Blood Disorders Flashcards
(5 cards)
Acute Leukaemia
White blood cells develop from stem cells in the bone marrow. Sometimes the development goes awry, and pieces of chromosomes get rearranged. The resulting abnormal chromosomes interfere with normal control of cell division, so that affected cells multiply uncontrollably or are resistant to normal cell death, resulting in leukemia.
Classification Leukemias are grouped into four main types: Acute lymphocytic leukemia Acute myelogenous leukemia Chronic lymphocytic leukemia Chronic myelogenous leukemia
Acute leukemias progress rapidly and consist of immature cells.
Chronic leukemias progress slowly and consist of more mature cells.
Lymphocytic leukemias develop from cancerous changes in lymphocytes or in cells that normally produce lymphocytes.
Myelogenous (myelocytic, or myeloid) leukemias develop from cancerous changes in cells that normally produce neutrophils, basophils, eosinophils, and monocytes.
Acute Lymph Leuk
a life-threatening disease in which the cells that normally develop into lymphocytes become cancerous and rapidly replace normal cells in the bone marrow
Acute lymphocytic leukemia (ALL) occurs in people of all ages but is the most common cancer in children, accounting for 25% of all cancers in children younger than 15 years. ALL most often affects young children between the ages of 2 and 5 years. Among adults, it is somewhat more common in people older than 45.
In ALL, very immature leukemia cells accumulate in the bone marrow, destroying and replacing cells that produce normal blood cells. The leukemia cells are carried in the bloodstream to the liver, spleen, lymph nodes, brain, and testes, where they may continue to grow and divide. However, ALL cells can accumulate anywhere in the body. They can spread to the layers of tissue covering the brain and spinal cord (leukemic meningitis) and can cause anemia, liver and kidney failure, and other organ damage.
Symptoms
Early symptoms of ALL result from the inability of the bone marrow to produce enough normal blood cells.
Fever and excessive sweating may indicate infection. A high risk of infection results from too few normal white blood cells.
Weakness, fatigue, and paleness, which indicate anemia, result from too few red blood cells. Some people may have a rapid heart rate or chest pain.
Easy bruising and bleeding, sometimes in the form of nosebleeds or bleeding gums, result from too few platelets.
Other symptoms occur when leukemic cells invade other organs.
Leukemia cells in the brain may cause headaches, vomiting, and disturbances of vision, equilibrium, hearing, and facial muscles.
Leukemia cells in the bone marrow may cause bone and joint pain.
A sense of fullness in the abdomen and sometimes pain can result when leukemia cells enlarge the liver and spleen.
Treatment
Chemotherapy
Chemotherapy is highly effective and is administered in phases:
Induction
Consolidation with preventive treatment of the brain
Intensification
Maintenance
AML
a life-threatening disease in which the cells that normally develop into neutrophils, basophils, eosinophils, and monocytes become cancerous and rapidly replace normal cells in the bone marrow
Acute myelogenous leukemia (AML) is the most common type of leukemia among adults, although it affects people of all ages. AML sometimes is caused by chemotherapy or radiation therapy given to treat another cancer.
In AML, immature leukemia cells rapidly accumulate in the bone marrow, destroying and replacing cells that produce normal blood cells. The leukemia cells are released into the bloodstream and are transported to other organs, where they continue to grow and divide. They can form small masses (chloromas) throughout the body, including in or just under the skin or gums or in the eyes.
There are several subtypes of AML, which are identified based on characteristics of the leukemia cells.
Acute promyelocytic leukemia is an important subtype of AML. In this subtype, chromosomal changes in promyelocytes—cells that are at an early stage in the development into mature neutrophils—allow accumulation of these immature cells. The underlying abnormality is complicated and involves the cellular receptors for retinoic acid.
Symptoms
The first symptoms of AML are very similar to those of acute lymphocytic leukemia. People may have fever and excessive sweating, indicating infection. A high risk of infection results from too few normal white blood cells. Weakness, fatigue, and paleness may indicate anemia,which results from too few red blood cells. The gums may be inflamed and swollen.
AML cells can spread to the layers of tissue covering the brain and spinal cord (meninges), leading to headaches, vomiting, and disturbances of vision, hearing, and facial muscles (leukemic meningitis). Leukemic meningitis occurs more often in acute lymphocytic leukemia. In acute promyelocytic leukemia, bleeding or blood clotting problems often occur.
Treatment
Chemotherapy
Treatment of AML is aimed at bringing about prompt remission—the destruction of the vast majority of leukemia cells. AML responds to fewer drugs than does acute lymphocytic leukemia. In addition, treatment often makes people sicker before they get better.
Treatment suppresses bone marrow activity, resulting in very few white blood cells, particularly neutrophils. Having too few neutrophils makes infection likely. Treatment also disrupts the mucosae (such as the lining of the mouth), which makes it easier for bacteria to enter the body. Meticulous care is taken to prevent infections, and infections that occur must be promptly treated.
Red blood cell and platelet transfusions are invariably also needed.
Chronic Lymphocytic Leukaemia
Is usually a slowly progressing disease in which mature-appearing lymphocytes become cancerous and gradually replace normal cells in lymph nodes
More than three fourths of the people who have chronic lymphocytic leukemia (CLL) are older than 60, and the disease does not occur in children. This type of leukemia affects men 2 to 3 times more often than women. CLL is the most common type of leukemia in North America and Europe. It is rare in Japan and Southeast Asia, which indicates that genetics plays some role in its development.
The number of cancerous, mature-appearing lymphocytes increases first in the blood, bone marrow, and lymph nodes. Cancerous lymphocytes then spread to the liver and spleen, both of which begin to enlarge. In the bone marrow, cancerous lymphocytes may crowd out normal cells, resulting in a decreased number of red blood cells and a decreased number of normal white blood cells and platelets in the blood. The level of antibodies, proteins that help fight infections, also decreases. The immune system, which ordinarily defends the body against foreign organisms and substances, sometimes becomes misguided, reacting to and destroying normal body tissues. This misguided immune activity can result in the destruction of red blood cells and platelets.
In the great majority of cases, CLL is a disorder of B lymphocytes ( B cells). There are other types of CLL other than B-cell CLL, including
Hairy cell leukemia
T-cell leukemia
Hairy cell leukemia, a slow-growing uncommon type of B-cell leukemia, produces a large number of abnormal white blood cells with distinctive hairlike projections that are visible under a microscope. T-cell CLL (leukemia of T lymphocytes) is much less common than B-cell CLL.
Sezary syndrome is sometimes regarded as a type of CLL. It occurs when the cells of mycosis fungoides (a T-cell lymphoma of the skin) spread into the blood.
Symptoms
In early stages of CLL, most people have no symptoms, and the disease is diagnosed only because of an increased white blood cell count. Later symptoms may include
Enlarged lymph nodes
Fatigue
Loss of appetite
Weight loss
Shortness of breath when exercising
A sense of abdominal fullness resulting from an enlarged spleen
As CLL progresses, people may appear pale and bruise easily. Bacterial, viral, and fungal infections generally do not occur until late in the course of the disease.
Diagnosis
Blood tests
Bone marrow examination
Sometimes CLL is discovered accidentally when blood counts ordered for some other reason show an increased number of lymphocytes.
A bone marrow evaluation is frequently done to confirm the diagnosis and to determine how far CLL has progressed (staging). Specialized tests to characterize the abnormal lymphocytes can be done on the cells in the blood. Blood tests also may show that the numbers of red blood cells, platelets, and antibodies are low.
Treatment
Chemotherapy
Because CLL progresses slowly, many people do not need treatment for years—until the number of lymphocytes begins to increase and cause symptoms, the lymph nodes begin to enlarge, or the number of red blood cells or platelets decreases.
Drug treatment
Drugs, including corticosteroids, chemotherapy drugs, and monoclonal antibodies, help relieve symptoms and shrink enlarged lymph nodes and spleen but do not cure the disease. Treatment can control CLL for many years and can often be used again with success when the leukemia regrows.
For B-cell CLL, initial drug treatment includes drugs such as fludarabine and cytoxan, which kill cancer cells by interacting with DNA. Currently, chemotherapy and a monoclonal antibody called rituximab are used to treat CLL. This combination therapy usually is successful in controlling CLL (inducing remission).
Chronic Myel Leukae
slowly progressing disease in which cells that normally would develop into neutrophils, basophils, eosinophils, and monocytes become cancerous
Chronic myelocytic leukemia (CML) may affect people of any age and of either sex but is uncommon in children younger than 10 years. The disease most commonly develops in adults between the ages of 40 and 60. The cause usually is a rearrangement of two particular chromosomes into what is called the Philadelphia chromosome. The Philadelphia chromosome produces an abnormal enzyme (tyrosine kinase), which is responsible for the abnormal growth pattern of the white blood cells in CML. Additional gene abnormalities (called mutations) that make CML more resistant to treatment sometimes occur.
CML has three phases
Chronic phase: An initial period that may last months to years during which the disease progresses very slowly
Accelerated phase: The disease begins to progress more quickly, treatments are less effective, and symptoms worsen
Blast phase: Immature leukemia cells (blasts) appear and the disease becomes much worse, with complications such as serious infections and excessive bleeding
In CML, most of the leukemia cells are produced in the bone marrow, but some are produced in the spleen and liver. In contrast to the acute leukemias, in which large numbers of blasts are present, the chronic stage of CML is characterized by marked increases in the numbers of normal-appearing white blood cells and sometimes platelets. During the course of the disease, more and more leukemia cells fill the bone marrow and others enter the bloodstream.
Eventually the leukemia cells undergo more changes, and the disease progresses to an accelerated phase and then inevitably to the blast phase. In the blast phase, only immature leukemia cells are produced, a sign that the disease has become much worse. Massive enlargement of the spleen is common in the blast phase, as well as fever and weight loss.
Symptoms
Early on, in its chronic stage, CML may cause no symptoms. However, some people become fatigued and weak, lose their appetite, lose weight, develop a fever or night sweats, and notice a sensation of being full—which is usually caused by an enlarged spleen. As the disease progresses to the blast phase, people become sicker because the number of red blood cells and platelets decreases, leading to infections, paleness, bruising, and bleeding.
Diagnosis
Blood tests
Chromosome analysis
The diagnosis of CML is suspected when the results of a simple blood count show an abnormally high white blood cell count. In blood samples examined under a microscope, less mature white blood cells, normally found only in bone marrow, may be seen. However, many times, the circulating white blood cells are normal in appearance.
Tests that analyze chromosomes (cytogenetics or molecular genetic testing) are needed to confirm the diagnosis by detecting the Philadelphia chromosome. If treatment appears to be less effective than expected, people are tested for other mutations that can make CML resistant to treatment.
Treatment
A tyrosine kinase inhibitor, sometimes with older chemotherapy drugs
Sometimes stem cell transplantation
Hodgkins
type of lymphoma distinguished by the presence of a particular kind of cancer cell called a Reed-Sternberg cell.
The cause of Hodgkin lymphoma is unknown. Although there are some families in which more than one person has Hodgkin lymphoma, it is not contagious.
Symptoms
People with Hodgkin lymphoma usually become aware of one or more enlarged lymph nodes, most often in the neck but sometimes in the armpit or groin. Although usually painless, sometimes the enlarged lymph nodes may be painful for a few hours after a person drinks alcoholic beverages.
People with Hodgkin lymphoma sometimes experience fever, night sweats, and weight loss. They can also have itching and fatigue. Some people have Pel-Ebstein fever, an unusual pattern of high temperature for several days alternating with normal or below-normal temperature for days or weeks. Other symptoms may develop, depending on where the cancerous cells are growing. For example, enlargement of lymph nodes in the chest may partially narrow and irritate airways, resulting in a cough, chest discomfort, or shortness of breath. Enlargement of the spleen or lymph nodes in the abdomen may cause discomfort in the abdomen.
Diagnosis
Doctors suspect Hodgkin lymphoma when a person with no apparent infection develops persistent and painless enlargement of lymph nodes that lasts for several weeks. The suspicion is stronger when lymph node enlargement is accompanied by fever, night sweats, and weight loss. Rapid and painful enlargement of lymph nodes—which may occur when a person has a cold or infection—is not typical of Hodgkin lymphoma. Sometimes enlarged lymph nodes deep within the chest or abdomen are found unexpectedly when a chest x-ray or computed tomography (CT) is done for another reason.
Abnormalities in blood cell counts and other blood tests may provide supportive evidence. However, to make the diagnosis, doctors must do a biopsy of an affected lymph node to see if it is abnormal and if Reed-Sternberg cells are present. Reed-Sternberg cells are large cancerous cells that have more than one nucleus (a structure inside a cell that holds the cell’s genetic material). Their distinctive appearance can be seen when a biopsy specimen of lymph node tissue is examined under a microscope.
The type of biopsy depends on which node is enlarged and how much tissue is needed. Doctors must remove enough tissue to be able to distinguish Hodgkin lymphoma from other disorders that can cause lymph node enlargement, including non-Hodgkin lymphomas, infections, or other cancers.
The best way to obtain enough tissue is with an excisional biopsy ( a small incision made to remove a piece of the lymph node). Occasionally, when an enlarged lymph node is close to the body’s surface, a sufficient amount of tissue can be obtained by inserting a hollow needle through the skin and into the lymph node (needle biopsy). When an enlarged lymph node is deep inside the abdomen or chest, surgery may be needed to obtain a piece of tissue.
Staging
Before treatment is started, doctors must determine how extensively the lymphoma has spread—the stage of the disease. The choice of treatment and the prognosis are based on the stage. An initial examination may detect only a single enlarged lymph node, but procedures to find if and where the lymphoma has spread (staging) may detect considerably more disease.
The disease is classified into four stages based on the extent of its spread (I, II, III, IV). The higher the number, the more the lymphoma has spread. The four stages are subdivided, based on the absence (A) or presence (B) of one or more of the following symptoms:
Unexplained fever (more than 100° F [about 37.5° C] for 3 consecutive days)
Night sweats
Unexplained loss of more than 10% of body weight in the preceding 6 months
Treatment and Prognosis
With chemotherapy, with or without radiation therapy, most people who have Hodgkin lymphoma can be cured.
Chemotherapy is used for all stages of disease. Doctors usually use more than one chemotherapy drug. Several combinations may be used. Involved field radiation therapy (radiation therapy delivered only to the affected areas of the body, avoiding exposing unaffected areas to radiation) may be added after chemotherapy. Radiation therapy is usually given on an outpatient basis over about 3 to 4 weeks.
More than 80% of people with stage I or stage II disease are cured with chemotherapy alone or with chemotherapy plus involved field radiation therapy. The cure rate of people with stage III disease ranges from 70 to 80%. Cure rates for people with stage IV disease, while not as high, are above 50%.
Although chemotherapy greatly improves the chances for a cure, side effects can be serious. The drugs may cause temporary or permanent infertility, an increased risk of infection, potential damage to other organs, such as the heart or lungs, and reversible hair loss. After radiation therapy, there is an increased risk of cancer, such as lung, breast, or stomach cancer, occurring 10 or more years after treatment in organs that were in the radiation field. Non-Hodgkin lymphomas may develop in some people many years after successful treatment for Hodgkin lymphoma, regardless of the treatment used.
Platelet functional disorders
Platelets are cell fragments that function in the clotting system. Thrombopoietin helps control the number of circulating platelets by stimulating the bone marrow to produce megakaryocytes, which in turn shed platelets from their cytoplasm. Thrombopoietin is produced in the liver at a constant rate and its circulating level is determined by the extent to which circulating platelets are cleared, and possibly by bone marrow megakaryocytes. Platelets circulate for 7 to 10 days. About one third are always transiently sequestered in the spleen. The platelet count is normally 140,000 to 440,000/μL. However, the count can vary slightly according to menstrual cycle phase, decrease during near-term pregnancy (gestational thrombocytopenia), and increase in response to inflammatory cytokines (secondary, or reactive, thrombocytosis). Platelets are eventually destroyed by apoptosis, a process independent of the spleen.
Thrombocytopenia
deficiency of platelets (thrombocytes), which increases the risk of bleeding.
Causes
Many disorders can cause thrombocytopenia.
Thrombocytopenia can occur when the bone marrow does not produce enough platelets, as happens in leukemia and some anemias.
Infection with hepatitis C virus, the human immunodeficiency virus (HIV, the virus that causes AIDS), Epstein-Barr virus (the usual cause of mononucleosis), and many other viruses may result in thrombocytopenia.
Platelets can become entrapped in an enlarged spleen, as happens in cirrhosis of the liver, myelofibrosis, and Gaucher disease, reducing the number of platelets in the bloodstream.
Massive blood transfusions can dilute the concentration of platelets in the blood.
Some drugs can also cause thrombocytopenia.
Finally, the body may use or destroy too many platelets, as occurs in many disorders, three of the most notable being immune thrombocytopenia, thrombotic thrombocytopenic purpura, and hemolytic-uremic syndrome.
Symptoms and Complications
Bleeding in the skin may be the first sign of a low platelet count. Many tiny red dots (petechiae) often appear in the skin on the lower legs, and minor injuries may cause bruises (ecchymoses). The gums may bleed, and blood may appear in the stool or urine. Menstrual periods may be unusually heavy. Bleeding may be hard to stop.
Bleeding worsens as the number of platelets decreases. People who have very few platelets may lose large amounts of blood into the digestive tract or may develop life-threatening bleeding in the brain even though they have not been injured.
The rate at which symptoms develop can vary depending on the cause of thrombocytopenia.
Diagnosis
Blood tests to measure platelet count
Doctors suspect thrombocytopenia in people who have abnormal bruising and bleeding. They often check the number of platelets routinely in people who have disorders that cause thrombocytopenia. Sometimes they discover thrombocytopenia incidentally when blood tests are done for other reasons in people who have no bruising or bleeding.
Treatment
Avoidance of injury and drugs that affect platelets
Sometimes platelet transfusion
