Гемолитическая болезнь новорожденных

[PIV]

Уважаемые коллеги и Vladlen!
Современные показания для операции заменного переливания крови при гемолитической болезни новорожденных, рекомендации AAP. если кто может опубликуйте.
С уважением

[Vladlen]

Вопрос о том когда и кому проводить EXCHANGE TRANSFUSION при гемолитической б-ни новорожденных нельзя отнести к однозначно решенным. Ниже приведен отрывок из Нельсона, отражающий современное состояние этого вопроса.

EXCHANGE TRANSFUSION.
When an infant's clinical condition at birth does not require an immediate full or partial exchange transfusion, the decision to perform one should be based on a judgment that the infant has a high risk of rapid development of a dangerous degree of anemia or hyperbilirubinemia. Cord hemoglobin of 10 g/dL or less and bilirubin of 5 mg/dL or more suggest severe hemolysis but inconsistently predict the need for exchange transfusion. Some physicians consider previous kernicterus or severe erythroblastosis in a sibling, reticulocyte counts greater than 15%, and prematurity to be additional factors supporting a decision for early exchange transfusion. Intrauterine, intravascular transfusions have decreased the need for exchange transfusion.
The hemoglobin concentration, Hct, and serum bilirubin level should be measured at 4-6 hr intervals initially, with extension to longer intervals if and as the rate of change diminishes. The decision to perform an exchange transfusion is based on the likelihood that the trend of bilirubin levels plotted against hours of age indicates that serum bilirubin will reach the levels indicated in Tables 91-2 and 91-3 (Прилагаются). Term infants with levels of 20 mg/dL or higher have an increased risk of kernicterus. Ordinary transfusions of compatible Rh-negative irradiated RBCs may be necessary to correct anemia at any stage of the disease up to 6-8 wk of age, when the infant's own blood-forming mechanism may be expected to take over. Weekly determinations of hemoglobin or Hct should be done until a spontaneous rise has been demonstrated.
Careful monitoring of the serum bilirubin level is essential until a falling trend has been demonstrated in the absence of phototherapy. Even then, an occasional infant, particularly if premature, may experience an unpredicted significant rise in serum bilirubin as late as the 7th day of life. Attempts to predict the attainment of dangerously high levels of serum bilirubin based on observed levels exceeding 6 mg/dL in the 1st 6 hr or 10 mg/dL in the 2nd 6 hr of life or on rates of rise exceeding 0.5-1.0 mg/dL/hr can be unreliable. Measurement of unbound bilirubin may be a more sensitive predictor of the risk associated with hyperbilirubinemia.
Blood for exchange transfusion should be as fresh as possible. Heparin or citrate-phosphate-dextrose-adenine solution may be used as an anticoagulant. If the blood is obtained before delivery, it should be taken from a type O, Rh-negative donor with a low titer of anti-A and anti-B antibodies and should be compatible with the mother's serum by the indirect Coombs test. After delivery, blood should be obtained from an Rh-negative donor whose cells are compatible with both the infant's and the mother's serum; when possible, type O donor cells are generally used, but cells of the infant's ABO blood type may be used when the mother has the same type. A complete cross match, including an indirect Coombs test, should be performed before the 2nd and subsequent transfusions. Blood should be gradually warmed and maintained at a temperature between 35 and 37°C throughout the exchange transfusion. It should be kept well mixed by gentle squeezing or agitation of the bag to avoid sedimentation; otherwise, the use of supernatant serum with a low RBC count at the end of the exchange will leave the infant anemic. Whole blood or packed irradiated RBCs reconstituted with fresh frozen plasma to an Hct of 40% should be used. The infant's stomach should be emptied before transfusion to prevent aspiration, and body temperature should be maintained and vital signs monitored. A competent assistant should be present to help monitor, tally the volume of blood exchanged, and perform emergency procedures.
With strict aseptic technique, the umbilical vein is cannulated with a polyvinyl catheter to a distance no greater than 7 cm in a full-term infant. When free flow of blood is obtained, the catheter is usually in a large hepatic vein or the inferior vena cava. Alternatively, the exchange may be performed through peripheral arterial (drawn out) and venous (infused in) lines. The exchange should be carried out over a 45-60 min period, with aspiration of 20 mL of infant blood alternating with infusion of 20 mL of donor blood. Smaller aliquots (5-10 mL) may be indicated for sick and premature infants. The goal should be an isovolumetric exchange of approximately two blood volumes of the infant (2 × 85 mL/kg).

Infants with acidosis and hypoxia from respiratory distress, sepsis, or shock may be further compromised by the significant acute acid load contained in citrated blood, which usually has a pH between 7 and 7.2. The subsequent metabolism of citrate may result in metabolic alkalosis later if citrated blood is used. Fresh heparinized blood avoids this problem. During the exchange, blood pH and Pao2 should be serially monitored because infants often become acidotic and hypoxic during exchange transfusions. Symptomatic hypoglycemia may occur before or during an exchange transfusion in moderately to severely affected infants; it may also occur 1-3 hr after exchange. Acute complications, noted in 5-10% of infants, include transient bradycardia with or without calcium infusion, cyanosis, transient vasospasm, thrombosis, apnea with bradycardia requiring resuscitation, and death. Infectious risks include CMV, HIV, and hepatitis. Necrotizing enterocolitis is a rare complication of exchange transfusion.
The risk of death from an exchange transfusion performed by an experienced physician is 0.3/100 procedures. However, with the decreasing use of this procedure because of the use of phototherapy and prevention of sensitization, the general level of physician competence is decreasing. Thus, it is best if this procedure is performed in experienced neonatal referral centers.
After exchange transfusion, the bilirubin level must be determined at frequent intervals (every 4-8 hr) because bilirubin may rebound 40-50% within hours. Repeated exchange transfusions should be carried out to keep the indirect fraction from exceeding the levels indicated in Table 91-2 for preterm infants and 20 mg/dL for term infants. Symptoms suggestive of kernicterus are mandatory indications for exchange transfusion at any time.
LATE COMPLICATIONS.
Infants who have hemolytic disease or who have had an exchange or an intrauterine transfusion must be observed carefully for the development of anemia and cholestasis. Late anemia may be hemolytic or hyporegenerative. Treatment with supplemental iron, erythropoietin, or blood transfusion may be indicated. A mild graft vs host reaction may be manifested as diarrhea, rash, hepatitis, or eosinophilia.
Inspissated bile syndrome refers to the rare occurrence of persistent icterus in association with significant elevations in direct and indirect bilirubin in infants with hemolytic disease. The cause is unclear, but the jaundice clears spontaneously within a few weeks or months.
Portal vein thrombosis and portal hypertension may occur in children who have been subjected to exchange transfusion as newborn infants. It is probably associated with prolonged, traumatic, or septic umbilical vein catheterization.

[Vladlen]

И еще одна таблица

[Vladlen]

По поводу рекомендаций ААР ( приведена и в Нельсоне)

Age,h Total serum bilirubin level, mg/dL (pmol/L)
------------A ------B---------C ---------D
25-48 >12 (210) >15 (260) >20 (340) >25 (430)
49-72 >15 (260) >18 (310) >25 (430) >30 (510)
>72 _ >17 (290) >20 (340) >25 (430) >30 (510)

A- Consider Phototherapy†
B-Phototherapy
C-Exchange Transfusion if Intensive Photo therapy Fails‡
D-Exchange Transfusion and Intensive Phototherapy

† Phototherapy at these TSB levels is a clinical option, meaning that the intervention is available and may be used on the basis of individual clinical judgment.

‡ Intensive phototherapy (Appendix) should produce a decline of TSB of 1 to 2 mg/dL within 4 to 6 hours and the TSB level should continue to fall and remain below the threshold level for exchange transfusion. If this does not occur, it is considered a failure of phototherapy.

Источник:
Practice Guideline.
Management of Hyperbilirubinemia in the Healthy Term Newborn.
AMERICAN ACADEMY OF PEDIATRICS - 1994

Обращаю Ваше внимание, что рекомендации для недоношенных детей особенно расплывчаты.

------------------------------------------------
Кроме этого следует не забывать о возможности использования IVIG

[Vladlen]

И еще одна полезная таблица для ведения гипербилирубинемии.

-----------------------------------------
Figure 91-8 Risk designation of term and near-term well newborns based on their hour-specific serum bilirubin values. The high-risk zone is designated by the 95th percentile track. The intermediate-risk zone is subdivided into upper and lower risk zones by the 75th percentile track. The low-risk zone has been electively and statistically defined by the 40th percentile track. (Dotted extensions are based on less than 300 total serum bilirubin values/epoch.) (From Bhutani VK, Johnson L, Sivieri EM: Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns. Pediatrics 1999;103:9) - абстракт этой статьи -

Abstract:
OBJECTIVE: To assess the predictive ability of a universal predischarge serum bilirubin measurement to screen for risk of subsequent significant hyperbilirubinemia in the direct Coombs negative healthy term and near-term newborn during the first postnatal week. METHODS: Total serum bilirubin (TSB) levels were obtained at the time of the routine metabolic screen in all term and near-term newborns cared for in the Pennsylvania Hospital Well Baby Nursery (n = 13 003). Postnatal age (in hours) at the time of TSB measurement was recorded. A percentile-based bilirubin nomogram for the first week was constructed from hour-specific predischarge and postdischarge TSB values of newborns (n = 2840; median BW = 3230 g and median gestational age = 39 weeks) who met classification criteria for healthy newborns (excluding those with a positive direct Coombs test or those requiring phototherapy before age 60 hours) and who were enrolled in a hospital supervised home or outpatient follow-up program. The accuracy of the predischarge TSB as a predictor of subsequent degree of hyperbilirubinemia was determined. RESULTS: The study patients in the nomogram were racially diverse. Nearly 60% were breastfed. Predischarge, 6.1% of the study population (172/2840) had TSB values in the high-risk zone (>/=95th percentile) at 18 to 72 hours; of these, 39.5% (68/172) remained in that zone (likelihood ratio [LR] = 14.08, sensitivity = 54%; specificity = 96.2%, probability = 39.5%). Predischarge, 32.1% of the population (912/2840) had TSB values in the intermediate-risk zone. In a clinically significant minority of these newborns (58/912 or 6.4%), the postdischarge TSB moved into the high-risk zone (LR of this move: 3.2 from the upper-intermediate zone and.48 from the lower-intermediate risk zone). The predischarge TSB in 61.8% of the newborns (1756/2840) was in the low-risk zone (<40th percentile) and there was no measurable risk for significant hyperbilirubinemia (LR = 0, sensitivity = 100%; specificity = 64.7%; probability = 0%). CONCLUSIONS: An hour-specific TSB before hospital discharge can predict which newborn is at high, intermediate or low risk for developing clinically significant hyperbilirubinemia (specifically defined as TSB levels >/=95th percentile for age in hours). Risk designation and subsequent increases or decreases of in TSB can be easily monitored on an hour-specific percentile based predictive bilirubin nomogram. A predischarge TSB measured as a universal policy would facilitate targeted intervention and follow-up in a safe, cost-effective manner. In conjunction with bilirubin practice parameter of the American Academy of Pediatrics, it could reduce the potential risk for bilirubin-induced neurologic dysfunction.

[PIV]

Уважаемый Vladlen!
Вы бы в своей клинике стали делать ОЗПК ребенку от титровой женщины, с весом 2300, с результатом ОАК - гемоглобин 214 г/л, с билирубином в возрасте 16 часов 150 мкмоль/л. Через 2 часа после рождения билирубин 70 мкмоль/л.
С уважением

[Vladlen]

Что такое "титрованная женщина"?
_____________________

Это решение зависит прежде всего от нескольких факторов, вами не указанных:
- возраст беременности;
- что сделано до этого и каков эффект;
-"болен" ли ребенок и пр.

Однако, думаю, что нет.

[PIV]

Титровая женщина - женщина у которой в крови есть титр антител к Д.
Срок гестации 34-35 недель.
Положительная реакция Кумбса в крови ребенка.
Ребенок с рождения получает инфузионную терапию и фототерапию.
Данному ребенку сделали уже 2 /два/ ОЗПК. Планировали третью при уровне вилирубина на 5 сутки 330 мкмоль/л, но крови на СПК не оказалось, а потом уровень билирубина снизился до 270 мкмоль/л.
Напишите пожалуйста об использовании внутривенного иммуноглобулина при ГБН и механизм действия, если ВАс это не затруднит.
С уважением

[Vladlen]

Несколько ссылок
______________________

1. Dagoglu T, Ovali F, Samanci N, Bengisu E: High-dose intravenous immunoglobulin therapy for Rhesus haemolytic disease. J Int Med Res 23:264, 1995

2. Ergaz Z, Arad I: Intravenous immunoglobulin therapy in neonatal immune hemolytic jaundice. J Perinat Med 21:183, 1993

3. Gottvall T, Selbing A: Alloimmunization during pregnancy treated with high-dose intravenous immunoglobulin. Effects on fetal hemoglobin concentration and anti-D concentration in the mother and fetus. Acta Obstet Gynecol Scand 74:777, 1995

4.Mukhopadhyay K: Intravenous immunoglobulins in rhesus hemolytic disease. - Indian J Pediatr - 01-SEP-2003; 70(9): 697-9


Обычно назначают 500 -750 мг/кг в течение 2 - 6 часов при положительном Кумбсе. Вероятный механизм действие - конкурентное ингибирование действия материнских антител.

Один из последних обзоров по поводу "Immunohematologic disorders" прилагается (файл).

[Vladlen]

Приложение

[drs.Van]

Уважаемый Владлен!
Если ВАС не затруднит, добавляйте еще ISBN-....
с уважением,
drs. Van

[PIV]

Уважаемый Владлен!
Какие рекомендации есть для проведения ОЗПК в первые сутки.
В наших руководствах есть графики для проведения ОЗПК, в которых для ребенка в возрасте 16 часов уровень билирубина 120-150 мкмоль/л рекомендуют проведение ОЗПК, также при почасовом приросте
более 5 мкмоль/л/час, то есть если при рождении 60-70 мкмоль/л, а через 8 часов уже 110-130 мкмоль/л, то рекомендуется ОЗПК. При этом может быть нормальный уровень гемоглобина.
В своей клинике вы пользуетесь шкалой показания к заменному переливанию крови?
С уважением

[NICU]

Хоть и с опозданием, но предлагаю всем интересную публикацию по поводу лечения желтух новорожденных, в том числе, и информацию об использовании иммуноглобулина.

[PIV]

Уважаемая Мария!
Спасибо Вам за интересную ссылку, в которой указаны действия для первых суток жизни ребенка.
В настоящее время, исходя из экономических условий, нам проще сделать ОЗПК /кровь для больниц фининсируется бюджетно/, чем использовать иммуноглобулины, которые стоят дорого и не входят в наши стандарты.

[BronEw]

Ув.PIV! Вы, как "зачинщик" дискуссии, пожалуйста скажите: проводите ли Вы индивидуальный подбор донора для ОЗПК? Если эта операция выполняется экстренно, то какие показания для Вас определяющие? Используете ли Вы лабораторию при проведении проб на совместимость или, как и я , смотрите через лупу? Какой приказ МинЗдрава Вы используете в своей работе при проведении ОЗПК? Эти вопросы у меня возникли потому, что в своей работе редко использую эту процедуру (неонатальная реанимация), возможно, потому что ее выполняют в роддоме. БронЕв