Agranulocytosis

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Agranulocytosis
Specialty Hematology, immunology
Symptoms Rigors, fever, sore throat, rapid infection
Complications Sepsis
Causes Idiosyncratic reactions to certain drugs
Risk factors Cocaine use
Diagnostic method Complete blood count, bone marrow examination
Differential diagnosis Aplastic anemia, paroxysmal nocturnal hemoglobinuria, myelodysplasia, leukemia

Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous lowered white blood cell count (leukopenia, most commonly of neutrophils) and thus causing neutropenia in the circulating blood. [1] It is a severe lack of one major class of infection-fighting white blood cells. People with this condition are at very high risk of serious infections due to their suppressed immune system.

Contents

In agranulocytosis, the concentration of granulocytes (a major class of white blood cells that includes neutrophils, basophils, and eosinophils) drops below 200 cells/mm3 of blood.

Signs and symptoms

Agranulocytosis may be asymptomatic, or may clinically present with sudden fever, rigors and sore throat. Infection of any organ may be rapidly progressive (e.g., pneumonia, urinary tract infection). Sepsis may also progress rapidly.[ citation needed ]

Causes

A large number of drugs [2] have been associated with agranulocytosis, including antiepileptics (such as carbamazepine and valproate), antithyroid drugs (carbimazole, thiamazole, and propylthiouracil), antibiotics (penicillin, chloramphenicol and trimethoprim/sulfamethoxazole), H2 blockers (cimetidine, famotidine, nizatidine, ranitidine), [3] ACE inhibitors (benazepril), cytotoxic drugs, gold salts, analgesics (aminophenazone, indomethacin, naproxen, phenylbutazone, metamizole), mebendazole, allopurinol, [4] the antidepressants mianserin and mirtazapine, and some antipsychotics. [5] The atypical antipsychotic clozapine in particular is largely restricted to treatment-resistant cases and mandatory blood count monitoring in most countries. [6]

Although the reaction is generally idiosyncratic rather than proportional, experts recommend that patients using these drugs be told about the symptoms of agranulocytosis-related infection, such as a sore throat and a fever.[ citation needed ]

The Centers for Disease Control and Prevention traced outbreaks of agranulocytosis among cocaine users, in the US and Canada between March 2008 and November 2009, to the presence of levamisole in the drug supply. The Drug Enforcement Administration reported that, as of February 2010, 71% of seized cocaine lots coming into the US contained levamisole as a cutting agent. [7] Levamisole is an antihelminthic (i.e. deworming) drug used in animals. The reason for adding levamisole to cocaine hydrochloride is unknown, [8] although it is likely due to their similar melting points, solubilities, and appearance.

Diagnosis

The diagnosis is made after a complete blood count, a routine blood test. The absolute neutrophil count in this test will be below 500, and can reach 0 cells/mm3. Other kinds of blood cells are typically present in normal numbers. To formally diagnose agranulocytosis, other pathologies with a similar presentation must be excluded, such as aplastic anemia, paroxysmal nocturnal hemoglobinuria, myelodysplasia and leukemias. This requires a bone marrow examination that shows normocellular (normal amounts and types of cells) blood marrow with underdeveloped promyelocytes. These underdeveloped promyelocytes, if fully matured, would have been the missing granulocytes.[ citation needed ]

Classification

The term "agranulocytosis" derives from the Greek: a, meaning without; granulocyte, a particular kind of white blood cell (containing granules in its cytoplasm); and osis, meaning condition [esp. disorder]. Consequently, agranulocytosis is sometimes described as "no granulocytes", but a total absence is not required for diagnosis. However, "-osis" is commonly used in blood disorders to imply cell proliferation (such as in "leukocytosis"), while "-penia" to imply reduced cell numbers (as in "leukopenia"); for these reasons, granulocytopenia is a more etymologically consistent term, and as such, is sometimes preferred to "agranulocytosis" (which can be misinterpreted as "agranulocyt-osis", meaning proliferation of agranulocytes (i.e. lymphocytes and monocytes). Despite this, "agranulocytosis" remains the most widely used term for the condition.[ citation needed ]

The terms agranulocytosis, granulocytopenia and neutropenia are sometimes used interchangeably. Agranulocytosis implies a more severe deficiency than granulocytopenia. Neutropenia indicates a deficiency of neutrophils (the most common granulocyte cell) only.

To be precise, neutropenia is the term normally used to describe absolute neutrophil counts (ANCs) of less than 500 cells per microlitre, whereas agranulocytosis is reserved for cases with ANCs of less than 100 cells per microlitre.

The following terms can be used to specify the type of granulocyte referenced:

In a general sense the pathogenesis of neutropenia can be divided into two categories;

Treatment

In patients that have no symptoms of infection, management consists of close monitoring with serial blood counts, withdrawal of the offending agent (e.g., medication), and general advice on the significance of fever. Transfusion of granulocytes would be a solution to the problem. However, granulocytes live only ~10 hours in the circulation (for days in spleen or other tissue), which gives a very short-lasting effect. In addition, there are many complications of such a procedure.[ citation needed ]

See also

Related Research Articles

<span class="mw-page-title-main">Clozapine</span> Atypical antipsychotic medication

Clozapine is a psychiatric medication and is the first atypical antipsychotic to be discovered. It is primarily used to treat people with schizophrenia and schizoaffective disorder who have had an inadequate response to two other antipsychotics or who have been unable to tolerate other drugs due to extrapyramidal side effects. It is also used for the treatment of psychosis in Parkinson's disease.

<span class="mw-page-title-main">Neutropenia</span> Abnormally low concentration of neutrophils (a type of white blood cell) in the blood

Neutropenia is an abnormally low concentration of neutrophils in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria, bacterial fragments and immunoglobulin-bound viruses in the blood. People with neutropenia are more susceptible to bacterial infections and, without prompt medical attention, the condition may become life-threatening.

<span class="mw-page-title-main">Neutrophilia</span> Medical condition

Neutrophilia is leukocytosis of neutrophils, that is, a high number of neutrophils in the blood. Because neutrophils are the main type of granulocytes, mentions of granulocytosis often overlap in meaning with neutrophilia.

<span class="mw-page-title-main">Granulocyte colony-stimulating factor</span> Mammalian protein found in Homo sapiens

Granulocyte colony-stimulating factor, also known as colony-stimulating factor 3, is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream.

<span class="mw-page-title-main">Granulocyte</span> Category of white blood cells

Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear, that is, they have varying shapes (morphology) of the nucleus ; and are referred to as polymorphonuclear leukocytes. In common terms, polymorphonuclear granulocyte refers specifically to "neutrophil granulocytes", the most abundant of the granulocytes; the other types have varying morphology. Granulocytes are produced via granulopoiesis in the bone marrow.

Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that affect the patient's immune system. Examples of these extrinsic factors include HIV infection and environmental factors, such as nutrition. Immunocompromisation may also be due to genetic diseases/flaws such as SCID.

<span class="mw-page-title-main">Leukopenia</span> Medical condition

Leukopenia is a decrease in the number of leukocytes (WBC). Found in the blood, they are the white blood cells, and are the body's primary defense against an infection. Thus the condition of leukopenia places individuals at increased risk of infection.

Absolute neutrophil count (ANC) is a measure of the number of neutrophil granulocytes present in the blood. Neutrophils are a type of white blood cell that fights against infection.

Cytopenia is a reduction in the number of mature blood cells. It commonly occurs in people with cancer being treated with radiation therapy or chemotherapy.

The term leukemoid reaction describes an increased white blood cell count, which is a physiological response to stress or infection. It often describes the presence of immature cells such as myeloblasts or red blood cells with nuclei in the peripheral blood.

Myelokathexis is a congenital disorder of the white blood cells that causes severe, chronic leukopenia and neutropenia. The disorder is believed to be inherited in an autosomal dominant manner. Myelokathexis refers to retention (kathexis) of neutrophils in the bone marrow (myelo). The disorder shows prominent neutrophil morphologic abnormalities.

Cyclic neutropenia (CyN) is a rare hematologic disorder and form of congenital neutropenia that tends to occur approximately every three weeks and lasting for few days at a time due to changing rates of neutrophil production by the bone marrow. It causes a temporary condition with a low absolute neutrophil count and because the neutrophils make up the majority of circulating white blood cells it places the body at severe risk of inflammation and infection. In comparison to severe congenital neutropenia, it responds well to treatment with granulocyte colony-stimulating factor (filgrastim), which increases the neutrophil count, shortens the cycle length, as well decreases the severity and frequency of infections.

Severe congenital neutropenia (SCN), also often known as Kostmann syndrome or disease, is a group of rare disorders that affect myelopoiesis, causing a congenital form of neutropenia, usually without other physical malformations. SCN manifests in infancy with life-threatening bacterial infections. It causes severe pyogenic infections. It can be caused by autosomal dominant inheritance of the ELANE gene, autosomal recessive inheritance of the HAX1 gene. There is an increased risk of leukemia and myelodysplastic cancers.

Hemopoietic growth factors regulate the differentiation and proliferation of particular progenitor cells. Made available through recombinant DNA technology, they hold tremendous potential for medical uses when a person's natural ability to form blood cells is diminished or defective. Recombinant erythropoietin (EPO) is very effective in treating the diminished red blood cell production that accompanies end-stage kidney disease. Erythropoietin is a sialoglycoprotein hormone produced by peritubular cells of kidney.

Autoimmune neutropenia (AIN) is a form of neutropenia which is most common in infants and young children where the body identifies the neutrophils as enemies and makes antibodies to destroy them.

In hematology, myelopoiesis in the broadest sense of the term is the production of bone marrow and of all cells that arise from it, namely, all blood cells. In a narrower sense, myelopoiesis also refers specifically to the regulated formation of myeloid leukocytes (myelocytes), including eosinophilic granulocytes, basophilic granulocytes, neutrophilic granulocytes, and monocytes.

<span class="mw-page-title-main">White blood cell</span> Type of cells of the immunological system

White blood cells, also called leukocytes or immune cells also called immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. White blood cells include three main subtypes; granulocytes, lymphocytes and monocytes.

Levamisole induced necrosis syndrome (LINES) is a complication of adulterated cocaine recognized in 2011, caused by the use of levamisole as a cutting agent for cocaine. Spontaneous bruising of the earlobes is considered characteristic of this condition, but lesions can present anywhere on the body.

<span class="mw-page-title-main">White blood cell differential</span> Blood test

A white blood cell differential is a medical laboratory test that provides information about the types and amounts of white blood cells in a person's blood. The test, which is usually ordered as part of a complete blood count (CBC), measures the amounts of the five normal white blood cell types – neutrophils, lymphocytes, monocytes, eosinophils and basophils – as well as abnormal cell types if they are present. These results are reported as percentages and absolute values, and compared against reference ranges to determine whether the values are normal, low, or high. Changes in the amounts of white blood cells can aid in the diagnosis of many health conditions, including viral, bacterial, and parasitic infections and blood disorders such as leukemia.

A granulocyte transfusion is a medical procedure in which granulocytes are infused into a person's blood. Granulocyte transfusions were historically used to prevent and treat infections in people with neutropenia, but the practice declined in popularity in the 1980s. Interest in the procedure increased in the 1990s due to the development of more effective methods for harvesting granulocytes and a growing population of people with severe neutropenia from chemotherapy. However, the treatment's efficacy remains poorly understood and its use is controversial.

References

  1. ↑ Neutropenia at eMedicine
  2. ↑ Andersohn F, Konzen C, Garbe E (2007). "Systematic review: agranulocytosis induced by nonchemotherapy drugs". Ann. Intern. Med. 146 (9): 657–65. doi:10.7326/0003-4819-146-9-200705010-00009. PMID   17470834. S2CID   15585536.
  3. ↑ Vallerand, April Hazard (2014-06-05). Davis's drug guide for nurses. Sanoski, Cynthia A.,, Deglin, Judith Hopfer, 1950- (Fourteenth ed.). Philadelphia. ISBN   978-0-8036-4085-6. OCLC   881473728.{{cite book}}: CS1 maint: location missing publisher (link)
  4. ↑ Elisa Mari; Franco Ricci; Davide Imberti; Massimo Gallerani (June 2011). "Agranulocytosis: an adverse effect of allopurinol treatment". Italian Journal of Medicine. 5 (2): 120–3. doi: 10.1016/j.itjm.2011.02.006 .
  5. ↑ Diaz, Jaime (1996). How Drugs Influence Behavior. Englewood Cliffs: Prentice Hall. ISBN   978-0132815604.
  6. ↑ Mijovic A, MacCabe JH (November 2020). "Clozapine-induced agranulocytosis". Ann Hematol. 99 (11): 2477–2482. doi:10.1007/s00277-020-04215-y. PMC   7536144 . PMID   32815018.
  7. ↑ U.S. Department of Justice; National Drug Intelligence Center (February 2010). "Colombian Cocaine Producers Increase Use of a Harmful Cutting Agent". National Drug Threat Assessment 2010. Archived from the original on 2012-05-18. Retrieved 2020-11-22.
  8. ↑ Centers for Disease Control Prevention (CDC) (December 2009). "Agranulocytosis associated with cocaine use — four States, March 2008–November 2009". MMWR Morb. Mortal. Wkly. Rep. 58 (49): 1381–5. PMID   20019655. Archived from the original on 2018-10-09. Retrieved 2017-09-08. Cited in Hsu, Jeremy (18 December 2009). "Majority of U.S. Cocaine Supply Cut with Veterinary Deworming Drug". Popular Science. Archived from the original on 25 February 2018. Retrieved 21 December 2009.
  9. ↑ Kumar, Vinay (2007). Robbins Basic Pathology (8 ed.). Elsevier. p. 441.
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