-7637-7663-3. Retrieved June 25, 2012. See esp. pp. 513-514 CS1 maint: Uses authors parameter (link)
Lammi-Keef CJ, Couch SC, Philipson EH, eds. (2008). "Dietary diversification and modification of iron". Handbook of Nutrition and Pregnancy. Nutrition & Health. Totowa, New Jersey: Humana Press. pp. 350–351. doi:10.1007/978-1-59745-112-3. ISBN 978-1-59745-112-3. Retrieved June 25, 2012. CS1 maint: Uses editors parameter (link)
Panel on Micronutrients; Subcommittees on Upper Reference Levels of Nutrients and of Interpretation and Uses of Dietary Reference Intakes; the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes (2001). "Iron". Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, D.C: Food and Nutrition Board, Institute of Medicine. pp. 290–393. ISBN 978-0-309-07279-3. Retrieved June 25, 2012.
Reilly C (2004). "Iron". The Nutritional Trace Metals. Oxford, UK & Ames, Iowa: Blackwell Publishing. pp. 35–81. ISBN 1-4051-1040-6. Retrieved June 25, 2012.
External links[edit]
A comprehensive NIH factsheet on iron and nutrition
Iron Disorders Institute: A nonprofit group concerned with iron disorders; site has helpful links and information on iron-related medical disorders.
An interactive medical learning portal on iron metabolism
Information about iron outside the body
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Pentose phosphate pathway
Fructolysis
Galactolysis
Glycosylation
N-linked
O-linked
Nonhuman
Photosynthesis
Anoxygenic photosynthesis
Chemosynthesis
Carbon fixation
Xylose metabolism
Radiotrophism
Lipid metabolism
(lipolysis, lipogenesis)
Fatty acid metabolism
Fatty acid degradation (Beta oxidation)
Fatty acid synthesis
Other
Steroid metabolism
Sphingolipid metabolism
Eicosanoid metabolism
Ketosis
Reverse cholesterol transport
Amino acid
Amino acid synthesis
Urea cycle
Nucleotide
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Purine metabolism
Nucleotide salvage
Pyrimidine metabolism
Other
Metal metabolism
Iron metabolism
Ethanol metabolism
[show]
v
t
e
Metabolism: Metal metabolism
Transition metal
Iron metabolism
Absorption in
Duodenum
Iron(II) oxide:
DMT1 (SLC11A2)
Ferritin
Hephaestin/Ferroportin (SLC11A3/SLC40A1)
Transferrin to Transferrin receptor
TFR1
TFR2
Iron(III) oxide:
Duodenal cytochrome B
Integrin
Calreticulin/mobilferrin
Ferritin
Other
Iron-binding proteins:
Ferritin
Hepcidin/HAMP
Hemojuvelin
Iron-responsive element-binding protein
Aconitase
Ceruloplasmin
HFE
Hemosiderin
Lactoferrin
Copper metabolism
ATP7A
ATP7B
Ceruloplasmin
SLC31A1
ATOX1
Zinc metabolism
TMC6
TMC8
SLC30A1
SLC39A4
Electrolyte
Sodium metabolism
Na+/K+-ATPase
Phosphate metabolism
Phosphoric acids and phosphates
Magnesium metabolism
Magnesium transporter
Calcium metabolism
Calcium-sensing receptor
Calcium-binding protein
Retrieved from "https://en.wikipedia.org/w/index.php?title=Human_iron_metabolism&oldid=824346301"
Categories:
Iron metabolism
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Biology and pharmacology of chemical elements
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Left shift (medicine)
From Wikipedia, the free encyclopedia
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Neutrophilic band cell
Left shift or blood shift is an increase in the number of immature leukocytes in the peripheral blood, particularly neutrophil band cells.[1]
Less commonly, left shift may also refer to a similar phenomenon in severe anemia, when reticulocytes and immature erythrocyte precursors appear in the peripheral circulation.[2]
Contents
[hide]
1 Definition
2 Morphology
3 Pathogenesis
4 See also
5 References
Definition[edit]
The standard definition of a left shift is an absolute band form count greater than 700/microL.[3] There are competing explanations for the origin of the phrase "left shift," including the left-most button arrangement of early cell sorting machines[4][5] and a 1920s publication by Josef Arneth, containing a graph in which immature neutrophils, with fewer segments, shifted the median left.[6]
Morphology[edit]
It is usually noted on microscopic examination of a blood smear. This systemic effect of inflammation is most often seen in the course of an active infection and during other severe illnesses such as hypoxia and shock. Döhle bodies may also be present in the neutrophil's cytoplasm in the setting of sepsis or severe inflammatory responses.[7]
Pathogenesis[edit]
It is believed that cytokines (including IL-1 and TNF) accelerate the release of cells from the postmitotic reserve pool in the bone marrow, leading to an increased number of immature cells.[1]
See also[edit]
Blood shift
Leukocytosis
Band cell
Reticulocyte
References[edit]
^ Jump up to: a b Kumar, Vinay; Fausto, Nelso; Abbas, Abul (2004). Robbins & Cotran Pathologic Basis of Disease (7th ed.). Philadelphia, PA: Saunders. pp. 84–85. ISBN 978-0-7216-0187-8.
Jump up ^ Rodak, Bernadette F.; Fritsma, George A.; Doig, Kathryn (2007). Hematology: clinical principles and applications (3rd ed.). Elsevier Health Sciences. p. 171. ISBN 978-1-4160-3006-5.
Jump up ^ Coates, Thomas D (December 22, 2008), "Approach to the patient with neutrophilia", UpToDate Online, 17.3, Wolters Kluwer, retrieved December 21, 2009
Jump up ^ http://medicineoutofthebox.com/2010/10/26/the-meaning-of-a-shift-to-the-left/
Jump up ^ http://www.pathologystudent.com/?p=318
Jump up ^ Rodak, B.F.; Fritsma, G.A.; Keohane, E. (2012). Hematology: Clinical Principles and Applications, 4th Ed. Saunders. p. 205. ISBN 978-1437706925. Retrieved 14 Apr 2015.
Jump up ^ Kumar, Vinay; Fausto, Nelso; Abbas, Abul (2004). Robbins & Cotran Pathologic Basis of Disease (7th ed.). Philadelphia, PA: Saunders. pp. 663–664. ISBN 978-0-7216-0187-8.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Left_shift_(medicine)&oldid=795747479"
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List of best-selling fiction authors
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This is a list of best-selling fiction authors to date, in any language. While finding precise sales numbers for any given author is near-impossible, the list is based on approximate numbers provided or repeated by reliable sources. "Best-selling" refers to the estimated number of copies sold of all fiction books written or co-written by an author. To keep the list manageable, only authors with estimated sales of at least 100 million are included. Authors of comic books are not included unless they have been published in book format (for example: comic albums or Tankōbon).
Authors such as Miguel de Cervantes, Alexandre Dumas, Charles Dickens, Jane Austen, Arthur Conan Doyle, Victor Hugo, Jules Verne, Rick Riordan, Jack Higgins and Leon Uris have not been included in the table because no exact figures could be found—although there are indications that they too have more than 100 million copies of their work in print.[citation needed]
This is a dynamic list and may never be able to satisfy particular standards for completeness. You can help by expanding it with reliably sourced entries.
Author
Min. estimated sales
Max. estimated sales
Original language
Genre or title
Number of books
Citizenship
Christie, AgathaAgatha Christie 2 billion[1] 4 billion[2] English Whodunits including the Miss Marple and Hercule Poirot series 85 British
Shakespeare, WilliamWilliam Shakespeare 2 billion[3] 4 billion[2] English Plays and poetry 42 English
Cartland, BarbaraBarbara Cartland 500 million[4] 1 billion[5] English Romance 723 British
Steel, DanielleDanielle Steel 500 million[6] 800 million[7] English Romance 120 American
Robbins, HaroldHarold Robbins 750 million[8] 750 million[9] English Adventure 23 American
Simenon, GeorgesGeorges Simenon 500 million[10] 700 million[11] French Detectives, Maigret, romans dur 570 Belgian
Sheldon, SidneySidney Sheldon 370 million[12] 600 million[13] English Suspense 21 American
Blyton, EnidEnid Blyton 300 million[14] 600 million[15] English Children's literature, Noddy, The Famous Five, The Secret Seven 800 British
Rowling, J. K.J. K. Rowling 450 million[16] 500 million[17] English Harry Potter 11 British
Seuss, Dr.Dr. Seuss 100 million[18] 500 million[19] English Children's literature 44 American
Patten, GilbertGilbert Patten 125 million[20] 500 million[21] English Adolescent adventures 209 American
Oda, EiichiroEiichiro Oda 320 million[22] 430 million[23] Japanese One Piece, Manga 86 Japanese
Tolstoy, LeoLeo Tolstoy 413 million[24] Russian War and Peace, Anna Karenina 48 Russian
Tellado, CorínCorín Tellado 400 million[25] 400 million[26] Spanish Romance 4,000 Spanish
Collins, JackieJackie Collins 250 million[27] 400 million[28] English Romance 25 British
Alger, HoratioHoratio Alger 200 million[29] 400 million[30] English Dime novels 135 American
Stine, R. L.R. L. Stine 100 million[31] 400 million[32] English Goosebumps series, Fear Street series, horror, comedy 430+ American
Koontz, DeanDean Koontz 325 million[33] 400 million[34] English Horror, thriller, science fiction, fantasy 91 American
Roberts, NoraNora Roberts 145 million[35] 400 million[36] English Romance 200+ American
Pushkin, AlexanderAlexander Pushkin 357 million[24] Russian Plays, poetry, prose, Eugene Onegin 17 Russian
King, StephenStephen King 300 million[37] 350 million[38] English Horror, science fiction, fantasy, It, The Shining, The Stand, Bag Of Bones, Needful Things, The Green Mile 70 American
Coelho, PauloPaulo Coelho 200 million[39] 350 million[40] Portuguese The Alchemist 28 Brazilian
L'Amour, LouisLouis L'Amour 230 million[41] 330 million[42] English Western 101 American
Gardner, Erle StanleyErle Stanley Gardner 100 million[43] 325 million[44] English Mystery, Perry Mason 140 American
Jin Yong 100 million[45] 300 million[46][47] Chinese Wuxia 15 Hong Kong Chinese
Akagawa, JirōJirō Akagawa 300 million[48] Japanese Mystery 500+ Japanese
Dailey, JanetJanet Dailey 300 million[49] 300 million[50] English Romance 93 American
Wallace, EdgarEdgar Wallace 300 million[51] English Detective 175 British
Ludlum, RobertRobert Ludlum 110 million[52] 290 million[53] English Espionage, Jason Bourne 40 American
Patterson, JamesJames Patterson 150 million[54] 275 million[55] English Thriller, Alex Cross 98 American
Dard, FrédéricFrédéric Dard 200 million[56] 270 million[57] French Detective, San Antonio 300 Swiss
Archer, JeffreyJeffrey Archer 120 million[58] 270 million[59] English Crime thriller 30 British
Berenstain, Stan and JanStan and Jan Berenstain 200 million[60] 260 million[61] English Berenstain Bears 300+ American
Dahl, RoaldRoald Dahl 200 million[62] 250 million[63] English Children's literature 50 British
Grisham, JohnJohn Grisham 100 million[64] 250 million[65] English Legal thriller 22 American
Grey, ZaneZane Grey 250 million[66] English Western American
Wallace, IrvingIrving Wallace 250 million[67] English Suspense American
Tolkien, J. R. R.J. R. R. Tolkien 200 million[68] 250 million[69] English The Lord of the Rings, The Hobbit, classical fantasy 36 British
Toriyama, AkiraAkira Toriyama 240 million[70] Japanese Dragon Ball, Dr. Slump, Manga 60 Japanese
Kishimoto, MasashiMasashi Kishimoto 220 million[71] Japanese Naruto, Manga 72 Japanese
May, KarlKarl May 100 million[72] 200 million[73] German Western, adventure 80 German
Spillane, MickeyMickey Spillane 100 million[74] 200 million[75] English Detective, Mike Hammer American
Lewis, C. S.C. S. Lewis 100 million[76] 200 million[77] English The Chronicles of Narnia, fantasy, popular theology 38 British
Nishimura, KyotaroKyotaro Nishimura 200 million[78] Japanese Mystery 400+ Japanese
Brown, DanDan Brown 200 million 200 million[79] English Thriller, Robert Langdon 6 American
Martin, Ann M.Ann M. Martin 172 million[80] 180 million[81] English The Baby-sitters Club 335 American
Shiba, RyōtarōRyōtarō Shiba 180 million[82] Japanese Historical 350 Japanese
Hailey, ArthurArthur Hailey 150 million[83] 170 million[84] English Thriller 11 British/Canadian
Villiers, Gérard deGérard de Villiers 150 million[85] French Detectives, SAS 170 French
Potter, BeatrixBeatrix Potter 100 million[86] 150 million[87] English Peter Rabbit 23 British
Crichton, MichaelMichael Crichton 150 million[88] 150 million[89] English Techno thriller 25 American
Scarry, RichardRichard Scarry 100 million[90] 150 million[91] English Illustrated children's books 250 American
Cussler, CliveClive Cussler 40 million[92] 150 million[93] English Adventure, Dirk Pitt 37 American
MacLean, AlistairAlistair MacLean 150 million[94] English Adventure, thriller, war stories 32 British
Follett, KenKen Follett 90 million[95] 150 million[96] English Spy thriller, historical thriller 30 British
Lindgren, AstridAstrid Lindgren 100 million[97] 145 million[98] Swedish Children's literature 100 Swedish
Macomber, DebbieDebbie Macomber 60 million[99] 140 million[100] English Romance American
EL James 100 million 125 million English Fifty Shades of Grey 3 British
Yoshikawa, EijiEiji Yoshikawa 120 million[101] Japanese Musashi 7 Japanese
Cookson, CatherineCatherine Cookson 100 million[102] 120 million[103] English Romance 103 British
Meyer, StephenieStephenie Meyer 100 million[104] 116 million[105] English The Twilight Saga, The Host, romance 6 American
Bridwell, NormanNorman Bridwell 100 million[106] 110 million[107] English Clifford the Big Red Dog 80 American
Baldacci, DavidDavid Baldacci 110 million[108] English Thriller 25 American
Nicholas Sparks 90 million[109] 105 million[110] English Romance 22 American
Hunter, EvanEvan Hunter 100 million[111] 100 million[112] English Detective (Ed McBain) 94 American
Neiderman, AndrewAndrew Neiderman 100 million[113] 100 million[114] English V. C. Andrews, The Devil's Advocate 60 American
Hargreaves, RogerRoger Hargreaves 100 million[115] 100 million[116] English Children's literature, Mr. Men British
Rice, AnneAnne Rice 75 million[117] 100 million[118] English Gothic fiction, vampires, Interview with the Vampire (The Vampire Chronicles) 27 American
Cook, RobinRobin Cook 100 million[119] 100 million[120] English Medical thriller 27 American
Smith, WilburWilbur Smith 80 million[121] 100 million[122] English African adventure 32 South African/British
Caldwell, ErskineErskine Caldwell 80 million[123] 100 million[124] English Literature 25 American
Judith Krantz 80 million[citation needed] 100 million[citation needed] English Romance 12 American
Hibbert, EleanorEleanor Hibbert 100 million[125] 100 million[126] English Romance, historical, suspense 200 British
Carroll, LewisLewis Carroll 100 million[127] English Alice's Adventures in Wonderland, absurdist literature 5 British
Robins, DeniseDenise Robins 100 million[128] English Romance 200 British
Xueqin, CaoCao Xueqin 100 million[129] Chinese Dream of the Red Chamber Chinese
Fleming, IanIan Fleming 100 million[130] 100 million[131] English James Bond 14 British
Hesse, HermannHermann Hesse 100 million[132] 100 million[133] German Steppenwolf, Siddhartha, The Glass Bead Game 45 German-Swiss
Stout, RexRex Stout 100 million[134] 100 million[135] English Nero Wolfe 50 American
Golon, AnneAnne Golon 100 million[136] 100 million[137] French Angélique 14 French
Slaughter, Frank G.Frank G. Slaughter 100 million[138] English Medical 62 American
Burroughs, Edgar RiceEdgar Rice Burroughs 100 million[139] 100 million[140] English Tarzan, Barsoom and Pellucidar series, science fantasy American
Creasey, JohnJohn Creasey 100 million[141] English Crime thriller 600 British
Michener, James A.James A. Michener 100 million[142] English Historical 47 American
Uchida, YasuoYasuo Uchida 100 million[143] Japanese Mystery 130+ Japanese
Morimura, SeiichiSeiichi Morimura 100 million[143] Japanese Mystery 350+ Japanese
Higgins Clark, MaryMary Higgins Clark 100 million[144] 100 million[145] English Thriller American
Jordan, PennyPenny Jordan 90 million[146] 100 million[147] English Romance 200+ British
Cornwell, PatriciaPatricia Cornwell 100 million[148] English Thriller 34+ American
Clancy, TomTom Clancy 100 million[149] English Thriller American
See also[edit]
Lists of writers
Literature
List of best-selling books
List of best-selling novels in the United States
Notes[edit]
Jump up ^ News.com.au on Agatha Christie: "With more than two billion copies of her 80 crime masterpieces sold there is a ready-made audience for television adaptations." (8 February 2008)
^ Jump up to: a b Times Online on William Shakespeare and Agatha Christie: "Christie wrote 80 detective novels mostly featuring Poirot or Marple and it has been suggested that only the Bible and Shakespeare’s canon have outsold an estimated 4 billion copies of her books. " (15 September 2008)
Jump up ^ Times Online on William Shakespeare: "Christie sold more than two billion books, translated into 103 languages. Only the Bible and Shakespeare’s works are said to have sold more." (September 14, 2005)
Jump up ^ The Telegraph on Barbara Cartland: "Barbara Cartland, who, we are informed (on www.condor-sj.com), 'is the most widely read author in the world with more than 500 million books in print'?" (25 February 2007)
Jump up ^ CBS News on Barbara Cartland: "Dame Barbara Cartland, 98. Considered the world's most prolific author and Britain's queen of romantic fiction, with total sales of 1 billion books." (December 20, 2000)
Jump up ^ CBC on Danielle Steel: "The reclusive Steel, who lives in San Francisco and Paris, has published more than 70 bestselling romance novels, which have sold more than 500 million copies worldwide." (21 April 2010)
Jump up ^ Forbes on Danielle Steel: "Yes, you read that right, 800 MILLION copies sold. Best known for romance and drama, Danielle Steel’s novels have spent over 390 consecutive weeks on The New York Times Best Seller list and 22 have been adapted for television." (6 June 2011)
Jump up ^ The Independent on Harold Robbins: "During his 50-year career (he died in 1997) he sold an estimated 750 million books and, in the process, transformed himself into a brand." (23 September 2008)
Jump up ^ USA Today on Harold Robbins: "Starting in 1948, he sold 750 million books, including megasellers such as The Carpetbaggers, A Stone for Danny Fisher and The Betsy." (9 October 2007)
Jump up ^ The Age on Georges Simenon: "With worldwide sales of 500 million, he was the most widely read living writer of his era." (14 September 2003)
Jump up ^ The Wall Street Journal on Georges Simenon: "In his lifetime Simenon published some 570 books, using 17 pen names, which have sold more than 700 million copies in 40 countries and were translated into 57 languages." (1 April 2003)
Jump up ^ Variety on Sidney Sheldon: "A NEW MILESTONE FOR Sidney Sheldon, who has sold more than 370 million books" (6 October 1995)
Jump up ^ The Columbus Dispatch on Sidney Sheldon: "He was one of the world's most translated authors, selling more than 600 million books in 180 countries." (January 31, 2007)
Jump up ^ Encyclopædia Britannica on Enid Blyton: "By the late 20th century her books had sold more than 300 million copies and been translated into at least 90 languages." (24 November 2007)
Jump up ^ The Huddersfield DailyExaminer on Enid Blyton: "She has been translated into 90 languages, is the sixth most popular writer worldwide according to UNESCO and almost equal to Shakespeare, and has sold 600 million copies." (25 August 2008)
Jump up ^ The BBC on J. K. Rowling: "The Harry Potter novels have sold more than 450 million copies through Bloomsbury in Britain, and Scholastic in the United States." (23 June 2011)
Jump up ^ Forbes on "Harry Potter": "It and the six subsequent books have now sold 500 million copies worldwide." (31 June 2015)
Jump up ^ The Daily Utah Chronicle on Dr. Seuss: "The Pulitzer Prize-winning Seuss wrote and illustrated 47 books and sold more than 100 million copies in 18 languages." (5 March 2001)
Jump up ^ The New York Times on Dr. Seuss: "Today Dr. Seuss's 44 books have been translated into 21 languages, selling more than 500 million copies." (2 March 2004)
Jump up ^ Susan Edgerton e.a. in Imagining the Academy: Higher Education and Popular Culture page 53, on Gilbert Patten: "It is estimated that at least 125 million copies of the Frank Merriwell series (which itself ran to at least 209 books) were sold." (2004)
Jump up ^ LeRoy Ashby in With Amusement For All: A History of American Popular Culture Since 1830 page 145, on Gilbert Patten: "[...] the Merriwell brothers, the heroes of almost 250 children's books, whose total sales of 500 million copies surpassed those of the Bible between 1896 and 1918." (2006)
Jump up ^ Guinness World Records June 26, 2015 "In the space of less than two decades, the series has accumulated an incredibly loyal following and has gone on to sell an incredible 320,866,000 units, with a substantial 77 volumes of the comic book released over that period."
Jump up ^ "One Piece Manga Has 430 Million Copies in Print Worldwide". Anime News Network. October 16, 2017. Retrieved October 16, 2017. Hiroyuki Nakano, editor-in-chief of Shueisha's Weekly Shonen Jump magazine, announced at a press event for Shueisha's new 2017 publications on Monday that Eiichiro Oda's One Piece manga has more than 430 million copies in print worldwide. The series has 360 million copies in print in Japan and 70 million copies in print outside of Japan.
^ Jump up to: a b New York Times February 15, 1987
Jump up ^ Latin American Herald Tribune on Corin Tellado: "In the course of her life she published more than 4,000 romance novels that sold 400 million copies, which earned her a place in the Guinness Book of Records where she has been a fixture since 1994." (11 April 2009)
Jump up ^ AFP on Corin Tellado: "Corin Tellado, Spain's most prolific romantic novelist whose books sold over 400 million copies, died Saturday at the age of 81, three days after she finished her last novel, a hospital official said." (11 April 2009)
Jump up ^ Chicago Tribune on Jackie Collins: "More than 250 million copies of her books have been sold to fans in more than 40 countries" (1 January 2007)
Jump up ^ The Guardian on Jackie Collins: "One of the world's bestselling writers with more than 400 million books sold in over 40 countries. " (27 June 2004)
Jump up ^ The Chinook Observer on Horatio Alger, Jr.: "Americans bought 200 million copies of his dime novels -- with intriguing titles like Raggedy Dick and Sink or Swim. " (30 March 2005)
Jump up ^ Time magazine on Horatio Alger: "[...] that have sold from 100 million to 400 million copies, depending on which literary historian you believe." (12 February 1973)
Jump up ^ The Hindu on R. L. Stine: "As R.L. Stine points out (and he should know, having sold over a 100 million copies of over 160 different spooky stories)" (7 September 2003)
Jump up ^ Pittsburgh Post-Gazette on R. L. Stine: "Altogether, Stine has sold more than 400 million books." (8 April 2007)
Jump up ^ The OC Register on Dean Koontz: "Admitting to finally having found a great editor at Bantam, the author, who has sold 325 million books in 38 languages, talked about his craft. " (September 25, 2007)
Jump up ^ Daily Pilot on Dean Koontz: "He's now the world's sixth most highly paid author, tied with John Grisham at $25 million in annual sales, and his novels have sold more than 400 million copies." (7 January 2011)
Jump up ^ BBC on Nora Roberts: "Nora Roberts currently has 145 million books in print." (6 June 2002)
Jump up ^ The Washington Post on Nora Roberts: "Today, Roberts, 61, has published her 200th novel, “The Witness,” and is at the helm of a cottage industry: about 400 million copies of her books in print..." (16 Apr 2012)
Jump up ^ ABC Australia on Stephen King: "Stephen King, author of more than 40 novels with sales of around 300 million copies, [...]" (12 November 2006)
Jump up ^ BBC on Stephen King: "But - after selling 350 million copies of his horror and suspense books - the author's latest work draws on a series of events which almost broke him." (22 November 2006)
Jump up ^ L'Illustré on Paulo Coelho: "the man with 200 million books sold" (6 April 2016)
Jump up ^ The Washington Post on Paulo Coelho: "the writer has sold an estimated 350 million books." (20 December 2016)
Jump up ^ Ray Broadmus Browne and Pat Browne in The Guide to United States Popular Culture page 473, on Louis L'Amour: "His books have sold over 230 million copies, making him one of the best- selling authors in modern literary history. " (2001)
Jump up ^ The Jamestown Sun on Louis L'Amour: "More than 330 million copies of his books have been sold, translated into 27 languages." (29 October 2001)
Jump up ^ The New York Sun on Erle Stanley Gardner: "Erle Stanley Gardner (whose Perry Mason stories sold more than a 100 million books)" (20 July 2005)
Jump up ^ The New York Times on Erle Stanley Gardner: "Gardner's books continue to be reissued regularly both here and abroad. Sales to date exceed 325 million copies." (22 November 1992)
Jump up ^ I. B.Tauris & Company on Jin Yong: "Jin Yong (1924-) is China's bestselling living novelist. His 15 books have sold more than 100 million copies worldwide..."
Jump up ^ Shue Yan Newsletter on Jin Yong: "Professor Cha adopted ‘Jin Rong’ as his pen-name for his 15 martial arts novels of which over 300 million copies have been sold to-date. Although Professor Cha stopped writing martial arts novels almost forty years ago, they remain in print and have been translated into English, Japanese, Korean, Thai, Vietnamese and other languages for his countless readers worldwide."
Jump up ^ Lewis Manalo. "The Billion Copy Opportunity". Publishing Perspectives. Without rival, the twentieth century’s king of the genre is Louis Cha. Estimates of his book sales reach up to 300 million copies. One editor at the Far Eastern Economic Review estimated that, if one also counted the pirated copies, over 1 billion of Cha’s books have been sold. His fourteen novels have been adapted into countless comic books, television shows, and films.
Jump up ^ Nishi-Nippon Shinbun (Japanese Language, 25 February 2007)
Jump up ^ BBC AudioBooks catalogue on Janet Dailey: "Janet Dailey has written more than 100 novels and is one of the world's topselling women writers, with more than 300 million copies of her books sold in nineteen languages in ninety-eight countries" (2007)
Jump up ^ Pamela Regis in A Natural History of the Romance Novel page 159 on Janet Dailey: "There are 300 million copies of her books in print, making her the third best-selling author of all time" (2007)
Jump up ^ The "American mystery and detective novels: a reference guide" on Edgar Wallace: "Christie alone has sold 500 million copies; Edgar Wallace, 300 million; Georges Simenon, 300 million; and Mickey Spillane, 150 million." (1999)
Jump up ^ BBC on Robert Ludlum: "He has sold more than 110 million books in 40 countries and 32 languages." (13 March 2001)
Jump up ^ BBC on Robert Ludlum: "The author, who died in 2001, has sold more than 290 million books worldwide." (11 August 2005)
Jump up ^ ABC News on James Patterson: "Interesting that James Patterson has sold nearly 150 million books." (13 March 2008)
Jump up ^ Daily Express on James Patterson: "At the last count the 65-year-old American has sold 275 million copies of his books." (26 February 2013)
Jump up ^ The New York Times on Frédéric Dard: "Mr. Dard wrote almost 300 books, of which more than 200 million copies have been sold." (15 June 2000)
Jump up ^ The Washington Post on Frédéric Dard: "Mr. Dard worked as a journalist in Lyon from 1942 to 1950 before dedicating himself to novels, theater and film. He used a number of pseudonyms, among them Frederic Charles, Kaput and L'Ange Noir (The Black Angel), and sold more than 270 million books." (9 June 2000)
Jump up ^ Hello Magazine on Jeffrey Archer: "To date he has notched up sales of over 120 million books worldwide." (2008)
Jump up ^ The Australian on Jeffrey Archer: "The 270 million copies he has sold of his 28 books over three decades argue that he is." (1 April 2014)
Jump up ^ The Daily Nebraskan on the Berenstains: ""They've sold over 200 million copies of their books," said director James Larson." (21 November 2005)
Jump up ^ Variety on the Berenstains: "The company also is offering a new animated series based on the Berenstain Bears, the hugely popular children's brand that has sold more than 260 million books worldwide." (7 April 2002)
Jump up ^ BBC on Roald Dahl: "With his stories available in 59 languages and with more than 200 million book sales worldwide." (6 July 2015)
Jump up ^ "Roald Dahl: As popular - and profitable - as ever". BBC. 18 August 2016. Retrieved 30 August 2016.
Jump up ^ The New York Times on John Grisham: "Over the last 15 years, more than 100 million copies of Mr. Grisham's books have been published in hardcover and paperback worldwide." (19 January 2005)
Jump up ^ BBC on John Grisham: "While legal thriller writer Grisham - who has sold more that 250 million books in his 20-year career - picked up a lifetime achievement award, Ian Rankin's The Naming of the Dead won best crime thriller." (28 March 2007)
Jump up ^ The Payson Roundup on Zane Grey: ""Zane Grey had 250 million books published," Wolfe said." (22 November 2005)
Jump up ^ The Writer's Almanac on Irving Wallace: "Although often scorned by critics, his 16 novels and 17 works of nonfiction have sold some 250 million copies worldwide." (19 March 2003)
Jump up ^ USA Today on J. R. R. Tolkien: "Tolkien's franchise has resulted in more than 200 million books sold globally and $3.5 billion in box office revenue — not to mention tens of millions of DVDs sold." (23 April 2007)
Jump up ^ Vancouver Sun on J. R. R. Tolkien: "Since its publication in the mid 1950s, the series (plus its prequel The Hobbit) has sold an estimated 250 million copies and has inspired legions of fans who revere the books." (November 20, 2008)
Jump up ^ [1] "The manga has sold over 240 million copies."
Jump up ^ Anime News Network "To put Naruto's incredible worldwide sales in perspective, Sasaki told fans that 220 million copies of Naruto have sold around the world."
Jump up ^ The Wall Street Journal on Karl May: "the best-selling German author of all time, with 100 million books" (1 January 2004)
Jump up ^ Deutsche Welle on Karl May: "With sales of over 200 million books, Karl May remains a household name in today's Germany." (4 April 2001)
Jump up ^ CBC obituary of Mickey Spillane: "He sold more than 100 million books, and Hammer inspired several TV series and movies." (18 July 2006)
Jump up ^ The Washington Post on Mickey Spillane: "According to today's industry estimates, his 26 books have sold more than 200 million copies." (22 August 2001)
Jump up ^ BBC on C. S. Lewis: "favourite Northern Irish author has sold over 100 million books and inspired the Harry Potter and the Lord of the Rings novels." (8 February 2008)
Jump up ^ The Daily Herald on C. S. Lewis: "C.S. Lewis may not be on the best-seller list, but it is estimated that his 38 books have sold more than 200 million copies worldwide and remain in print 38 years after his death." (20 October 2001)
Jump up ^ Famitsu.com (Japanese language, May 11, 2007)
Jump up ^ ^ https://www.independent.co.uk/arts-entertainment/books/news/dan-browns-inferno-publishers-poised-for-biggestsales-since-harry-potter-as-da-vinci-code-authors-latest-robert-langdon-story-hits-shelves-8614082.html
Jump up ^ Benjamin M. Compaine and Douglas Gomery, 'Who Owns the Media?: Competition and Concentration in the Mass Media Industry' page 115"
Jump up ^ The Wall Street Journal on Ann M. Martin: "A year earlier, however, the movie version of "The Baby-Sitters Club" -- based on a series of young-adult books that have sold more than 180 million copies -- sold only $10 million in tickets, barely exceeding its $6.5 million budget." (8 October 2004)
Jump up ^ Japan Inc. on Ryōtarō Shiba: "Altogether, including such genres as dialogues with other authors, more than 180 million copies of his books have been printed" (22 June 2006)
Jump up ^ The Age on Arthur Hailey: "Arthur Hailey, who has died at his home in the Bahamas aged 84, was one of the most commercially successful authors of all time, producing 11 books which sold more than 150 million copies, were translated into about 40 languages, and brought him tens of millions of dollars" (28 November 2004)
Jump up ^ The Washington Post on Arthur Hailey: "He wrote 11 books, which were published in 40 countries and 38 languages, with about 170 million copies in print." (27 November 2004)
Jump up ^ Sunday Herald on Gerard De Villiers: "De Villiers, now 78, claims to have sold an extraordinary 150 million books over his career - with every year a million more added to the total in France alone." (November 19, 2007)
Jump up ^ Lucia Marginean in Collecting Beatrix Potter Figurines page 2, on Beatrix Potter: "Beatrix Potter's books have been translated into more than 35 languages and sold over 100 million copies. " (2008)
Jump up ^ USA Today on Beatrix Potter: "Potter's story of the rabbit who is nearly killed after defying his mother's warnings to avoid the garden of a farmer named McGregor has sold more than 150 million copies in 35 languages." (23 June 2003)
Jump up ^ The Telegraph on Michael Crichton: "His books have sold more than 150 million copies." (1 July 2007)
Jump up ^ The Wall Street Journal on Michael Crichton: "Although it is always difficult to gauge the total sales of any author, Mr. Crichton's Web site states that he has sold more than 150 million books, and that 13 of them have been adapted into movies." (16 November 2006)
Jump up ^ Encyclopædia Britannica on Richard Scarry: "His "busy" books and dictionaries sold more than 100 million copies worldwide, and in 1989 eight of his books made the list of the top 50 best-selling children's books of all time." (2008)
Jump up ^ World Screen on Richard Scarry: "More than 150 million books by Richard Scarry have been sold worldwide and translated into 30 languages." (2 April 2007)
Jump up ^ The Rocky Mountain Collegian on Clive Cussler: "An audit later revealed the number of Cussler books sold was around 40 million at the time the contract was negotiated in 2000." (5 March 2007)
Jump up ^ The Telegraph on Clive Cussler: "His widely popular novels - his new one, Golden Buddha, the first in an adventure series called The Oregon Files, is published next month - have sold 150 million copies in 40 languages and have made the author a very wealthy man." (23 February 2004)
Jump up ^ Dominic Head in The Cambridge Guide to Literature in English page 431 on Alistair MacLean: "Alistair MacLean's works have sold more than 150 million copies worldwide." (2006)
Jump up ^ CBS on Ken Follett: "In all, he's sold 90 million books." (7 October 2007)
Jump up ^ Tampa Bay 10 News on Ken Follett: One of the world's best-loved novelists, Follett has sold over 150 million copies of his books worldwide." (13 October 2014)
Jump up ^ BBC on Astrid Lindgren: "Lindgren's books have sold over 100 million copies in some 80 languages." (28 January 2002
Jump up ^ BusinessWeek on Astrid Lindgren: "True, Lindgren's books, which have sold more than 145 million copies the world over, remain bestsellers to this day and the films based on her scripts continue to be immensely popular." (16 November 2007)
Jump up ^ Publishers Weekly on Debbie Macomber: "Last year her new books sold 2.8 million copies, bringing her total in print to more than 60 million." (19 June 2006)
Jump up ^ The Minneapolis Star-Tribune on Debbie Macomber: "She is constantly on one bestseller list or another, and right now there are more than 140 million copies of her novels in print" (25 April 2010)
Jump up ^ The New York Times on Eiji Yoshikawa: "It has remained on the Japanese best-seller list ever since its initial publication as a novel in 1971, and has sold an estimated 120 million copies." (13 September 1981)
Jump up ^ The Age on Catherine Cookson: "One hundred million copies of her 103 books have been sold worldwide." (6 October 2008
Jump up ^ Hastings Chronicle on Catherine Cookson: "When Dame Catherine died, in June 1998, she had completed 103 novels, sold over 120 million books worldwide and had £20 million in the bank - all of which went to charities." (2008)
Jump up ^ The Montreal Gazette on Stephenie Meyer: "In book form, "Twilight" and its sequels "New Moon," "Eclipse" and "Breaking Dawn", have sold 100 million copies worldwide, according to Little, Brown Book Group." (31 March 2010)
Jump up ^ Publishers Weekly on Stephenie Meyer: "Little, Brown to Publish Official 'Twilight' Guide." (6 October 2011)
Jump up ^ The Library of Congress on Norman Bridwell: "Now more than 80 Clifford books have been published, close to 100 million books are in print, and Clifford's adventures are published in several languages worldwide." (2002)
Jump up ^ KRCB television on Norman Bridwell: "Scholastic’s beloved, best-selling children’s books by Norman Bridwell, with more than 160 titles and 110 million books in print." (2008)
Jump up ^ The National on David Baldacci: "At last count, David Baldacci had sold 110 million copies of his incredibly popular thrillers." (9 August 2011)
Jump up ^ Bachko, Katia. "Touring MoMA with The Longest Road Author Nicholas Sparks". Vanity Fair. Retrieved 2017-09-14.
Jump up ^ "'The Notebook' author Nicholas Sparks coming to Wichita". kansas. Retrieved 2017-09-14.
Jump up ^ The New York Times on Ed McBain: "Ms. Gelfman, his agent, estimated that in 50 years of writing, he had sold more than 100 million copies of his work." (July 7, 2005)
Jump up ^ The Hollywood Reporter on Ed McBain: "Evan Hunter, 78, a best-selling cop novel author who sold more than 100 million books under his own name and the pseudonym Ed McBain." (December 30, 2005)
Jump up ^ The Sun Runner on Andrew Neiderman: "Aside from the fact that “The Devil’s Advocate” is a film classic featuring Al Pacino, Keanu Reeves and Charlize Theron, Neiderman has over 100 million books in print and has been published in 95 countries. " (2005)
Jump up ^ Authors' Den on Andrew Neiderman: "Neiderman has over 100 million books in print and has been published in 95 countries." (3 August 2006)
Jump up ^ The Independent on Roger Hargreaves: "The popularity of the original characters led to a television series, sold 100 million books and created a business worth £130m" (22 January 2003)
Jump up ^ News Australia on Roger Hargreaves: "The popular series featured characters like Mr Strong, Mr Tickle and Mr Muddle, and it has been estimated that more than 100 million books from the Mr Men range had been sold worldwide." (February 11, 2008)
Jump up ^ The Dallas Morning News on Anne Rice: "All told, her books have sold more than 75 million copies worldwide, been made into movies and inspired a Broadway musical." (5 October 2008)
Jump up ^ Tampa St. Petersburg Times on Anne Rice: "Her 27 novels have sold some 100-million copies." (5 October 2008)
Jump up ^ Variety on Robin Cook: "Cook, who with more than 100 million books in print virtually owns the medical-thriller genre, appears to be branching out of his element by adding an extraterrestrial component." (2 May 1997)
Jump up ^ Wesleyan University on Robin Cook: "He has sold more than 100 million books worldwide, which have been translated into approximately 40 languages." (2007)
Jump up ^ The Telegraph on Wilbur Smith: "Translated into 26 languages, they have sold more than 80 million copies worldwide." (28 April 2007)
Jump up ^ The Herald on Wilbur Smith: "He is the author of 25 best-sellers and claims in court papers to have sold about 100 million books." (21 May 2002)
Jump up ^ Augusta Chronicle on Erskine Caldwell: "Mr. Caldwell's books have sold 80 million copies and have been published in 43 languages. " (11 February 2007)
Jump up ^ The New York Times on Erskine Caldwell: "More than 100 million copies of his books have been printed around the world, and his short stories continue to be included in anthologies" (1 December 1982)
Jump up ^ The Independent on Eleanor Hibbert: "She sold staggering amounts, in the region of 100 million copies." (28 September 2008)
Jump up ^ The New York Times on Eleanor Hibbert: "Eleanor Hibbert, a prolific and popular novelist whose books, written under the pen names Jean Plaidy, Victoria Holt and Philippa Carr, sold more than 100 million copies, died on Monday aboard a Mediterranean cruise ship." (January 21, 1993)
Jump up ^ The New York Times on Lewis Carroll: "Over 100 million copies of Carroll's book have been sold, Mr. Allen said." (18 April 1985)
Jump up ^ Miami Herald on Denise Robins: "Miss Robins' novels, translated into 15 languages, sold more than 100 million copies. " (3 May 1985)
Jump up ^ China.org on Cao Xueqin: "Sun said that the book has sold over 100 million copies worldwide so far. " (14 December 2005)
Jump up ^ The Times of India on Ian Fleming: "Faulks took up where Fleming left off in 1966 with Octopussy and the Living Daylights, the last of 14 Bond books which have sold 100 million copies since." (13 July 2007)
Jump up ^ The New Zealand Herald on Ian Fleming: "Faulks took up where Fleming left off in 1966 with Octopussy and the Living Daylights, the last of 14 Bond books which have sold 100 million copies since." (July 11, 2007-
Jump up ^ Eckhard Bernstein in Culture and Customs of Germany page 101 on Hermann Hesse: "Over 100 million copies of his works have been sold worldwide" (2004)
Jump up ^ The International Herald Tribune on Hermann Hesse: "Hesse's novels appear in 68 languages and have been sold more than 100 million copies worldwide" (28 October 1999)
Jump up ^ The Capital Journal on Rex Stout: "During his 88-year life, he had written about 50 books and 75 novellas and short stories, which had been translated into 26 languages and sold more than 100 million copies." (21 September 2003)
Jump up ^ The Philadelphia Inquirer on Rex Stout: "Readers have snapped up more than 100 million copies of the books." (29 November 1986)
Jump up ^ Dr. Jaap van Ginneken in Screening Difference: How Hollywood's Blockbuster Films Imagine Race, Ethnicity and Culture page 124, on Anne Golon: "All together, they published thirteen titles, translated into forty-five languages and selling more than 100 million copies. " (2007)
Jump up ^ The Age on Anne Golon: "Somehow, despite her books having sold more than 100 million copies in 45 countries, Golon is living in straitened circumstances" (13 November 2004)
Jump up ^ Kevin McCarthy's The Book Lover's Guide to Florida on Frank G. Slaughter: "Through 1990, Slaughter's books have averaged more than a million sales per title, totaling over 100 million copies." (1992)
Jump up ^ Steven R. Serafin in The Continuum Encyclopedia of American Literature, p. 145, on Edgar Rice Burroughs: "[...] sales of his novels exceed 100 million copies." (2005)
Jump up ^ Bret E. Carroll in American Masculinities: A Historical Encyclopedia, page 449, on Edgar Rice Burroughs: "The twenty-five novels that followed between 1912 and 1947 were a huge commercial success, with over 100 million copies sold" (2003)
Jump up ^ Neil Shulman e.a. in Get Between the Covers: Leave a Legacy by Writing a Book, page 225, on John Creasey: "Over his lifetime, he managed to write over 600 novels and to sell approximately 100 million copies of his books worldwide." (2006)
Jump up ^ Thomas D. Hamm in The Quakers in America page 208, on James Michener: "Michener produced a steady stream of books for the rest of his life, with total sales of over 100 million." (2003)
^ Jump up to: a b Zenkoku Shoten Shinbun (Japanese language, March 21, 2008)
Jump up ^ Deseret News on Mary Higgins Clark: "Mary Higgins Clark has been on The New York Times Best Seller list 27 times and has more than 100 million copies in print in the United States" (29 March 2009)
Jump up ^ Forbes on Mary Higgins Clark: "Sales:100 million books sold" (6 June 2011)
Jump up ^ The Telegraph on Penny Jordan: "selling more than 90 million copies of nearly 190 titles" (19 January 2012)
Jump up ^ The Washington Post on Penny Jordan: "sold more than 100 million copies worldwide" (21 January 2012)
Jump up ^ The Christian Science Monitor on Patricia Cornwell: "Cornwell’s books have sold more than 100 million copies." (21 February 2013)
Jump up ^ Los Angeles Times Sales figures, by the numbers: "100 million: Estimated number of books in print." (2 October 2013)
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