Thrombocytopenia in children

Thrombocytopenia in children is a group of diseases complicated by hemorrhagic syndrome, resulting from a decrease in the number of platelets (less than 150 × 10 ⁹ / l) due to their increased destruction or insufficient production.

Thrombocytopenia occurs in 25% of newborns from the intensive care unit and intensive care unit, with half of them having platelet counts below 100 × 10 ⁹ / l, and 20% have less than 50 × 10 ⁹ / l.

What causes thrombocytopenia in children?

Thrombocytopenia in children can be caused by increased platelet destruction; decrease in their production or to be of mixed origin.

Increased destruction of platelets may be due to:

• immunopathological process (transimmune, isoimmune or heteroimmune thrombocytopenia in children);
• Vasopathy (Kazabaha-Merritt syndrome, systemic inflammatory response syndrome, respiratory distress syndrome of any origin, aspiration syndrome, pneumonia, pulmonary hypertension, infections without systemic inflammatory response syndrome); DIC syndrome;
• thrombocytopathies (primary hereditary - Wiskott-Aldrich, Mey-Hegglin, Shvakhman-Dayemonda, and others; secondary - medicinal, with hyperbilirubinemia, acidosis, generalized viral infections, prolonged parenteral nutrition, etc.);
• isolated and generalized thrombosis in injuries, hereditary deficiencies of anticoagulants (antithrombin III, protein C, etc.), maternal antiphospholipid syndrome;
• replacement transfusions of blood, plasma exchange, hemosorption, etc.

Disturbance of platelet production occurs when megakaryocytic hypoplasia (TAR syndrome, aplastic anemia, congenital leukemia, neuroblastoma, trisomy 9, 13, 18, 21 chromosome pairs) and a decrease in the intensity of thrombocytopoiesis during the drug treatment of the mother (tolbutamide, typhasyses, and in the presence of izyme, thymes, cystine typhasyses, tiazythymes, tiazythymes, tiazythymes, tiazythia, izymes, tiazyptostipoeza in the case of drug treatment of the mother (tolbutamide, izythytase cytosis, izyme, thymes, cystine typhasyses, ihythylases, thymes, cystine typhasyses, thymes, cystine typhasms, tyzymes, tyzymes, tytides, and other therapy). And eclampsia in the mother, extremely low body weight at birth, severe antenatal hemolytic disease of the newborn, deficiency in the synthesis of thrombocytopoietin, etc.

Pathology of mixed genesis: thrombocytopenia in children, arising from polycythemia, severe asphyxia, severe infections, sepsis, thyrotoxicosis, etc.

In the vast majority of cases, thrombocytopenia in newborns is due to increased destruction of platelets. Only less than 5% of all thrombocytopenia is caused by their reduced production.

Symptoms of thrombocytopenia in children

Thrombocytopenia in children is characterized by microcirculatory vascular type of bleeding: petechial hemorrhage, single or merging into extravasation, bleeding from mucous membranes and from injection sites, hemorrhages in the sclera, in the internal organs, including intracranial hemorrhages.

Isoimmune (alloimmune) trobocytopenia in children

Thrombocytopenia of the fetus and newborn due to the antigenic incompatibility of the mother and fetus platelets.

The disease is diagnosed in one newborn out of every 5,000 to 10,000. This pathology can occur both during the first and repeated pregnancies. Antigenic incompatibility occurs in the absence of maternal platelet antigens P1a1 (in 50% of cases of isoimmune thrombocytopenia) or Pb2, Pb3, Onro, Co., etc., which leads to isosensitization and the production of antithrombocytic antibodies to fetal platelets in the mother's body.

Symptoms

The clinical picture of isoimmune thrombocytopenia in children is characterized (immediately after the birth of the child) by petechial rash and small-blooded hemorrhages of the skin and mucous membranes. In severe cases (10-12% of patients), during the first hours and days of life, the hemorrhagic syndrome increases, melena, pulmonary, umbilical hemorrhage, and intracranial hemorrhages occur. Typical moderate splenomegaly. Characterized by severe thrombocytopenia, an increase in bleeding time. PV and APTTV are not changed, do not detect FDP. Thrombocytopenia persists for 4-12 weeks, gradually fading away.

The diagnosis is confirmed by the formulation of the thrombogaglutination reaction of the child's platelets in the mother's serum.

In 10-12% of cases, death is possible due to hemorrhage in vital organs, but in general the prognosis is favorable, the disease lasts for 3-4 months and gradually fades away until complete recovery.

Treatment

Isoimmune thrombocytopenia therapy in children begins with the correct feeding of the newborn. For 2-3 weeks (depending on the severity of the disease) the child should be fed with donor milk or milk formulas.

Since the disease ends with spontaneous recovery after 3-4 months, drug treatment is indicated when the number of platelets is less than 20 × 10 ⁹ / l and the presence of bleeding. Human immunoglobulin is prescribed as normal for intravenous administration at the rate of 800 mg / kg (daily drip, slowly, for 5 days) or at the rate of 1000-1500 mg / kg (1 time in 2 days, 2-3 times intravenously, drip, slowly).

Glucocorticoids are also used: prednisone 1-2 mg / (kg × days) by mouth (2/3 doses in the morning, 1/3 at 16 h) for 3-5 days.

In severe thrombocytopenia in children, transfusion of washed maternal platelets at a dose of 10–30 ml / kg or washed platelets of an antigen-negative donor (with an individual selection for antigen compatibility) is also effective at 10–30 ml / kg intravenously. To prevent the graft versus host reaction, blood components obtained from the patient’s relatives should be exposed to radiation.

In the absence of bleeding and moderate thrombocytopenia (platelet count not lower than 20-30 × 10 ⁹ / l), sodium etamzilate (Dicynon) is administered intramuscularly or intravenously at a dose of 0.5-1.0 ml 1 time per day for 7-10 days. Also prescribed calcium pantothenate 0.01 g 3 times a day inside for 7-10 days.

Transimmune thrombocytopenia in children

Transimmune thrombocytopenia is transient thrombocytopenia in children born to mothers suffering from immune forms of thrombocytopenia (Verlhof disease and Fisher-Evans disease).

Transimmune thrombocytopenia occurs in 30-50% of children born to mothers suffering from these diseases (regardless of whether they have undergone splenectomy or not). The disease develops as a result of the transplacental transmission of maternal antiplatelet antibodies or a clone of sensitized lymphocytes, as a result of which thrombolysis and thrombocytopenia occur. More often (in 50% of cases) with transimmune thrombocytopenia in children they find an isolated decrease in the number of platelets, determined by laboratory and without clinical manifestations. When the platelet level is less than 50x10 ^{9 /} l, hemorrhagic syndrome of the microcirculatory type appears: petechial rashes, single extravasates. Bleeding from the mucous membranes and hemorrhages in the internal organs are rarely observed. The typical duration of hemorrhagic syndrome is 6-12 weeks.

Diagnostics

Diagnosis is based on the presence of family history (thrombocytopenia in the mother). The platelet count in the blood is reduced, the bleeding time is increased, the clotting time, PV, APTT is normal. Anti-platelet antibodies are detected in the blood and breast milk of the mother (including in cases where the mother had previously had a splenectomy).

Treatment

Treatment of transimmune thrombocytopenia in children begins with the correct feeding of the child (donor milk or milk formulas).

Drug therapy is indicated only for severe hemorrhagic syndrome. Human immunoglobulin used is normal for intravenous administration (800 mg / kg, 1-3 times), sodium etamsylate and prednisolone are also prescribed. In severe cases, the treatment regimen completely coincides with that in isoimmune thrombocytopenia of the newborn.

[1]

Heteroimmune thrombocytopenia in children

Heteroimmune thrombocytopenia in children is an immune form of thrombocytopenia, caused by the destruction of platelets under the influence of antibodies produced by the immune system of the child's body to platelets loaded with haptens of medicinal, microbial and viral origin.

[2], [3], [4]

The reasons

The causes of the disease are respiratory and other viruses, antibiotics (cefalotin, penicillin, ampicillin, rifampicin, chloramphenicol, erythromycin), thiazide diuretics (acetazolamide, furosemide), barbiturates. Adsorbed on the surface of red blood cells, these substances (haptens) stimulate the production of anti-erythrocyte antibodies, which leads to cell lysis.

Symptoms

Usually, after 2-3 days from the onset of a viral infection or taking a medicine, there appears scant microcirculatory hemorrhagic syndrome (petechiae, ecchymosis). Bleeding from the mucous membranes is rarely observed, there is no hemorrhage in the internal organs. The duration of hemorrhagic syndrome usually does not exceed 5-7 days.

Diagnostics

Diagnosis of heteroimmune thrombocytopenia in children is based on anamnestic data: association with infection, prescription of drugs, development in the late neonatal period. The number of platelets is moderately reduced, the bleeding time is normal or slightly increased, the clotting time, PV, THT is normal.

Treatment

Usually no treatment is required. The abolition of drugs is necessary, after which the hemorrhagic syndrome disappears within 2-5 days.

[5], [6], [7],

Congenital hypo (a) megakaryocytosis

TAR syndrome (Thrombocytopenia-Absent Radii) - embryopathy in the form of atresia of the radius and thrombocytopenia in children due to hypo- or amegakaryocytosis.

The etiology and pathogenesis of the disease are not precisely established, for the development of the autosomal recessive form of the TAR syndrome, 11 genome microdeletions of chromosome lq21.1 are required, which leads to embryogenesis disorders at 7-9 weeks of gestation, resulting in hypo- or amegaryocytosis, atresia of the radius, malformations of the heart, kidneys and brain.

Symptoms

The clinical symptom complex includes atresia of both radial bones, various malformations and severe hemorrhagic syndrome of the microcirculatory type: multiple petechiae, ecchymosis, melena, hemorrhages from the kidneys and lungs, into the internal organs. The disease often leads to death in the neonatal period (from hemorrhage to vital organs) or in the first year of life (from various congenital malformations).

Diagnostics

Laboratory characteristic of marked thrombocytopenia in children (up to single blood plates in the preparation), an increase in bleeding time at normal clotting time, normal PV and slightly elongated PTT, normal fibrinogen level, and the absence of FDP, which excludes DIC. On myelogram: hypomegakaryocytosis (up to single megakaryocytes in preparations). At the same time, there are no signs of leukemic infiltration and myelodysplastic syndrome.

Treatment

In hypo (a) fibrinogenemia, a patient’s group blood thromboconcentrate is used (20–30 ml / kg intravenously, drip). If necessary, repeat the transfusion after 3-4 days. If the platelet count in the blood is less than 20,000 in 1 µl of blood, stem cells or bone marrow transplantation is performed.

[8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19]

Kazabaha-Merritta syndrome

Congenital malformations - giant hemangioma in combination with thrombocytopenia and hemolytic anemia.

The reason for the formation of a giant hemangioma is not known, it causes deposition, sequestration and lysis of platelets and erythrocytes. In a laboratory study, a rapid decrease in platelet count and increased red blood cell lysis are found. A bleeding tendency, anemia and jaundice are clinically observed.

The diagnosis is established clinically. To assess the severity of the disease, platelet count, bilirubin level and degree of anemic syndrome are determined.

Treatment

Surgical treatment. In preparation for the operation, correction of thrombocytopenia in children (transfusion of the thromboconcentrate) and anemia (transfusion of the erythrocyte mass) is necessary. Effective hormone therapy, prednisone prescribed in tablets of 4-8 mg / (kgshut), depending on body weight and age of the child. More often, the drug is taken every other day without reducing the dosage. Course duration 28 days. If necessary, after 6-8 weeks, repeat the course.

Anomaly of May-Hegglin

Hereditary autosomal dominant disease: moderate thrombocytopenia in children due to increased platelet lysis and, less commonly, microcirculatory hemorrhagic syndrome.

Clinically, an increased tendency to bleeding is observed during the pinching and inking procedures. In a laboratory study: large platelet sizes - up to 8-12 microns (giant platelets), moderate thrombocytopenia, changes in the morphology of platelets and neutrophils. The abnormal size of the platelets is the reason for their increased lysis. At the same time, basophil inclusions are determined in neutrophils (Gyöle body). No treatment is required.

[20], [21]

Thrombocytopenia in children with congenital and acquired neonatal infections

Thrombocytopenia in children with congenital and acquired neonatal infections manifest hemorrhagic syndrome not associated with DIC, which often occurs in severe infectious diseases (both viral and bacterial) of the newborn.

Thrombocytopenia in the neonatal period is found in 10-15% of cases of severe infections. Their most common cause is congenital cytomegalovirus infection. Less commonly, thrombocytopenia occurs in congenital toxoplasmosis, syphilis, as well as herpes virus and enterovirus infections. From acquired diseases, sepsis, necrotizing enterocolitis, phlegmon, and peritonitis can cause thrombocytopenia. Causes of thrombocytopenia in severe infections without the development of DIC syndrome: hypersplenism, leading to sequestration and lysis of platelets, suppression of platelet exfoliation from megakaryocytes, increased destruction of platelets due to fixation of toxins on them and increased consumption of platelets when endothelial damage is damaged. Each of these factors or their combinations cause a decrease in the number of platelets, which leads to the development of hemorrhagic syndrome.

The clinical picture of the disease depends on the underlying pathology and is complicated by the hemorrhagic syndrome of the microcirculatory-vascular type (petechiae, hematomas at injection sites, bleeding from the mucous membranes, more often the gastrointestinal tract). Hemorrhagic syndrome is transient, easily reversible.

In a laboratory study, a decrease in the number of platelets is found, an increase in bleeding time during normal clotting time, TV and PTT, the amount of PDF in the blood is not elevated, which distinguishes thrombocytopenia in children with infections from DIC.

Treatment

Special treatment is usually not required. Adequate therapy of the underlying disease is required. In severe bleeding and platelet levels of less than 20 × 10 ⁹ / l, replacement transfusion of the patient’s blood group thrombocontinent (10–30 ml / kg, intravenous drip) is indicated.

Diagnosis of thrombocytopenia in children

In children with thrombocytopenia, it is necessary to determine the platelet count in peripheral blood, clotting time, bleeding time, PV, antibodies to fetal platelets in the blood and mother’s milk or a Coombs test (father’s platelets with the mother’s blood plasma). According to the testimony conducted a study of the bone marrow (myelogram) with the collection of material from three points. To assess the degree of blood loss determine the content of red blood cells, hemoglobin and hematocrit.

[22], [23], [24], [25]

Differential diagnosis

Differential diagnosis of thrombocytopenia in children is necessary to determine the tactics of treatment. Diagnosis is carried out primarily with immune forms of hereditary and congenital diseases, as well as with thrombocytopathy (hereditary and secondary) and secondary thrombocytopenia in infections without DIC.

Differential diagnosis of thrombocytopenic conditions in newborns

Disease	Etiology and pathogenesis	Laboratory signs
Isoimmunular thrombocytopenia	Isoimmune conflict due to maternal and fetal platelet incompatibility	Thrombocytopenia, increased bleeding time, the presence of isoimmune antibodies to fetal platelets
Transmembrane thrombocytopenia	Transplacental transition of maternal in the immune form of Verlgof's disease and Evans' disease in the mother	Corresponding history, thrombocytopenia, increased bleeding time, antibodies to mother's platelets
TAR-syndrome	Congenital hypo- or amegakaryocytosis in combination with atresia of the radius	Thrombocytopenia, increased bleeding time, the absence or low content of megakaryocytes in the myelogram. Atresia of radial bones, other malformations
Kazabaha- Merritt's syndrome	Congenital massive hemangioma resulting in thrombocytopenia due to platelet sequestration and lysis	Thrombocytopenia, increased bleeding time, giant hemangioma
Syndrome Viskotta- Aldrich	Hereditary pathology, including eczema, thrombocytopenia due to increased lysis of platelets and insufficient production of antiendotoxin antibodies	Thrombocytopenia, shortening of life span of platelets, small platelet size
Anomaly of May-Hegglin	Hereditary thrombocytopenia caused by increased lysis of abnormally large platelets	Thrombocytopenia, shortening of life span of platelets. Large platelets
Thrombocytopenia for infections	For severe viral and bacterial infections at the height of toxemia	Thrombocytopenia, increased bleeding time, other symptoms of infection
Thrombocytopathy	Hereditary; medicinal (ethyl Biscumate, phenobarbital, carbenicillin, cephalosporins, etc.)	Normal or increased platelet count, impaired platelet adhesion, increased bleeding time
Immune Thrombocytopenia	The formation of antibodies to platelets loaded with haptens of viral or medicinal origin	Relationship with medication and / or ARVI

[26], [27]

Differential diagnosis

Differential diagnostics of thrombocytopenia in children is needed to determine treatment strategy. Diagnostics is made primarily with immune forms of hereditary and congenital diseases, as well as with thrombocytopathies (hereditary and secondary) and secondary thrombocytopenia with infections without DIC.

Differential diagnostics of thrombocytopenic conditions in newborns

Disease	Etiology and pathogenesis	Laboratory signs
Isoimmune thrombocytopenia	Isoimmune conflict due to incompatibility of mother and fetus platelet	Thrombocytopenia, increased bleeding time, presence of isoimmune antibodies against platelets of fetus
Transimmune thrombocytopenia	Transplacental passage of maternal form with immune form of Werlhof's disease and Evans disease in a mother	Relevant history, thrombocytopenia, increased bleeding time, antibodies to mother`s platelets
ТАR- syndrome	Congenital hypo or amegakaryocytosis, combined with atresia of radial bones	Thrombocytopenia, increased bleeding time, absence or low content of megakaryocytes in myelogram. Atresia of radial bones, other malformations
Kazabah-Merritt syndrome	Congenital massive hemangioma, leading to thrombocytopenia due to sequestration and lysis of platelets	Thrombocytopenia, increased bleeding time, giant hemangioma
Wiskott-Aldrich syndrome	Hereditary diseases, including eczema, thrombocytopenia due to increased lysis of platelets and lack of production of antiendotoxin antibodies	Thrombocytopenia, shortening of platelet life span, small size of platelets
Mei Hegglin anomaly	Hereditary thrombocytopenia due to increased lysis of abnormally large platelets	Thrombocytopenia, shortening of platelet life span. Platelets are large
Thrombocytopenia with infections	In severe viral and bacterial infections at highest toxicity	Thrombocytopenia, increased bleeding time, other symptoms of infection
Thrombocytopathies	Hereditary; medical (Aethylii biscoumacetas, phenobarbital, carbenicillin, cephalosporins etc.)	Normal or elevated platelet count, platelet adhesion failure, increased bleeding time
Immune thrombocytopenia	Antibodies to platelets, loaded with haptens of drug or viral origin	Connection with intake of medications and / or SARS