Immune thrombocytopenia ( ITP ) is a type of thrombocytopenic purpura defined as the number of isolated low thrombocytopenia (thrombocytopenia) with normal bone marrow and no other cause of thrombocytopenia. This causes a typical purpuric rash and an increased tendency to bleed. Two different clinical syndromes manifest as acute conditions in children and chronic conditions in adults. The acute form often follows an infection and has spontaneous resolution within two months. Chronic immune thrombocytopenia lasts longer than six months with an unknown specific cause.
ITP is an autoimmune disease with detectable antibodies against some platelet surface antigens.
ITP is diagnosed with low platelet counts in complete blood count (common blood test). However, since the diagnosis depends on the exclusion of other causes of low platelet counts, additional investigations (such as bone marrow biopsy) may be necessary in some cases.
In mild cases, only careful observation may be necessary but very low amounts or significant bleeding may lead to treatment with corticosteroids, intravenous immunoglobulin, anti-D immunoglobulin, or immunosuppressive drugs. refractory ITP (unresponsive to conventional treatment) may require splenectomy, surgical removal of the spleen. Platelet transfusions can be used in heavy bleeding along with very low amounts. Sometimes the body can compensate by making large abnormal platelets.
Video Immune thrombocytopenic purpura
Signs and symptoms
Signs include spontaneous bruising (purpura) and petechiae (small bruises), especially on the extremities, bleeding from the nostrils and/or gums, and menorrhagia (excessive menstrual bleeding), wherever may occur if platelet counts are below 20,000 per l. Very low amounts (& lt; 10,000 per μL) can lead to spontaneous hematoma (blood mass) formation in the mouth or other mucous membranes. Bleeding time from mild lacerations or blisters is usually prolonged.
Serious complications and possibly fatal due to very low numbers (& lt; 5.000 per μL) include subarachnoid or intracerebral hemorrhage (bleeding within the skull or brain), lower gastrointestinal bleeding or other internal bleeding. An extremely low ITP patient is susceptible to internal bleeding caused by blunt stomach trauma, as may be experienced in motor vehicle accidents. This complication is unlikely to occur when platelet counts are above 20,000 per l.
Maps Immune thrombocytopenic purpura
Pathogenesis
In about 60 percent of cases, antibodies to platelets can be detected. Most often these antibodies against platelet membrane glycoproteins IIb-IIIa or Ib-IX, and from immunoglobulin G (IgG) type. The Harrington-Hollingsworth experiment, establishes the pathogenesis of immunity from ITP.
Platelet plating with IgG makes them susceptible to opsonization and phagocytosis by spleen macrophages, as well as by Kupffer cells in the liver. The IgG autoantibodies are also considered to destroy megakaryocytes, precursor cells for platelets, although these are believed to contribute only a small amount to the decrease in platelet count. Recent research now shows that the thrombopoietin glycoprotein hormone production disturbance, which is a stimulant for platelet production, may be a factor that contributes to the reduction of platelet circulation. These observations have led to the development of a class of drugs targeted by ITP called thrombopoietin receptor agonists.
The stimulus for automated antibody production in ITP is probably an abnormal T-cell activity. Preliminary findings suggest that T cells may be affected by drugs targeting B cells, such as rituximab.
Diagnosis
The diagnosis of ITP is an exclusion process. Firstly, it should be determined that there is no blood disorder other than low platelet counts, and no physical signs other than bleeding. Then, secondary causes (5-10 percent alleged cases of ITP) should be excluded. These secondary causes include leukemia, drugs (eg, quinine, heparin), lupus erythematosus, cirrhosis, HIV, hepatitis C, congenital causes, antiphospholipid syndrome, von Willebrand factor deficiency, onyalai and others. In about one percent of cases, autoimmune and coexisted hemolytic anemia of ITP, a condition referred to as Evans syndrome, a condition that leads to CLL as a possible cause.
Although thrombocyte damage by spleen macrophages, the spleen is usually not enlarged. In fact, an enlarged spleen should lead to looking for other possible causes for thrombocytopenia. Bleeding is usually prolonged in ITP patients. However, the use of bleeding time in diagnosis is not recommended by the American Society of Hematology practice guidelines and normal bleeding time does not rule out platelet disorders.
Bone marrow examination may be performed in patients over age 60 and those who do not respond to treatment, or when the diagnosis is in doubt. In bone marrow examination, increased megakaryocyte production can be observed and may be helpful in diagnosing ITP. An analysis for anti-platelet antibodies is a matter of physician preference, as there is disagreement as to whether the specificity of 80 percent of these tests is sufficient to be clinically useful.
Treatment
With rare exceptions, it usually does not need to be treated based on platelet counts. Many older recommendations suggest a certain thrombocyte threshold (usually somewhere under 20.0/Âμl) as an indication for hospitalization or treatment. Current guidelines recommend treatment only in cases of significant bleeding. Treatment recommendations are sometimes different for adult and childhood ITP.
Steroids
Initial treatment usually consists of administering corticosteroids, a group of drugs that suppress the immune system. The dosage and mode of administration is determined by the number of platelets and whether there is active bleeding: in urgent situations, infusion of dexamethasone or methylprednisolone may be used, whereas oral prednisone or prednisolone may be adequate in less severe cases. Once the platelet count improves, the steroid dose is gradually reduced while the possibility of relapse is monitored. 60-90 percent will experience relapse during dose reduction or discontinuation. Long-term steroids are avoided if possible due to potential side effects including osteoporosis, diabetes and cataracts.
Anti-D
Another option, suitable for Rh-positive patients with functional spleen is intravenous administration of Rho (D) immune globulin [Human; Anti-D]. The anti-D action mechanism is not fully understood. However, after administration, the red cell compound of anti-D-coated saturates Fc? receptor sites in macrophages, resulting in the destruction of red blood cells (red blood cells) that are special, therefore leaving platelet-coated antibodies. There are two anti-D products indicated for use in patients with ITP: WinRho SDF and Rhophylac. The most common side effects are headache (15%), nausea/vomiting (12%) chills (& lt; 2%) and fever (1%).
Anti-steroidal agents
There is an increased use of immunosuppressants such as mycophenolate mofetil and azathioprine because of their effectiveness. In chronic refractory cases, where immune pathogenesis has been confirmed, off-label use of vinca alkaloids and vincristine chemotherapy agents may be attempted. However, vincristine has significant side effects and its use in treating ITP should be approached with caution, especially in children.
Intravenous immunoglobulin
Intravenous immunoglobulin (IVIg) may be infused in some cases to decrease the rate at which macrophages consume platelets with antibodies. However, while sometimes effective, it is expensive and produces repairs that generally last less than a month. However, in the case of an ITP patient already scheduled for surgery that has a very low platelet count and has experienced a poor response to other treatments, IVIg can rapidly increase platelet counts, and may also help reduce the risk of major bleeding by increasing platelet counts in a transients.
Thrombopoietin receptor agonists
Thrombopoietin receptor agonists are pharmaceutical agents that stimulate platelet production in the bone marrow. In this case, they differ from the previously discussed agents acting by attempting to limit the destruction of platelets. These two products are currently available:
- Romiplostim (trade name Nplate) is a thrombopoiesis that stimulates the Fc-peptide (peptibody) fusion protein provided by subcutaneous injection. Designated an orphan drug in 2003 under US law, clinical trials show romiplostim to be effective in treating chronic ITP, especially in recurrent splenectomy post-patients. Romiplostim was approved by the United States Food and Drug Administration (FDA) for long-term treatment of adult chronic ITP on August 22, 2008.
- Eltrombopag (trade name Promacta in the US, Revolade in the European Union) is an orally-administered agent with effects similar to romiplostim. It has also been shown to increase platelet counts and reduce dose-dependent dose bleeding. manner.Ã, developed by GlaxoSmithKline and also designated as an orphan drug by the FDA, Promacta has been approved by the FDA on November 20, 2008.
Side effects of thrombopoietin receptor agonists include headache, joint or muscle pain, dizziness, nausea or vomiting, and an increased risk of blood clots.
Surgery
Splenectomy (removal of the spleen) may be considered in patients unresponsive to steroid treatment, frequent recurrence, or may not taper steroids after several months. Platelets that have been bound by antibodies are taken by macrophages in the spleen (which has Fc receptors), and thus removal of the spleen will reduce platelet damage. This procedure is potentially at risk in cases of ITP because of the likelihood of significant bleeding during durable surgery after splenectomy is achieved in 60 to 65 percent of ITP cases, less on older subjects. The use of splenectomy to treat ITP has decreased since the development of steroid therapy and other pharmaceutical drugs.
Platelet transfusion
Platelet transfusions alone are not recommended except in emergencies, and are usually unsuccessful in producing an increase in the number of long-term platelets. This is because the underlying autoimmune mechanism destroying the patient's platelets will also destroy the donor platelets, and platelet transfusion is not considered a long-term treatment option.
H. pylori eradication
In adults, especially those living in areas with a high prevalence of Helicobacter pylori (which normally inhabit the stomach wall and have been associated with gastric ulcers), the identification and treatment of these infections has been shown to improve platelets. the number of one-third of patients. In a fifth, the platelet count is fully normalized; this response rate is similar to that found in treatment with rituximab, which is more expensive and less secure. In children, this approach is not supported by evidence, except in areas with high prevalence. The urea breath test and stool antigen testing perform better than serology-based tests; In addition, serology may be a false positive after treatment with IVIG.
Other agents
- Dapsone (also called diphenylsulfone, DDS, or avlosulfone) is an anti-infective sulfone drug. Dapsone can also help treat lupus, rheumatoid arthritis, and as a second-line treatment for ITP. The mechanism by which dapsone helps in ITP is unclear but increased platelet counts are seen in 40-60 percent of recipients.
- The use of rituximab off-label, chimeric monoclonal antibody against CD20 cell surface antigen, can sometimes be an effective alternative to splenectomy. However, significant side effects may occur, and randomized controlled trials can not be inferred. Epidemiology
- Mother with a history of splenectomy for ITP
- Mothers with previous infants were exposed to ITP
- The number of gestational (mothers) thrombocytes is less than 100,000/uL
Normal platelet counts are considered to be in the range of 150,000-450,000 per microliter (ll) of blood for the healthiest individual. Therefore, thrombocytopenic is considered below that range, although the threshold for diagnosis of ITP is not bound. to a specific number.
The incidence of ITP is estimated at 50-100 new cases per million per year, with children accounting for half of that amount. At least 70 percent of childhood cases will end in remission within six months, even without treatment. one-third of the remaining chronic cases will usually transmit during follow-up observation, and the other third will only end up with mild thrombocytopenia (defined as platelet counts above 50,000). A number of immune related genes and polymorphisms have been identified as affecting predisposition for ITP, with FCGR3a-V158 alleles and KIRDS2/DL2 increasing susceptibility and KIR2DS5 proven to be protective.
ITP is usually chronic in adults and the likelihood of long-lasting remission is 20-40 percent. The ratio of men and women in the adult group varied from 1: 1.2 to 1.7 in most age ranges (cases of children more or less the same for both sexes) and the average age of adults in the diagnosis was 56- 60. The ratio between adult males and females tends to widen with age. In the United States, the adult chronic population is estimated at about 60,000 - with more women than men. about 2 to 1, which resulted in ITP being defined as an orphan disease.
The mortality rate due to chronic ITP varies but tends to be higher than that of the general population for all age ranges. In a study conducted in the UK, it was noted that ITP caused mortality rates about 60 percent higher than in gender. and subjects of the same age without ITP. The increased risk of death with ITP is largely concentrated in middle-aged and elderly. Ninety-six percent of reported ITP-related deaths were individuals 45 years or older. No significant difference was noted in survival rates between males and females.
Pregnancy
Anti-platelet anti-platelet antibodies in pregnant women with ITP will attack the patient's own platelets and will also cross the placenta and react to fetal platelets. Therefore, ITP is a significant cause of fetal and neonatal immune thrombocytopenia. About 10% of newborns exposed to ITP will have platelet counts & lt; 50,000/uL and 1% to 2% will have a risk of intracerebral hemorrhage comparable to infants with neonatal alloimmune thrombocytopenia (NAIT).
No laboratory tests can reliably predict whether neonatal thrombocytopenia will occur. The risk of neonatal thrombocytopenia is increased by:
It is recommended that pregnant women with thrombocytopenia or previous ITP diagnosis should be tested for serum antiplatelet antibodies. A woman with symptomatic thrombocytopenia and identifiable antiplatelet antibodies should be initiated in therapy for their ITP which may include steroids or IVIG. Fetal blood analysis to determine platelet count is not generally performed because ITP-induced thrombocytopenia is generally more severe than NAIT. Platelet transfusions may be performed in newborns, depending on the level of thrombocytopenia. It is recommended that the neonate be followed by the number of serial platelets for the first few days after birth.
History
After a preliminary report by Portuguese physician Amato Lusitano in 1556 and Lazarus de la RiviÃÆ'¨re (doctor for the King of France) in 1658, German physician and poet Paul Gottlieb Werlhof who in 1735 wrote the most complete initial report on purpura from ITP. Platelets are not known at the time. The name "Werlhof disease" is used more widely before the current descriptive name becomes more popular. Platelets were described at the beginning of the 19th century, and in the 1880s some researchers linked purpura with abnormalities in platelet counts. The first successful therapeutic report for ITP was in 1916, when a young Polish medical student, Paul Kaznelson, described the response of a female patient to splenectomy. Splenectomy remained the first-line drug until the introduction of steroid therapy in the 1950s.
References
External links
Source of the article : Wikipedia
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