Hemorrhagic disease of the newborn.

Hemorrhagic disease of the newborn is a disease of children in the neonatal period, manifested by increased bleeding due to a deficiency of blood clotting factors, the activity of which depends on the content of vitamin K.

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Epidemiology

The incidence of the disease in our country is 0.25-1.5%. Abroad, in countries where parenteral administration of vitamin immediately after birth has been introduced into clinical practice, the incidence of hemorrhagic disease has sharply decreased and is 0.01% or less.

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What causes hemorrhagic disease of the newborn?

The biological role of vitamin K is the activation of the gamma-carboxylation process of glutamic acid residues in blood coagulation factors: prothrombin (factor II), proconvertin (factor VII), antihemophilic globulin B (factor IX) and Stuart-Prower factor (factor X); also in plasma proteins C and S, which participate in anticoagulant mechanisms; osteocalcin and some other proteins. With a deficiency of vitamin K, inactive acarboxy-factors II, VII, IX and X (Protein induced by vitamin K-absence - PIVKA) are formed in the liver, which are unable to bind calcium and fully participate in blood coagulation.

Vitamin K penetrates the placenta very poorly. Primary hemorrhagic disease is associated with the fact that the content of vitamin K in the fetus is low (does not exceed 50% of the adult level). After birth, little vitamin K enters the body with breast milk, and its active production by the intestinal microflora begins on the 3rd-5th day of the child's life.

Factors contributing to primary K-hypovitaminosis in newborns: prematurity; administration of indirect anticoagulants, anticonvulsants, broad-spectrum antibiotics to pregnant women; gestosis; hepato- and enteropathies, intestinal dysbacteriosis.

In prematurity, the synthesis of polypeptide precursors of plasma factors (PPPF) of blood clotting in the child’s liver is reduced.

In secondary hemorrhagic disease, the disruption of the synthesis of blood coagulation PPPF occurs in liver diseases (hepatitis, biliary atresia, etc.). There is also a second variant of the development of secondary hemorrhagic disease - disruption of the synthesis of vitamin K, caused by long-term parenteral nutrition, malabsorption syndrome, or the administration of vitamin K antagonists - coumarin and neodicumarin.

In this case, children with very low levels of vitamin K in the blood and children with elevated levels of PIVKA are identified.

Pathogenesis

Disruption of the synthesis of PPPF and/or disruption of the carboxylation of glutamic acid residues of coagulation PPPF leads to disruption of the production of factors II, VII, IX and X. This is manifested by an increase in prothrombin time (PT) and activated partial thromboplastin time (APTT).

Symptoms of hemorrhagic disease of the newborn

The early form of hemorrhagic disease of the newborn is characterized by the appearance in the first days of life of bloody vomiting (hematemesis), pulmonary hemorrhage, hemorrhage into the abdominal organs and retroperitoneal space, especially often into the adrenal glands, liver, spleen. Hemorrhagic disease of the newborn can begin in utero, and intracranial hemorrhages (with neurosonography) and skin hemorrhages are detected in the child already at birth.

The classic form of hemorrhagic disease is typical for a child on breastfeeding and manifests itself on the 3rd-5th day of life with bloody vomiting, melena (intestinal bleeding), there may be skin hemorrhages (ecchymosis, petechiae), bleeding when the remainder of the umbilical cord falls off, cephalohematomas. In children with severe hypoxia, birth injuries, vitamin K deficiency may manifest itself in the form of intracranial hemorrhages, hemorrhages under the aponeurosis, as well as internal hematomas and bleeding.

Children with melena may have hyperbilirubinemia due to increased breakdown of red blood cells in the intestine. Melena is caused by the formation of small ulcers on the mucous membrane of the stomach and duodenum, in the genesis of which the leading role is given to excess glucocorticoids in the newborn (due to birth stress), ischemia of the stomach and intestine. Gastroesophageal reflux and peptic esophagitis play a certain role in the origin of melena and bloody vomiting.

Clinical symptoms of late hemorrhagic disease of the newborn may include: intracranial hemorrhages (more than 50%), extensive skin ecchymosis, melena, hematemesis, bleeding from the umbilical wound, hematuria, cephalohematoma.

Complications of hemorrhagic disease of the newborn include hypovolemic shock, which manifests itself as weakness, pallor, often a decrease in body temperature to subnormal levels, and a drop in blood pressure.

Classification

There are primary and secondary forms of the disease. Primary hemorrhagic disease of the newborn is associated with the fact that the content of vitamin K in the fetus is low and after birth its intake with breast milk is insignificant, and active production by intestinal microflora begins on the 3rd-5th day of the child's life. In secondary hemorrhagic disease, a violation of the synthesis of blood clotting PPPF occurs due to liver disease, prolonged parenteral nutrition or malabsorption syndrome in the newborn.

In addition, there is an early form of the disease, which is characterized by the appearance of bleeding on the 1-2 day of life, a classic form - bleeding on the 3-5 day of life and a late, often secondary, form, in which bleeding can develop on any day of the neonatal period.

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Diagnosis of hemorrhagic disease of the newborn

To diagnose hemorrhagic disease of the newborn, the blood clotting time, bleeding time, and platelet count are first examined. Later or simultaneously, the PT, APTT, thrombin time (TT), and red blood cell count, hemoglobin, and hematocrit (to detect anemia) are determined.

Hemorrhagic disease is characterized by prolongation of blood clotting time, with normal bleeding time and platelet count. The diagnosis is confirmed by prolongation of PT and APTT with normal TT.

With significant blood loss, anemia is observed, which, however, fully manifests itself 2-3 days after the bleeding.

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Differential diagnostics

Hematemesis and melena in infants must be differentiated from "maternal blood ingested syndrome," which occurs in one in three infants who have blood in their vomit or stool on the first day of life. The APT test is used for this: bloody vomit or stool is diluted with water to obtain a pink solution with hemoglobin. After centrifugation, 4 ml of the supernatant is mixed with 1 ml of 1% sodium hydroxide solution. A change in the color of the liquid (assessed after 2 minutes) to brown indicates the presence of hemoglobin A (maternal blood), and the preservation of the pink color indicates fetal (alkaline-resistant) hemoglobin G, i.e. the child's blood.

Differential diagnostics are also performed with other coagulopathies (hereditary), neonatal thrombocytopenic purpura and disseminated intravascular coagulation syndrome (DIC syndrome). For this purpose, a detailed coagulogram and, if necessary, a thromboelastogram are performed.

Laboratory data for the most common hemorrhagic syndromes in newborns

Indicators	Norm for full-term babies	Hemorrhagic disease	Hemophilia	Thrombocytopenia	DIC syndrome
Clotting time (according to Burker)	Start - 4 min End - 4 min	Extended	Extended	Norm	Extended
Bleeding time	2-4 min	Norm	Norm	Extended	Extended
Platelet count	150-400x10 9 /l	Norm	Norm	Reduced	Reduced
PV	13-16 sec	Extended	Norm	Norm	Extended
TV	10-16 sec	Norm	Norm	Norm	Extended
APTT	45-60 sec	Extended	Extended	Norm	Extended
Fibrinogen	1.5-3.0 g/l	Norm	Norm	Norm	Reduced
Fibrinogen /fibrin degradation products (FDP)	0-7 mg/ml	Norm	Norm	Norm	Increased

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Treatment of hemorrhagic disease of the newborn

Vitamin K3 (Vicasol) is used to treat hemorrhagic disease of the newborn. Intramuscular administration of a 1% solution at a rate of 0.1-0.15 ml/kg once a day for 2-3 days is indicated.

In case of severe bleeding, life-threatening bleeding, fresh frozen plasma 10-15 ml/kg or a concentrated prothrombin complex preparation (PP5B) 15-30 U/kg is administered simultaneously by intravenous bolus.

When hypovolemic shock develops, infusion therapy is first performed (after transfusion of fresh frozen plasma at a dose of 20 ml/kg) and, if necessary, red blood cell mass is transfused at a rate of 5-10 ml/kg.

How is hemorrhagic disease of the newborn prevented?

Prevention is not carried out for all newborns, but only for those from the high-risk group. These include premature babies, especially very premature babies; children deprived of breastfeeding, on parenteral nutrition, receiving antibiotics. In addition, children who have suffered severe perinatal hypoxia and asphyxia, birth trauma, children after cesarean section, children from pregnancies with gestosis against the background of low estrogen synthesis, as well as children from pregnancies with hepatopathy, enteropathy, dysbiosis and intestinal dysbacteriosis in the mother.

Risk factors also include the mother taking a number of medications in the last stages of pregnancy (anticonvulsants, indirect anticoagulants, broad-spectrum antibiotics and anti-tuberculosis drugs).

For prophylactic purposes, a 1% solution of Vikasol is prescribed at a rate of 0.1 ml/kg intramuscularly once for 1-3 days.

In the United States, on the recommendation of the American Academy of Pediatrics, since 1960, vitamin K (phytomenadione) (1 mg) has been administered intramuscularly to all newborn children.