Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report on a patient with Klippel-Trenaunay (KT) syndrome, a factor VII deficiency and a copper metabolism disorder. The KT syndrome involved the left leg and, histologically, the liver. Dermatological examination, duplex ultrasonography and a skin and liver biopsy verified the KT syndrome. A long prothrombin time prompted clotting studies revealing a factor VII deficiency while the other factors were in the normal range. Further laboratory examinations showed a copper metabolism disorder similar to Wilson's disease with a low serum ceruloplasmin level, elevated copper concentration in the urine and increased copper deposition in the liver. Neither liver cirrhosis nor a Kayser-Fleischer corneal ring was present. Sequencing analysis of the Wilson's disease gene ATB7B showed no mutations. The occurrence of these three uncommon pathologies in a single patient has not been described to date, which may suggest a mutation in a hypothetical common regulatory gene leading to this unusual phenotype.
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PMID:Factor VII deficiency and a copper metabolism disorder in a patient with Klippel-Trenaunay syndrome. 1203 56

Acquired factor X deficiency has been described in patients with amyloidosis but acquired factor V deficiency is quite rare. We report here a case of life-threatening bleeding and acquired factor V deficiency associated with primary amyloidosis. A 50-year-old man who had no previous hemorrhagic diathesis was referred to our hospital because of recurrent epistaxis, gingival bleeding and hemospermia. The laboratory examination revealed that both the prothrombin time (PT) and the activated partial thromboplastin time (aPTT) were significantly prolonged, and factor V activities were markedly decreased to 14-39% of the normal value. Other coagulation factors such as fibrinogen, prothrombin, factor VII, factor VIII, factor IX and factor X were subnormal and normal. Transaminases were slightly elevated but serological tests of hepatitis B and hepatitis C were negative. Mild hepatosplenomegaly was noted without sign of liver cirrhosis. The PT and aPTT obtained 8 years ago when he received a cholecystectomy due to cholecystitis were both normal. Specific assays for the detection of factor V inhibitor were repeatedly performed but no factor V inhibitor was found. Furthermore, a significant recovery of the infused factor V was noted shortly after an intravenous administration of 5-10 U fresh frozen plasma, but it did not last more than 6 h. Melena, bleedings into the left shoulder and buttock, and finally mortal retroperitoneal hemorrhage developed despite repeated infusions of large amounts of fresh frozen plasma. Acquired factor V deficiency associated with primary amyloidosis was suspected but histological diagnosis was not obtained because of the severe bleeding tendency. Autopsy revealed hepatosplenomegaly and massive deposits of AL amyloid in the liver, spleen, heart and other parenchymal organs. Perivascular amyloid deposition and factor V deficiency are both thought to be the cause of the severe hemorrhagic tendency seen in this patient.
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PMID:Life-threatening bleeding and acquired factor V deficiency associated with primary systemic amyloidosis. 1219 8

Pro-hemostatic therapy aims at an improvement of hemostasis, which may be achieved by amelioration of primary hemostasis, stimulation of fibrin formation or inhibition of fibrinolysis. These treatment strategies may be applied to specifically correct a defect in one of the pathways of coagulation, but have in some situations also been shown to be effective in reducing bleeding in patients without a primary defect in coagulation. Besides the transfusion of platelets in case of thrombocytopenia or severe platelet disorders, a pharmacological improvement of primary hemostasis may be achieved by the administration of desmopressin. The administration of DDAVP results in a marked increase in the plasma concentration of Von Willebrand factor (and associated coagulation factor VIII) and (also by yet unexplained additional mechanisms) a remarkable potentiation of primary hemostasis as a consequence. DDAVP is used for the prevention and treatment of bleeding in patients with von Willebrand disease or mild hemophilia A, and further in patients with an impaired function of primary hemostasis, such as in patients with uremia, liver cirrhosis or in patients with aspirin-associated bleeding. Based on the current insight that activation of coagulation in vivo predominantly proceeds by the tissue factor/factor VII(a) pathway, recombinant factor VIIa has been developed as a prohemostatic agent and has recently become available for clinical use. Indeed, in uncontrolled clinical studies this compound has been shown to exert a potent procoagulant activity and appeared to be highly effective in the prevention and treatment of bleeding, although most experience so far has been obtained in patients with severe and complicated coagulation defects. At present, a more general use of this agent for bleeding patients without an apparent coagulation defect is the subject of a number of ongoing clinical trials. Agents that exert anti-fibrinolytic activity are aprotinin and the group of lysine analogues. The pro-hemostatic effect of these agents proceeds not only by the inhibition of fibrinolysis (thereby shifting the procoagulant/anticoagulant balance towards a more procoagulant state), but also due to a protective effect on platelets, as has been demonstrated at least for aprotinin. The mechanism of this platelet-protective effect has, besides a potential prevention of plasmin-mediated loss of platelet receptors not been elucidated. Whether the pro-hemostatic effect of the anti-fibrinolytic agents will eventually result in a higher incidence of thromboembolic complications is still a matter of debate (see further), however, this has so far not been shown in straightforward clinical trials.
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PMID:Management of bleeding disorders by prohemostatic therapy. 1243 Sep 14

Low levels of vitamin K-dependent coagulation factors, synthesized in the liver, play a key role in the hypocoagulable state of end-stage liver disease patients. Recombinant factor VII (rFVIIa) has been developed for, and currently is used in the treatment of patients with hemophilia A and B with inhibitors. Some experience was gained with rFVIIa in liver diseases since 1995. We used a low dose of rFVIIa to perform percutaneous liver biopsy in three patients, all of them with abnormal coagulation, impeditive of the percutaneous liver biopsy. The first one was a 29 years old man with alcoholic cirrhosis and a liver nodule; the second was a 32 years old man with post hepatitis C cirrhosis and excessive alcohol intake; the third was a 53 years old man with chronic hepatitis C and a congenital deficit of factor VII. A single dose of 5 micrograms/Kg of rFVII administered before liver biopsies raised levels of factor VII to acceptable values during more than 5 hours in the first two patients. We conclude that a small dose of rFVIIa can be enough to correct the abnormal coagulation of cirrhotic patients, permits percutaneous liver biopsy, and is cost-effective, compared to transjugular access.
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PMID:Small dose of recombinant factor VIIa (rFVIIa) to perform percutaneous liver biopsies in cirrhotic patients. 1247 36

Bleeding from gastroesophageal varices is a frequent and often deadly complication of cirrhosis. The key factor in the natural history of esophageal varices is increased portal pressure, which in cirrhosis is due to the combination of increased hepatic vascular resistance and increased portal collateral blood flow. The maintenance and aggravation of this situation leads to the progressive dilation of the varices and thinning of the variceal wall, until the tension exerted by the variceal wall exceeds the elastic limit of the vessel, leading to variceal hemorrhage. Mortality from a variceal bleeding episode has decreased in the last two decades from 40% to 20% due to the implementation of effective treatments and improvement in the general medical care. Initial treatment should include adequate fluid resuscitation and transfusion to maintain the hematocrit at 25% to 30%, and prophylactic antibiotics (norfloxacin or amoxicillin-clavulanic acid). It is currently recommended that a vasoactive drug be started at the time of admission. Drug therapy may be started during transferal to hospital by medical or paramedical personnel and maintained for up to five days to prevent early rebleeding. Terlipressin, a vasopressin derivative, is the preferred agent because of its safety profile and proven efficacy in improving survival. Somatostatin is as effective as terlipressin, but may require higher than the usually recommended dosage. Octreotide is effective in conjunction with endoscopic therapy, but is the second choice because it has not been shown to reduce mortality. Vasopressin may be used where terlipressin is not available, but should be given in combination with transdermal nitroglycerin. Endoscopic elastic band ligation is the recommended endoscopic treatment, but injection sclerotherapy is still employed in many centres for active variceal bleeding. Failures of medical therapy (drugs plus endoscopic therapy) should undergo a second course of endoscopic therapy before proceeding to transjugular intrahepatic portosystemic shunt or, in rare occasions, to portosystemic shunt surgery. Administration of recombinant activated factor VII may decrease the number of treatment failures among patients with advanced liver failure (Child-Pugh class B and C).
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PMID:Medical management of variceal bleeding in patients with cirrhosis. 1499 22

Patients undergoing orthotopic liver transplantation (OLT) have excessive blood loss during surgery that requires blood transfusions, leading to increased postoperative morbidity and mortality. We studied the efficacy and safety of activated recombinant factor VII (rFVIIa) in reducing transfusion requirements in OLT. This multicenter, randomized, double-blind, placebo-controlled trial enrolled patients undergoing OLT because of cirrhosis (Child-Turcotte-Pugh class B or C). Patients received a repeated intravenous bolus regimen of rFVIIa 60 or 120 microg/kg or placebo. The primary efficacy endpoint was the total number of red blood cell (RBC) units transfused during the perioperative period. A total of 182 patients were analyzed for efficacy and 183 for safety. No significant effect of rFVIIa was observed on the number of RBC units transfused or intraoperative blood loss compared with the placebo group. A significantly higher number of patients in the rFVIIa study groups avoided RBC transfusion. Administration of rFVIIa but not placebo restored the preoperative prolonged prothrombin time to normal value during surgery. Patients receiving rFVIIa and placebo did not experience a significant difference in rate of thromboembolic events. Additionally, there was no statistically significant effect of rFVIIa treatment on hospitalization rate, total surgery time, and the proportion of patients undergoing retransplantation. In conclusion, use of rFVIIa during OLT significantly reduced the number of patients requiring RBC transfusion. There was no increase in thromboembolic events with rFVIIa administration compared with placebo.
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PMID:Efficacy and safety of repeated perioperative doses of recombinant factor VIIa in liver transplantation. 1603 71

Patients with cirrhosis and impaired coagulation often pose major therapeutic problems during bleeding episodes or invasive procedures. Recombinant activated factor VII (rFVIIa), which has been licensed for the treatment of haemophilia patients with factor VIII or IX inhibitors, has been occasionally used in cirrhotic patients. We present five patients with cirrhosis and coagulopathy who received 1-4 recombinant activated factor VII infusions either prophylactically in order to safely undergo an invasive procedure or therapeutically in order to control a severe bleeding episode which did not respond to standard supportive care. In particular, recombinant activated factor VII infusions were given in two patients before a percutaneous liver biopsy, in one patient before teeth extraction and in two patients with haemoperitoneum after an invasive procedure. Infusions of recombinant activated factor VII achieved rapid correction of prothrombin time in all cases allowing the safe performance of invasive procedures or resulting in efficient control of the bleeding episode. In conclusion, recombinant activated factor VII seems to be a rather promising agent for the prevention or treatment of complications of haemostasis impairment in cirrhotic patients. However, its exact role in this setting needs to be evaluated within well-designed, controlled clinical trials.
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PMID:Prophylactic and therapeutic use of recombinant activated factor VII in patients with cirrhosis and coagulation impairment. 1678 69

Intra-abdominal thrombotic complications in orthotopic liver transplantation can cause devastating results. The management of these patients after thrombosis remains a difficult clinical problem. We present a case report of a patient who developed recurrent venous, thrombosis after liver transplantation performed because of cirrhosis due to autoimmune hepatitis. She had bleeding episodes during and early after the transplantation procedure and developed portal vein thrombosis after a single dose of recombinant factor VII, which was given for treatment of hemorrhage. She had her second thrombotic attack while she was on warfarin therapy which was initiated after the first bout. No hereditary or immunologic risk factors were found. Management of these patients can be difficult because of the liver's effect on the coagulation profile.
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PMID:Management of recurrent thrombosis in liver transplant recipients: a case report. 1826 18

Haemorrhagic complications significantly increase mortality and cost of treatment in cardiac surgery. A few years ago recombinant activated factor VII has been introduced to decrease such complications. In our department recombinant activated factor VII has been used in 11 patients between 2004 and 2007. Nine of them underwent a combined (simultaneous CABG and valve replacement) high risk surgery with long aortic cross clamp time and long extracorporeal circulation time. One patient underwent a repeat coronary artery bypass operation and one was operated for aortic dissection. The average dose given was 6.5 mg (2.4-9.6 mg). The average amount of bleeding without NovoSeven given was 5440 ml, however it was only 987 ml when NovoSeven was used. Nine of the patients were completely recovered and discharged from hospital, but two of them died in the postoperative period for delayed use of the recombinant factor VII-a and for severe co-morbidities (bowel ischaemia, cirrhosis of the liver). NovoSeven given in the proper time and dose significantly reduces bleeding following cardiac surgery, even if it cannot be stopped surgically. Using recombinant factor VIIa can save life in case of severe non-surgical diffuse bleeding or in case of suture insufficiency caused by friable soft tissues following high risk combined surgery with extremely long aortic cross clamp time and extracorporeal circulation time. Significant delay in the use of NovoSeven should be avoided because the temporary reduction of bleeding usually does not change fatal outcome.
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PMID:[Our experience with recombinant activated factor VII (NovoSeven) in the high risk cardiosurgical patients with bleeding complication]. 1850 37

Recombinant activated factor VII, a bypassing hemostatic agent originally developed for the treatment of hemorrhages in hemophilic patients with inhibitors, is increasingly being employed on a compassionate use basis for the treatment of uncontrolled massive bleeding from various causes. In this review, we present the current knowledge on the use of this agent in patients with severe coagulopathy due to end-stage liver disease. In particular, the role of recombinant activated factor VII for treating gastrointestinal bleeding episodes in patients with decompensated cirrhosis or for prophylaxis before liver surgical or invasive procedures will be addressed. The pathogenesis of complex coagulopathy in chronic liver diseases and the mechanisms by which recombinant activated factor VII might improve coagulation in such patients will also be described. Given the paucity of the published data and the lack of randomized trials, there is not enough evidence to support the extensive use of recombinant activated factor VII in any of the clinical indications analyzed. In conclusion, further large randomized, controlled clinical trials are needed to better define the role of recombinant activated factor VII in the treatment of bleeding complications of liver disorders.
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PMID:The use of recombinant factor VIIa in liver diseases. 1860 80


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