Rituximab for thrombocytopenia. thrombocytopenia

ZHOVTEN - breast 2008 r

About N Cohematology

Rituximab (MabThera) in combination with dexamethasone in the therapy of chronic idiopathic thrombocytopenia

M. O. Volkova

For materials additional at the press conference and plenary session of the American Society of Hematology 7 breast 2008 r San Francisco

In the last few years, there was a news about the intake of rituximab (MabThera, anti-C020-anti-antibody) in the therapy of autoimmune anemia and thrombocytopenia. More often than not, autoimmune accelerated during chronic lymphocytic leukemia, Ridsche Mabthera was victorious in the therapy of autoimmune patients with lymphomas, innocent - with heart disease and rheumatoid problems. Є Sometime about the success of anti-C020 antibodies against chronic thrombocytopenic purpura in children. All publications of the dosi were intertwined with data about the decal of ailments.

At the 50th Congress of the American Hematological Suspension in San Francisco, the results of a randomized, randomized trial of dexamethasone or dexamethasone in the case of MabThera were first reported in a large group of guardians. Presented by the Roche Company. Until now, MabThera has not been approved for the treatment of autoimmune thrombocytopenic purpura in the USA.

Additional information from Dr. Francesco Zaja (m Udine, Italy) wikipedia to great interest. Additional information was presented in two: the 6th breast of the 2008 rock at the press conference and the 7th of the 2008 rock at the plenary session of the congress, and the offense was violent in the face of all the more important ones.

In pre-admission boules, 101 ailments were included with autoimmune and idiopathic thrombocytopenic purpura with the number of thrombocytes, but not 20 x 109 / l. Of the foreign cases of illnesses, 52 boules were randomized for treatment with dexamethasone, 49 - with dexamethasone in the presence of Mabthera. All ailments were treated with dexamethasone at a dose of 40 mg per dose for 4 days. Ailments randomized to reject combined therapy, except for the prescribed dose of dexamethasone, were treated with MabThera at a dose of 375 mg / m2 1 time per day for 4 days. (7, 14, 21 and 28th days). As a result, the increase in the number of platelets was not less than 50 x 109 / l during a month and it was saved for at least 6 months. pislya papinennya lykuvannya. For an hour, additional results are available and 6 ms. assessed in 26 ailments, who took the combined therapy, and in 38 - only dexamethasone. A persistent effect of reaching ailments in 22 (85%) out of 26 ailments in a group who had eliminated combined therapy, and in 15 (39%) out of 38 ailments in a group who had only dexamethasone (p< 0,001). При этом число тромбоцитов более 100 х 109/л устойчиво сохранялось у 37 % больных, получавших дексаметазон, и у 77 % - дексаметазон в сочетании с Мабтерой (р < 0,001).

Ailments from the group, which took only dexamethasone, when they had an effect lasting 30 days per ear of therapy (the number of thrombocytes was not more than 20 x 109 / l), they took Mabthera into such

the most dose, as well as patients from the group of combined therapy. In 59% of the sick men, the increase in the number of thrombocytes was reached to the level of more than 50 x 109 / l.

Author mali namir included in the number 198 ailments, altogether they added 101 ailments to the list, some analysis of the results of the first 50 ailments showed 52% of the difference between groups for measles combined therapy. There was no sign of any sign that would allow the transfer of the effect of the aforementioned liking. The concentration of Mabteria in the blood of the ailments, who were taking the combined therapy, did not correlate with the step of reaching the defect.

Dr. Zaja pidkresliv, that the combined therapy is guilty but it is stalled until (often) the splenectomy is replaced, especially in sick people who may have a great risik for operational acceleration... Predoslidnitsa group of mannamir in a given assessment of the effectiveness of the smallest dose of Mabteri is 100 mg / m2.

Head of Press Conference, Professor of Medicine, University of San Diego, Dr. Kaushansky, and Head of the Plenary, Professor of Medicine, University of Oklahomi, Dr. James George, took note of the importance of the report. Immune thrombocytopenic purpura occurs at a frequency of 7 per 100,000 population and has not been the subject of randomized dosages before. Trivial and repeated stagnation of corticosteroids through the instigation of an unstable effect to produce before the ailing is rich in the side effects of such a deceit and more important than the manifestation of the ailment itself. To this, the achievement of a persistent effect in a greater number of ailments when Mabteria is included in therapy is an important result in the treatment of ailments.

Rituximab - synthetic, chimeric monoclonal , Vivedeni for additional genetic engineering of Misha / people. Rechovina for its structural budget is brought before immunoglobulin IgG1 kappa ... The basis of the molecule is an enduring human segment, for which variable fragments of important and lungs of mischief have grown antityl .

We wish to stock up on 2 important (451 amino acid ) I 2 lungs (213 amino acids ) Lantsyugiv, yogo molecular weight = 145 CD.

Pharmacological diya

Prototype.

Pharmacodynamics and pharmacokinetics

The river is specifically ringing with antigen CD20 , Yaky disassembly on the surface of the growth and pre-B-lymphocytes ... This kind of day is pro-in-cells , Healthy cells of growing tissues, stovburoy hematopoietic and normal plasma cells. DC20 I take an active part in all stages of maturation B-lymphocytes , Є the strumu regulator ionic calcium through a semi-impermeable cell membrane. For that, yak molecule antigen called s by speech, Confirmed not to slip into space, not to sleep in the blood of a viglyad, and not to internelize.

antineoplastic action z'є antigen CD-20 on the surface and іndukuvati immunological reactions , Yaki produce to lysis In-klіtin . clitinniy lizis see two mechanisms: AZTST і KZCT ... Dodatkovo Rituximab to apoptosis clitin human in-class lymphocy on the line DHL-4 .

Injection on limfoidnye thymus clitini , Peripheral blood, spleen ( bila pulp ), lymphatic universities .

median number In-klіtin renewed to the cob ryvn through the ric, sent to the likarsky zasoba. antichimeric antibodies people viyavili in 1% of patients, who were treated with rituximab. In 3 out of 356 people, it is possible to postpone an active clinical response to therapy.

The internal infusion of lykarskiy is promoted in proportion to the growth of the maximum concentration and the period of time. The negative correlation of the syrovatkovy ravnіv with the size of the chubi is evident. Rituximab accumulates in the body, and it can appear in the body for 3-6 months after the last dose is administered.

Bully held a clinical trial, in which they took the part of the children step by step gravity non-Hodgkin lymphomy і vikoristovvalirovyvali diagrams of treatment.

During the cob therapy, 4 іn'єktsії per week, 42% of patients had a partial remission, 6% - a new one. The body has started to return to the drug in the middle on the 50th day, by sending a cob to the preparation. Zahvoryuvannya resumed progress in 11.2 months. In 23% of the ailments on the cob during the experiment, there were present signs and symptoms of illness, and in 64% of them they smelled.

With the cobbled therapy and vikorstanny scheme of treatment for 8 injections of scrubbing, the onset indicators were spontaneous: partial remission - 43%, recurrent remission - 14%, progressing ailments - after 13.4 months. However, yaksho pukhlinna masa bully with a size greater than 10 cm, or if it was repeated again, then these indicators will be lower.

Patients who have been abducted during the abduction did not suffer from any changes in the frequency and severity of showing side effects, the frequency of remission and relapse.

Shown to sucking

Sucking rituximab:

• for lykuvannya follicular abo low level of evil In a classic non-Hodgin's lymph ;
• with recurrent abo chemically stable V-clerical lymphomy ;
• for the liking of the other species limfomi in the warehouse of complex therapy;
• in active form, as well as the methods of treatment turned out to be insufficiently effective.

Prototype

Pobichna diya

At about an hour from 12 years before the first infusion of the drug, symptoms characteristic of lysis pukhlini syndrome : hypercalysemia, hyperuricemia , Zboi in robotic nirok, hypocalcemia, hyperphosphatemia .

Also, after an hour of speech, there was a serious reaction from the side of the mucous membranes and shkiri: peraneoplastic powder , Stevens-Johnson syndrome , toxic epidermal necrolysis .

Є About the development of fatal infusion reactions from the hour of the introduction of the first information. Fatal result , Іnfіltratsієyu legen, gostriy respiratory distress syndrome, cardiogenic shock i. Most of the fatal reactions were caused by the first infusion.

I have also seen about vipad development guest nirkova lack , Yaka vimagala conduction, neridko side reactions this kind was brought to the death of a patient.

The following side reactions can occur (it was spasmed for an hour when monotherapy was carried out with the drug):

• , Development of secondary infections, head bill, back pain, chills , asthenia ;
• heat up the blood , Adjustment or decrease AT ;
• blues, constipation , Nudota;
• anemia , leukopenia, thrombocytopenia ;
• neutropenia, lymphopenia, hyperglycemia;
• embankments around the periphery, arthralgia, mialgia ;
• anxiety, spoilage, and cough;
• dyspnoe , Pitlivist, sverbіzh on shkіrі;
• angiodema, bronchospasm , Adjustment of the activity of liver enzymes.

It has been reported that 8 doses of liquor have been introduced in the day of the increase in the number of side reactions.

First of all, the first time to find out:

• fever, chills, tremtinnya by tilu ;
• sverbіzh, nudota, asthenia, head b_l, reduction AT ;
• pershinnya at the throat, undead , Blues, hypertension, kropivyanka .

Pererakhovani vische symptoms persist even after 30 hilines - 2 years after the internal introduction and pass over the period of re-infusion. Important vipadkas are shown symptomatic therapy, Internal introduction fiz. difference , і .

For an hour of monotherapy, there can also be some hematological side effects: hypoplasia of the cystic marrow , piznya neutropenia , prolonged pancytopenia .

Lykarsky zasib to reduce, visnazhennya In-klіtin , Zmenshennya Rivnya, lymphopenia ... In 31% of patients treated with the drug, the development of bacterial infections, fungal infections and winter diseases was observed.

In individuals who are sick before the diagnosis, or from the beginning of the hour, the introduction of the drug should respectfully follow the robot of the heart.

Registered reactivation vials, after the end of the process. The poisoning occurred for 4 months after the first infusion or 1 month after the last dose of rituximab was administered.

I was in the development uveite , green jade ,systemic vasculitis ,pleurisy , syrovatkovoihvorobi , .

Pіd hour of post-marketing information buv registration vipadok viniknennya progressive multifocal leukoencephalopathy .

Rituximab

The scheme of lykuvannya indicates a lykar fallen into the stage of illness and the type of chubby.

lіkuvannya rituximab

inject the drug internally, dropwise .

Before the vicarious speech, it is necessary to dissolve it in an infusion bag, either in bottles with a solution of 9% or an aqueous 5% solution glucose to a concentration of 1 to 4 mg per ml.

Introduce lykarskiy zasib in drops of 375 mg per square meter of surface. The dose can be administered 1 to 8 times per day. If one infusion is carried out in 7 days, the course of treatment becomes one month.

Infusion fluidity - 50 mg per year at the first injection. Potency can be increased step by step by 50 mg per year, skin 30 khilin. The maximum fluidity is 400 mg per year. When dimming infusions, the cob injection rate is 100 mg per hour.

Overdose

In key minds, overdoing was not discouraged. The maximum number of speech, yak was administered to patients at a time, did not exceed 500 mg per square meter of surface.

vzaєmodiya

The drug Rituximab is not possible with monoclonal antibodies , There are many important allergic reactions.

Likas, how to adjust the function of the blood formation of the cystic marrow, to increase the risk of development mієlosupresії .

Mind the sale

Prescription required.

Umovi zberigannya

The river is secured in the stolen access from the sleepy walkways of the city, with a temperature regime from 2 to 8 degrees Celsius. It is not possible to allow the preparation to be frozen.

Term of attachment

30 months.

special requests

Efficiency and inheritance immunization no rituximab therapy was given for an hour.

Іnfusії slіd to conduct in the minds of the hospital for a visual hematologists abo oncologists , I didn’t have enough information about the data. Before the hour of the therapy, especially at the first introduction, it is necessary to trim the possession for reanimation. 12 years before the cob, the therapy should be tightened with antihypertensive drugs .

For the first year before the inauguration, premedication is shown: febrile, febrile, antihistamines, corticosteroids behind the show.

Likas can not be injected internally by means of a bolus.

As soon as the introduction of the speech is made, it is easy to avoid side reactions, the speed of the introduction needs to be reduced.

If the size of the chickens is 10 cm, or the number of circulating malignant clines is more than 25,000 per mm3, then an hour is going to take a little extra care, you can win lizisu pukhlini syndrome ... The syndrome can be fatal. When you come in, it is recommended to take care of the sick person, carry out laboratory monitoring, control the function of nirok and rivnya elektrolitiv at the blood.

Preparations in which revenge (Analogues)

Likas, we are active in the speech of such є Rituximab: , Acellbia, Rituximab .

IAT - congestion, which is characterized by an isolated decrease in the number of platelets in peripheral blood (less than 150x10 * 9 / l) due to the reaction of autoantitils with antigens of platelets, especially in rural areas

Epidemiology.
The frequency of the population of the IAT becomes 60% per 1 million population in the middle. Women are sick more often for the choloviks.

Ethiology not installed.
The connection of the IAT diagnosis is indicated with a virus abo, rіdsche, bacterial infection.

Pathogenesis.
IAT - anti-immune (autoimmune) and immunocomplex (heteroimmune) disease. It develops as a result of the infusion of antiplatelet AT on platelets, which is assigned to Fg class G.
The main meteorite of anti-trombonate AT is spleen.
Vona will serve as the main vehicle for the administration of AT platelets.
Term of life of platelets with IAT of speed up to decilcoh years, todіyak in normі become 8-10 days.

Klinichny show Hemorrhagic disease of the petechial-plamy type develops with thrombocytopenia less than 30x10 * 9 / l.
It is characteristic that small-point hemorrhagic visipans - petechiae and (abo) plyamistikh (about 1-2 cm in diameter), which are not stressed, but not “swollen tissues of hemorrhagic”, appear on the skin and mucous membranes of painless, without signs of burning.
May there be a few repeated nasal bleeding, bleeding from the intestinal tract, uterine bleeding, Hematuria, hemorrhage in the eye girdle from the second eye and hemorrhage in the brain and the th membrane, in the inner hemorrhage.
Typical localization of hemorrhagic visipans on lower kintsivkakh and the lower half of the tulub, the head rank on the anterior surface of the cranial stem. Especially often hemorrhages are for the first time squeezed in places like rubbing shkiri with oily.
IAT can be a guest (often with children) and chronic (older).

Diagnostics.
Show hemorrhagic disease of the petechial-pyramous type. Peripheral shelter: for the presence of IAT, there will be no reduction in the number of platelets without any changes in the number of blood platelets, often a decrease in the number of platelets.
With large blood loss, reticulocytosis and hypochromic (microcytic) anemia may develop.
SHOE addicted.
The triviality of bleeding according to Duke's fault.
An hour of blood loss for the Lee-White method is in between the norms. Retraction of the blood clot is good.
It is necessary to remember about the possibility of pseudo-thrombocytopenia (artifact) with an automatic increase in the number of thrombocytes on the analyzer from the EDTA test.

The detection of circulating autoantibodies appears less than 50% of patients.
The rate of antibodies before platelets does not determine the diagnosis of IAT.
For residual verification, the diagnosis is required morphological dosage the cystic brain and immunological prescription.

Pathomorphology cystic marrow: hyperplasia of megacariocytic elements without signs of dysplasia.
During the day, the change of the erythroidal and small steam rooms.
The number of adult megacariocytes is increased, in the middle of them they cross over cells with a great nucleus and a wide cytoplasm, as thrombocytes are actively "detached".
With IT with the number of platelets less than (20-10) x10 * 9 / L, megakaryocytes are transplanted into the cystic marrow without the sign of active “seen”, which is not linked to the impaired function of megakaryocytes, but due to the effect of the enlarged spinal cord.

Differential diagnostics.
The diagnosis of IAT is performed on the basis of thrombocytopenia, even if all of them any reason victories:
1. Progeny non-immune thrombocytopenia.
2. Secondary autoimmune thrombocytopenia in HIV infection, autoimmune diseases(Colagenosi, especially VKV, HAG), chronic lymphoproliferations, on the basis of drugs, Induce autoimmune thrombocytopenia (heparin-induced thrombocytopenia).
3.Additional immunity thrombocytopenia (posttransfusion thrombocytopenia, induced by drug drugs, - kinin, kinidin, gold, sulfanilamidi, digitoxin, thiazidi etc.).
4. Addition of non-immune thrombocytopenia (important infections, thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, snake bites, hypoxia, heart defects, opioids, hypersplenism, licks).
5. Thrombocytopenia on aphids of malignant ailments.

Likuvannya.
Required services and sanitation of infections.
Patients with thrombocyte level 30x10 * 9 / l do not require a drink, as the stench does not go into taking into account the rapid development of bleeding (surgery, extractions of teeth, curtains).

Acceptable thrombocytes in case of early involvement:
1. Dentistry - big 10x10 * 9 / l
2. Extraction of the tooth - more than 30x10 * 9 / l
3. Small operations - ponad 50x10 * 9 / l
4. Great operations - ponad 80x10 * 9 / l.
However, vikoristovuchi perakhovanі vische criteria, it is necessary to vrahovuvati INDIVIDUAL PIDHID before the patient and the manifestation of hemorrhagic disease.

In the capacity of the preparations in the first line, GCS is used - oral prednisolone at a dose of 2 mg / kg of mass for 2-4 days. Signs of the effectiveness of therapy are the appearance of new hemorrhagic symptoms and (abo) bleeding. The thrombocyte change begins to move on the 5th-6th day after the cob is thrown.

For normalization of indicators in peripheral blood, the dose of prednisolone should be repaired as often as possible.
When administered parenterally, the GCS dose is guilty of being increased (when the intravenous dose is administered, the dose is increased three times in proportion to the dose, taken orally).
In / m method of administration of any drug preparations for thrombocytopenia of any etiology is unacceptable through high rhiziku development of internal hematomas.
Even though the definitions of terms do not support the effect of the therapy, or the result is not satisfactory, then the dose of prenizolone will be increased twice or twice.
If the effect is reached, you should lower it to another view.
In 2/3 of patients, GCS therapy is allowed to cope with more changes.
As soon as you take the drug, or if you try to lower the dose, you will need to relapse, you need to turn it to a higher or higher dose of hormones.
Therapy with corticosteroids is guilty but has been used in patients during the 4th day of therapy.

In case of an unreasonable abnormal effect of GCS therapy by stretching out 3 or 4 months, it is shown before another line of therapy - splenectomy, which gives a very positive effect of 3/4.

Prognostically sympathetic to the efficacy of splenectomy є a good, rather unstable effect of GCS therapy.
Misce splenectomy in IAT therapy in Danish hour є spirnim. Bagatma splenectomy clientele as well as earlier vikorystvuyutsya in the capacity of another line of therapy in patients resistant to GCS therapy or early relapses of GCS.

Інshі author vazhayut for more beautifully victorious splenectomy in the capacity of the third and the fourth line of writing for the victorious Mabteria and immunoglobulin.
Splenectomy is observed in case of platelet levels of 30x10 * 9 / l and food.
For patients with big poor performance corticosteroids therapy is required (prednisolone 1-2 mg / kg / day or dexamethasone 40 mg / day x 4 days) or intravenous immunoglobulin.

In some cases, it is necessary to change the therapy of platelet suspension or freeze-frozen plasma before the hour of the operation.

In case of splenectomy, the level of platelets is practically indicated immediately by the application of ligature on the spleen's vessels, and in the first days of splenectomy, thrombocytosis is often diagnosed, which is very prognostic.

Immunoglobulin.
In some countries, immunoglobulins in the combined corticosteroids become stagnant in the first line of therapy.
Also shown is immunoglobulin vikoristannya in the capacity of another line.
Intravenous immunoglobulin is effective in 75% of patients, unfortunately, the effect of monotherapy with immunoglobulins in most patients does not change 3-4 cases, due to which the main indications are prior to the given therapy and necessary

Rituximab (mabthera) - MCA to the antigen B-lymphocytes CD20, in this hour it is more and more often vicious in other or third line of dosplenectomy: 375 mg / m2 i / v drop 1 time in no time up to 4 infusions.
Therapy of patients with recurrent IAT during splenectomy, or if there is evidence of contraindication (vidmovu) before splenectomy, includes:
1. High doses of corticosteroids
A. Dexamethasone 40 mg x 4 days orally for skin 28 days x 6 courses. B. Methylprednizolone 30 mg / kg / day IV x 3 days with further dose reductions up to 20 mg / kg / day for 4 days; 5 mg / kg / day x 1 syrup; 2 mg / kg / day x 1 syrup; 1 mg / kg / day x 1 suspension.
Thrombocyte rinsection increases for 3-5 days in all patients, however, the triviality of the effect does not change the decile of the disease, and it is possible to test for immunoglobulins.
Recommended for fast transient thrombocyte adjustment.

2. High doses of intravenous immunoglobulin: 1 g / kg per day x 2 days, often in the presence of corticosteroids.
Internal anti-D immunoglobulin indications for only Rh + patients and with thrombocyte level in 79-90% of mature ailments.

3. Alkaloid erysipelas (vincristin, vinblastin).
Vincristine 1 mg IV 1 time per day x 4-6 weeks.
Vinblastin 5-10 mg intravenous fluid x 4-6 weeks.

4. Danazol 200 mg x 2-4 times a day not less than 2 ms.
Approximately 60% of the patients should be encouraged to do so.
In case of continuous reception of the risk of remission, it is possible to take a decision to take the drug.
With a stagnation of 6 months and less, a part of relapse occurs.
5.Immunosuppressants: azathioprine 2 mg / kg (maximum 150 mg / day) or cyclophosphamide 200-400 mg / day in a course dose of 6-8 m
Cyclosporin A; dapsone - 75-100 mg / day orally, which is more likely to occur in 50% of patients.

6. Interferon-a.
7. Rituximab (mabthera) MCA up to CD20.
8. Campas (campath-lH) MCA up to CD 56.
9. Sell-sept (Mecophenolate mofetil).

Immunoadsorption and lasmopheresis can also be carried out.
symptomatic lykuvannya hemorrhagic disease is included in the main mіscevі zasobi: Hemostatic sponge, cryotherapy, electrocoagulation, tampon with e-aminocaproic acid.
In a number of vipads, it is possible to vicoristovuvati preparations, which are capable of painting aggregates of thrombocytes, - etamzilate abo dicinone.

Transfusion of thrombocytes must be carried out only after suvorim are indicated, such as a threat of bleeding in the brain or the importance of uncontrolled bleeding.

Thrombocyte mass eliminated by the method of apparatus thrombocytapheresis as a result of the minimum number of donors is required to be highly purified from the peripheral blood cells.

Forecast.
With adequate therapy, the prognosis of ailments with IAT is friendly. Lethality is close to 10%.
The main reason for the bend of ailments is blood in the brain.
Prevention. Effective prophylaxis of IAT is not insane.
Rizik the development of IAT as a follow-up to the intake of medications can be reduced to rational victories for those who like pobichna diya, Yak IAT.

Kuzmich A.

9 st Minsk City Clinical Hospital, Belarus

Modern methods of treatment of immune thrombocytopenia

Summary. A short critical assessment of the evidence base on the effectiveness and safety of the first and other lines of therapy is given. immune thrombocytopenia(I T.P). A bit more information about the need for new drug strategies in the most beautiful efficiency / safety profile, based on the active information, adopted in some of the classroom reports. Presented recent data on the results of clinical vaccination in case of ITP of an innovative oral active drug with a unique mechanism of the drug (thrombopoietin receptor agonist) - eltrombopag. It has been designed for those who are eltrombopag, which is a high efficiency and a friendly profile of safety, as well as new opportunities for short and new years of life for children from IT, which is included in the first

Key words: chronic immune thrombocytopenia, clinical efficiency, safety, eltrombopag, rituximab, splenectomy, evidence-based medicine.

Summary. The review is devoted to the main problems and the ways of improvement of treatment program in chronic immune thrombocytopenia (CIT) in adult patients. There is a short assessment of evidence base on the effectiveness and safety of treatment methods used for primary and secondary therapy of CIT. There was made a conclusion on the importance of introduction of the new treatment strategies with a better profile of effectiveness / safety. These strategies should be based on objective information received in clinical research. There are given modern data on the results of clinical study of an innovative orally active drug with a unique action mechanism (antagonist of thrombopoietin receptor) - eltrombopag. There was proved that eltrombopag is very effective and safe drug. It opens new possibilities in management of patients with CIT, which means possible inclusion of eltrombopag in the national standards of CIT management.

Keywords: chronic immune thrombocytopenia, clinical effectiveness, safety, eltrombopag, rituximab, splenectomy, evidence-based medicine.

Meditsinskie novosti. - 2014. - N3. - P. 11-14.

Chronic immune (idiopathic) thrombocytopenia (ITP) is an immune-mediated thrombocytopenia, which is characterized by increased proliferation and impaired platelet production, which are susceptible to persistent transient diseases. In general, in Europe, close to 50 new ITP vipadkiv per milion cholovik will be re-organized.

I see the first diagnostics of the ITP, persistent (from 3 to 12 months) and chronic, since it appears more than 12 months from the moment of the diagnosis. In 50-60% of patients with ITP, platelets are tied with antibodies - immunoglobulins of class G (IgG), which develop one of them on the surface of the platelet membrane. Tied with antibodies, platelets are activated by receptors of tissue macrophages, in which, as a result, they are phagocytized. Reacting with platelet autoantigens T- and B-lymphocytes can be detected in the peripheral blood and splenosis of patients with ITP, as well as the production of autoantibodies by cells of the spleen and cerebral blood cells has been demonstrated. The introduction of thrombocyte life cycle in patients with ITP often shows normal abnormally fast platelet production. Tse to inform you about the fitting of products, as well as about the improvement of the destruction of platelets. recent release in vitro showed a decrease in the production and dosage of megakaryocytes in the presence of plasmas of the patient's ITP, which, ymovirno, indicate on cinnamon induced antibodies suppression of megakaryocytes.

Diagnosis of the primary ІТП will be established by way of victories. When taking an anamnesis, it is necessary to exclude the infection with the virus, immunodeficiency in humans and / or the virus hepatitis C, thrombocytopenia decay, post-transfusion purpura, and also thromopathy, which could have been taken by the drug. ITP can be developed in patients for systemic chervoniy vovchak, antiphospholipid syndrome, In-cell pukhlins, as well as in patients who underwent autologous transplantation of hematopoietic stovbury cells.

Antiplatelet antibodies if necessary rіznі thoughts... Vikorisovvani for the detection of antiplatelet antibodies, antigen specific methods may show sensitivity of approximately 49-66%, specificity of 78-92% and diagnostic value of 80-83% for diagnosed patients in health and wellness. Positive antigen-specific analysis unambiguously confirms the diagnosis of immune thrombocytopenia, prote negative test can’t be yogo sooner.

Actualproblems thoroughlyprogram lykuvannyaІ T.P

The main therapeutic meta for ITP is stored in the minimally necessary therapeutic visits for the development of a sufficient level of thrombocyte (more than 30'10 9 / l) for the reduction of hemorrhagic syndrome (more than 30'10 At the core of the American Society of Hematology, the number of platelets is 30-50'10 9 / L without the other factors in the risk of taking into account enough for the prevention of severe delayed ІТП (intramuscular thrombosis and the importance of bleeding / intestinal) »For the health of the invasive ones.

In the course of therapy, the first line of development of pre-old groups and clinical criteria recommend glucocorticosteroids (GCS). Prednizolone 0.5-2 mg / kg / day є with a pre-taken starting dose for patients with ITP. For that, as the number of platelets reaches 50'10 9 / l, it is recommended to reduce the dose to the minimum effective, sufficient for the detection of platelets at the level of 30-50'10 9 / l. From one to a few cycles of dexamethasone 40 mg / add for 4 days є with an important regimen of GCS at an equal rate of 50-80% in older patients with a known diagnosis of ITP. It is well known to the international cosensus, assigned to the last dose of ITP, prednizolone, dexamethasone and methylprednizolone, however, are accepted in the first line of therapy. With resistance to corticosteroids, the triviality of therapy is not to blame for the change of 4 types.

Intravenous immunoglobulin and antiresus immunoglobulin (anti-D) is effective for the reduction of platelet counts; These preparations are recommended in the first line therapy in supernumerary situations.

For patients with chronic ITP, who have not been diagnosed with corticosteroids or have serious side effects, splenectomy is recognized as a therapy of another line. However, approximately 15-20% of patients are not diagnosed with splenectomy, and 15-20% of respondents develop relapses through pregnancy, mishaps. In addition, a lot of patients with chronic ITP are seen from splenectomy through happy Such bleeding, infection, thrombosis, and the risk of a lethal result (0.2-1.0%), as well as infection (testimony of the ugov).

Oncological information about the intake of vincristine, cyclophosphamide, azathioprine, dapsone, cyclosporin A, mycophenolate mofetil and rituximab in patients with refractory to splenectomy, recurrent symptoms surgical engagement... The level of recovery in case of stagnation of food-related types of therapy is from 20 to 80%. However, a large number of reports from the assessment of the effectiveness of immunosuppressive drugs have not been randomized, but to indicate that there is a proven basis for the effectiveness and safety of such a sign of deficiency. Besides, trivial їkh stasosuvannya can be supervised by serious side effects, Zokrema development of secondary chills and infectious accelerated.

Thus, in a prospective clinical trial of the II phase, patients with ITP receiving rituximab at a dose of 375 mg / m 2 for a duration of 4 years allowed to reach 50 thrombocytes in one third of patients in one third of patients. From the presenter N. Cooper and spivavt. It was revealed that a stable general or partial remission was reached in one third of patients, however, a trivial relapse-free period was not registered. Rituximab in Danish hour is not registered for the treatment of chronic ITP. Zgіdno of danimi Fianchi spіvavt i., Mauger Rituximab viklikati fulmіnantny nosіїv hepatitis in hepatitis B, that Yogo zastosuvannya protipokazano patsієntam of active hepatitis B. Krіm order povіdomlyaєtsya bіlsh nіzh about 50 vipadkah progresuyuchoї multifokalnoї leykoentsefalopatії, pov'yazanoї іz zastosuvannyam rituximab at patsієntіv with lymphoid and systemic chervonia Vovchak. The first step is to recommend it in the standard ITP therapy, it is necessary to take into account the results of additional predictions from the assessment of its effectiveness and safety in case of any pathology.

The assignment of problems and intercourse in the management of the patients from the ITP made it possible to increase the need for new people lykarsky zasobiv with the best profile of improved efficiency and safety, including on the basis of new pathophysiological and pharmacological approaches.

It is obvious from the results of numerical dosages, that the destruction of platelet production is more likely to occur in patients with ITP. In addition, the stimulation of megacariocytopoiesis of thrombopoietins by thrombopoietin-like agents can be pathogenetically primed in treatment of ITP. Prolongation of recombinant thrombopoietin demonstrating the possibility of increasing the number of thrombocytes in patients with ITP, aloof association with the production of autoantigenic thrombopoietin, leading to neutralization of the importance of thrombocyte

In the early 2000s, two agonists of the thrombopoietin receptor (TPO-R), romiplostim (Nplate; Amgen) and elthrombopag (Revolade, Promacta; GlaxoSmithKline), were licensed for the treatment of chronic ITP. According to the recommendations of the most popular international consensus, thrombopoietin receptor agony is indicated for relapses in splenectomized patients with chronic ІТП, resistant to other types of therapy, abnormal diseases

Eltrombopag- first oral low molecular weight synthetic non-peptide agonist of the thrombopoietin receptor, registered in Bilorus. The drug has good bioavailability in case of oral intake with peak concentration in blood plasma after 2-6 years and for the period of 21-32 years. Mechanism of eltrombopag polyagi in feasible production of platelets by way of induction of proliferation and differentiation of cystocytic cells in relation to the megacariocytic line. It is highly competitive up to human plasma levels (> 99%). On the basis of the native thrombopoietin, which binds to the lateral domain of the thrombopoietin receptor, the eltrombopag vibrates to the transmembrane region of the receptor and does not compete with the endogenous thrombopoietins. The drug is indications for splenectomized patients with ІТП, non-removable up to іnshiy lykuvannya (for example, GCS, immunoglobulins). The recommended starting dose of eltrombopag is 50 mg once a day. As soon as there is a daily increase in platelet level in 2-3 days, the dose can be increased. For the dosage of a stable platelet level, the dose is guilty of but was scored to the lowest level with the mark of platelet level close to 50'10 9 / L with minimal hemorrhagic manifestations.

short look around the main clientele doslidzhen on sucking eltrombopag at І T.P

Clinical efficacy of elthrombopag in chronic ITP was assessed in 6-day early childhood, 6-month and 6-month early therapy of phase III, pre-early adult therapy, 3-day delay

Using the first 6-tier dosage, the optimal effective dose of eltrombopag was determined. In a total of 118 patients with chronic ITP, they were randomized in the chotiri group: 30 mg, 50 mg, 75 mg of eltrombopag or placebo were taken for 6 days. According to the criteria for inclusion in the longevity of the boule, the patients of the ITP took 6 months and the basic level of platelets less than 30'10 9 / l. Anamnestically, the patients did not take on the anterior therapy, including splenectomy, or the illness recurred for 3 months during the anterior therapy. The main method for eltrombopag is that it reaches the platelet level more than 50'10 9 / l. On the middle day, on the 43rd day, the number of platelets in patients with a dose of eltrombopag 50 and 75 mg / day was 128'10 9 / L and 183'10 9 / L apparently, in the placebo group - 16'10 9 / L. The price of the increase in the number of thrombocytes in the groups of elthrombopagus was accompanied by significant rapid bleeding symptoms. Equivalent thrombopoietin boules in the normal range in both groups (54-57 ng / l) and were left unimportant during therapy with eltrombopag.

The obtained data formed the basis for the planning of the 6-day pre-trial phase III, in which 114 patients were randomized in a 2: 1 ratio in the group of therapy with eltrombopag 50 mg / add or placebo for the vicarious conditions. Significantly more patients from the group of elthrombopag (n = 73) showed an increase in platelets of more than 50'10 9 / L per day in patients from the placebo group (n = 37) (59% versus 16%; p<0,0001). У 34 пациентов, получавших элтромбопаг, дозировка была увеличена до 75 мг/сут после 22-го дня лечения при отсутствии ответа на дозировку 50 мг/сут. Из них 10 пациентов (29%) на 43-й день достигли количества тромбоцитов более 50´10 9 /л. У пациентов, получавших элтромбопаг, риск кровотечения был ниже по сравнению с пациентами из группы плацебо (p=0,029) .

In both 6-year-olds, there is a suspicion on therapy with elthrombopagus, independently of splenectomy in the anamnesis, of the accompanying therapy of ITI, and of an out-of-the-box level of thrombocytes 9/9 years old. In patients who were admitted to therapy, a number of thrombocytes were repaired during the 1st period and reached the maximum during the 2nd period.

In a subordinate blind, randomized, placebo-controlled 6-month-old pre-stage III RAISE, the safety and effectiveness of the trivial elimination of thrombopagus in patients with ITP was assessed. A total of 197 patients were randomized in a 2: 1 ratio in the treatment group with eltrombopag 50 mg / dobu (n = 135) or placebo (n = 62). Approximately 80% of the patients in the placebo and eltrombopag groups received two methods of treatment, and more than 50% in the skin group took three or more methods of treatment. As a result, the patients who were eliminated eltrombopag, Mali 8 times more than the number of platelets in the 50 and 400'10 9 / L in patients from the group<0,001). В группе плацебо количество тромбоцитов не превысило 30´10 9 /л. Среднее число тромбоцитов в группе элтромбопага повысилось до 36´10 9 /л после 1-й недели приема и оставалось на уровне 52-91´10 9 /л до окончания исследования. С 15-го дня приема препарата у пациентов в группе элтромбопага был менее выражен геморрагический синдром по сравнению с пациентами из группы плацебо (79 против 93%). В общей сложности 59% пациентов, получавших элтромбопаг, уменьшили или прекратили прием сопутствующих препаратов (в группе плацебо - 32%) (p=0,02).

By the method of the multicenter trivial test report EXTEND, there was an assessment of the state of the art safety and portability of the eltrombopag based on the data of clinical laboratory tests and the frequency of side effects. An available analysis of 299 patients who can accept therapy with eltrombopag is trivial up to 3 years. The frequency of reaching the level of platelets is 50'10 9 / L and more than the middle of the splenectomized and non-splenectomized patients were 80 and 88% of the total. The Daniye effect in the case of pre-construction stasis of elthrombopagus became stable, but it allowed some patients (69 out of 100 were discouraged from pre-treatment therapy) to try to reduce or reduce the doses of 65% of those in the majority. The frequency of symptoms of bleeding, the yaka became 56% when included in pre-treatment, decreased to 20% after 2 diseases of treatment and to 11% - after 3 cases of treatment.

The incomparable REPEAT dosage for the assessment of frequent intake of elthrombopag buli included patients with pre-treated chronic ITP and a baseline platelet count of 20-50'10 9 / L (n = 66). The patients took 3 cycles of eltrombopag at a dose of 50 mg / day for up to 6 months with interruptions in therapy up to 4 months. Consider the therapy of the thrombocyte level more than 50'10 9 / l. Patients who were not admitted to therapy in the 1st cycle, became ill for a long time. By the end of the day, the value of realizing the regularity is the preservation of the child's life, which occurred in the 1st cycle and also occurred in the 2nd and 3rd cycles. In total, 80% of patients were admitted in cycle 1 and bully admitted to advanced participation in pre-admission, 87% of respondents in the 1st cycle were also admitted in cycle 2 or 3. The average number of platelets in cycle 2 or 3. The average number of thrombocytes in cycle 2 or 3. The average number of thrombocytes in the cycle of 70 days was 9/9 elthrombopag in all three cycles.

13 out of 301 patients (4.5%) had a trivial remission (in the middle 50 years) without additional therapy and ITP in the pre-admission period, conducted by G. Cheng, 13 out of 301 patients (4.5%) were given an admission to an elthrombopag.

look aroundyoung classicallysignificant side-by-sideeffectiveeltrombopag

Approximately 10% of patients who had eliminated eltrombopag in preanalyzed food, but three times in accordance with the upper boundary norm of ALAT (in the case of a group of> 0.05%). In the case of many children, the ALAT levels are normalized for an hour when they receive an eltrombopag, for example, without a bargain. In the pre-season EXTEND period, the promotion to bilirubin was referred to as an indirect faction, but not as an indicator of an important liver function.

In such a rank, in Denmark, there is no key evidence that eltrombopag in the recommended dose can lead to a serous nonvolatile liver failure. However, functional tests of guilt are carried out regularly, and in the presence of progressive improvement of syrovatous aminotransferases, the drug is guilty of buty cuts.

In pre-RAISE patients in three patients (2%), who had eliminated eltrombopag, thromboembolic pods developed, and were mated to therapy. In all three patients, the factor of the development of venous thrombosis and the number of thrombocytes in the period of thrombotic events was less than 50'10 9 / l. In pre-EXTEND patients, 16 patients (5%) developed 20 additional thromboembolic pods; glib venous thrombosis (n = 9) і cerebrovascular thrombosis (n = 5) boule nibilsh enlarged. All 16 patients had one of the factors in the risk of thrombosis, such as arterial hypertension, fatigue or obesity. The frequency of thromboembolic events in patients who were treated with eltrombopag in the pre-EXTEND period was similar in the population of patients with ITP.

In such a rank, the dans of children do not allow the development of visnovoks about the development of thromboembolic rhizics in case of stagnation of elthrombopagus. However, in patients with risk factors for thrombosis, elthrombopagus is guilty of being guarded by a thrombocyte, with a retinal control of the number of thrombocytes and the achievement of the minimum level of thrombocytes, which is sufficient for hematopoietic disease.

Є Theoretical understanding of the possibility of increasing the risk of deposition of Reticulin fibers in the cystic marrow in the presence of agonizing receptors in thrombopoietin. In the last few days of EXTEND, 147 cells were analyzed in the cystic brain, of which more than 100 patients were undergoing trivial therapy with elthrombopag. Overconfused tributes for the development or the progress of fibrosis were not revealed.

visnovok

According to the data of the children, the assessment of the new methods in the treatment of patients with chronic ITP, there are only two methods that have been brought to a high degree of efficiency: splenectomy of thrombosis and conservative treatment of the receptor agony. However, the risk of operative involvement, the development of infection, the development of infection is surrounded by the storage of splenectomy. Thus, eltrombopag is the first representative of thrombopoietin receptor agonists, registrations in the Republic of Belarus and recommendations for the therapy of chronic ITP in patients with a lack of insight into early therapy, is the evidence of new medicine

The head of the conservative treatment with eltrombopag - the clinical efficiency (up to 80%) and the visoka without baking is varied, including the daytime immunosuppressive or little of the risk of health problems. In addition, by the important positive powers of the new strategy for the administration of the ITP є the possibility of oral intake once per day, a step-by-step improvement, for example, a decrease in the dose in case of critical need, in the presence of certain benefits. However, of looking around at Visoko vartіst danogo new pharmaceuticals pіdhodu, provіdnі svіtovі EXPERT s farmakoekonomіchnimi mіrkuvan rekomenduyut іndivіdualny pіdhіd to the tactics of patsієntіv c ІTP on osnovі retelnoї otsіnki klіnіchnoї situatsії i require patsієnta, of urahuvannyam novіtnіh NAUKOVO danih i rozglyadu vsіh Suchasnyj mozhlivostey lіkuvannya, including receptor agony in thrombopoietin.

In zv'yazku of CIM hotіlosya b zvernuti fahіvtsіv uwagi, scho in bіlshostі patsієntіv scho vіdpovіdayut on terapіyu eltrombopagom, Quantity trombotsitіv pochinaє zbіlshuvatisya pіslya Perche tizhnya terapії i dosyagaє pіku on another tizhnі, tobto given strategіya not Yea zasobom nadannya nevіdkladnoї Relief that ekstrenoї terapії ... At the same hour, eltrombopag can buy vicories for the induction of remission during the preparation of patients with a chronic ITP 2 days before the planned surgical entitlement.

The current scientific information has been presented to allow the adoption of a rusted solution for the inclusion of an innovative Likarskiy eltrombopag (Revolide) in the national standards for the prevention and improvement of new developments.

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Uwaga!The article is addressed to lykar-fakhivtsy. Before the hands of the given statty or fragments in the Internet without a hyperpower to look at the first time, the copyright has been violated

RCHRH (Republican Center for Development of Health Protection of the Ministry of Health of the Republic of Kazakhstan)
Version: Clinical protocols of the Ministry of Health of the Republic of Kazakhstan - 2015

Idiopathic thrombocytopenic purpura (D69.3)

oncohematology

General information

Short description

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Ministry of Health Protection
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Protocol No. 6

Classification

CLINIC CLASSIFICATION:

ClassificationAmericanSocietyofHematology, 2013 .

Podil immune thrombocytopenia:
· Forward diagnostics (up to 3 months);
Persistent (3-12 months);
Chronic (12 months).
Due to the immune thrombocytopenia, the IWG has not been formally validated and not recommended for registration and choice of tactics of treatment.
Resistant ITP before corticosteroid therapy - the appearance of symptoms after 3 corticosteroid therapy (prednisolone 0.5-2 mg / kg / dobu).
Refractory ITP - the visibility of the appearance (platelets less than 30x10 9 / l) during splenectomy.

diagnostics

Switching of the main and additional diagnostic entries:
The main (obov'yazkovy) diagnostics of the condition, which is carried out on an outpatient basis:
UAC (thrombocyte podrakhunok, reticulocytes in a smear).

Dodatkovi diagnostics of the situation, which is carried out on an outpatient basis:
OAM;
· Coagulogram;


· Antinuclear factor;
· Cyanocobalamin, folic acid;
Biochemistry analysis of blood (gallbladder block, albumin, zagalny bilirubin, direct bilirubin, creatinin, sechovina, ALT, AST, glucose, LDH, C-reactive block, puddle phosphatase);

· IPA on the VIL marker;
· IPA for virus markers;

· Antinuclear factor;
· Cytological dosage of the cystic marrow;
EKG;


· FGDS;
· Seeding tank for Helicobacterpylori.

The minimal change of the situation, which must be carried out when directed to the planned hospitalization:
UAC (thrombocyte podrakhunok, reticulocytes in a smear);
· Syrovatkovy zaliza, feritin;
· IPA for markers of viral hepatitis;
· IPA on the VIL marker;
· IPA for markers of viruses herpes - groups;
EKG;
· Blood group and Rh factor;
Biochemistry analysis of blood (zalny bilirubin, albumin, zagalny bilirubin, direct bilirubin, creatinin, sechovina, ALT, AST, glucose, LDH, C-reactive bilok);
· Ultrasonic examination of organs in the worm and spleen;
· Ultrasound examination of the pelvic organs - for women;
· Radiography of the organs of the breast.

The main (obov'yazkovy) diagnostics of the situation, which is carried out at a stationary station:
OAC (thrombocyte і reticulocytes in a smear);
· Blood group and Rh factor;
· Direct test of Coombs;
· Haptoglobin;
Biochemistry analysis of blood (block, albumin, ALT, AST, bilirubin, lusen phosphatase, creatinine, sechovina, sechovic acid, LDH, glucose, C - reactive block);
· Coagulogram;
OAM;
· IPA for markers of viral hepatitis (HbsAg);
· IPA for markers of viral hepatitis HCV;
· IPA on VIL markers.

Additional diagnostics of the situation, which are carried out at the stationary hospital:
· Mієlogram;
· Biochemistry analysis: GGTP, electrolity;
· Cytological dosage of biological material;
Cyanocobalamin, folic acid
· IPA for antithrombotic antibodies;

· Immunogram;
· Gistologicheskie prelіdzhennya biopsy (spleenka, lymfovuzol, comb of the club іstka);
· Standard cytogenetic dosage;
· Immunophenotyping of peripheral blood cells;
· Antiphosphol_p_dn_ anti_la;
· Antiteka to native and denatured DNA;
· Bacteriological advancement of biological material;
PLR for viral infections (viral hepatitis, cytomegalovirus, herpes simplex virus, Epstein-Barr virus, Varicella / Zoster virus);
· Echocardiography;
Ultrasonic examination of organs in the black empty (pechinka, spleenka, pidshlunkovoi zloza, zhovchny michur, lymphatic universities, nirki), in females - a small pelvis;
· X-ray of the organs of the breast;
· Radiography of cysts and suglobs;
· CT scan of the thoracic segment, cranial segment, head, small pelvis;
· MRI of the thoracic segment, transverse segment, head, small pelvis;
· FGDS;
· Seeding tank for Helicobacterpylori;
· UZDG sudin;
· Bronchoscopia;
· Colonoscopy;
· Dobove monitors AT;
· Dobove monitoring of the EHC.

Diagnostics come in, which will be carried out at the stage of medical aid:
· Zbir skarg and history of illness;
· Physical regulation.

Diagnostic criteria for diagnosis:
Primary immune thrombocytopenia is diagnosed in case of decreased platelets less than 100 × 10 9 / l in case of other causes of thrombocytopenia. ...

skargi on:
· Increased bleeding from mucous membranes;
· Hemorrhagic visibility at viglyadi petechii and ekhimosi on shkiri;
· Weakness;
· Blіdіst;
· Stomaluvanism.

anamnesis: slid beastly respect for:
· Noses, ash bleeding;
· Menorrhages, subways;
· Blood in the sclera;
· Blood in the brain;
· Hematuria;
· Bleeding from the intestinal tract (bloody vomit, melena);
· Hemorrhagic visibility at viglyadi petechii and ekhimosi in shkiri.

Physical detail [2 - 4 ]:
· Hemorrhagic visipannya - petekhi, ekhimozi;
· Blіdіst shkіrnyh curves;
· Zadishka;
· Takhіkardіya.

Laboratory Doslidzhennya:
· zagalny blood analysis:іmunna trombotsitopenіya harakterizuєtsya zmenshennyam kіlkostі trombotsitіv in periferichnoї krovіvplot to odinichnih at normal abo navіt pіdvischenomu rіvnі megakarіotsіtov.Morfologіcheskіe zmіni in platelets: zbіlshennya їh rozmіrіv appeared malozernіstih Blakytny klіtin, takozh їh poikilocytosis i zmenshennya Process trombotsіtov.Anemіya forms at krovotech digit;
· mylogram: an increase in the number of megacariocytes, the appearance of a small number of thrombocytes lying down, the appearance of the swelling (sign of swelling) in the cystic brain;
· coagulogram: hypocoagulation is not characteristic;
· Immunological dosage: detection of antiplatelet thrombocytoassociated (TpA-IgG) antiplatelets in the blood.

instrumental doslіgennya :
· FGDS: Evidence of bleeding dzherela, signs of esophagitis, gastritis, bulbitis, duodenitis (superficial, catarrhal, erosive, reddened).
· bronchoscopia: revealing dzherela bleeding.

Shown for consultations of university faculties:
· Lykar for X-ray endovascular diagnostics and lіkuvannya - installation of a central venous catheter from a peripheral access (PICC);
· Hepatologist - for diagnostics and treatment of viral hepatitis;
· Gynecologist - vagіtnіst, metroragії, menorahії, consultation in case of recognized combined oral contraceptives;
Dermatovenereologist - shkirny syndrome
· Infectious diseases - suspicion of viral infections;
· Cardiologist - uncontrolled hypertension, chronic heart failure, impaired heart rhythm and conduction;
· Neuropathologist GOSTRE damaged cerebral blood circulation, meningitis, encephalitis, neuroleukemia;
· Neurosurgical-gostre collapse of cerebral blood circulation, dislocation syndrome;
· Nephrologist (EFFERENTOLOGIST) - nirkova lack;
· Oncologist - doze on solid chin;
· Otorhinolaryngologist - for diagnostics and treatment of igneous diseases of the paranasal sinuses and middle air;
· Ophthalmologist - desecrated zoru, fired up zoruvannya eyes and appendages;
· Proctologist - anal trіschina, paraproctitis;
· Psychiatr -psychozy;
· Psychologist - Depression, anorexia, etc.;
· Reanimatologist - treatment of important sepsis, septic shock, the syndrome of severe leneous ear in the syndrome of differentiation and terminal stagnation, installation of central venous catheters.
· Rheumatologist - Sweet's syndrome;
· Thoracic surgery - exudative pleurisy, pneumothorax, pulmonary zygomycosis;
· Transfusiologist - for selection of transfusion mediums with positive indirect antiglobulin test, ineffectiveness of transfusions, hostile blood loss;
· Urologist - infectious and igneous disease of the secular system;
Phthyziatr - dose for tuberculosis;
· Hirurg-surgical acceleration (infection, hemorrhagic);
· Slap-and-face surgery - infectious-igniting disease of the tooth-slit system.

Differential diagnosis

Differential diagnosis:
Differential diagnosis in immune thrombocytopenia transmission of other conditions of thrombocytopenia. Includes aplastic anemia, paroxysmal non-hemoglobinuria (Markiafavi-Mikeli disease), hairy cell leukemia, megaloblastic anemia, mylodysplastic syndrome, TAR syndrome, thrombotic thrombocytopenic purpura. Paroxysmal nichna hemoglobinuria. For PNH, the characteristic hemosіderіnurіya, hemoglobinurіya, the adjustment of іvnіv bilirubіnu, LDH, a decrease in the volume of haptoglobin. Bleeding is rarely susceptible, typical hypercoagulation (activation of inducers of aggregation). When the APG is present, the clone will follow the IFT results.
aplastic anemia in blood smears, thrombocytopenia is isolated often gliboka to the appearance of single blood plates. Aspirate of the cystic brain with nuclear elements. Reduced the total percentage in the place of key elements. In histological preparations trepanobioptate of club cysts aplasia of the cystic marrow with replacements of adipose tissue, vyklyuchaє ІТП. Zmіst zlіzo is normal abo alarms.
Myelodysplastic syndromes. For MDS, there are characteristic signs of dyspoeza, an excess of blasts in the cystic marrow, chromosomal aberrations, and a cytokinesis.
Hairy leukemia. At the debut of the disease, pancytopenia and hemorrhagic syndrome can be diagnosed. Results of flow cytometry, immuno-stochastic, histological pre-diagnosed cytometric cerebral cytometry ІТП.
TAR-syndrome. The characteristic of the appearance of interchangeable cysts, the pathology of megakaryocytes and thrombocytes from their hypoplasia and dysfunction, causing them to bleed. Children with ailments are most likely to suffer from congenital organ abnormalities (often heart defects).
Megaloblastic anemia. The main diagnostic method is the assessment of vitamins B12 and folate acid. Indirect signs characteristic of megaloblastic anemias are the increase in the average hemoglobin in the erythrocytes, the increase in the average volume of the erythrocytes, the megaloblastic type of blood formation for these micrograms. On the basis of ІТП with megaloblastic anemias, thrombocytopenia is not affected by the hemorrhagic syndrome.
Thrombotic thrombocytopenic purpura. To become susceptible to the presentation of neurological symptoms, multiple blood clots, lump syndrome, often liver and spleen disorders.

Likuvannya beyond the cordon

Take a lykuvannya in Korea, Izrail, Nimechchin, USA

Otrimati the consultation on medturism

lykuvannya

Cіlі lіkuvannya:
Reaching and reducing the level of platelets, necessary for the preparation of adequate hemostasis.

tactics of addiction:
Non-drug treatment:
mode: general protection, unique trauma.
dієta:№ 15.

Drug treatment:
Vibir of therapy is guilty of negotiating with the patient and vrahovuvati maybutny operatively, I can beat the choice of drugs and tied to the health of life.

Likuvannya for the first time diagnostics of ITP:
Likuvannya of patients for the first time diagnosed with ITP is carried out with platelets less than 30 × 10 9 / l.

The first line of therapy
Prior to the first line of therapy, take glucocorticoids, Anti-D immunoglobulin human and internal blood plasma of humans ( level of proofD).

Glucocorticosteroids. Appointment of corticosteroids to standard clinical treatment of patients with immune thrombocytopenia.

Hirurgichesky lіkuvannya:

Splenectomy. On the basis of pediatric patients, it is not planned to have a splenectomy performed earlier than 12 months at the time of the diagnosis, for older patients, when there is an ongoing disease, it is recommended to take therapy. ... Laparoscopic and laparotomic splenectomy is, however, equally effective, although it is updated in the operative period more often than for laparoscopic splenectomy. (Level of evidence C)

Preparations (such as speech), which can become stagnant during treatment

A group of drugs in the absence of ATC, which can become stagnant in case

hospitalization

Indicated for hospitalization:
Indicated for the emergency hospital:
· Immune thrombocytopenia and / or the presence of hemorrhagic syndrome have been detected.

Indicated for planned hospitalization:
· Carrying out splenectomy.

prophylaxis

Prophylactic come in: dumb.

information

Dzherela and Literature

1. Protocols to send the Expert for the sake of RCHRH MHSD RK, 2015
   1. List of victorious literature: 1. Scottish Intercollegiate Guidelines Network (SIGN). SIGN 50: a guideline developer's handbook. Edinburgh: SIGN; 2014. (SIGN publication no. 50). ... Available from URL: http://www.sign.ac.uk. 2. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia Cindy Neunert, Wendy Lim, Mark Crowther, Alan Cohen, Lawrence Solberg, Jr and Mark A. Crowther 2011; 16: 4198-4204 3. Hematology; New assistant. Read the in-house editorial office of the Doctor of Medical Sciences. Professori K.M. Abdulkadirova. Moscow: Vidavnitstvo Exmo; St. Petersburg: Vidavnitstvo Sova, 2004; 414-422. 4. Mashhadi MA, Kaykhaei MA, Sepehri Z, Miri-Moghaddam E. Single course of high dose dexamethasone is more effective than conventional prednisolone therapy in the treatment of primary newly diagnosed immune thrombocytopenia. Daru. 2012 Aug 28; 20 (1): 7.doi: 10.1186 / 2008-2231-20-7 5. Nakazaki K, Hosoi M, Hangaishi A, Ichikawa M, Nannya Y, Kurokawa M Comparison between pulsed high-dose dexamethasone and daily corticosteroid therapy for adult primary immune thrombocytopenia: a retrospective study. Intern Med. 2012; 51 (8): 859-63. Epub 2012 Apr 15. 6. Van der Meer JW, van Beem RT, Robak T, Deptala A, Strengers PF Efficacy and safety of a nanofiltered liquid intravenous immunoglobulin product in patients with primary immunodeficiency and idiopathic thrombocytopenic purpura. Vox Sang. 2011 Aug; 101 (2): 138-46. doi: 10.1111 / j.1423-0410.2011.01476.x. Epub 2011 Mar 29. 7. Robak T, Mainau C, Pyringer B, Chojnowski K, Warzocha K, Dmoszynska A, Straub J, Imbach P. Efficacy and safety of a new intravenous immunoglobulin 10% formulation (octagam® 10%) in patients with immune thrombocytopenia. Hematology. 2010 Oct 15 (5): 351-9. doi: 10.1179 / 102453310X12719010991867. 8. Montalvo J1, Velazquez D, Pantoja JP, Sierra M, López-Karpovitch X, Herrera MF. Laparoscopic splenectomy for primary immune thrombocytopenia: clinical outcome and prognostic factors. J Laparoendosc Adv Surg Tech A. 2014 Jul; 24 (7): 466-70. doi: 10.1089 / lap.2013.0267. Epub 2014 Jun 6. 9. Moulis G1, Lapeyre-Mestre M, Mahévas M, Montastruc JL, Sailler L. Need for an improved vaccination rate in primary immune thrombocytopenia patients exposed to rituximab or splenectomy. A nationwide population-based study in France. Am J Hematol. 2015 Apr; 90 (4): 301-5. doi: 10.1002 / ajh.23930. Epub 2015 Mar 2. 10. Carpenedo M, Cantoni S, Coccini V, Fedele M, Morra E, Pogliani EM. Feasibility of romiplostim discontinuation in adult thrombopoietin-receptor agonist responsive patients with primary immune thrombocytopenia: an observational retrospective report in real life clinical practice. Hematol Rep. 2015 Feb 24; 7 (1): 5673.doi: 10.4081 / hr.2015.5673. eCollection 2015.11 Mahévas M1, Fain O, Ebbo M, Roudot-Thoraval F, Limal N, Khellaf M, Schleinitz N, Bierling P, Languille L, Godeau B, Michel M. The temporary use of thrombopoietin-receptor agonists induce a prolonged remission in adult chronic immune thrombocytopenia. Results of a French observational study. Br J Haematol. 2014 Jun; 165 (6): 865-9. doi: 10.1111 / bjh.12888. Epub 2014 Apr 12. 12. Decroocq J1, Marcellin L, Le Ray C, Willems L. Rescue therapy with romiplostim for refractory primary immune thrombocytopenia during pregnancy. Obstet Gynecol. 2014 Aug; 124 (2 Pt 2 Suppl 1): 481-3. doi: 10.1097 / AOG.0000000000000371 13. Song T.B. et al. // Fetal Diagn Ther. 1999. Vol. 14 (4) P. 216-219.

information

List of Proceedings in the Protocol from the Values ​​of Qualitative Tributes:

1) Kemaykina Vadim Matviyovich - Candidate of Medical Sciences, AT "National Science Center of Oncology and Transplantology", head of oncohematology and cystic brain transplantation.
2) Klodzinsky Anton Anatoliyovich - Candidate of Medical Sciences, AT "National Science Center of Oncology and Transplantology", a hematologist in the field of oncohematology and transplantation of the cystic brain.
3) Ramazanova Raigul Mukhambetovna - Doctor of Medical Sciences, Professor of AT "Kazakh Medical University of Uninterrupted Education", supervising the course of hematology.
4) Gabbasova Sauli Telembaevna - RSE at the REM "Kazakh Science and Preceding Institute of Oncology and Radiology", depending on hematological malignancies.
5) Karakulov Roman Karakulovich - Doctor of Medical Sciences, Professor, Academician of the MAI RSE at the RGP "Kazakh Science-Preceding Institute of Oncology and Radiology" is the leading scientific specialist in the diagnosis of hemoblastosis.
6) TABARI Adlet Berikbolovich - Head of the Department of Innovative Management of the Republican State Enterprise on the REM "Likarnya to the Medical Center of the Office on the Right of the President of the Republic of Kazakhstan", a clinical pharmacologist.
7) Rapilbekova Gulmira Kurbanovna, Doctor of Medical Sciences. AT "National Science Center of Motherhood and Childhood" - the head of obstetric departments №1.

Ordering for the presence of a conflict of interest:Відсутнє.

reviewer:
1) Afanas'ev Boris Volodimirovich - Doctor of Medical Sciences, Director of the Scientific and Pre-Slavic Institute of Child Oncology, Hematology and Transplantology imeni R.M. Gorbachovo, Head of the Department of Hematology, Transfusiology and Transplantology of the State Budgetary Educational Foundation of the First St. Petersburg State Medical University. I.P. Pavlova.
2) Rakhimbekova Gulnar Ayapbekkizi - Doctor of Medical Sciences, Professor, AT "National Scientific Medical Center"
3) Iryna Oleksiyivna Pivovarova - Medicinae Doctor, Master of Business Administration, Head postnatal hematologist of the Ministry of Health Protection and Social Development of the Republic of Kazakhstan.

Letting the minds look at the protocol: re-examination of the protocol in 3 ways і / or with the appearance of new methods of diagnostics і / аlіkuvannya with a higher level of proof.

Attached files

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