Thrombocytopenic purpura in children. Idiopathic thrombocytopenic purpura in children
Idiopathic thrombocytopenic purpura (Werlhof's disease) - causes, symptoms, diagnosis, treatment
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Idiopathic thrombocytopenic purpura(Werlhof's disease) refers to hemorrhagic diathesis with a change (decrease) in the number of platelets ( thrombocytopenia).Typically, thrombocytopenic purpura first develops in children aged 2-6 years (up to 10 years), regardless of gender. In adults, the disease is not as common, and women are more likely to suffer from it.
Characteristic of this disease is a decrease in the number of platelets in the blood serum below the level of 100 x10 9 /l against the background of sufficient formation in the bone marrow, and the presence of antibodies on the surface of platelets and in the blood that cause their destruction.
Depending on the duration and cyclicity of the course of the disease, there are several forms of thrombocytopenic purpura:
1.
Spicy.
2.
Chronic.
3.
Recurrent.
The acute form is characterized by an increase in the level of blood platelets of more than 150x10 9 /l within 6 months from the date of development of the disease, in the absence of relapses (repeated cases of the disease) subsequently. If recovery of platelet levels is delayed for more than 6 months, a diagnosis of chronic thrombocytopenic purpura is made. When their number decreases below normal again after their recovery, recurrent thrombocytopenic purpura occurs.
Causes of thrombocytopenic purpura
The exact cause of the development of thrombocytopenic purpura has not been established. It is believed that this disease can manifest itself within about 3 weeks after: 1. Previous viral or bacterial infection (HIV infection, infectious mononucleosis, chicken pox).
2. After vaccination (BCG).
3. Hypothermia or excessive sun exposure.
4. Injuries and surgical interventions.
5. As a result of using certain medications:
- Rifampicin;
- Vancomycin;
- Bactrim;
- Carbamazepine;
- Diazepam;
- Sodium valproate;
- Methyldopa;
- Spironolactone;
- Levamisole;
Symptoms
With this disease, there is the appearance of a spotted bruise on the skin and hemorrhages in the mucous membranes. Elements of the rash can be of varying sizes, externally resemble bruises, are painless when pressed, are located asymmetrically, and can appear without trauma, most often at night. The color of the rash varies: from bluish to yellow. Hemorrhages can occur not only on the mucous membranes of the oral cavity and tonsils, but also in the eardrum, vitreous body, sclera and fundus of the eye. Rarely, cerebral hemorrhage is possible, which significantly worsens the patient’s condition. This is preceded by the appearance of dizziness and headache, as well as bleeding in other organs.
When the platelet level decreases to less than 50x10 9 /l, nosebleeds and gum bleeding appear, which are more dangerous when a tooth is removed. In this case, bleeding occurs immediately and usually does not resume after it stops. In teenage girls with thrombocytopenic purpura, uterine bleeding during menstruation poses a certain danger.
Stages of thrombocytopenic purpura
1. Hemorrhagic crisis – characterized by severe bleeding and a bruised rash, changes in the general blood test (thrombocytopenia, decreased hemoglobin levels).2. Clinical remission – there are no visible clinical manifestations, but changes in the blood persist.
3. Clinical and hematological remission – restoration of laboratory blood parameters against the background of the absence of visible manifestations of the disease.
Diagnostics
When diagnosing idiopathic thrombocytopenic purpura, differential diagnosis is carried out with various blood diseases (infectious mononucleosis, leukemia, microangiopathic hemolytic anemia, systemic lupus erythematosus, thrombocytopenia while taking medications, and others).The examination complex includes the following diagnostic procedures:
- complete blood count with platelet count;
- determination of antiplatelet antibodies in the blood and Coombs test;
- bone marrow puncture;
- determination of APTT, prothrombin time, fibrinogen level;
- biochemical blood test (creatinine, urea, ALT, AST);
- Wasserman reaction, determination of antibodies to the Epstein-Barr virus, parvovirus in the blood.
Thrombocytopenic purpura in children
Idiopathic thrombocytopenic purpura (ITP) develops in children between 2 and 8 years of age. Boys and girls have an equal risk of developing this pathology. ITP begins in children acutely after infectious diseases (infectious mononucleosis, bacterial infectious diseases, chickenpox), vaccination, or trauma. It should be noted that the incidence begins seasonally: more often in the spring. In children under 2 years of age, the infantile form of thrombocytopenic purpura is registered. In this case, the disease begins acutely, without the presence of a previous infection, and is extremely difficult: the platelet level drops below 20x10 9 /l, treatment is ineffective, and the risk of chronicity of the disease is very high.
The clinical manifestations of ITP depend on platelet levels. The onset of the disease is characterized by the appearance of spotty-bruised rashes on the skin and mild hemorrhages on the mucous membranes. When the platelet level decreases to less than 50 x10 9 /l, various bleedings may occur (nasal, gastrointestinal, uterine, kidney). But most often, large “bruises” in places of contusions attract attention; there may be hematomas during intramuscular injections (injections). An enlarged spleen is characteristic. A general blood test reveals thrombocytopenia (decreased platelets), eosinophilia (increased number of eosinophils), anemia (decreased hemoglobin).
Treatment
If the patient does not have bleeding from the mucous membranes, the bruises are moderate, and the level of platelets in the blood is at least 35x10 9 /l, then treatment is usually not required. It is recommended to avoid possible injury and avoid engaging in contact sports (any type of wrestling).Treatment of idiopathic thrombocytopenic purpura is aimed at reducing the production of antiplatelet antibodies and preventing their binding to platelets.
Diet for thrombocytopenic purpura
As a rule, no special diet is required. It is recommended to exclude legumes from the diet, as it is believed that their consumption may reduce the level of platelets in the blood. If there is bleeding in the oral cavity, food is served chilled (not cold) to reduce the risk of trauma to the mucous membrane.Drug therapy
1.
Glucocorticosteroids.
Hormonal drugs are prescribed orally as follows:
- The general dose is prednisolone at a dose of 1-2 mg/kg per day for 21 days, then the dose is gradually reduced until completely discontinued. A repeat course is possible in a month.
- In high doses - prednisolone at a dose of 4-8 mg/kg per day is taken for a week, or methylprednisolone at a dose of 10-30 mg/kg per day, with rapid subsequent withdrawal of the drug, a second course is carried out after 1 week.
- "Pulse therapy" with hydrocortisone - 0.5 mg/kg per day, taken 4 days after 28 days (the course is 6 cycles).
With long-term use and individually, each patient may experience side effects from taking glucocorticoids: an increase in blood glucose levels and a decrease in potassium levels, stomach ulcers, decreased immunity, increased blood pressure, growth retardation.
2. Immunoglobulins for intravenous administration:
- Normal human immunoglobulin for intravenous administration;
- Intraglobin F;
- Octagam;
- Sandoglobulin;
- Venoglobulin, etc.
With the use of immunoglobulins, headaches, allergic reactions, increased body temperature to high levels and chills may occur. To reduce the severity of undesirable effects, Paracetamol and Diphenhydramine are prescribed orally, and Dexamethasone intravenously.
3.
Interferon alpha.
Indicated for chronic purpura in case of ineffective treatment with glucocorticoids. 2x106 units of interferon-alpha are injected under the skin or into the muscle for a month, 3 times a week, every other day.
Often during treatment with interferon appear
Hematologist
Higher education:
Hematologist
Samara State Medical University (SamSMU, KMI)
Level of education - Specialist
1993-1999
Additional education:
"Hematology"
Russian Medical Academy of Postgraduate Education
Every childhood illness causes genuine concern among loving parents. What if it's not a common cold? Frequent hemorrhages and varying degrees of bleeding are a serious problem. In most cases, they are caused by manifestations of thrombocytopenic purpura - an inadequate immune response of the body to its own platelets.
The essence of pathology
Thrombocytopenic purpura (Werlhof's disease) indicates a deficiency of platelets responsible for blood clotting. The child’s body perceives platelets as foreign agents and eliminates them, turning on the immune system. Loss of platelets disrupts the blood clotting process and promotes bleeding. Blood vessels become thinner and lose elasticity. This condition causes:
- hemorrhages (from minor pinpoint to large-scale hematomas);
- ischemic vascular lesions (formed blood clots disrupt blood flow in the brain and internal organs).
The disease may be:
- acute (lasts from a month to six months, usually ends with recovery);
- chronic (lasts more than six months, exacerbations alternate with remissions).
With minor pauses between remissions, we are talking about a continuously relapsing form of the disease. According to the mechanisms of progression, several types of thrombocytopenic purpura are distinguished:
- Autoimmune – a consequence of another pathology combined with damage to the immune system (hemolytic anemia, lupus erythematosus);
- Neonatal - the result of the entry of the corresponding antibodies of the mother into the fetus during intrauterine development;
- Alloimmune – caused by incompatibility of mother and fetus in platelet antigens;
- Heteroimmune - develops with structural changes in platelets caused by exposure to a virus or foreign antigen.
- Idiopathic – occurs for unknown reasons;
- Symptomatic (non-immune) – observed in certain diseases (infections, anemia, leukemia).
Causes of thrombocytopenic purpura
Purpura has no genetic “links”; it is an acquired disease. Pathology can be caused by:
- injury;
- surgical intervention;
- infection;
- taking certain medications;
- carrying out certain preventive vaccinations.
More often, thrombocytopenic purpura develops in children against the background of existing diseases (endocarditis, malaria) or after previous diseases (influenza, chicken pox, measles, whooping cough). Cases of the disease have been reported after influenza vaccination.
There are a number of factors that influence decreased platelet secretion in children:
- cancerous tumors in the nervous system;
- chromosomal pathologies;
- general disorders of the hematopoietic process;
- intrauterine intoxication with nitrofurans, diuretics, antidiabetic and hormonal drugs;
- severe gestosis accompanying the mother's pregnancy;
- premature birth.
Symptomatic thrombocytopenic purpura indicates the development of chronic systemic pathology.
Manifestations of the disease
Thrombocytopenic purpura in children manifests itself:
- hemorrhagic diathesis;
- external bleeding and internal bleeding.
In both cases, multiple hematomas appear on the child’s skin; their color ranges from yellowish-green to purple. Bruises are localized in the bends of the elbows, knees, on the face, neck, chest, abdomen and are more noticeable in the morning. The second form of pathology, in addition, is characterized by frequent nosebleeds, bleeding of mucous membranes, and redness of the whites of the eyes. Manifestations of pathology in children are characterized by:
- asymmetry, multicolor, unpredictability;
- discrepancy between the intensity of external influences;
- manifold.
The most serious, but extremely rare consequence of the pathology is hemorrhage in the brain area. It is accompanied by:
- dizziness and headaches;
- vomiting;
- muscle spasms;
- signs of meningitis;
- neurological symptoms;
- coma.
Diagnosis of pathology
When diagnosing thrombocytopenic purpura, the type of bleeding and provoking factors are determined. The doctor is interested in previously observed cases of bleeding in a young patient and his immediate family.
A physical examination reveals concomitant diseases (anomalies in the development of organs and tissues). In most cases, a pinch test and a cuff test are performed. An exception is the presence of generalized cutaneous hemorrhagic syndrome, bleeding of mucous membranes and the child’s age is less than three years. Additional diagnostic measures include:
- general blood test (determining the concentration of blood platelets and red blood cell precursors);
- taking a bone marrow sample and assessing myelogram (megakaryocyte concentration);
- blood test for the presence of antibodies, viruses, immunoglobulins;
- urine analysis;
- chest x-ray;
- chromosome set assessments;
- Ultrasound examination of the thyroid gland, peritoneal organs.
Before the puncture, the child is given sedatives, since increased intracranial pressure can cause cerebral hemorrhage. If indicated, the morphology and functionality of blood platelets in a young patient and his family members are examined, and blood clotting indicators are assessed. When diagnosing idiopathic thrombocytopenic purpura in children, specialists face a difficult task: it is necessary to exclude pathologies with similar manifestations:
- hereditary nephritis;
- Roberts syndrome;
- hypoplastic form of thrombocytopenic purpura of newborns;
- Gasser's disease;
- thrombohemorrhagic syndrome;
- anemia caused by vitamin B12 deficiency;
- cancerous blood pathologies;
- helminth infection.
Therapy of thrombocytopenic purpura in children
If the pathology is accompanied by complications, urgent treatment is required at any concentration of platelets in the blood plasma. In the absence of complications, the decision on the need for therapy is made by a hematologist. The duration of thrombocytopenic purpura is influenced by the lifespan of antibodies to platelets - from 4-6 weeks to six months.
If there is no bleeding, the young patient is usually monitored without treatment. Under such circumstances, subcutaneous hemorrhages disappear within 7-10 days. The platelet count in the blood gradually normalizes. For minor hemorrhages and mild thrombocytopenia in newborns, symptomatic treatment is prescribed (calcium pantothenate, sodium ethamsylate).
For any symptoms of skin hemorrhage, the child is admitted to the hospital. In the acute phase of the disease, mandatory bed rest is indicated to avoid accidental injury. As the intensity of hemorrhage decreases, the restrictions on bed rest are expanded. A young patient is prescribed glucocorticosteroid therapy. They relieve increased sensitivity of the body, suppress unwanted immune reactions, and have anti-inflammatory and anti-allergic effects. At the same time, the platelet concentration increases.
To assess the effectiveness of therapy, the level of antibodies to platelets in the blood is examined. When treating anemia that has developed in children due to blood loss, drugs that stimulate hematopoietic processes are indicated. Transfusion of individually selected washed red blood cells is carried out only in cases of severe anemia in an acute form.
Splenectomy
Complete or partial removal of the spleen is indicated:
- with life-threatening blood loss;
- with intractable blood loss;
- when the concentration of blood platelets drops below 30 thousand/µl.
In children with a chronic form of the disease, splenectomy is performed if stable remission does not occur after several courses of glucocorticosteroid therapy. If the planned surgical intervention was carried out strictly according to indications, remission is observed in 98% of young patients.
Necessary diet
The diet of a child with immune thrombocytopenic purpura should be complete. Typically, experts recommend dietary table No. 5. Glucocorticosteroids promote weight loss and affect mineral metabolism, so children need foods high in calcium salts and proteins. It is necessary to consume foods enriched with vitamins C, A, and P. Dishes containing vinegar and canned food should be excluded from the diet - they may contain aspirin. Vinegar and aspirin reduce the functional ability of blood platelets.
Food allergens can increase the severity of thrombocytopenia; they should also be excluded from the menu. With anemia that develops as a result of blood loss and severe bleeding, the child needs to drink plenty of fluids. Food should be taken in small portions, chilled. Puree dishes are preferred. For neonatal thrombocytopenic purpura, the baby should be given donor milk for two to three weeks. Then breastfeeding is allowed, but with monitoring of the content of blood platelets in the patient’s blood.
Prevention of pathology
Dynamic monitoring of a small patient with acute thrombocytopenic purpura is carried out for five years. The chronic form of the pathology implies similar observation until the child is transferred to an adult clinic based on age. In case of pronounced bleeding, the child’s movement regime is limited - in order to avoid injury, even outdoor games are prohibited.
Immune thrombocytopenia in children that is not accompanied by bleeding does not require therapy. If the child is active, for prevention he should alternately undergo a course of herbal medicine and take angioprotective agents (traumeel, dicynon, ascorutin). For herbal medicine the following is used:
- water pepper;
- harelip;
- strawberries;
- St. John's wort;
- nettle;
- shepherd's purse;
- yarrow.
The decision to use angioprotectors and herbs for prevention should be made by a specialist. The components of the herbal collection depend on the child’s concomitant diseases. In addition, you must:
- exclude the use of aspirin, anticoagulants, antiplatelet agents, nitrofurans;
- refuse physical therapy using UHF and UV radiation;
- for three to five years, refrain from moving to a region with different climatic conditions;
- with minor bleeding and platelet levels less than 100 thousand/µl, avoid intramuscular infusions;
- carry out routine medical examinations to identify chronic infections and cure them;
- prevent viral diseases;
- carry out preventive vaccinations only during remission.
Features of the course of the disease in children
Children with thrombocytopenic purpura attend school and participate in games just like healthy children. Restrictions apply only to acute situations, when the level of blood platelets decreases to 20 thousand/µl. Under such circumstances, the child should be protected from injury by temporarily protecting him from active movements. A decrease in platelet count to a level of 10 thousand/μl is an indication for immediate hospitalization.
If bleeding from the nose occurs, the child should be seated comfortably, firmly pressing the area under the bone on the bridge of the nose with your fingers for 10 minutes. Then the baby needs to be kept calm for another five minutes and warned against participating in active games over the next couple of hours. Urgent medical attention is required by:
- a hematoma that appears after a minor injury and grows rapidly;
- continuous hemorrhage from the nose or gums (after dental manipulations), non-healing scratches, cuts;
- head injury;
- signs of blood in urine, feces and vomit;
- significant swelling after a sprain or dislocation.
Relatives, nannies, educators, and teachers should monitor the development of such manifestations. It is recommended to provide the baby with a small card indicating the diagnosis. A child can participate in sports competitions and active games with appropriate blood test results. When the platelet level is 30-50 thousand/µl, he is allowed to engage in non-contact sports. But even in this case, you should take care of protection: knee pads, helmet, elbow pads.
Treatment of acute forms of thrombocytopenic purpura often leads to complete recovery. The pathology is significantly complicated by the manifestations of serious hemorrhages, including in the ovaries and brain. Chronic forms of purpura occur in waves - phases of exacerbation alternate with persistent remissions. Therapy should eliminate bleeding and anemic manifestations and prevent relapses.
107. Thrombocytopenic purpura in children. Etiology, pathogenesis, classification, clinic, treatment.
Idiopathic (autoimmune) thrombocytopenic purpura is a disease characterized by an isolated decrease in the number of platelets (less than 100,000/mm3) with a normal or increased number of megakaryocytes in the bone marrow and the presence of antiplatelet antibodies on the surface of platelets and in the blood serum, causing increased destruction of platelets.
Prevalence, risk factors and etiology. The frequency of idiopathic thrombocytopenic purpura in children is about 1.5-2 per 100,000 children, without differences by gender, with an equal frequency of acute and chronic forms. In adolescence, the number of sick girls becomes twice as many as boys.
The cause of thrombocytopenic purpura is not precisely established; Among the factors preceding the development of idiopathic thrombocytopenic purpura are viral and bacterial infections (40% of cases), vaccinations and administration of gamma globulin (5.5%), surgeries and injuries (6%); in 45% of cases the disease occurs spontaneously without previous causes. In most patients with idiopathic thrombocytopenic purpura, the premorbid background, physical and psychomotor development do not differ from healthy children.
The term "idiopathic" indicates a spontaneous onset of the disease and a hitherto unidentified etiology.
Pathogenesis of thrombocytopenic purpura. Thrombocytopenia leads to disruption of the platelet hemostasis and contributes to the development of petechial-spotted (microcirculatory) type hemorrhagic syndrome. Thrombocytopenia is accompanied by angiotrophic insufficiency, which causes dystrophic changes in the endothelium of small vessels and capillaries and leads to a decrease in the resistance of the vascular wall and an increase in its porosity for red blood cells. This manifests itself as pinpoint hemorrhages (petechiae) in areas of higher hydrostatic pressure (lower limbs); the number of petechiae can be easily increased by using compression of the limbs with a tourniquet.
Hemorrhagic syndrome in idiopathic thrombocytopenic purpura is characterized by prolonged bleeding from small vessels, due to the inability of platelets to form a platelet plug at sites of endothelial damage. Significant changes occur in the vascular wall and under the influence of the pathoimmune process. Due to the commonality of the antigenic structures of platelets and endothelial cells, endothelial cells are destroyed by antiplatelet antibodies, which enhances the clinical manifestations of hemorrhagic syndrome.
In the pathogenesis of idiopathic thrombocytopenic purpura, the immunopathological synthesis of antiplatelet autoantibodies (IgG) by spleen lymphocytes, which are fixed on various membrane receptors of platelets and megakaryocytes, is of key importance, which confirms the pathoimmune nature of the disease and the hypothesis of primary dysfunction of the lymphoid system in idiopathic thrombocytopenic purpura. As a result of the autoimmune process, platelets lose their adhesive-aggregation properties and quickly die, being absorbed by mononuclear cells in the spleen, and in more severe cases - in the liver and other organs of the reticuloendothelial system (“diffuse” type of sequestration). With the “diffuse” type of platelet sequestration, splenectomy is not effective enough. The half-life of their disappearance is half an hour or less.
In idiopathic thrombocytopenic purpura, although the number of megakaryocytes in the bone marrow increases significantly, they are characterized by functional immaturity (the number of immature forms increases, and the number of functionally active ones decreases).
Idiopathic (autoimmune) thrombocytopenic purpura can be acute, chronic and recurrent. In the acute form, the platelet count is normalized (more than 150,000/mm3) within 6 months after diagnosis without relapse. In the chronic form, thrombocytopenia less than 150,000/mm3 lasts more than 6 months. In the recurrent form, the platelet count decreases again after returning to normal levels. The acute form is more typical for children, and the chronic form for adults.
Due to the fact that idiopathic thrombocytopenic purpura often occurs transiently, the true incidence has not been established. The reported incidence is about 1 per 10,000 cases per year (3-4 per 10,000 cases per year among children under 15 years of age).
As stated above, the pathogenesis of idiopathic thrombocytopenic purpura is based on increased destruction of platelets loaded with autoantibodies by cells of the reticulohistiocytic system. In experiments with labeled platelets, it was found that the lifespan of platelets decreases from 1-4 hours to several minutes. The increase in the content of immunoglobulins (IgG) on the surface of platelets and the frequency of platelet destruction in idiopathic thrombocytopenic purpura are proportional to the level of platelet-associated IgG (PAIgG). The targets of autoantibodies are platelet membrane glycoproteins (Gp): Gp Ilb/IIIa, Gp Ib/IX and Gp V.
People with HLA phenotype B8 and B12 have an increased risk of developing the disease if they have precipitating factors (antigen-antibody complexes).
The peak incidence of idiopathic thrombocytopenic purpura occurs between the ages of 2 and 8 years, with boys and girls affected with equal frequency. In children under 2 years of age (infantile form), the disease is characterized by an acute onset, a severe clinical course with the development of deep thrombocytopenia less than 20,000/mm3, a poor response to exposure and frequent chronicity of the process - up to 30% of cases. The risk of the onset of chronic idiopathic thrombocytopenic purpura in children is also increased in girls over 10 years of age with a disease duration of more than 2-4 weeks before diagnosis and a platelet count of more than 50,000/mm3.
In 50-80% of cases, the disease occurs 2-3 weeks after an infectious disease or immunization (smallpox, live measles vaccine, etc.). Most often, the onset of idiopathic thrombocytopenic purpura is associated with nonspecific infections of the upper respiratory tract, in approximately 20% of cases - specific (measles rubella, measles, chicken pox, whooping cough, mumps, infectious mononucleosis, bacterial infections).
Symptoms of idiopathic thrombocytopenic purpura depend on the severity of thrombocytopenia. Hemorrhagic syndrome manifests itself in the form of multiple petechial bruises on the skin and hemorrhages on the mucous membranes. Since petechiae (1-2 mm), purpura (2-5 mm) and ecchymoses (more than 5 mm) can also accompany other hemorrhagic conditions, the differential diagnosis is based on the number of platelets in the peripheral blood and the duration of bleeding.
Bleeding occurs when the platelet count decreases to less than 50,000/mm3. The threat of serious bleeding occurs with deep thrombocytopenia less than 30,000/mm3. At the onset of the disease, nasal, gingival, gastrointestinal and renal bleeding are usually uncharacteristic, and vomiting of coffee grounds and melena are rare. Severe uterine bleeding is possible. In 50% of cases, the disease manifests itself in a tendency to form ecchymosis in places of bruises, on the anterior surface of the lower extremities, over bone protrusions. Deep muscle hematomas and hemarthrosis are also not typical, but can be the result of intramuscular injections and extensive trauma. With deep thrombocytopenia, hemorrhages occur in the retina of the eye, and rarely - bleeding in the middle ear, leading to hearing loss. Cerebral hemorrhage occurs in 1% of cases with acute idiopathic thrombocytopenic purpura, in 3-5% of cases with chronic idiopathic thrombocytopenic purpura. It is usually preceded by headache, dizziness and acute bleeding of some other location.
An objective examination can reveal splenomegaly in 10-12% of children, especially young children. In this case, the differential diagnosis is made with leukemia, infectious mononucleosis, systemic lupus erythematosus, and hypersplenism syndrome. There should be no enlargement of the lymph nodes in idiopathic thrombocytopenic purpura, unless it is associated with a previous viral infection.
Secondary thrombocytopenic purpura
As stated earlier, thrombocytopenia can be idiopathic or secondary to a number of known causes. Secondary thrombocytopenia, in turn, can be divided depending on the number of megakaryocytes.
Thrombopoietin deficiency
A rare congenital cause of chronic thrombocytopenia with the appearance of numerous immature megakaryocytes in the bone marrow is thrombopoietin deficiency.
Treatment consists of plasma transfusions from healthy donors or patients with idiopathic thrombocytopenic purpura, which results in increased platelet counts and signs of megakaryocyte maturation, or thrombopoietin replacement.
Laboratory diagnosis of thrombocytopenic purpura
Laboratory examination reveals thrombocytopenia less than 100,000/mm3, an increase in the mean platelet volume (MPV) according to an automatic blood analyzer to 8.9±1.5 μm3.
In the peripheral blood of patients with idiopathic thrombocytopenic purpura, in addition to thrombocytopenia, there may be moderate eosinophilia. With severe blood loss, anemia develops.
In bone marrow puncture, which is carried out to exclude other oncohematological diseases, irritation of the megakaryocyte lineage and weak “lacing” of platelets with normal erythroid and myeloid lineages are found. Some patients exhibit moderate eosinophilia.
When studying the coagulation profile, which is optional in standard idiopathic thrombocytopenic purpura, an increase in bleeding time, a decrease or absence of clot retraction, and impaired prothrombin utilization with normal levels of fibrinogen, prothrombin time and activated partial thromboplastin time are revealed.
Laboratory tests in patients with thrombocytopenia include:
complete blood count with smear and determination of platelet count;
bone marrow puncture examination;
blood test for ANF, anti-DNA, complement fractions C3, C4, antiplatelet antibodies, plasma glycocalycin level, Coombs test;
determination of prothrombin time, activated partial thromboplastin time, fibrinogen level, fibrinogen breakdown products;
determination of urea, blood creatinine, liver tests;
blood test for opportunistic infections (HIV, Epstein-Barr virus, parvovirus);
exclusion of secondary forms of thrombocytopenia.
The main criteria for diagnosing idiopathic thrombocytopenic purpura are:
absence of clinical signs of systemic and oncohematological diseases;
isolated thrombocytopenia with normal numbers of red and white blood cells;
normal or increased number of megakaryocytes in the bone marrow with normal erythroid and myeloid elements;
exclusion of secondary forms of thrombocytopenia in hypersplenism, micro-angiopathic hemolytic anemia, DIC syndrome, drug-induced thrombocytopenia, systemic lupus erythematosus, viral infections (Epstein-Barr virus, HIV, parvovirus).
Since the pathogenesis of idiopathic thrombocytopenic purpura is based on the destruction of platelets loaded with autoantibodies by cells of the reticulohistiocytic system, the main principles of treatment of thrombocytopenic purpura are:
decreased production of autoantibodies;
impaired binding of autoantibodies to platelets;
elimination of destruction of platelets sensitized by antibodies by cells of the reticulohistiocytic system.
In the absence of bleeding from the mucous membranes, mild ecchymosis after bruises, and a platelet count of more than 35,000/mm3, treatment is usually not required. Patients should avoid contact sports. Menstruating girls benefit from long-acting progesterone medications (Depo-Provera and others) to delay menstruation for several months in order to prevent intense uterine bleeding.
Glucocorticoids
Mechanism of action
Inhibition of phagocytosis of platelets with antibodies fixed on their surface in the spleen.
Impaired antibody production.
Impaired binding of autoantibodies to antigen.
Indications
Bleeding from mucous membranes; severe purpura and abundant hematomas at the sites of bruises, especially on the head and neck; progressive purpura; thrombocytopenia for more than 3 weeks; recurrent thrombocytopenia; platelet count less than 20,000/mm3 in primary patients with minimal purpura.
Administration modes
Standard doses of oral corticosteroids are prednisolone 1-2 mg/kg per day or 60 mg/m2 per day for 21 days with gradual withdrawal. The dose is reduced regardless of the platelet count, remission is assessed at the end of the course. In the absence of remission or a decrease in the platelet count after reaching normal levels, glucocorticoid exposure is not continued. In the absence of a complete hematological response during a standard course of corticosteroids, prednisolone is discontinued in an “intermittent course” (5 mg every other day after the break). It is possible to repeat the course of corticosteroids after 4 weeks. Long-term use of corticosteroids for idiopathic thrombocytopenic purpura is undesirable, as it can lead to depression of thrombocytopoiesis.
High doses of oral corticosteroids 4-8 mg/kg per day for 7 days or 10-30 mg/kg per day methylprednisolone for 3-7 days with rapid drug withdrawal. A week later the courses are repeated (2-3 courses).
High doses of parenteral corticosteroids 10-30 mg/kg per day methylprednisolone or solumedrol 500 mg/m2 per day intravenously for 3-7 days in severe cases for faster relief of hemorrhagic syndrome. If further treatment is necessary, the patient is transferred to standard doses orally.
For steroid-resistant patients with idiopathic thrombocytopenic purpura, “pulse therapy” with dexamethasone is possible - 6 cycles of 0.5 mg/kg per day (maximum 40 mg/day) for 4 days every 28 days, taken orally.
The effectiveness of taking cotricosteroids, according to various authors, is 50-80%. Side effects when using them: symptoms of hypercorticism, peptic ulcer, hyperglycemia, hypertension, increased risk of infection, myopathy, hypokalemia, steroid psychosis, ovarian dysfunction in girls, growth retardation.
Intravenous immunoglobulin
Mechanism of action:
reversible blockade of macrophage Fc receptors;
suppression of autoantibody synthesis by B lymphocytes;
protection of platelets and/or megakaryocytes from antibodies;
modulation of helper and suppressor activity of T lymphocytes;
suppression of complement-dependent tissue damage;
recovery from persistent viral infections due to the introduction of specific antibodies.
Indications for acute idiopathic thrombocytopenic purpura:
if possible, first-line exposure;
neonatal symptomatic immune thrombocytopenia;
children under 2 years of age who are resistant to corticosteroids.
Modern intravenous immunoglobulin (IVIG) preparations must meet WHO requirements defined in 1982: at least 1000 units of blood, at least 90% immunoglobulin G, native immunoglobulin G (high Fc fragment activity), normal division of immunoglobulin G into subclasses, physiological half-life . In addition, IVIGs should have low anticomplementary activity and dual virus inactivation (pure immunoglobulin G).
Intravenous immunoglobulin administration regimens
For acute idiopathic thrombocytopenic purpura - a total dose of 1-2 g/kg per course according to the scheme: 400 mg/kg per day for 5 days or 1 g/kg per day for 1-2 days. Children under 2 years of age can more easily tolerate a 5-day protocol for taking drugs of the 1st and 2nd generations.
For chronic idiopathic thrombocytopenic purpura - an initial dose of 1 g/kg per day for 1-2 days, then single infusions at a dose of 0.4-1 g/kg, depending on the response, to maintain a safe platelet level (more than 30,000/ mm3). It is useful to combine the use of IVIG with alternating courses of corticosteroids.
Response to exposure in patients with acute idiopathic thrombocytopenic purpura occurs in 80-96.5% of cases. Compared with corticosteroids, platelet counts increase more rapidly during bleeding episodes of comparable duration. About 65% of children with idiopathic thrombocytopenic purpura resistant to corticosteroids achieve long-term remission after a course of IVIG.
Side effects of IVIG drugs:
anaphylactic reactions (in patients with reduced IgA levels);
headache (20% of cases);
fever with chills (1-3% of cases);
hemolytic anemia with a positive Coombs test.
The scientific literature described a case of the development of aseptic meningitis after IVIG infusion, as well as infection of IVIG recipients (Gammagard\Baxter) with the hepatitis C virus, but since 1994, after the improvement of drug production technology, such situations have no longer occurred.
Prophylactic administration of paracetamol (10-15 mg/kg every 4 hours) and diphenhydramine (diphenhydramine) (1 mg/kg every 6-8 hours) reduces the frequency and severity of fever with chills, and intravenous administration of dexamethasone at a dose of 0.15-0. 3 mg/kg helps relieve headaches during IVIG infusions.
Combined use of glucocorticoids and intravenous immunoglobulin
Indications:
bleeding from mucous membranes;
extensive petechiae, purpura and ecchymoses;
symptoms and/or signs of internal bleeding, especially intracranial bleeding.
Combined use causes a more rapid increase in platelet counts than either drug alone. It is used for life-threatening bleeding and in preparation for surgery. In emergency cases, methylprednisolone 30 mg/kg per day for 3 days or solumedrol at a dose of 500 mg/m2 can be used as a glucocorticoid.
Anti-RhD immunoglobulins
Mechanism of action:
blockade of macrophage Fc receptors by antibody-loaded erythrocytes;
suppression of the formation of antiplatelet antibodies;
immunomodulatory effect.
Conditions for use in idiopathic thrombocytopenic purpura are RhD-positive non-splenectomized patients.
Anti-RhD immunoglobulin preparations: “WinRho” (Winnipeg, Manitoba, Canada), “NABI” (Boca Ration, FL, USA), “Partogamma” (Biagini, Pisa, Italy), “Resogam” (Genteon Pharma, Germany) .
Administration mode:
the optimal course dose is 50 mcg/kg per course in the form of a single intravenous infusion or fractional intramuscular administration over 2-5 days;
if the hemoglobin concentration in the patient’s blood is less than 100 g/l, the dose of the drug is 25-40 mcg/kg per course, with hemoglobin 100 g/l - 40-80-100 mcg/course;
repeated courses of anti-D immunoglobulin at intervals of 3-8 weeks to maintain platelet counts above 30,000/mm3.
The platelet count and hemoglobin level are monitored 3-4 days after the start of exposure. The absence of a hematological response to the first course of anti-D immunoglobulin is not a contraindication for a second course, since 25% of patients who do not respond to treatment achieve a hematological response when the drug is repeated. Among patients resistant to corticosteroids, 64% achieve remission after a course of anti-D immunoglobulin. A significant increase in the number of platelets is noted 48 hours after administration of the drug, so it is not recommended for use in life-threatening situations.
Adverse reactions:
flu-like syndrome (fever, chills, headache);
a drop in hemoglobin and hematocrit levels due to hemolysis, confirmed by a positive Coombs test.
There have been no cases of viral infection with the use of anti-D immunoglobulin preparations. Acute allergic reactions are unlikely. IgE-mediated and immune complex-induced allergic reactions have been described. Allergic reactions have not been described in patients with IgA deficiency. Hemolysis is usually extravascular. In the few cases of intravascular hemolysis described, chronic renal failure did not develop. The average decrease in hemoglobin levels is 5-20 g/l and can be short-term (1-2 weeks).
The use of anti-RhD immunoglobulin is safe, convenient, cheap and effective in 79-90% of patients with chronic idiopathic thrombocytopenic purpura, more often in children than in adults.
Interferon-alpha
Interferon alfa-2b may be used in the treatment of patients with chronic idiopathic thrombocytopenic purpura who are refractory to corticosteroids. Hematologic response is achieved in 72% of patients, including 33% of non-responders to corticosteroids.
Mechanism of action in idiopathic thrombocytopenic purpura: suppression of autoantibody production due to the inhibitory effect of interferon-alpha-2b on the production of immunoglobulins by B lymphocytes.
Administration mode: 0.5-2x106 units, depending on age, subcutaneously or intramuscularly 3 times a week (usually Monday-Wednesday-Friday) for 1-1.5 months. Hematological response is noted on the 7-39th day from the start of treatment. In the absence of a hematological response, treatment is stopped; if present, it is continued for up to 3 months. After completion of the course, the drug is either discontinued or prescribed in a maintenance dose, reducing the frequency of administration to 1-2 times a week (selected individually). If the disease relapses (usually 2-8 weeks after the end of use), a second course is indicated, which has the same effectiveness. The duration of maintenance treatment with interferon alfa-2b in the presence of hematological response has not been determined.
Side effects: flu-like syndrome (fever, chills, headache, myalgia), pain and redness at the injection site, liver toxicity, inhibition of myelopoiesis (at doses exceeding 2x106 units), depression in adolescents.
To reduce the severity of side effects (flu-like syndrome), prophylactic administration of paracetamol is recommended before the first administration of the drug.
Danazol is a synthetic androgen with weak virilizing activity and immunomodulatory effects (restoration of T-suppressor function).
The mechanism of action of danazol in idiopathic thrombocytopenic purpura:
modulates the expression of Fc-gamma receptors on mononuclear phagocytes and prevents the destruction of platelets loaded with antibodies;
suppresses the production of autoantibodies;
has synergism with corticosteroids, promotes the release of steroids from connection with globulins and increases their access to tissues.
Administration mode:
10-20 mg/kg per day orally (300-400 mg/m2) in 2-3 doses for 3 months or more to stabilize the effect.
Side effects:
acne, hirsutism, weight gain, liver toxicity.
Hematologic response occurs in approximately half of children with chronic idiopathic thrombocytopenic purpura, including those refractory to corticosteroids. The effectiveness of treatment increases after splenectomy. In most cases the answer is incomplete.
Vincristine
Vincristine is used at a dose of 0.02 mg/kg (maximum 2 mg) intravenously, weekly, for a total of 4 administrations.
Vinblastine
Vinblastine is used at a dose of 0.1 mg/kg (maximum 10 mg) intravenously, weekly, for a total of 4 injections.
When vincristine and vinblastine are effective, the platelet count increases rapidly, often to normal levels. Most children require repeated doses of the drug at 2-3 week intervals to maintain a safe platelet count. If there is no response to treatment within 4 weeks, further use of drugs is not indicated.
Complete hematological remission within 0.5-4 years is described in approximately 10% of patients, a transient response in half.
Side effects: peripheral neuropathy, leukopenia, alopecia, constipation, necrosis when released into the subcutaneous tissue.
Cyclophosphamide
Cyclophosphamide (cyclophosphamide) is used as an immunosuppressant. Hematological response in patients with chronic idiopathic thrombocytopenic purpura during treatment reaches 60-80% and lasts longer compared to other drugs. Complete hematological response after completion of treatment occurs in 20-40% of cases. The best results are shown in splenectomized patients with a short duration of the disease.
The mechanism of action is the suppression of the proliferation of lymphocytic clones involved in the immune response.
Administration mode: 1-2 mc/kg per day, taken orally. Hematological response is achieved within 2-10 weeks from the start of the course.
Side effects: inhibition of myelopoiesis, alopecia, liver toxicity, hemorrhagic cystitis, leukemia (long-term complication).
Azathioprine
In patients with autoimmune diseases, azathioprine is used as an immunosuppressant. An increase in platelet count is observed in 50% of patients with idiopathic thrombocytopenic purpura, and a complete hematological response is observed in 10-20%.
Administration mode: 1-5 mg/kg per day (200-400 mg). Until the maximum response is achieved, the duration of treatment can be 3-6 months. Since the disease recurs after stopping the use of the drug, maintenance treatment is necessary.
Side effects: anorexia, nausea, vomiting, moderate neutropenia, lymphoma (long-term complication).
The advantage of this drug in children is the lower incidence of tumors compared to cyclophosphamide (cyclophosphamide).
Cyclosporine
Cyclosporine (cyclosporine A) is a non-steroidal immunosuppressant that causes inhibition of cellular immunity. The drug acts on activated T-lymphocyte effectors, suppressing the production of cytokines (interleukin-2, interferon-gamma, tumor necrosis factor).
Administration mode: taken orally at a dose of 5 mg/kg per day for several months. A hematological response is observed 2-4 weeks from the start of treatment in the form of some stabilization of clinical and hematological parameters, a decrease in the level of antiplatelet antibodies. Relapses of the disease occur immediately after discontinuation of the drug.
Side effects: hypomagnesemia, hypertension, liver and kidney toxicity, secondary tumors (long-term complications). The serious side effects and inconclusive effect caused by the use of cyclosporine make its use in idiopathic thrombocytopenic purpura undesirable.
Platelet transfusions
Platelet transfusion is indicated in case of development of neurological symptoms indicating the possibility of intracranial hemorrhage, as well as during surgical interventions in patients with deep thrombocytopenia, resistant to conservative treatment. Although the lifespan of platelets is short, platelet transfusions may have a temporary hemostatic effect. At the same time, the fear of increasing the duration of idiopathic thrombocytopenic purpura due to the risk of sensitization is only theoretical. Platelet transfusions are used in patients with high-risk idiopathic thrombocytopenic purpura with positive clinical effect. Transfusion of platelet concentrate is carried out in fractional doses of 1-2 doses per hour or 6-8 doses every 4-6 hours until a clinical and hematological response is achieved. The effect of transfusion is enhanced by preliminary administration of IVIG.
Splenectomy
In the absence of effect from conservative treatment of thrombocytopenic purpura, the presence of deep thrombocytopenia, hemorrhagic syndrome and the threat of life-threatening bleeding, patients are advised to undergo splenectomy. The question of surgery is decided individually in each case.
Indications for splenectomy:
severe acute idiopathic thrombocytopenic purpura with the presence of life-threatening bleeding in the absence of response to medication;
disease duration greater than 12 months, thrombocytopenia less than 10,000/mm3 and a history of bleeding;
chronic idiopathic thrombocytopenic purpura with signs of bleeding and a constant platelet level of less than 30,000/mm3 with no response to treatment for several years.
In patients who lead an active lifestyle and are often injured, splenectomy may be performed earlier.
Due to the risk of developing generalized infections after surgery, splenectomy is performed only if there are clear indications. Surgery is rarely necessary within 2 years of diagnosis as thrombocytopenia is well tolerated and easily controlled with corticosteroids and IVIG. Spontaneous recovery of the platelet count may occur after 4-5 years, therefore, a very careful approach to the operation is required. In children with chronic idiopathic thrombocytopenic purpura, cases of spontaneous remission are observed in 10-30% of cases several months or years after diagnosis; in adults it is very rare.
Preparation for splenectomy includes administration of corticosteroids, IVIG, or anti-D immunoglobulin. Corticosteroids are prescribed in full dose the day before, on the day of surgery and for several days after it, since most patients have adrenal insufficiency due to previous use. If active bleeding occurs immediately before surgery, platelet and red blood cell transfusion may be required, as well as the administration of methylprednisolone (solumedrol) at a dose of 500 mg/m2 per day. Before a planned operation, an ultrasound examination of the abdominal organs is mandatory to identify additional spleens (15% of cases), and in controversial cases, radioisotope scanning.
Complete and lasting recovery of platelet counts after splenectomy occurs in approximately 50% of patients. A good prognostic sign is the response to taking corticosteroids and IVIG before surgery (the effectiveness of splenectomy is 80-90%), as well as the absence of antiplatelet antibodies after surgery. 25% of children who have undergone splenectomy do not achieve a clinical and hematological response and require further treatment.
It is preferable to perform the operation using the laparoscopic method (possible in 90% of patients) to reduce the volume of surgical intervention, the level of surgical blood loss, provide the patient with a faster return to active life and shorten the length of hospitalization. The postoperative scar is about 1 cm long and does not cause discomfort.
Cases of death from bacterial infections in the late postoperative period, especially in children who underwent splenectomy before 5 years of age, amount to 1:300 patients per year. Most of them occur within 2 years after surgery. The main causes include pneumococcal and meningococcal infections, developing as fulminant sepsis with disseminated intravascular coagulation and hemorrhages in the adrenal glands. Therefore, no later than two weeks before surgery, it is recommended to administer pneumococcal, meningococcal and Haemophilus influenzae vaccines and long-term, at least 2 years, prophylactic use of benzylpenicillin after splenectomy. Some authors suggest limiting the administration of bicillin-5 (benzathine benzylpenicillin + benzylpenicillin procaine) monthly for 6 months after surgery.
A possible alternative to splenectomy is endovascular occlusion of the spleen, which can also be performed in patients with profound thrombocytopenia. To achieve a lasting clinical and hematological effect, it is necessary to phase out 90-95% of the organ parenchyma. The immunological reactivity of the body after endovascular occlusion of the spleen is preserved due to the functioning of 2-5% of the splenic tissue, which maintains blood supply due to collaterals, which is important in pediatric practice. It is possible to use proximal endovascular occlusion of the spleen several days before splenectomy to reduce the risk of surgery.
Plasmapheresis
In patients with persistent thrombocytopenia and life-threatening bleeding despite medical intervention and splenectomy, reinfusion of plasma through protein A columns may be used to rapidly remove antiplatelet antibodies. In patients with severe idiopathic thrombocytopenic purpura, this accelerates the elimination of circulating antiplatelet factor.
Treatment of children with life-threatening bleeding:
platelet transfusions;
solyumedrol 500 mg/m2 per day intravenously in 3 injections;
intravenous immunoglobulin 2 g/kg per course;
immediate splenectomy.
These measures can be performed individually or in combination depending on the severity and response to treatment.
Prognosis in children with idiopathic thrombocytopenic purpura
In 70-80% of patients, remission occurs within 6 months, in 50% - within 1 month from the onset of the disease.
The onset of spontaneous remission after a year of the disease is uncharacteristic, but can be noted even after several years.
The prognosis of the disease does not depend on gender, the severity of the initial condition and the detection of eosinophilia in the bone marrow.
Once the cause of idiopathic thrombocytopenic purpura is identified, the prognosis depends on its elimination.
Approximately 50-60% of patients with chronic idiopathic thrombocytopenic purpura will stabilize without any treatment or splenectomy
Thrombocytopenic purpura refers to hemorrhagic diathesis that occurs with a violation of the platelet component of hemostasis, where the number of blood platelets falls below the acceptable level (150 x 10 9 / l). This phenomenon occurs under circumstances that contribute to the fact that bone marrow begins to be over-degraded, over-consumed, or under-proliferate.
Most often (TP) occurs with increased cell destruction, although all these processes are also not excluded in one patient, they are combined with each other, run in parallel and, naturally, aggravate the situation. The platelet count in such cases drops to critical levels, which in turn determines the severity of the disease.
Prerequisites for the occurrence of thrombocytopenia
Most thrombocytopenias, as has already been proven, are acquired., that is, genetically programmed defects are not the basis of the disease, although isolated cases of hereditary pathology still sometimes occur:
- Impaired synthesis of thrombocytopoietins in the human body is associated with hereditary thrombocytopenia;
- The deficiency of enzymes that carry out glycolysis or the Krebs cycle is also a genetic abnormality.
All other conditions characterized by a decrease in the platelet level are divided into immune and non-immune, which have their own specific causes.
Non-immune thrombocytopenia
The starting factors for the occurrence of non-immune thrombocytopenia are:
- Mechanical effects on platelets, causing their injury (vascular prosthetics, splenomegaly, giant hemangiomas);
- Tumors with metastases to the bone marrow;
- A disorder of hematopoiesis, accompanied by sluggish cell proliferation, which is characteristic of aplastic disease, which is often accompanied by;
- Exposure to radiation or chemical compounds that damage myelopoiesis;
- High need for platelets with a lack of folic acid or Vit B 12, disseminated platelet aggregation - DAT, RDS - respiratory distress syndrome, thrombosis, long-term therapy with low doses of heparin).
Thrombotic thrombocytopenic purpura is also classified as a non-immune variant of TP.(TTP), which has an acute onset and is characterized by a malignant course. The etiology of this disease is still unclear, but it is known that it is usually fatal. It has been noted that TTP occurs more often in adults in the following cases:
- Previous bacterial or viral infection;
- Vaccinations;
- Presence of HIV infection;
- Pregnancy;
- Use of oral contraceptives;
- Treatment with certain anticancer drugs;
- Collagenoses;
- As a hereditary pathology (very rare).
Thrombotic thrombocytopenic purpura is characterized by the deposition of hyaline platelet thrombi, the formation of which was caused by spontaneous aggregation of platelets in small-caliber vessels, as a result of which they close the vessel. Platelet blood clots invade the entire human body and damage the microvessels of many organs, so TTP is characterized by the presence of symptoms:
- Hemolytic anemia;
- Fever;
- Neurological symptoms;
- Acute renal failure.
The death of the patient usually occurs as a result of kidney failure (RF).
Production of antiplatelet antibodies is a path to immune thrombocytopenia
Immune thrombocytopenic purpura has several types:
Autoimmune thrombocytopenia also has its own division depending on the direction of antibodies and the cause of its occurrence. Autoimmune thrombocytolysis is called idiopathic when the cause of aggression against one’s own cells is not established, symptomatic if it is possible to establish why the blood platelets suddenly begin to collapse. Symptomatic thrombocytopenic purpura is often a companion to chronic pathological conditions:
- Scleroderma;
- Chronic forms (usually chronic lymphocytic leukemia);
- Inflammatory diseases of the liver and kidneys;
With AITP, the immune system suddenly begins not to recognize its own platelet, which is completely normal in all respects, and, mistaking it for a “stranger,” responds by producing antibodies against it.
Immune thrombocytopenic purpura occurs at any age, starting from the neonatal period, so it is far from uncommon in children. The disease primarily affects females. The course of the pathological process often takes on a chronic relapsing form, especially for idiopathic thrombocytopenic purpura, since existing hypotheses of its occurrence do not explain the true cause of the disease.
Development of purpura
The development of thrombocytopenic purpura largely depends on thrombocytolysis (cell death under the influence of antibodies). In the bone marrow, megakaryocytes begin to be actively produced, which are quickly consumed and increase the number of platelets entering the bloodstream, where the blood platelets die within a short time. Instead of their allotted week of life, they exist for several hours, thereby forcing the bone marrow to work intensively and replenish losses. Such thrombocytopenias are called hyperregenerative, which mainly occur in children and make up the majority of clinical forms in pediatrics. But it happens that antibodies, in addition to platelets, are also directed at megakaryocytes, which devastates the sprout and prevents blood platelets from forming. This is the so-called hyporegenerative thrombocytopenia, which is not necessarily immune.
A major role in the pathogenesis of TP is given to the functional characteristics of platelets, their participation in hemostasis and nutrition of the vascular wall, as well as adhesive-aggregation ability, because they are able to stick to each other and to the damaged endothelium with the formation of a platelet plug.
It can be concluded that the main factor triggering bleeding is thrombocytopenia. When the vascular walls stop receiving platelet feeding, their degeneration occurs, which cannot prevent the passage of red blood cells through the vessels. The slightest injury in such cases can cause prolonged bleeding.
Diagnostics
A diagnosis of thrombocytopenic purpura can be suspected if there are frequent and hemorrhagic petechial-spotted rashes, which differ from allergic ones in that they do not disappear with pressure. A reduced platelet count in a blood test confirms the diagnosis of TP.
When diagnosing TP in a hemostasiogram, you can get an increase in Duke bleeding time to 30 minutes or more and a decrease (less than 60%) in blood clot retraction, while Lee White coagulation will remain normal. Thrombocytopenic purpura is differentiated from hereditary thrombocytopathy (thrombocytopenia) using family history. Hereditary thrombocytopathy is characterized by a shortening of the life of blood platelets due to defective membranes or a lack of enzymes in the cells themselves.
Hemorrhagic rash means purpura
Thrombocytopenic purpura is characterized by the appearance of a petechial-spotted type of bleeding. And in case of major injuries, ecchymatoses can be observed. Thus, the symptoms of thrombocytopenic purpura can be presented as follows:
- Hemorrhages that appeared at injection sites;
- Severe bleeding from the mucous membranes (oral cavity, tonsils, pharynx);
- Infection one to two weeks before the rash appears;
- Body temperature is normal even in children and, with only rare exceptions, it can rise to low-grade fever;
- Single or multiple spontaneous hemorrhages (sometimes after minor trauma);
- Asymmetrical skin lesions, and of different sizes;
- Hemorrhages vary in color: from purple (bright red) to blue-green and yellow;
- Bruises resolve within 3 weeks;
- Inconsistency of injury and hemorrhage;
- The appearance of hemorrhages at night (during sleep);
- The appearance of a hemorrhagic rash on the legs, arms and torso;
- Bleeding from the nose and into natural cavities;
- Gastrointestinal bleeding (black stool or red blood);
- Bloody vomiting, which is secondary in nature, as it occurs as a result of swallowing blood from the nose;
- Anemia that develops due to constant blood loss;
- Possible, which is a very dangerous symptom.
In addition, bleeding from the ears, hemoptysis and hemorrhage into the vitreous body of the eye, which led to complete blindness, were described in medical practice.
People often confuse thrombocytopenic purpura with Henoch-Schönlein purpura, which is characterized by a vasculitic purpuric type of rash, which is why the disease is called. What is confusing is that the rash is similar to the petechial macular rash seen in TP. Henoch-Schönlein disease can be described as follows:
- A bright red papular rash that fades over time and leaves bluish pigment spots;
- Itching sensation before the rash;
- Body temperature often rises;
- The rashes are located symmetrically on the legs and arms;
- Damage to the vessels of the kidneys (micro- and macrohematuria).
The rash in the case of hemorrhagic vasculitis is very similar to an allergic one, but it does not disappear with pressure. Henoch-Schönlein disease has a chronic course, where, in addition to the skin, joints, gastrointestinal tract, and mucous membranes can be affected, therefore there are 4 forms of this disease:
- Skin:
- Abdominal;
- Articular;
- Mixed.
How to treat thrombocytopenic purpura?
If thrombocytopenic purpura is suspected, the patient should be hospitalized, because strict bed rest with such a disease is mandatory until platelets are restored to the minimum physiological level.
If there is bleeding, the first step is to use local (ε-aminocaproic acid, hemostatic sponge, thrombin, adroxon) and general (ascorutin and calcium chloride for intravenous administration) hemostatic agents. At the first stage of treatment, corticosteroid therapy is included, which lasts up to 3 months.
There is not much interest in treating thrombocytopenic purpura by transfusion of platelet mass, due to the fact that the donor's platelets must still take root in the recipient, and not immunize him even more (individual selection is indicated), therefore, in case of severe anemia that has arisen against the background of blood loss, preference is given to washed red blood cells.
Splenectomy (radical method) is performed at the second stage of treatment in cases of persistent bleeding, aseptic inflammation or threat of splenic rupture. However, if removal of the spleen also does not have an effect, then treatment is continued with small doses of corticosteroids. Although they will not restore the platelet count, they will at least reduce the risk of bleeding in the brain.
For such patients, barbiturates, caffeine, aspirin and other drugs that help reduce the platelet component in the blood are absolutely contraindicated, so the patient is strictly warned about this.
After completing the course of treatment and being discharged from the hospital, the patient is registered at the clinic at the place of residence for further observation. In this case, it is mandatory to sanitize all foci of chronic infection, and the oral cavity in particular. Deworming is also carried out.
Considering that thrombocytopenic purpura is not uncommon in children, part of the responsibility for the further course of the disease rests with the parents. A conversation is held with them about what can provoke a relapse of the disease (ARVI, exacerbation of focal infections). In addition, parents should know how to gradually introduce hardening, physical therapy and keep a food diary (elimination of allergenic foods). To protect the child from injury, he is exempt from school for this period and is advised to study at home.
A person is registered at a dispensary for recovery for at least 2 years. The prognosis of the disease, if it is not thrombotic thrombocytopenic purpura, is usually favorable.
Video: thrombocytopenia and hemorrhagic syndrome
Official medicine tends to classify thrombocytopenic purpura as one of the most common causes of increased bleeding in young patients. The disease manifests itself with acute symptoms and requires immediate medical intervention. There have been cases of spontaneous disappearance of signs of the disease that are not related to treatment. However, the danger of negative consequences for the child’s health suggests that signs of pathology cannot be ignored.
Description of Werlhof's disease
Thrombocytopenic purpura, or Werlhof's disease, is characterized by the formation of blood clots by platelets, which are responsible for stopping bleeding. As a result, there is a drop in the number of platelets (thrombocytopenia) in the blood passing through the vessels.
Doctors divide the disease into two main types:
- bleeding, expressed in small and large hematomas (we recommend reading:);
- ischemic changes in tissues and organs associated with blockage of small vessels by blood clots and causing disruptions in the blood flow of the brain and internal organs.
The result of negative formations is the reaction of the immune system, which perceives platelets as foreign bodies. To protect the body, it begins to produce antiplatelet complexes that settle on “hostile” platelets. The labeled platelets travel to the spleen, where they are attacked and consumed by macrophages. The number of platelets decreases sharply, which provokes their increased production by the body. As a result, the supply of cells is depleted, they become severely deformed, and serious disorders occur that are dangerous to the child’s health.
Causes of the disease
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There are no scientifically substantiated and precisely proven reasons for the formation of Werlhof's disease. All information has been collected by doctors into theoretical assumptions, presented in two options:
- A genetic factor that involves a mutation of the gene responsible for the proper formation and functioning of platelets. A mutating gene changes the structure of cells in which defects are formed, leading to their “gluing” and subsequent destruction.
- Immune failure in the body of children, leading to platelet damage. Antiplatelet complexes produced by the immune system neutralize cells, provoking their destruction. The number of platelets in the blood drops.
There is no consensus regarding the triggering factors, so the list includes all diseases and negative changes that can trigger the development of thrombocytopenic purpura.
Doctors refer to them as:
- progressive pathologies of an immune nature;
- prematurity and poor development of the newborn;
- problems with blood clotting;
- complications after viral and infectious diseases (chickenpox, influenza, whooping cough);
- malignant tumors in the brain;
- congenital abnormalities of cell structure;
- chromosomal diseases;
- pathologies of the hematopoietic system;
- antiphospholipid syndrome;
- consequences of DIC syndrome;
- independent use of various medications during pregnancy;
- severe forms of eclampsia and preeclampsia.
Classification of the disease
The classification of the disease includes two categories: the nature of the disease and the mechanism of its development. The first category is divided into two types:
- Acute form, which can last from 1 to 6 months. The prognosis for the child's recovery is positive.
- Chronic form, duration of which exceeds 6 months. Characterized by alternating periods of exacerbation and remission. If there are no periods of exacerbation between remissions, Werlhof's disease acquires a chronic relapsing status.
- The autoimmune type, which occurs due to diseases associated with malfunctions of the child’s immune system (autoimmune hemolytic anemia, systemic lupus erythematosus).
- Transimmune, or neonatal type, manifested in newborns who received antiplatelet antibodies from the mother during pregnancy.
- Isoimmune type. The development of this type is associated with blood transfusion.
- Heteroimmune is formed when the antigenic structure of platelets is disrupted.
- The symptomatic form is non-immune in nature and develops with leukemia, anemia and infections.
- Idiopathic type, the causes of which have not been identified.
Symptoms of thrombocytopenic purpura
A characteristic symptom of thrombocytopenic purpura is clearly visible small or large hemorrhages on the skin and mucous membranes of the child.
They appear as bruises with a light touch or occur spontaneously, without provoking factors. Symptoms in the form of noticeable hemorrhages occur when the platelet count is less than 50 thousand.
If the platelet count drops below 30,000, the child is at risk of bleeding in the brain. The risk group includes 1-2% of children. The greatest danger is faced by young patients who have the following disorders:
- hemorrhages on the mucous membranes;
- hemorrhages in the eye (in the sclera or retina);
- long-term use of Aspirin and other salicylates;
- extensive rashes on the skin;
- head injury.
Rashes on the mucous membranes and skin with thrombocytopenic purpura are distinguished by size, shape, color and asymmetrical location. The types of rashes are clearly shown in the photo.
Along with skin symptoms, the disease can manifest itself with other signs:
- severe and prolonged bleeding after tooth extraction;
- causeless nosebleeds;
- frequent bleeding gums;
- the appearance of blood in the child’s urine;
- long and heavy menstruation in girls.
Diagnosis of the disease
Diagnosis of thrombocytopenic purpura begins with a thorough examination of the anamnesis. The doctor conducts a survey of the parents and the child, finds out the duration of the symptoms, the time of their onset, and the presence of provoking factors.
The final diagnosis is established using laboratory tests:
Treatment of thrombocytopenic purpura
A treatment plan for thrombocytopenic purpura is developed by a doctor after full confirmation of the diagnosis. The complex of treatment measures includes:
Prognosis for recovery
With a good prognosis, the disease can last several weeks or months, and then spontaneous recovery occurs. The maximum period for this course of the disease is 6 months. Statistics show that thrombocytopenic purpura is successfully cured in 80% of children. In the remaining 20%, the disease becomes chronic. Mortality from thrombocytopenic purpura accounts for 1% of all patients.
Prevention
Science does not know the etiological causes of idiopathic thrombocytopenic purpura, so it is difficult to develop effective preventive measures. General recommendations from experts include the following:
- protect the child from bacterial and viral diseases;
- prepare healthy and balanced food for your baby;
- exclude self-treatment of the child with antibiotics;
- avoid factors that cause allergic reactions, promptly scan foci of chronic infection.
To prevent recurrence of the disease, the child is observed by a hematologist for 5 years without fail. The child's body should be dewormed periodically and chronic infections should be treated in a timely manner. It is advisable to exempt the little patient from physical education lessons. Try to protect your treasure from head injuries and general injuries.
