Cytopenia

DEFINITION:

Cytopenia is a reduction in the number of blood cells. It takes a number of forms:
*Low red blood cell count: anemia.
*Low white blood cell count: leukopenia or neutropenia (because neutrophils make up at least half of all white cells, they are almost always low in leukopenia).
*Low platelet count: thrombocytopenia.
*Low granulocyte count: granulocytopenia
*Low red blood cell, white blood cell, and platelet counts: pancytopenia..

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Blood cell development. A blood stem cell goes through several steps to become a red blood cell, platelet, or white blood cell.

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Cancer patients may frequently develop cytopenia, a disorder in which the production of one or more blood cell types ceases or is greatly reduced. Cancer and chemotherapy used to treat cancer, and sometimes radiation therapy, may sometimes cause cytopenia.

TYPES:
A deficiency of red blood cells which  is called anemia; a deficiency of white blood cells, or leukocytes, leukopenia or neutropenia (neutrophils make up over half of all white blood cells); and deficiency of platelets is called  thrombocytopenia.

Pancytopenia is the deficiency of all three blood cell types and is characteristic of aplastic anemia, a potentially life-threatening disorder that requires a stem cell transplant.

Blood Cells
The blood consists of three different  types of cells: red blood cells (erythrocytes), white blood cells (leukocytes), and platelets. Erythrocytes contain hemoglobin, the protein that carries oxygen from the lungs to all cells in the body. Proper cell function depends on an adequate oxygen supply. When cells are oxygen deprived, organ function can be seriously impaired.

Leukocytes (white blood cells) protect the body against viral, bacterial, and parasitic infection and detect and remove damaged, dying, or dead tissues. Someone with a deficiency of white blood cells is extremely vulnerable to infection.

The term “leukocyte” refers to all six types of white blood cells; each plays a unique role in the immune system:

1. Basophils circulate in the blood and initiate the inflammatory response.
2.Eosinophils kill infecting parasites and produce allergic reactions.
3.Lymphocytes produce antibodies and regulate immune responses.
4. Mast cells are fixed in tissues and initiate the inflammatory response.
5. Monocytes capture infecting organisms for identification, ingest infecting organisms, and remove damaged or dying cells and cell debris. When monocytes become fixed in tissue, they are called macrophages.
6.Neutrophils identify and kill infecting organisms, and remove dead tissue.

Platelets are essential factors for blood clotting. Sudden blood loss triggers platelet activity at the site of the wound. Exposure to oxygen in the air causes platelets to break apart and combine with a substance called fibrinogen to form fibrin. Fibrin has a thread-like structure and forms a scab, or external clot, as it dries. Platelet deficiency causes one to bruise and bleed easily. Blood does not clot at an open wound, and there is greater risk for internal bleeding.

All blood cells have a lifespan: erythrocytes have a lifespan of about 120 days; leukocytes, 1 to 3 days; and platelets, approximately 10 days. The body continually replenishes the blood supply through a process called hematopoiesis.

Blood Cell Formation—Hematopoiesis, the formation and development of blood cells, occurs in bone marrow. Bone marrow is a nutrient-rich spongy tissue located mainly in the central portions of long flat bones (e.g., sternum, pelvic bones) in adults and all bones in infants.

All blood cells derive from blood-forming stem cells that reside in bone marrow. Stem cells replicate indefinitely and develop into mature, specialized cells. A hormone produced in the kidneys, erythropoietin, stimulates blood stem cells to produce all three types of blood cells.

CAUSES & RISK FACTORS:-

Chemotherapy and radiation therapy both reduce the number of blood-forming stem cells in cancer patients, but chemotherapeutic agents have a greater adverse effect because they suppress bone marrow function in several ways.The degree of damage is related to the particular drug(s) and the dose.

Chemotherapeutic agents can produce deficiencies in all blood cell types by

* damaging blood-forming stem cells,
* suppressing the kidneys? production of erythropoietin (hormone that stimulates blood cell production), and
* triggering red cell destruction (hemolysis) by inducing an immune response that causes the body to mistakenly identify erythrocytes as foreign bodies and destroy them.

Malignant tumors can cause anemia and other cytopenias when they directly invade bone marrow and suppress marrow function. Malignant cells also can migrate from tumors in other parts of the body to bone marrow. Tumors also can replace normal blood-forming stem cells with abnormal clones.

SIGN & SYMPTOMS:-

Anemia
A deficiency in erythrocytes reduces the amount of oxygen reaching all cells in the body, thus impairing all tissue and organ function. Severe fatigue is the most common symptom of anemia and is experienced by approximately 75% of chemotherapy patients. Patients find it more disabling than other treatment side effects, including nausea and depression.

Anemia also produces these symptoms:

* Confusion
* Dizziness
* Headache
* Lightheadedness
* Loss of concentration
* Pallor (pale skin, nail beds, gums, linings of eyelids)
* Rapid heart rate (tachycardia)
* Shortness of breath (dyspnea)

Neutropenia
Patients with a white blood cell deficiency experience frequent and/or severe bacterial, viral, and/or fungal infections; fever; and mouth and throat ulcers.

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Complications—Bacteremia, the form of sepsis characterized by the presence of bacteria in the blood, can develop in immunocompromised patients who have neutropenia. Fever, rapid heart rate, and quick shallow breathing are signs of early sepsis, usually a reversible condition.

Untreated bacteremia can lead to severe sepsis, in which one or more organs become dysfunctional. Septic shock is severe sepsis with low blood pressure. The risk for death increases with the development of septic shock. Even aggressive treatment can fail to reverse the condition.

Thrombocytopenia
Platelet deficiency causes patients to bruise and bleed easily. Bleeding occurs most often in the mucous membranes lining the mouth, nose, colon, and vagina. Tiny reddish-purple skin lesions (petechiae), evidence of pinpoint hemorrhages, may appear on the skin or in the mouth.

Pancytopenia
Patients who are deficient in all blood cell types experience signs and symptoms associated with each, but bleeding from the nose and gums, and easy bruising usually appear first. Symptoms of anemia (e.g., fatigue, shortness of breath) are also common. Patients may look and feel well, otherwise, despite the seriousness of their condition.

Anemia
People with anemia (reduced red cell production) are advised to rest and eat foods high in iron (meat, fish, poultry, lentils, legumes, iron-enriched grains and flours).

If immediate remedy is necessary, treatment may include medication that helps restore the red blood supply and a transfusion of packed red blood cells.

Epoetin alpha (Epogen®, Procrit®)is a synthetic erythropoietin (normally produced by the kidneys) that stimulates stem cells to produce red blood cells. Restoration of the red blood cell supply with medication is gradual.

Darbepoetin alfa (Aranesp®) also stimulates red blood cell production but requires fewer doses and less disruption of daily living.

In March 2007, the Food and Drug Administration (FDA) issued a warning about these medications in response to studies indicating that they may increase the risk for blood clots, strokes, and heart attacks in some patients (e.g., patients who have kidney disease).

Thrombocytopenia
People with an abnormally low platelet count should avoid bruising or breaking the skin, and should carefully brush their teeth. A persistently decreased platelet count may be treated with a transfusion of platelets.

Neutropenia
The patient with a low white blood cell count is advised to  do the following:

*Avoid contact with people who are ill,
*Monitor closely for signs of infection (e.g., fever), and
*Take antibiotics when appropriate.

Medication, a colony-stimulating factor (CSF), may be prescribed to speed the development of white blood cells and shorten the period of susceptibility to infection.

Growth Factors
Growth factors are synthetic versions of substances involved in stimulating red and white blood cell production. Physicians exercise caution when prescribing these medications for people with tumors that involve the bone marrow, because growth factors might stimulate malignant cell growth.

These medications include the following:

Epoetin alpha (Procrit®, Epogen®; stimulates red blood cell production)
G-CSF (granulocyte colony-stimulating factor; e.g., filgrastim [Neupogen®]; stimulates neutrophil production)
GM-CSF (granulocyte-macrophage colony-stimulating factor; stimulates production of several white blood cells, including macrophages)

Leukocytes and other cells that contain granules are also called granulocytes.

Side effects
Fever, fatigue, dizziness, diarrhea, nausea, vomiting, weakness, and paresthesia (prickling sensation) are side effects associated with epoetin alpha.

Bone pain, malaise, headache, flu-like symptoms, muscle ache, redness at the injection site, and skin rash may occur with GM-CSF.

G-CSF commonly produces bone pain.

MEDICATIONS:-

Medications used to treat bacterial infection and other illnesses also can contribute to immune system suppression.

Some of these are :

* Antacids: cimetidine (Tagamet®)
* Antibiotics: chloramphenical (Chloromycetin®), sulfonamide (Thiosulfil®, Gantanol®); cephalosporin (Cephalaxin®), vancomycin (Vancocin®)
* Anticonvulsants: phenytoin/hydantoin (Dilantin®), felbamate (Felbatol®), carbamazepine (Tegretol®)
* Antimalarials: chloroquine (Aralin®)
* Antivirals: ganciclovir (Vitrasert®), zidovudine (AZT®)
* Cardiac drugs: diltiazem (Cardizem®), nifedipine (Procardia®), verapamil (Calan®)
* Diabetes drugs: glipizide (Glucotrol®), glyburide (Micronase®)
* Hyperthyroid drug: propylthiouracil
* NSAIDs (nonsteroidal anti-inflammatory drugs): phenylbutazone (Butazolidine®), indomethacin (Indocin®, Indochron E-R®)—Due to potentially severe gastrointestinal and cardiovascular side effects, NSAIDs should only be used as instructed.
* Rheumatoid arthritis drugs: auranofin (Ridaura®), aurothioglucose (Solganal®), gold sodium thiomalate (Myochrisine®)

Bone Marrow and Stem Cell Transplantation:-
The treatment of choice for the pancytopenic patient with a matched bone marrow donor is stem cell transplantation. The goal of transplantation is to restore blood-forming stem cells to the marrow.

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

Resources:
http://www.oncologychannel.com/cytopenia/index.shtml
http://en.wikipedia.org/wiki/Cytopenia
http://www.cancer.umn.edu/cancerinfo/NCI/CDR378089.html

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