What causes abnormal red blood cells
- Acute leukemia
- Chronic leukemia
- Low-grade non-Hodgkin lymphomas
- Highly malignant non-Hodgkin lymphomas
- Hodgkin's disease
Plasmacytoma (multiple myeloma)
- Disturbances in the formation of red blood cells
- Increased breakdown of red blood cells
- Combined red blood cell disorders
- Decreased coagulability - tendency to bleed
- Increased coagulability - tendency to thrombosis
Leukemias are cancers of the blood. They are based on the uncontrolled formation of abnormal blood cells, which impair normal blood formation in the bone marrow to a greater or lesser extent and appear as leukemia cells in the flowing blood.
The cause of leukemia often remains unexplained in individual cases. Some forms are favored by chemicals, e.g. benzene or organic solvents, cigarette smoking or radioactive radiation. The chemical and physical influences mentioned can change the genetic material of a blood-forming cell so that a normal cell becomes a leukemia cell. The changes in the genome can often be characterized in more detail by examining the cell's chromosomes.
According to the course of the disease, a distinction is made between acute leukemias, which lead to a severe clinical picture within a few weeks, and chronic leukemias, which are often discovered as incidental findings. According to the cell of origin, the genetic makeup of which has been altered, a distinction is made between myeloid leukemia, which usually originates from progenitor cells of granulocytes and monocytes, less often from progenitor cells of erythrocytes and platelets, and lymphatic leukemia, which originates from the progenitor cells of lymphocytes.
Depending on the cell of origin, a distinction is made between acute myeloid and acute lymphatic leukemia. Both forms of leukemia are characterized by the fact that very immature leukemia cells, known as blasts, flood the bone marrow and almost completely bring normal blood formation to a standstill. The patient then feels the consequences of anemia (lack of red blood cells) as poor performance, tiredness and palpitations, the consequences of a reduction in normal leukocytes as susceptibility to infections with persistent sore throats or pneumonia, and the consequences of blood platelet deficiency (thrombocytopenia) as a tendency to bleed with nasal and gum bleeding or bruising.
Since acute leukemia leads to an almost complete loss of function of the bone marrow, if left untreated, it is fatal after a few days or weeks. The aim of treatment is to kill the leukemia cells. This allows normal blood formation to spread again in the bone marrow. The killing of the leukemia cells is achieved by chemotherapy, which is administered in several successive cycles with an interval of several weeks. This is intended to gradually remove the malignant cells completely.
Since the risk of relapse in some forms of acute leukemia is very high, the last resort recommended in many cases is a bone marrow transplant with hematopoietic cells from a healthy donor. The recommendation of a bone marrow transplant depends not only on whether the leukemia is myeloid or lymphatic, but also which subtype is present within the group of myeloid or lymphatic leukemia. For this purpose, special examinations are carried out during the first examination, which should reveal the changes in the genetic material of the leukemia cells.
In the narrower sense, in the case of chronic leukemia, a distinction is made between the very strictly defined chronic myeloid leukemia and the also very strictly defined chronic lymphatic leukemia. In a broader sense, this also includes other diseases that are associated with the flushing of malignant myeloid or lymphatic cells into the peripheral blood. All chronic leukemias have in common that normal blood formation in the bone marrow is often maintained very well over a long period of time, so that the patient notices little or nothing of his leukemia. The prognosis of chronic leukemia is extremely variable depending on the subtype.
Chronic myeloid leukemia is associated with a very strong increase in well-maturing blood cells and typically runs in several phases. In the so-called chronic phase, the patient is often symptom-free. If the white blood cells rise too high, they can often be reduced to the normal range by simple medicinal measures. Unfortunately, the chronic phase is followed by an acute phase in all patients, in which, as in acute leukemia, there is a severe hematopoietic disorder in the bone marrow. This phase is extremely difficult to influence. Only bone marrow transplants promise a cure for patients with chronic myeloid leukemia. This should be done in the chronic phase.
Chronic myeloid leukemia is related to a group of diseases that is also known as myeloproliferative syndrome. Either an increase in red blood cells (so-called polycythaemia vera rubra) or an increase in blood platelets is in the foreground (so-called essential thrombocythemia). In polycythemia vera rubra, the proportion of red blood cells in the flowing blood increases to 60 to 70%, which leads to circulatory disorders, e.g. in the brain, and a pronounced strain on the heart, which has to pump the viscous blood through the circulation. Treatment of the disease is frequent bloodletting, which reduces the volume of erythrocytes. The duration of the illness is often years or decades. The same applies to essential thrombocythemia, the greatest risk of which is the occurrence of thrombosis. It is therefore necessary to reduce the increased blood platelet counts through medication. After many years, both polycythemia vera rubra and essential thrombocythemia can lead to increasing sclerosing of the bone marrow with shifting of blood formation in the spleen and liver. This condition is then known as osteomyelosclerosis.
Chronic lymphocytic leukemia is the most common form of leukemia in Europe. It increases in frequency with age and is often associated with pronounced enlargement of the lymph nodes or swelling of the spleen. This is why chronic lymphocytic leukemia is also counted as a malignant lymphoma. Chronic lymphocytic leukemia can develop very differently depending on the extent to which normal blood formation in the bone marrow is suppressed and the lymph nodes and spleen are enlarged. Some patients do not need treatment for years or even decades. In other cases, the course is much more unfavorable despite the immediate initiation of therapy.
Related to chronic lymphocytic leukemia are other malignant lymphomas that are associated with the flushing of malignant lymphocytes into the blood. An example of such a disease is so-called hairy cell leukemia, in which the lymphocytes have hair-like extensions. The disease can be influenced therapeutically thanks to the drug developments of the last two decades.
Myelodysplasia is a heterogeneous group of diseases whose common feature is a highly abnormal blood formation in the bone marrow. As a rule, a patient with myelodysplasia becomes noticeable due to insufficient peripheral blood cells. Often this affects the erythrocytes as well as the leukocytes and platelets, a condition known as pancytopenia. In contrast to the blood formation disorder in leukemias, there is no monotonous picture of leukemic blasts in the bone marrow, but a colorful juxtaposition of malformed cell elements that are reminiscent of normal blood cells and perish prematurely. Depending on the type of changes found, the myelodysplasias are divided into different subgroups. The chromosome analysis provides additional information, which can reveal characteristic changes.
The course of the myelodysplasias is different depending on the subtype. Some of these diseases are rightly referred to as pre-leukemias because they develop into acute leukemia within a few months. These patients are treated similarly to those with acute leukemia. Other sub-forms are stable over time and rarely turn into leukemia. These patients need blood transfusions to replace their inadequate blood production. Attempts to influence the ineffective blood formation with drugs are successful in individual cases and are the subject of clinical studies, which are also carried out in our clinic.
Malignant lymphomas are cancers of the immune system. The cells of the immune system are mainly found in the lymph nodes, tonsils and spleen, but also in blood, bone marrow and thymus. Since they are distributed throughout the body via the bloodstream and lymphatic systems, it is understandable that malignant lymphomas can develop in any organ.
The cause of malignant lymphoma usually remains unexplained. Patients with pre-existing immune deficiencies show a particular tendency to develop these tumors. These can be caused, for example, by an infection with the human immunodeficiency virus or by long-term use of immunosuppressive drugs, e.g. after a kidney or heart transplant. In this type of lymphoma, certain viruses, in particular the Epstein-Barr virus known from Pfeiffer's glandular fever, appear to have a pacemaker function.
Depending on the type of lymphatic cell of origin, the type of cancer cell that develops, the favorable framework conditions and the course, numerous sub-forms of malignant lymphomas are distinguished, which have been classified in various classification systems. Most classification systems differentiate T-cell lymphomas from B-cell lymphomas according to the cell of origin.After the course, low-grade lymphomas with a chronic course are compared with high-grade lymphomas with a rapid course. A special form of a highly malignant B-cell lymphoma is Hodgkin's disease, which was described at the beginning of the 19th century and is characterized by a characteristic cell type. Depending on the presence of this cell type, malignant lymphomas are divided into Hodgkin's disease and the large group of non-Hodgkin's lymphomas.
Regardless of their precise assignment, malignant lymphomas very often manifest themselves as swelling of a lymph node or a swelling of another organ. Many patients also suffer from symptoms similar to those of an infectious disease, such as fever, night sweats or weight loss. A tissue sample must be taken for an accurate diagnosis. Then the stage of spread of the malignant lymphoma must be determined. In addition to a detailed physical examination, X-ray examinations of the abdomen and chest as well as tissue removal from the bone marrow and other organs are carried out. Since malignant lymphomas - unlike leukemia - can occur in localized locations, radiation plays a very important role in treatment alongside chemotherapy.
Low-grade non-Hodgkin lymphomas
Under low-grade non-Hodgkin lymphomas a group of diseases is summarized which show a chronic, often years, sometimes decades-long course. It is not uncommon for the patient to notice an enlarged lymph node by chance, which is affected by cells of the low-grade lymphoma, if the general condition is good. If the stage-classifying examinations show that a localized infestation is present, the disease can often be cured by radiation therapy. If the disease is in an extended stage, it is considered incurable. This is due to the fact that radiation therapy cannot be used in the case of a very extensive infestation for reasons of tolerability. The lymphoma cells usually only respond incompletely to chemotherapy because they divide very slowly. However, cell division is a prerequisite for the effectiveness of many chemotherapeutic agents. Due to the often very slow progression of the disease, in advanced stages of the disease one will sometimes decide to wait for the further course without treatment. If the patient feels impaired by the malignant lymphoma, the symptoms can usually be influenced by medicinal measures.
Highly malignant non-Hodgkin lymphomas
Highly malignant non-Hodgkin lymphomas are characterized by very rapid progression. The patient often notices a tumor that is rapidly increasing in size, and it is not uncommon for him to suffer from weight loss, fever or night sweats. Since the highly malignant non-Hodgkin lymphomas are characterized by very rapid cell division, they can be influenced very well by drugs that inhibit cell division. Regardless of the stage of spread, highly malignant non-Hodgkin lymphomas can in principle be cured. However, this requires intensive drug therapy, which is usually followed by radiation therapy in specific stages of the disease.
Despite very good therapeutic success, a not inconsiderable number of patients with highly malignant non-Hodgkin lymphomas suffer a relapse in the further course. In this situation, high-dose therapy with autologous blood stem cell transplantation promises the best chances of recovery. The principle of this treatment is outlined in the chapters "Types of treatment" and "Information brochures".
Hodgkin's disease is a historically founded special form of highly malignant lymphoma. Regardless of the stage of spread, the disease is characterized by excellent chances of recovery. In the early stages, combined chemo-radiotherapy is usually used, in advanced stages the emphasis is on very intensive chemotherapy. Similar to the highly malignant non-Hodgkin's lymphomas, the - fortunately quite rare - relapses are usually treated with high-dose therapy with autologous blood stem cell transplantation.
Multiple myeloma is a cancer of the bone that starts from antibody-producing plasma cells. Since these cells also belong to the immune system, multiple myeloma is also included in many classifications with malignant lymphomas. However, the symptoms and complications differ significantly from the disorders observed with the usual malignant lymphomas.
The symptoms leading to the diagnosis are extremely diverse. Often the patients suffer from severe bone pain, sometimes they are anemia, and in some cases the first symptom is a very high sedimentation rate. When the diagnosis is made, there is almost always a generalized stage of the disease with involvement of the entire bone marrow. The malignant plasma cells lead to painful bone resorption, suppress blood formation in the bone marrow and thus cause anemia. They also produce very large amounts of antibodies that are released into the blood and act like glue there. This results in a high rate of sedimentation of the blood cells and, in severe cases, dangerous circulatory disorders, especially in the eye and brain. The kidneys are particularly sensitive to the excess of antibodies. It is not uncommon for severe kidney dysfunction to develop in the further course, which sometimes necessitates dialysis treatment.
The further development of the disease is very variable. Many patients show a chronic course over many years without significant impairments. In other cases the disease takes a very rapid course, which is characterized by broken bones, a failure of the bone marrow function with exhaustion, susceptibility to infections and bleeding as well as disorders of the kidney function.
Similar to advanced low-grade non-Hodgkin lymphomas, multiple myeloma is considered an incurable disease. If there are no or only minor complaints, one will often decide to wait and see during treatment. If there are marked changes in the bone or bone marrow, kidneys or blood flow properties, the patient will be advised to seek therapy. Localized myeloma foci can be made to disappear with radiation therapy. If the disorders are generalized, chemotherapy is used. The most sustained influence on the course of the disease can be achieved through high-dose therapy with autologous blood stem cell transplantation, which is presented in the section "Treatment types" and "Information brochures". Of particular importance are supportive measures that inhibit the breakdown of the bone and alleviate the pain that this causes.
Anemia is anemia, i.e. a lack of red blood cells. As a rule, anemia is not a disease in its own right, but rather the consequence of another disorder that the doctor must uncover as part of his diagnosis.
From a systematic point of view, anemia can be divided into disorders of the formation of red blood cells and increased cell breakdown. In some diseases, both mechanisms are present at the same time.
Disturbances in the formation of red blood cells
The healthy bone marrow regenerates as many red blood cells as are lost through the aging process. About 1% of the red blood cells are replaced by new cells every day. There are numerous causes of erythrocyte dysfunction, some of which, such as iron deficiency, are extremely common.
The most serious form of erythrocyte formation disorder is aplastic anemia, in which blood formation in the bone marrow dries up under the action of toxins or an immune system directed against the body. Anemia in patients with severe kidney diseases, in which the shrunken kidneys are no longer able to produce sufficient amounts of the blood formation hormone erythropoietin, is similarly serious, but has been extremely treatable for several years. This hormone is now available as a drug and is used with great success in patients with kidney disease.
If there is an iron deficiency, the red blood pigment, hemoglobin, can no longer be produced in sufficient quantities. If an iron deficiency is found in a patient, the next step is to uncover the cause. In most cases, there is chronic blood loss, which depletes the body of iron. Common causes are excessive menstrual bleeding or bleeding stomach ulcers. Tumors in the gastrointestinal tract, especially in the large intestine, often initially manifest as iron deficiency anemia. Long-term use of iron supplements can usually clear up the anemia. However, if the symptom of anemia is a malignant tumor, iron intake alone will not stop the cancer from progressing.
A number of vitamins are also necessary for the formation of new blood cells, in particular vitamin B12 and folic acid. Some stomach and intestinal diseases lead to impaired absorption of these vitamins and, in the further course, to vitamin deficiency anemia. Treating these patients with regular vitamin injections is a very rewarding task.
Increased breakdown of red blood cells
An increased breakdown of erythrocytes is called hemolysis. A distinction is made between innate forms of rapid erythrocyte breakdown, such as the spheroidal cell anemia common in Germany or the sickle cell anemia common in Africa, from acquired disorders. The latter diseases are generally rare. Sometimes there is a disorder of the immune system, which makes antibodies against your own red blood cells and in this way causes them to be destroyed. This form of haemolytic anemia can often be favorably influenced by suppressing the immune system with drugs, e.g. using cortisone preparations.
Combined red blood cell disorders
The most important group of diseases associated with a combined disruption of the formation and breakdown of red blood cells is so-called thalassemia. This is an inherited disorder of the formation of the red blood pigment hemoglobin, which is extremely common in the warm countries of the world. As a result of this defect, unusually small, incorrectly composed red blood cells are formed, which have a significantly reduced survival time. The disease can have very different forms, ranging from an insignificant change that can only be determined through special laboratory tests to death in childhood. The treatment measures are correspondingly diverse. In very severe cases, attempts are made to cure them with a bone marrow transplant.
Congenital red blood cell disorders, such as thalassemia, are the most common hereditary diseases. These diseases are so common in warm countries because they protect people from malaria to a certain extent. The malaria pathogens attack the red blood cells. Infected children in particular often die from the infection. Malaria pathogens do not feel good in malformed red blood cells. The consequence of this is that people with inherited red blood cell abnormalities have particularly good chances of survival in malaria areas. Over the generations, therefore, the proportion of people with red blood cell abnormalities in the population of warm countries has steadily increased.
Blood clotting is used to repair damaged blood vessels. It runs in three phases. Following the injury, the blood vessel initially contracts. Then blood platelets (thrombocytes) are deposited on the injured vessel wall and close the lesion as a plug. Finally, the plug formed is stabilized by protein networks that arise from an extremely complicated chain reaction of various blood protein substances.
Blood clotting disorders can manifest themselves as underactive or overactive. An underactive coagulation system leads to an increased tendency to bleed. Overfunction, on the other hand, causes increased coagulability of the blood, which can give rise to thromboses (formation of blood clots) and embolisms (spreading of blood clots).
Decreased coagulability - tendency to bleed
An increased tendency to bleeding with the appearance of bruises, nosebleeds, prolonged menstrual bleeding or bleeding inside the body can in principle be caused by a disruption of the vessel walls, the platelets or the blood proteins. There are numerous innate and acquired causes for all three mechanisms.
The most common tendency to bleed caused by platelets is a quantitative lack of platelets, a so-called thrombocytopenia. A characteristic sign of thrombocytopenia is small punctiform bleeding, which occurs particularly on the lower legs and ankles. The causes of a platelet deficiency are diverse and include formation disorders in the bone marrow and an increased breakdown in the blood. A fairly common cause is so-called autoimmune thrombocytopenia, also known as idiopathic thrombocytopenia (ITP). Here there is a disorder of the body's own immune system, in the course of which antibodies against the own blood platelets are formed. The antibody-laden platelets are broken down very quickly in the organism. By dampening the immune system, e.g. with cortisone preparations, it is usually possible to slow down antibody production and normalize the platelet count. However, relapses are not uncommon. In these cases, the removal of the spleen (splenectomy) often brings about permanent healing.
The best-known blood protein disorders that lead to an increased tendency to bleed are the so-called von Willebrand-Jürgens syndrome and hemophilia, also known as hemophilia. Both diseases are usually an inherited abnormality. In the von Willebrand-Jürgens syndrome, the von Willebrand factor, a protein that anchors the platelets to the injured vessel wall, is synthesized to a reduced extent. The result is a tendency to bruise, increased nosebleeds and prolonged menstrual bleeding. In hemophilia, which typically only affects men, there is an inability to produce a protein necessary for the production of the clotting plug, factor VIII (hemophilia A) or factor IX (hemophilia B). Recurring joint and muscle bleeding, which can lead to permanent damage to the musculoskeletal system, is typical of this disease. Due to the availability of factor VIII and factor IX preparations, it is now possible to stop joint and muscle bleeding early or prevent it through prophylactic use.
Increased coagulability - tendency to thrombosis
An increased coagulability of the blood with the occurrence of thromboses and embolisms can in principle come about through a disruption of the vessel wall, the vessel contents, i.e. the blood composition, or the blood flow rate. Here, too, a distinction can be made between innate and acquired causes.
It is not uncommon for increased coagulability to be based on an inherited impairment of the formation of coagulation inhibitors. With special coagulation tests it is now possible to uncover numerous such disorders. Some of these defects are extremely common. People with a proven anticoagulant defect should avoid other influences that could promote thrombosis. These include, for example, taking the contraceptive pill, smoking cigarettes or sitting for a long time with knees bent (e.g. on a long flight), which prevent the blood from flowing rapidly in the veins. If a thrombosis occurs due to a blood coagulation disorder, a drug-based anti-coagulation therapy is carried out over a longer period of time. If the thrombosis occurs again after the end of this treatment, lifelong therapy is often recommended.
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