早产儿肺透明膜病多器官组织微血栓栓塞的病理因素研究

目的观察２４小时内死亡的早产儿肺透明膜病（ＨＭＤ）患儿各器官组织中微血栓发生率及组织病理改变；探讨微血栓栓塞的病理因素。方法４８例（Ａ组２８例，Ｂ组２０例）ＨＭＤ尸检后，在生物显微镜下观察肺、心肌、脑、肝、脾、肾、肾上腺、甲状腺、胸腺和胰腺组织切片中微血栓，计算每平方厘米中微血栓数，平均检查每个器官组织面积为５５／ｃｍ２。结果肺及肺外２个以上器官血栓数≥２／ｃｍ２占５８％（２８／４８）；器官组织有栓塞、退行性变、出血和坏死；肺微血管显示微循环障碍、肺动脉高压的病理改变。结论微循环障碍并发ＤＩＣ导致微血栓形成和栓塞是重度ＨＭＤ患儿死于多器官功能障碍的主要病因。     

Disseminated intravascular coagulation with intracranial haematoma in neonatal congenital syphilis

Disseminated intravascular coagulation (DIC) although a well known complication in neonatal sepsis is extremely rare in congenital syphilis and there are scanty reports of this entity in the literature. Intracranial bleeding following DIC in neonatal congenital syphilis is even rarer, and has been reported only once earlier. We are reporting the second case of neonatal DIC with intracranial haematoma due to congenital syphilis in a newborn. Our patient also had clinical and biochemical evidence of hepatitis which predisposes to DIC. Extensive investigations and emergent use of imaging modalities including ultrasound and CT scan led to early diagnosis and treatment in our patient, who could therefore be salvaged from an otherwise life threatening disease.     

Low antithrombin III in neonatal shock: DIC or non-specific protein depletion?

Low antithrombin III (AT III) levels in shock are usually ascribed to disseminated intravascular coagulation (DIC). However, decreased activities of clotting factors and their inhibitors could reflect a generalised fall in plasma proteins rather than DIC. AT III and albumin were compared in 48 asphyxiated and non-asphyxiated newborn rabbits (pH 6.70-7.30). Both AT III and albumin were markedly decreased in the sickest animals and there was a direct linear relationship between the two proteins (P less than 0.001). Similar results were obtained in ten newborn infants suffering from shock and haemorrhagic diathesis. In all cases AT III and albumin were decreased below the normal range and significantly correlated (P less than 0.01). Our findings suggest that AT III is not a useful diagnostic marker of DIC. Further, a similar fall of clottable and non-clottable proteins in shock questions the general assumption that the ensuing coagulopathy is due to intravascular coagulation.     

Disseminated intravascular coagulation and congenital neuroblastoma.

A newborn infant with congenital neuroblastoma complicated by disseminated intravascular coagulation is described. At birth the infant showed liver and spleen enlargement and shortly thereafter malignant cells were found in the bone marrow. On the fifth day of life the infant started to bleed and coabulation analysis indicated disseminated intravascular coagulation. Heparin therapy corrected the coagulation anomaly and irradiation and chemotherapy temporarily improved the general condition of the infant. The infant finally succumbed from tis primary neoplastic disease.     

PATHOLOGY OF LETHAL FETAL GROWTH RETARDATION SYNDROME WITH AMINOACIDURIA, IRON OVERLOAD, AND LACTIC ACIDOSIS (GRACILE)

Autopsy study of 17 newborn infants with lethal autosomal recessive disease presenting as growth retardation with lactic acidosis, Fanconi aminoaciduria, and hepatic hemosiderosis is reported. The patients succumbed between day 1 and 4 months of life; 9 patients died within the first month. All patients showed severe pathologic changes of liver with cholestasis in all livers. Extensive accumulation of stainable iron of the hepatocytes was present in 9/17 autopsy tissues and in two biopsy specimens. Moderate to abundant iron storage in the Kupffer cells was seen in all liver specimens. The amount of hepatocytic iron was high in livers up to 1 month of age and decreased thereafter. The general features and liver findings of this disorder suggest the name Growth Retardation Aminoaciduria Cholestasis Iron Overload, Lactacidosis and Early Death (GRACILE, OMIM 603358). Calcified concrements were seen in the medulla of 13/16 kidney specimens. Pancreas of 13/14 patients showed interstitial fibrosis and exocrine atrophy. Various pathologic findings such as renal tubular dysgenesis, paucity of hepatic bile ducts and iron storage in the macrophages of spleen and pulmonary alveoli were observed in some cases. Previous extensive clinical genetic and laboratory investigations have revealed that the patients had a previously unrecognized genetic disease. It is inherited as an autosomal recessive trait. The gene locus is 2q 33-37. The basic defect of the disease remains unknown.     

Purpura fulminans in a newborn infant with galactosemia

An 11-day-old neonate presented with purpura fulminans and was subsequently diagnosed with galactosemia. Neonatal purpura fulminans occurs predominantly in patients suffering from inherited protein C deficiency or disseminated intravascular coagulation associated with septicemia. Hemostatic changes in patients with liver disease may result in bleeding or, rarely, thrombosis. We suppose that in the present patient, deficiency of protein C, secondary to liver disease, was responsible for the development of purpura fulminans. Treatment consisted of blood and blood products and galactose-free formula. The patient recovered with residual mild psychomotor retardation and the lesions with minimal scarring. In conclusion, galactosemia also should be kept in mind as an uncommon cause of purpura fulminans in newborn infants.     

DISSEMINATED INTRAVASCULAR COAGULATION AND CONGENITAL NEUROBLASTOMA

ABSTRACT: Faxelius, G., Teger-Nilsson, A-C, Wilhelmsson, S., and åstrom, L. (Department of Pediatrics, Department of Clinical Chemistry, and Department of Blood Coagulation Research, Karolinska sjukhuset, Stockholm, Sweden). Disseminated intravascular coagulation and congenital neuroblastoma. Acta Paediatr Scand, 64:667, 1975. A newborn infant with congenital neuroblastoma complicated by disseminated intravascular coagulation is described. At birth the infant showed liver and spleen enlargement and shortly thereafter malignant cells were found in the bone marrow. On the fifth day of life the infant started to bleed and coabulation analysis indicated disseminated intravascular coagulation. Heparin therapy corrected the coagulation anomaly and irradiation and chemotherapy temporarily improved the general condition of the infant. The infant finally succumbed from its primary neoplastic disease.     

THREE CASES OF DISSEMINATED INTRAVASCULAR COAGULATION

Disseminated intravascular coagulation (DIC) was a complication in 3 patients with different primary diseases. The probable initiation of the DIC was a thromboplastic active tumor, a laceration wound at cesarean section with amniotic embolism in the foetus and probable endotoxin release in a newly kidney biopsied patient with subacute glomerulonephritis. The DIC was interrupted in the first patient by extirpation of the tumor, in the other two by treatment with heparin in spite of bleeding tendency. The diagnosis can be strongly suspected by demonstrating a decrease of the fibrinogen content combined with a diminished number of platelets. A normalization of the condition can occur after interruption of the intravascular clotting by treatment with heparin.     

Histiocytic Hemophagocytosis in the Bone Marrow in Children with Sepsis and Disseminated Intravascular Coagulation

Two children with systemic E. coli and candidial infections developed disseminated intravascular coagulation (DIC). Bone marrow examination in both cases showed histiocytic hemophagocytosis, consistent with the diagnosis of the hemophagocytic syndrome. Histiocytic hemophagocytosis in the bone marrow, one of the markers of the activated mono-nuclear phagocyte system, might be common in patients with severe sepsis and DIC, especially in immunodeficiency.     

Management of coagulopathy with recombinant factor VIIa in a neonate with echovirus type 7

A 5-day-old newborn presented with neonatal enteroviral infection. The patient's hospital course was complicated by acute liver dysfunction, renal insufficiency, fluid overload, respiratory failure, hypertension, catheter related thrombosis, Klebsiella pneumoniae sepsis, intracerebral and intraventricular hemorrhage, and disseminated intravascular coagulation (DIC). Administration of fresh frozen plasma (FFP) and cryoprecipitate failed to control the patient's hemostasis and led to significant fluid overload. Recombinant activated factor VII (rFVIIa, Novoseven NovoNordisk, Bagsvaerd, Denmark) was given to the neonate as a bolus (rFVIIa at 60-80 microg/kg body weight), followed by a continuous infusion (2.5-16 microg/kg/hr). Recombinant activated factor VII controlled hemostasis, until the patient's liver function recovered. The patient's blood product requirement significantly decreased and his fluid overload resolved. Administration of rFVIIa appears to have stabilized the coagulation process. The patient appears to have fully recovered from the infection's complications.     

Disseminated intravascular clotting in kwashiorkor.

The role of disseminated intravascular clotting (DIC) in the pathogenesis of the bleeding diathesis kwashiorkor was investigated in 22 patients. According to the severity of the clinical and haematological findings, two grades of DIC were observed. A severe grade of DIC was shown in 6 cases (5 fatal) presenting with thrombocytopenia, hypofibinogenaemia, and multiple coagulation defects, and with abnormally prolonged partial thromboplastin,prothombin, and thrombin times]. A second goups of 16 patients (7 fatal) showed a less severe grade of DIC manifested by thrombocytopenia, low fibringoen level, and a clotting factor defect shown by rpolonged prothrombin and thrombin times.     

Diffuse intravascular coagulation associated with brain tumor surgery in children

There have been numerous reported cases of diffuse intravascular coagulation (DIC) or defibrination syndrome associated with head trauma, but very few reported cases associated with primary brain tumor. This report concerns the findings in a case of DIC associated with brain tumor surgery in an infant. The patient died 2 days after surgery from acute renal and respiratory failure as a result of postoperative DIC. Therapy for DIC is controversial and shows mixed results.     

Haemostatic Failure in Babies with Rhesus Isoimmunization

Platelet counts, fibrinogen levels, thrombotest, thromboplastin generation screening test, thrombin ratio, and titre of circulating fibrin degradation products, were measured in 30 infants with Rh isoimmunization, of whom 5 had a bleeding tendency clinically, and 8 had laboratory evidence of disturbed haemostasis.At necropsy intravascular fibrin deposits were found in the tissues of 3 out of 4 babies who died with haemorrhage.An additional retrospective survey indicated that haemorrhage had been a major factor in causing death in 10 out of 18 newborn babies who died with rhesus isoimmunization in the period 1967-69.Sites of haemorrhage at necropsy were mainly intracranial (subarachnoid and intracerebral) and intrapulmonary, with microscopical evidence of intravascular fibrin deposits in 5 cases.It is concluded that disseminated intravascular coagulation is a major cause of haemostatic failure in babies with rhesus isoimmunization, but that disturbed hepatic synthesis of coagulation factors may also play a part.Babies at risk from haemostatic failure are those with cord Hb below 7 g/100 ml. It is suggested that a platelet count should be performed as an initial investigation on all such infants.     

MRI evaluation and follow-up of bone necrosis after meningococcal infection and disseminated intravascular coagulation

Disseminated intravascular coagulation (DIC) is a serious complication of meningococcal septicaemia. It often results in infarction of various tissues namely the skin, adrenal glands, kidneys, brain and, much less commonly, bones. We describe a patient who presented bone lesions after meningococcal septicaemia. In addition to plain radiography and scintigraphy the lesions were evaluated with MRI and have proved to be extensive and still progressive, approximately 18 months after the onset of the disease.     

Neonatal lupus erythematosus with microvascular hemolysis

A female, term newborn born to a mother with a history of idiopathic thrombocytopenic purpura and antinuclear antibodies, single-stranded A antibody, and IgM anticardiolipin antibodies presented with immune thrombocytopenia, disseminated intravascular coagulation (DIC), microangiopathic hemolytic anemia, and a characteristic lupus rash in the periorbital areas. She responded to combined treatment with dexamethasone and intravenous immunoglobulin (IVIG). At age 9 months, she was readmitted with severe thrombocytopenia, DIC, and microangiopathic hemolytic anemia. She again responded to IVIG. This suggests that microangiopathic hemolysis can be a presenting symptom in neonatal lupus erythematosus and that reoccurrence of the microangiopathic hemolysis may occur even after the disappearance of lupus antibodies.     

新生儿败血症合并早期弥散性血管内凝血相关因素的临床研究

目的 探讨新生儿败血症合并早期弥散性血管内凝血(DIC)的相关临床因素,为临床早期诊断新生儿败血症合并DIC 提供参考。方法 采用临床回顾研究方法对我院NICU 2012~2013 年确诊为新生儿败血症的100 例患儿进行研究。根据ISTH 显性DIC 评分系统将患儿分为凝血功能正常组、非显性DIC 组(早期DIC 组)及显性DIC 组(晚期DIC 组),对各组临床表现及相关临床因素进行统计分析。结果 100 例败血症患儿中合并早期DIC 者44 例(44%);3 组患儿硬肿的发生率差异有统计学意义(χ2=12.776,P<0.05);窒息、出血及G- 菌感染是败血症合并早期DIC 的独立危险因素。结论 对于临床有窒息、出血及G- 菌感染的新生儿应积极监测凝血功能并采取早期干预措施,预防患儿由早期DIC 进展为晚期DIC,降低新生儿败血症的病死率。     

INTRAVASCULAR COAGULATION IN GENERALIZED HERPES SIMPLEX INFECTION OF THE NEWBORN

A case of disseminated herpes simplex virus infection in a newborn associated with a fatal bleeding diathesis is reported. The presence of intravascular coagulation was suggested by thrombocytopenia, fibrinogenopenia, and reduced Factor V level. At necropsy localized fibrin and platelet deposition was found in liver and lung. It is postulated that intravascular coagulation resulted from local tissue necrosis and the subsequent release of thrombo-plastin-like substances into the general circulation. Heparin therapy did not alter the fatal outcome.     

Hemostatic changes in neonates with anoxia and sepsis

Hemostatic profile (prothrombin time (PT), thrombin time (TT), kaolin cephalin clotting time (KCCT), plasma fibrinogen, serum fibrin/fibrinogen degradation products (FDP) and platelet counts) was examined in 153 neonates with birth anoxia and 86 with sepsis. Remarkable hemostatic alterations occurred in neonates with severe anoxia and sepsis, while those with moderate anoxia exhibited minimal or no change. Vitamin K administration to anoxic babies showed no improvement in the hemostatic profile after 48-72 hours. The hemostatic alterations were presumably due to incipient disseminated intravascular coagulation (DIC). In spite of the marked coagulation changes, only 3 neonates with sepsis and none of the anoxic newborns presented with clinical bleeding indicating a well balanced hemostatic mechanism.     

Expression of tissue factor pathway inhibitor in human fetal and placental tissues

The coagulation system differs markedly between fetuses, neonates, and adults, and fetal and neonatal thrombotic abnormalities are poorly understood. Tissue factor pathway inhibitor (TFPI) is an important inhibitor of the extrinsic pathway of coagulation. To begin examining the role of TFPI in the maternal-fetal relationship, TFPI expression in human fetal and placental tissues was studied by immunohistochemical staining. TFPI was widely expressed in human fetal tissues from 8-24 weeks gestation, particularly in epithelial and endothelial tissues. Fetal liver, lung, kidney, and intestine were notably positive for TFPI staining. Within the tissues, TFPI was expressed in pneumocytes, hepatocytes, renal tubular and glomerular cells, muscle fibers, and enterocytes. In placental tissues, TFPI was expressed in syncytiotrophoblasts, cytotrophoblasts, vascular endothelium, and extravillus trophoblasts from 10 weeks through term. Advancing gestation had little effect on TFPI expression. Further studies are needed to determine the functional role of TFPI in fetal and placental tissues and to define perturbations in its expression during fetal and neonatal disease states.     

Mesenchymal hamartoma of the liver in an older child: association with disseminated intravascular coagulation

A 9-year-old black girl underwent right hepatectomy because of a large primary tumor in the right lobe of the liver. Histopathologic examination revealed the diagnosis of mesenchymal hamartoma, a rare benign tumor occurring mostly in children below the age of 2 years. Preoperatively, the patient had laboratory evidence of mild disseminated intravascular coagulation (DIC) but had no bleeding manifestations. In preparation for the surgery, the patient received whole blood exchange transfusion and platelet transfusion which re-resulted in marked improvement in hemostatic parameters. Despite what appeared to be adequate replacement of blood loss during the surgical procedure, the patient developed sudden cardiac arrest near the end of the procedure and died. The probable cause of death was hypovolemia. This case of mesenchymal hepatic hamartoma illustrates two unusual features: age of the patient and the association with DIC. The latter, to our knowledge, has not been reported before.