Thrombocytopenia in children

Thrombocytopenia in children is a group of diseases complicated by hemorrhagic syndrome, which occurs as a result of 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 in intensive care units, with half of them having a platelet count below 100×10 ⁹ /L, and 20% below 50×10 ⁹ /L.

What causes thrombocytopenia in children?

Thrombocytopenia in children can be caused by increased destruction of platelets; decreased production, or be of mixed genesis.

Increased platelet destruction may be a consequence of:

• immunopathological process (transimmune, isoimmune or heteroimmune thrombocytopenia in children);
• vasopathies (Kasabach-Merritt syndrome, systemic inflammatory response syndrome, respiratory distress syndrome of any genesis, aspiration syndrome, pneumonia, pulmonary hypertension, infections without systemic inflammatory response syndrome); DIC syndrome;
• thrombocytopathy (primary hereditary - Wiskott-Aldrich, May-Hegglin, Shwachman-Diamond, etc.; secondary - drug-induced, with hyperbilirubinemia, acidosis, generalized viral infections, long-term parenteral nutrition, etc.);
• isolated and generalized thromboses due to trauma, hereditary deficiencies of anticoagulants (antithrombin III, protein C, etc.), antiphospholipid syndrome in the mother;
• replacement blood transfusions, plasmapheresis, hemosorption, etc.

Impaired platelet production occurs with megakaryocytic hypoplasia (TAR syndrome, aplastic anemia, congenital leukemia, neuroblastoma, trisomy 9, 13, 18, 21 pairs of chromosomes) and a decrease in the intensity of thrombocytopoiesis during drug treatment of the mother (tolbutamide, thiazides, etc.), preeclampsia and eclampsia in the mother, extremely low birth weight, severe antenatal hemolytic disease of the newborn, deficiency of thrombocytopoietin synthesis, etc.

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

In the vast majority of cases, thrombocytopenia in newborns is caused by increased destruction of platelets. Only less than 5% of all thrombocytopenias are caused by decreased production.

Symptoms of Thrombocytopenia in Children

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

Isoimmune (alloimmune) thrombocytopenia in children

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

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

Symptoms

The clinical picture of isoimmune thrombocytopenia in children is characterized (immediately after birth) by petechial rash and small-spot 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 intensifies, melena, pulmonary, umbilical hemorrhages, and intracranial hemorrhages occur. Moderate splenomegaly is typical. Severe thrombocytopenia and increased bleeding time are characteristic. PT and APTT are unchanged, and PDF is not detected. Thrombocytopenia persists for 4-12 weeks, gradually fading.

The diagnosis is confirmed by performing a thromboagglutination reaction of the child's platelets in the mother's serum.

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

Treatment

Therapy for isoimmune thrombocytopenia in children begins with proper 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 platelet count is less than 20×10 ⁹ /l and there is bleeding. Normal human immunoglobulin is prescribed for intravenous administration at a rate of 800 mg/kg (daily drip, slowly, for 5 days) or at a rate of 1000-1500 mg/kg (once every 2 days, 2-3 times intravenously drip, slowly).

Glucocorticoids are also used: prednisolone 1-2 mg/(kg×day) orally (2/3 of the dose in the morning, 1/3 at 4 p.m.) 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 individual selection based on antigen compatibility) also at 10-30 ml/kg intravenously by drip is effective. To prevent the "graft versus host" reaction, blood components obtained from the patient's relatives must be irradiated.

In the absence of bleeding and moderate thrombocytopenia (platelet count not lower than 20-30×10 ⁹ /l), sodium etamsylate (Dicynone) is prescribed intramuscularly or intravenously at a dose of 0.5-1.0 ml once a day for 7-10 days. Calcium pantothenate is also prescribed at 0.01 g 3 times a day orally for 7-10 days.

Transimmune thrombocytopenia in children

Transimmune thrombocytopenia is a transient thrombocytopenia in children born to mothers suffering from immune forms of thrombocytopenia (Werlhof's 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 transplacental transfer of maternal antiplatelet antibodies or a clone of sensitized lymphocytes, resulting in thrombolysis and thrombocytopenia. More often (in 50% of cases), with transimmune thrombocytopenia in children, an isolated decrease in the number of platelets is found, determined in the laboratory and having no clinical manifestations. When the platelet level is less than 50x10 ^{9 /} l, hemorrhagic syndrome of the microcirculatory type appears: petechial rashes, isolated extravasates. Bleeding from the mucous membranes and hemorrhages into internal organs are rare. The typical duration of hemorrhagic syndrome is 6-12 weeks.

Diagnostics

Diagnosis is based on a family history (thrombocytopenia in the mother). The platelet count in the blood is reduced, bleeding time is increased, clotting time, PT, APTT are normal. Antiplatelet antibodies are determined in the mother's blood and breast milk (including in cases where the mother has previously undergone splenectomy).

Treatment

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

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

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Heteroimmune thrombocytopenia in children

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

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Reasons

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

Symptoms

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

Diagnostics

The diagnosis of heteroimmune thrombocytopenia in children is based on anamnestic data: association with infection, prescription of medications, development in the late neonatal period. The platelet count is moderately reduced, bleeding time is normal or slightly increased, clotting time, PT, PTT are normal.

Treatment

Usually, no treatment is required. It is necessary to discontinue medications, after which the hemorrhagic syndrome disappears within 2-5 days.

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Congenital hypo(a) megakaryocytosis

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

The etiology and pathogenesis of the disease have not been precisely established; for the development of the autosomal recessive form of TAR syndrome, a microdeletion of chromosome lq21.1 that affects 11 genes is necessary, which leads to embryogenesis disorders at 7-9 weeks of gestation, resulting in hypo- or amegakaryocytosis, atresia of the radial bones, and 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, bleeding from the kidneys and lungs, into internal organs. The disease often leads to death in the neonatal period (from hemorrhage into vital organs) or in the first year of life (from various congenital malformations).

Diagnostics

Laboratory findings include marked thrombocytopenia in children (up to single blood platelets in the specimen), increased bleeding time with normal clotting time, normal PT and slightly prolonged PTT, normal fibrinogen level, absence of FDP, which excludes DIC. Myelogram shows hypomegakaryocytosis (up to single megakaryocytes in specimens). There are no signs of leukemic infiltration or myelodysplastic syndrome.

Treatment

In case of hypo(a)fibrinogenemia, a thromboconcentrate of the patient's blood of the same group is used (20-30 ml/kg intravenously, drip). If necessary, the transfusion is repeated after 3-4 days. If the number of platelets in the blood is less than 20,000 in 1 μl of blood, a stem cell or bone marrow transplant is performed.

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Kasabach-Merritt syndrome

Congenital malformation - giant hemangioma combined with thrombocytopenia and hemolytic anemia.

The cause of giant hemangioma formation is unknown, it involves deposition, sequestration and lysis of platelets and red blood cells. Laboratory examination reveals rapid decrease in platelet count, increased lysis of red blood cells. Clinically, bleeding tendency, anemia and jaundice are observed.

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

Treatment

Treatment is surgical. In preparation for surgery, it is necessary to correct thrombocytopenia in children (thromboconcentrate transfusion) and anemia (red blood cell mass transfusion). Hormonal therapy is effective, prednisolone is prescribed in tablets at 4-8 mg / (kg x day) depending on the child's weight and age. Most often, the drug is taken every other day without reducing the dosage. The course duration is 28 days. If necessary, a repeat course is carried out after 6-8 weeks.

May-Hegglin anomaly

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 pinch and prick tests. Laboratory examination reveals large platelet sizes - up to 8-12 µm (giant platelets), moderate thrombocytopenia, changes in the morphology of platelets and neutrophils. Abnormal platelet sizes are the cause of their increased lysis. Basophilic inclusions in neutrophils (Döhle bodies) are simultaneously determined. No treatment is required.

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Thrombocytopenia in children with congenital and acquired infections of the neonatal period

Thrombocytopenia in children with congenital and acquired infections of the neonatal period manifests itself as a hemorrhagic syndrome not associated with DIC, which often occurs with severe infectious diseases (both viral and bacterial in nature) in newborns.

Thrombocytopenia in the neonatal period occurs in 10-15% of cases of severe infections. The most common cause is congenital cytomegalovirus infection. Less often, thrombocytopenia occurs in congenital toxoplasmosis, syphilis, as well as in herpesvirus and enterovirus infections. Of the acquired diseases, sepsis, ulcerative necrotic 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 detachment from megakaryocytes, increased destruction of platelets due to fixation of toxins on them, and increased consumption of platelets due to damage to the vascular endothelium. Each of these factors or their combinations cause a decrease in the number of blood platelets, which leads to the development of hemorrhagic syndrome.

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

Laboratory tests reveal a decrease in the number of platelets, an increase in bleeding time with normal clotting time, TT and PTT, and the content of PDF in the blood is not increased, which distinguishes thrombocytopenia in children with infections from DIC.

Treatment

Special treatment is usually not required. Adequate therapy of the underlying disease is necessary. In case of severe bleeding and platelet level less than 20×10 ⁹ /l, replacement transfusion of platelet concentrate of the patient's blood group (10-30 ml/kg, intravenously by drip) is indicated.

Diagnosis of thrombocytopenia in children

In case of thrombocytopenia in children, it is necessary to determine the platelet content in the peripheral blood, clotting time, bleeding time, PT, antibodies to fetal platelets in the blood and milk of the mother, or to conduct a Coombs test (paternal platelets with maternal blood plasma). According to indications, a bone marrow examination (myelogram) is performed with material taken from three points. To assess the degree of blood loss, the content of erythrocytes, hemoglobin and hematocrit are determined.

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Differential diagnosis

Differential diagnostics of thrombocytopenia in children is necessary to determine the treatment tactics. Diagnostics 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
Isoimmune thrombocytopenia	Isoimmune conflict due to incompatibility of maternal and fetal platelets	Thrombocytopenia, increased bleeding time, presence of isoimmune antibodies to fetal platelets
Transimmune thrombocytopenia	Transplacental transfer of maternal fluid in immune form of Werlhof's disease and Evans disease in the mother	Relevant history, thrombocytopenia, increased bleeding time, maternal antiplatelet antibodies
TAR syndrome	Congenital hypo- or amegakaryocytosis in combination with atresia of the radial bones	Thrombocytopenia, increased bleeding time, absent or low megakaryocyte count in myelogram. Radial atresia, other malformations
Kasabach- Merritt syndrome	Congenital massive hemangioma resulting in thrombocytopenia due to platelet sequestration and lysis	Thrombocytopenia, increased bleeding time, giant hemangioma
Wiskott- Aldrich syndrome	An inherited disorder that includes eczema, thrombocytopenia due to increased platelet lysis, and insufficient production of antiendotoxin antibodies	Thrombocytopenia, shortened platelet life span, small platelet size
May-Hegglin anomaly	Hereditary thrombocytopenia caused by increased lysis of abnormally large platelets	Thrombocytopenia, shortened life span of platelets. Large platelets
Thrombocytopenia in infections	In severe viral and bacterial infections at the height of toxicosis	Thrombocytopenia, increased bleeding time, other symptoms of infection
Thrombocytopathies	Hereditary; medicinal (ethyl biscoumacetate, phenobarbital, carbenicillin, cephalosporins, etc.)	Normal or increased platelet count, impaired platelet adhesion, increased bleeding time
Immune thrombocytopenia	Formation of antibodies to platelets loaded with haptens of viral or drug origin	Association with medication and/or acute respiratory viral infection

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