Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prothrombin complex concentrates are used in the treatment of the congenital bleeding disorders associated with Factors II, VII, IX, and X deficiencies. They have also been extensively used to treat acquired coagulation abnormalities secondary to vitamin K deficiency, warfarin ingestion, and various types of liver disease. The reported complications of prothrombin complex concentrates administration include hepatitis, anaphylaxis, and thrombosis. This paper documents the development of disseminated intravascular coagulation in association with the administration of prothrombin complex concentrates to patients with liver disease.
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PMID:Intravascular coagulation with use of human prothrombin complex concentrates. 93 80

Homozygosity for alpha 1-antitrypsin deficiency, usually of the genotype PIZZ, is one of the more common single gene defects in infants of European origin, occurring in about 1 in 2000 to 1 in 7000 of the newborn population. About 17% of such infants present with neonatal hepatitis and a small number with intracranial haemorrhage thought to be caused by vitamin K deficiency associated with cholestasis. At least 3% of PIZZ infants will die of cirrhosis in later childhood unless successfully treated by liver transplant. The pathogenesis of the liver disease is not understood and this is unsatisfactory both for treatment and for genetic counselling. The locus coding for alpha 1-antitrypsin (alpha 1AT) is designated PI for proteinase inhibitor. Careful study of the genotypes at this locus in neonatal disease shows that the only certain association is with the homozygous PIZZ genotype. The mutation results in a normal rate of synthesis of a polypeptide that becomes entrapped in the endoplasmic reticulum of the hepatocyte. Some other factor (or factors), as yet unidentified, determines whether severe liver damage results. The low level of alpha 1AT in the plasma seems unlikely to be the primary cause of damage but may play a secondary role. There is some evidence that the other factor(s) may be familial since in one study, though not in all, a high correlation for severity of liver disease was found between PIZZ siblings. The heterogeneity of the clinical course does not result from heterogeneity of PIZ alleles and there is no evidence that it is determined by variation in other related genes on chromosome 14. Only two possible clues have emerged so far. There is some evidence of a protective effect of breast-feeding, and a recent study has found the HLA class II DR3 antigen to be more common than expected in children with alpha 1-antitrypsin deficiency and liver disease. Accumulation of alpha 1AT protein in the hepatocytes may predispose them to some unidentified alteration of the immune response. It is possible that lack of antiprotease activity in the plasma might exacerbate the original damage, so the possibility of useful therapy with alpha 1AT cannot be ruled out entirely. At present, there is no valid way of predicting the severity of disease in a PIZZ child; hence, it is common for parents of a severely affected child to wish to terminate any future PIZZ pregnancy. The most direct method to diagnose the PIZZ genotype of a chorion villus sample is by allele-specific hybridization or sequencing of amplified DNA.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Genetics of alpha 1-antitrypsin deficiency in relation to neonatal liver disease. 218 61

In vitamin K deficiency or treatment with vitamin K antagonists, a precoagulant of prothrombin (Factor II) called preprothrombin has been established. We measured preprothrombin with Clarke-Freeman electrophoresis in 26 patients with acute viral hepatitis (21 HBS-AG positive) who did not suffer from vitamin K deficiency. Prothrombin and the vitamin-K dependent Factors VII, IX, and X were determined by standard coagulometric methods. Prothrombin was additionally estimated by immunoelectrophoresis according to Laurell. Three patients with acute HBS-AG positive hepatitis showed preprothrombin in their plasma. The activity of Factors II, VII, IX, and X was slightly below normal with normal concentration of Factor II in the immunoelectrophoresis. Liver parenchymal damage and cholestasis were slight; the pseudocholinesterase showed subnormal levels in all three patients. Possible causes for the appearance of preprothrombin in the peripheral blood in acute viral hepatitis and the possible connections with liver cell damage are discussed.
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PMID:[Preprothrombin in acute viral hepatitis B]. 717 63

The clinical details are reported of two premature infants who developed late onset haemorrhagic disease after receiving their initial doses of vitamin K1 prophylaxis intravenously. Both reported infants had received two doses of intravenous vitamin K1, 0.1 mg, in the 1st week of life, and a further oral dose, 1.0 mg, at 4 weeks. Bleeding due to vitamin K deficiency occurred on days 74 and 84, respectively. Vitamin K deficiency bleeding is rare in low birthweight infants, probably because it has been routine practice to give such infants intramuscular vitamin K1. One of the reported infants had cytomegalovirus hepatitis, the other did not have liver disease. These findings could be explained if intramuscular vitamin K1 were to have a longer duration of effect than intravenous vitamin K1. This may be because intramuscular vitamin K1 acts as a depot preparation. The findings suggest that intravenous vitamin K1 is less effective than intramuscular for long-term prophylaxis against late onset haemorrhagic disease. Intravenous vitamin K1 should not be used for long-term prophylaxis in the prevention of late onset haemorrhagic disease.
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PMID:Late onset haemorrhagic disease in premature infants who received intravenous vitamin K1. 882 51

Apart from inadequate surgical haemostasis, postoperative bleeding can be related to acquired disorders of platelet number, platelet function or coagulation proteins (e.g. Vitamin K deficiency, DIC or liver injury). We highlight our experience with three patients who suffered life-threatening bleeding in the postoperative setting. The three patients - a 47-year-old man and 70- and 74-year-old women -- all had negative histories for excessive bleeding with prior surgeries, and all had normal preoperative PT and aPTT tests. Surgeries were resection of ischaemic bowel, cholecystectomy and coronary artery bypass grafting. All patients experienced unexpected bleeding within the first few postoperative days requiring multiple red cell transfusions and surgical re-explorations. Evaluations within the first 4--7 days after surgery revealed that these three patients had developed prolonged aPTT due to demonstrable factor VIII antibodies initially at low titre. One patient was treated with high doses human factor VIII, corticosteroids, intravenous gammaglobulin and plasma exchanges. The inhibitor was no longer demonstrable after 6 weeks of such therapy, and he has remained in remission without therapy. The second patient was initially treated with high-dose human factor VIII infusions. Five months later, prednisone and 6-mercaptopurine were begun for worsening inhibitor titre and diffuse purpura and subcutaneous haematomas. The factor inhibitor remitted, but the patient died from liver failure related to post-transfusion hepatitis. The third patient was initially managed with high-dose human factor VIII. Two months later, worsening inhibitor titre and tongue haematoma was treated with activated prothrombin complex, corticosteroids and cyclophosphamide. Eight years later, she is on no therapy, demonstrates a mild bleeding tendency and has a stable low-titre inhibitor. There have been a few case reports of inhibitors to coagulation factors including factor VIII becoming manifest in the postoperative setting but surgery has not been widely recognized as an underlying cause for acquired haemophilia. This paper speculates on pathogenesis and reviews treatment options. This syndrome is remarkable for its abrupt onset in the first few postoperative days and for its substantial morbidity. The problem is potentially reversible with immunosuppressive therapy. Clinicians should be aware of this syndrome, considering acquired haemophilia in patients with unexpected postoperative bleeding.
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PMID:Surreptitious bleeding in surgery: a major challenge in coagulation. 1125 54

The objective of this study was to study etiologies and outcome of neonatal cholestasis in Thai infants. The medical records of infants aged less than 3 months with the diagnosis of neonatal cholestasis in Department of Pediatrics, Siriraj Hospital from 1993 to 2004 were retrospectively reviewed. The etiologies were diagnosed by history, physical examination, and proper investigations. There were 252 infants, including 135 males (53.6%) and 117 females (46.4%). The etiologies of cholestasis were idiopathic neonatal hepatitis (INH) 23%, extrahepatic biliary atresia (EHBA) 22.2%, total parenteral nutrition (TPN)-related cholestasis 18.3%, infection 9.9%, endocrine causes 6%, choledochal cyst 5.6%, Down syndrome 4.4%, hemolytic anemia 1.6%, and miscellaneous causes 9.1%, respectively. TPN-related cholestasis was increasingly found due to advance management of critically ill premature infants. Inborn error of metabolism were suspected in 8 patients (3.21%). Seventeen cases (6.7%) developed cholestasis during the first week of life due to hemolytic anemia, intrauterine infection, hypoxia and others. During the 3 month follow-up period, 6 cases died of progressive dysfunction of liver and one case with idiopathic neonatal hepatitis died from intracranial bleeding from vitamin K deficiency. In conclusion, INH and EHBA are the most common causes of neonatal cholestasis. Due to advance management and nutritional support in critically ill premature infants, TPN-related cholestasis is found more often. Inborn error of metabolism related to neonatal cholestases is uncommon in Thai infants. Overall short-term prognosis of neonatal cholestases is good.
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PMID:Neonatal cholestasis in Thai infants. 1685 19

Non-accidental trauma is the leading cause of intracranial hemorrhage (ICH) in infancy. In contrast, ICH as a part of vitamin K deficiency bleeding (VKDB) secondary to hepatobiliary disease is rare, but encountered even in the era of vitamin K (VK) prophylaxis. During 43 months, six cases with ICH were diagnosed as an initial presentation of VKDB. Clinical features and imaging findings of them were retrospectively reviewed. All cases were breastfed and received oral VK prophylaxis. Liver dysfunction was found in five. Brain CT showed hemorrhage in subdural and subarachnoid space in six, parenchyma in three, and ventricle in one. Abdominal ultrasound was positive in four with final diagnoses of biliary atresia in two, neonatal hepatitis in one, and milk allergy in one. Two cases with negative ultrasound were diagnosed as idiopathic VKDB. In conclusion, ICH with secondary VKDB is rare, but important in infancy in the era of VK prophylaxis.
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PMID:Vitamin K deficiency bleeding with intracranial hemorrhage: focus on secondary form. 1778 92

Alpha-1-antitrypsin (AAT) deficiency is a rare genetic disorder characterized by hepatitis in neonates, childhood and adulthood (protease inhibitor (PI)*ZZ) and emphysema with or without hepatitis (PI*ZZ)/(PI*SS,SZ or null) in adulthood. We report the case of a female neonate born at 40 weeks of gestation who presented with vitamin K deficiency-related intracranial bleeding and cholestasis of which she died at 28 days of age. At autopsy, the infant was found to have intracranial bleeding, hepatomegaly, and cholestasis with paucity of bile ducts in the liver. Small periodic acid-Schiff diastase positive intrahepatic granules and positive staining with antibodies against AAT protein suggested an AAT deficiency. AAT is a glycoprotein that has a protease inhibitor function. Its deficiency can be the result of various point mutations in Serpin 1 located on chromosome 14. The diagnosis AAT deficiency was confirmed by mutation analysis showing the PI*ZZ genotype in the neonate. In conclusion, AAT deficiency is a rare genetic disorder that can lead to a serious bleeding disorder in the neonatal period if not recognised on time. Pathological diagnosis together with verifying molecular analysis can be used to identify index patients.
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PMID:Diagnosis of alpha-1-antitrypsin deficiency in bleeding disorder-related neonatal death. 2081 7

Extrahepatic biliary atresia (EHBA) is a rare disease characterized by progressive and obliterative cholangiopathy in infants and is one of the major causes of secondary vitamin K deficiency bleeding (VKDB) due to cholestasis-induced fat malabsorption. Breast feeding increases the tendency of bleeding in EHBA patients because breast milk contains low amounts of vitamin K. A 2-month-old female infant unexpectedly died, with symptoms of vomiting and jaundice prior to death. She had been born by uncomplicated vaginal delivery and exhibited normal growth and development with breastfeeding. There was no history of trauma. She received vitamin K prophylaxis orally. In an emergency hospital, a CT scan showed a right intracranial hematoma and mass effect with midline shift to the left. In the postmortem examination, severe atresia was observed in the whole extrahepatic bile duct. Histologically, cholestasis, periductal fibrosis, and distorted bile ductules were noted. The gallbladder was not identified. A subdural hematoma and cerebellar tonsillar herniation were found; however, no traumatic injury in any part of the body was observed. Together, these findings suggest that the subdural hemorrhage was caused by secondary vitamin K deficiency resulting from a combination of cholestasis-induced fat malabsorption and breastfeeding. Subdural hemorrhage by secondary VKDB sometimes occurs even when vitamin K prophylaxis is continued. This case demonstrated that intrinsic factors, such as secondary VKDB (e.g., EHBA, neonatal hepatitis, chronic diarrhea), should also be considered in infant autopsy cases presenting with subdural hemorrhage.
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PMID:Subdural hemorrhage: A unique case involving secondary vitamin K deficiency bleeding due to biliary atresia. 2260 80