Introduction
Thrombocytopenia describes a clinical picture in which the number of thrombocytes (blood platelets) in the blood is reduced. The causes can roughly be divided into two categories. Either there is a disorder in the bone marrow, so that the formation of thrombocytes is reduced, or there is an increased breakdown, which is associated with a shortened life span of the thrombocytes. The thrombocytes play an important role in blood clotting. It follows that the first symptom of a deficiency is small spontaneous bleeding of the skin and mucous membrane.
What are the possible causes of thrombocytopenia?
Educational disorders: Fanconi anemia Toxic due to drugs, radiation or chemicals Infections Cancerous diseases – especially acute white blood cancer (acute leukemia), lymph gland cancer and bone metastases Osteomyelosclerosis Folic acid or vitamin B12 deficiency Shortened life span Antibodies against platelets due to idiopathic immunothrombocytopenic purpura (ITP) Tumors, autoimmune diseases, HELLP syndrome Medications, blood products Increased consumption due to mechanical damage Hemolytic-uremic syndrome Increased activity of coagulation Enlargement of the spleen
- Fanconi anaemia
- Toxic by drugs, radiation or chemicals
- Infections
- Cancer diseases – especially acute white blood cancer (acute leukemia), lymph gland cancer and bone metastases
- Osteomyelosclerosis
- Folic acid or vitamin B12 deficiency
- Antibodies to platelets due to Idiopathic Immunothrombocytopenic Purpura (ITP) tumors, autoimmune diseases, HELLP syndrome drugs, blood products
- Idiopathic immunothrombocytopenic purpura (ITP)
- Tumors, autoimmune diseases, HELLP syndrome
- Drugs, blood products
- Increased consumption due to mechanical damage Hemolytic-uremic syndrome Increased coagulation activity Enlargement of the spleen
- Mechanical damage
- Hemolytic-uremic syndrome
- Increased coagulation activity
- Enlargement of the spleen
- Idiopathic immunothrombocytopenic purpura (ITP)
- Tumors, autoimmune diseases, HELLP syndrome
- Drugs, blood products
- Mechanical damage
- Hemolytic-uremic syndrome
- Increased coagulation activity
- Enlargement of the spleen
The only congenital educational disorder of platelet production is Fanconi anemia. It is inherited autosomal recessively and leads to a weakness of the entire bone marrow. This means that not only the thrombocytes are reduced, but also all other blood cells produced by the bone marrow.
This is a rare clinical picture that is still accompanied by changes in the skeleton and organs. Patients are often rather small and have a small head circumference. About half of all patients with Fanconi anemia develop malignant diseases of the blood system such as white blood cancer (leukemia) during their lifetime.
Children with Fanconi anemia are noticed early on with symptoms such as fatigue, bleeding on the skin or mucous membranes and frequent infections. These symptoms can be explained by damage to the bone marrow. It follows that particularly severe infections and cerebral hemorrhages are feared in these patients.
The therapy consists of checking the blood count at close intervals and, if necessary, replacing the missing blood components with blood products. There is a variety of acquired thrombocyte formation disorders. Most of them are based on damage to the bone marrow, which limits the formation of thrombocytes.
Drugs, such as chemotherapeutic agents, can cause this damage, which must be accepted in order to be able to fight the tumor cells appropriately. Radiation, which is also important in tumor treatment, can also damage the bone marrow. Cancer itself, as well as other malignant diseases of the bone marrow, such as osteomyelosclerosis, can also lead to educational disorders.
Certain chemicals such as benzene, which is used in solvents, also belong to this group. In addition to the toxic causes, infections, such as the HI virus, play a role as causative agents.The virus mainly attacks immune cells that contain a specific characteristic on their surface. This results in the dreaded immune deficiency in these patients.
In addition, the patients also develop thrombocytopenia. Autoimmune diseases, i.e. diseases in which the body’s own structures are attacked by the immune system, also belong to the acquired educational disorders. In this group of diseases, the precursor cells of the thrombocytes are attacked by the immune system so that they can no longer mature into thrombocytes.
An antibody reaction against the thrombocytes without further underlying disease is described by the clinical picture Idiopathic Immunothrombocytopenic Purpura (ITP). In this disease, the body produces special proteins (antibodies) against the thrombocytes, which are recognized and broken down by the immune system. As a result, thrombocytopenia occurs to varying degrees.
It is not yet sufficiently clear how this misdirected reaction of the body occurs. It is believed that it can be triggered by common viral respiratory tract infections. It is important to note that ITP is the most common cause of a bleeding tendency in children.
How pronounced this tendency to bleed depends on the remaining platelet count. Thus, there may be patients who show no symptoms whatsoever, up to patients who are covered with small bleedings (petechiae) all over the body. An enlargement of the spleen is rather untypical.
A blood test is performed to diagnose ITP. Typical is an isolated decrease in platelets without the other blood cells showing abnormalities. In the bone marrow there are many precursor cells of the thrombocytes, because the body notices the thrombocyte deficiency and stimulates the bone marrow to produce more.
In addition, special methods can be used to detect antibodies against the thrombocytes. Important here is that ITP is a diagnosis of exclusion. This means that all other possibilities for this thrombocytopenia must first be excluded before a diagnosis can be made.
The therapy depends on the severity of the thrombocytopenia. Patients without symptoms can be monitored without further therapy. Symptomatic patients are first treated with high-dose glucocorticoids.
If this does not lead to success, the administration of immunosuppressants or immunoglobulins may be considered. If the spleen is the site of increased platelet degradation, removal of the spleen may be a further therapeutic option. Thrombocytopenia caused by an antibody reaction can also be triggered by an underlying disease.
Examples of such underlying diseases are lymph gland cancer, chronic lymphatic leukemia, autoimmune diseases such as systemic lupus erythematosus or HELLP syndrome occurring during pregnancy. The third group of antibody reactions are those triggered by the administration of drugs or blood products. When a certain heparin is administered to thin the blood, special antibodies can combine with the platelets and the heparin.
This leads to thrombocytopenia and in severe cases to thrombosis. After blood transfusions, patients who have already been in contact with foreign blood, e.g. after pregnancy or previous blood transfusions, may develop antibodies against their own platelets, which can affect them. An excessive activation of the coagulation occurs, for example, as a complication of shock or sepsis (colloquially known as blood poisoning), during operations on certain organs or during tumor decay.
Clotting is activated excessively and a large number of small blood clots are formed. These then block small vessels, which can lead to an undersupply of blood to various organs with subsequent tissue loss. Because the platelets and other factors of the coagulation system are used up in a very short time, increased bleeding can occur in the following phase.
In blood tests, a lack of platelets can be detected very early on. The therapy consists in the treatment of the underlying disease. In early phases of clot activation, blood thinning can interrupt the cascade.
In late phases, blood thinning should not take place, as there is already an increased risk of bleeding, which would only be made worse.In these phases, fresh plasma and certain factors of the coagulation system can be replaced via the vein. As a prophylactic measure, patients at risk of clot activation should be heparin thinned in advance. Thrombocytes can be damaged if they come into contact with surfaces that do not belong to the body.
An example of this is mechanical heart valves. They are usually made of metal and are used to replace the diseased heart valve. Since the mechanical valves do not move in the same way as normal heart valves, the thrombocytes can be damaged.
The artificial surface can also cause mechanical damage to the thrombocytes. Another example where the blood comes into contact with foreign materials is during dialysis. In this procedure, the blood of patients with severe kidney disease is pumped through a special machine and filtered using a membrane.
In healthy people, this function is performed by the kidney. This is where the thrombocytes come into contact with a surface foreign to the body and can be damaged in this process. A distribution disorder can be caused by an enlarged spleen (splenomegaly).
In the spleen, the thrombocytes are pooled, which means that they collect in the splenic tissue and are therefore not available for the rest of the body’s circulation and blood clotting. If blood is taken, thrombocytopenia would be detected because the platelets that are in the spleen cannot be measured. In the spleen the thrombocytes are then broken down.
This degradation can assume a high rate due to the high number of thrombocytes in the spleen tissue. A further cause of a distribution disorder of the thrombocytes is the performance of anesthesia, which leads to hypothermia. If thrombocytopenia is diagnosed in the laboratory without corresponding symptoms having been noticed before, pseudothrombocytopenia may be present.
This can have three causal causes. Firstly, the thrombocytes in the blood tube may have collected together, which means that they cannot be detected by the measuring devices in the laboratory. This agglomeration can be caused by an incorrect technique during blood collection.
Another possibility is the presence of certain proteins (EDTA-dependent agglutinins) in the blood tube, which bind to the platelets and thus lead to clumping. In the second case, a clumping of white blood cells and the thrombocytes takes place. Therefore, clumping also takes place and the result is again a lower measurable content of thrombocytes in the blood.
The third reason for pseudothrombocytopenia is the presence of so-called giant platelets. The presence of giant platelets can either be congenital or due to various diseases affecting the blood-forming system. Instead of thrombocytes, the functionless giant platelets are formed, which is why the number of platelets in the laboratory is reduced.
Pseudothrombocytopenia can be detected by using differently coated tubes (citrate tubes) or by determining the bleeding time. Heavy alcohol consumption can lead to a reduced production of platelets in the bone marrow. Not only the production of thrombocytes is disturbed, but also that of the entire bone marrow.
As a result, all blood cells may be reduced. The patient then shows symptoms such as fatigue, small bleedings and susceptibility to infections. The mechanism is probably similar to that of drug-induced thrombocytopenia.
However, research is still underway to find out which exact mechanisms are disrupted by alcohol so that damage to the bone marrow can occur. Late effects of severe alcoholism can be white blood cancer or other diseases of the bone marrow. A second mechanism by which increased alcohol consumption can lead to thrombocytopenia is via the development of liver cirrhosis.
Liver cirrhosis is caused by long-term damage to the liver by toxic substances such as alcohol. Since liver cirrhosis is a damage of the liver cells, the production capacity of various substances is also reduced. As a result, the liver can only produce an important growth factor of the thrombocytes in smaller quantities, which leads to a lowered platelet production in the bone marrow.
