Thrombotic thrombocytopenic purpura ( TTP ) is a complex of symptoms consisting of thrombocytopenia, hemolytic anemia and central nervous system disorders. The cause is a modification in the von Willebrand factor.
What is thrombotic thrombocytopenic purpura?
Thrombotic thrombocytopenic purpura is a multisystem disease associated with hemolytic anemia, neurological abnormalities, and thrombocytopenia. Renal insufficiency and fever are often associated. The disease usually begins around the age of 40. For diabetes mellitus dictionary definitions, please visit foodanddrinkjournal.com.
Women are twice as likely to develop TTP as men. Overall, the disease is rather rare with an incidence of three to ten cases per million people per year. The patient has a von Willebrand factor disorder. This fulfills important functions in the context of hemostasis.
TTP is caused by a change in the von Willebrand factor. Due to disturbed enzymes, there are unusually large multimers of the factor in the blood plasma. These are also referred to as UL-vWF. These multimers lead to increased aggregation of the thrombocytes and thus to thrombus formation.
Microthrombi form in particular in the area of the small blood vessels (capillaries). As the red blood cells pass through these thrombotic sites, they are mechanically destroyed by the friction. There is erythrocyte fragmentation. In addition, there is reduced blood flow in the capillary supply area and this also leads to organ damage.
There are several possible reasons for the change in the von Willebrand factor. Various rickettsial, fungal, viral or bacterial infections can be responsible for the disease. Sepsis is also a possible cause. The same applies to cancer, snakebite, pregnancy tonsils , preeclampsia, eclampsia, glomerulonephritis and collagenosis.
TTP can also be caused by various medications. Dangerous drugs include interferon-gamma, ticlotidine, valaciclovir, quinine, ticlopine, mytomycin, cisplatin, or carboplatin. Many of these drugs are used as chemotherapy drugs during cancer treatment.
Symptoms, Ailments & Signs
A triad of hemolytic anemia, thrombocytopenia and CNS symptoms is characteristic of thrombotic thrombocytopenic purpura. In hemolytic anemia, there is an increased breakdown of red blood cells. This creates a lot of bilirubin. The liver can no longer metabolize the bilirubin completely and the pigment is deposited in the skin. This causes yellowing of the skin, also known as jaundice.
The patients feel exhausted and complain about reduced performance. Dizziness, ringing in the ears or headaches can also occur. The heart rate is increased ( tachycardia ). The formation of thrombi in the vessels results in a lack of blood platelets (thrombocytes). This disrupts blood clotting, leading to bleeding into the skin.
These usually appear as small reddish-brown dots (petechiae). If it is more severe, purpura is present. Hemorrhages can also rarely be found in the mucosal area. Around a quarter of patients also complain of fever.
Numerous organs are affected by reduced blood flow. The kidneys can be so severely damaged that they stop functioning completely or partially. The result is renal insufficiency with an increase in the urinary substances in the blood. However, ischemia can also affect the central nervous system. In the case of renal insufficiency, the symptoms are aggravated by the uraemia. Confusion and seizures occur, and in worse cases delirium or coma.
Diagnosis & course of disease
The attending physician receives the first indications of thrombotic thrombocytopenic purpura from the typical symptoms. A medical history of the risk factors and possible causes as well as physical examinations can further strengthen the suspicion. However, only laboratory diagnostics are really meaningful. The differential blood count shows anemia, a lack of thrombocytes (thrombocytopenia) and an increased number of fragmentocytes. LDH and bilirubin are slightly to significantly elevated.
The serum electrolytes such as sodium or potassium and the urinary substances are also increased. Coagulation parameters such as prothrombin or fibrinogen are normal, but haptoglobin is reduced. About 80 percent of all patients with acquired thrombotic thrombocytopenic purpura have antibodies against metalloproteases in their blood.
In the familial form, a gene mutation can be detected. In addition, the abnormally enlarged multimers of the von Willebrand factor can be detected in both forms. TTP is life-threatening and must therefore be treated as soon as possible.
In the course of thrombotic-thrombocytopenic purpura, various symptoms and complications arise. In addition to the characteristic yellowing of the skin, which usually represents a cosmetic blemish for those affected, performance also decreases. Typical are symptoms such as exhaustion, dizziness and headaches, which increase in intensity in the later stages of the disease.
The formation of thrombosis leads to a lack of blood platelets and, as a result, to blood clotting disorders and bleeding into the skin. These can become inflamed and cause painful symptoms such as itching and burning. Hemorrhages in the mucous membrane area are also conceivable. A quarter of patients develop fever, which can lead to serious circulatory problems.
Furthermore, serious organ damage occurs again and again. Possible complications include renal insufficiency, liver failure and cardiac arrhythmia. This can result in a coma, which is often fatal. The treatment usually proceeds without major complications.
However, the typically prescribed drug prednisone can promote osteoporosis and disorders of the sugar metabolism. In addition, there is an increased risk of infection after ingestion. Antibiotics can cause drug-induced TTP, which if left untreated is almost always fatal.
When should you go to the doctor?
Since this disease cannot heal itself, the affected person should consult a doctor at the first signs and symptoms. Symptoms usually get worse if left untreated, and further complications develop. The sooner a doctor is consulted for this disease, the better the further course of the disease is usually. A doctor should be contacted at the first sign of the disease.
As a rule, the doctor should be consulted if the person concerned feels permanently exhausted and tired. Even sleep or rest cannot alleviate the symptoms. Furthermore, most of those affected also suffer from ringing in the ears and severe headaches. Bleeding on the skin can also indicate the disease and should always be checked by a doctor.
The disease can be detected by a general practitioner. However, further treatment is then carried out by a specialist and depends on the exact symptoms.
Treatment & Therapy
Plasmapheresis is the treatment option with the greatest chance of rapid success. During plasmapheresis, the blood plasma is completely exchanged. The patient’s plasma is centrifuged off, filtered and at the same time substituted by a plasma-like solution. Patients who have autoantibodies against the metalloprotease can be treated with glucocorticoids. Patients are given high doses of prednisone. Anti-CD20 drugs such as rituximab are also effective in these patients.
If therapy with rituximab or glucocorticoids is unsuccessful, surgical removal of the spleen (splenectomy) may be necessary. In the case of secondary thrombotic-thrombocytopenic purpura, therapy is carried out by treating the underlying disease. Bacterial infections are treated with antibiotics. In drug-induced TTP, the causative drugs are stopped as soon as possible.
Untreated TTP is almost always fatal. If TTP is recognized and treated early, the mortality rate is still around ten percent. In more than half of all disease courses, there are also recurrences. However, these can be treated just like the initial illness.
Since it is not known exactly when TTP actually occurs, there are no effective preventive measures for the disease.
The successful treatment of thrombotic thrombocytopenic purpura must be followed by intensive follow-up treatment in order to prevent the disease from breaking out again and the development of secondary diseases. The most important thing here is regular examinations of the platelet levels in the blood. If anemia is found again, blood must be exchanged immediately.
In addition, the heart, lungs, brain and blood vessels should be examined regularly using imaging methods (MRT, CT, ultrasound) in order to be able to detect and treat any blood clots before secondary diseases develop. If blood clots are present, the additional administration of blood-thinning medication (Macumar) may be necessary to ensure blood circulation.
In addition, the administration of anticoagulant medication (heparin) may be indicated to dissolve any clots that have formed. Long-term medication with acetylsalicylic acid (aspirin) can also help to slow down or prevent the platelets from sticking together. Smokers who have suffered from thrombotic thrombocytopenic purpura must stop smoking, as this also causes the blood platelets to stick together, constricts the vessels and thus contributes to reduced blood flow.
Alcohol consumption should also be avoided completely. If there is also increased blood pressure, this must also be treated with medication, since high blood pressure can also contribute to the formation of blood clots. In addition, patients should pay attention to a low-vitamin-K diet (avoidance of green vegetables) and exercise a lot (sport).
You can do that yourself
The therapy of thrombotic thrombocytopenic purpura can be supported by rest and taking the prescribed medication as prescribed.
Due to the risk of infection during plasmapheresis, any symptoms of inflammation should be monitored after the treatment. The doctor must be informed of any unusual symptoms. In addition, general measures such as bed rest and regular visits to the doctor apply. Avoid stress and other risk factors. Patients should not exert themselves physically in the first few days after treatment. Professional activity may be resumed after a few weeks in consultation with the doctor. The prerequisite is that the TTP has been successfully treated and no more complications are to be expected.
Patients can independently inform themselves about the details of the disease and therapy in order to resolve fears. The doctor can also put you in contact with a therapist who can support the treatment with talk therapy and other measures. Finally, when treating thrombotic thrombocytopenic purpura, a helper must always be available who can call the emergency doctor in the event of brain or kidney complications. As a rule, the doctor explains the possibilities to the patient.