Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An 18-year-old white male developed severe hepatic veno-occlusive disease (VOD) during an autologous bone marrow transplant for primary refractory nodular sclerosing Hodgkin's disease. As a result of VOD-induced hepatic dysfunction, coagulation studies revealed depression of vitamin K dependent procoagulant factor VII. Intravenous recombinant tissue plasminogen activator 20 mg over h on 4 consecutive days and continuous heparin infusion (1000 unit bolus followed by 150 units/kg/day) resulted in rapid reversal of the VOD syndrome. During treatment, procoagulant factors II, VII, IX and X levels increased indicating the return of hepatic synthesizing capacity. Factor V levels, which were elevated pre-therapy, also rose dramatically. Plasma antigen levels of protein C, a natural anticoagulant, remained severely depressed. No clinical evidence of bleeding and only minimal systemic fibrinolysis was noted. Despite concerns regarding the use of lytic therapy in a thrombocytopenic post-BMT patient, serial measurements of coagulation parameters during severe VOD suggested that low dose rt-PA improved portions of the systemic hemostatic profile.
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PMID:Treatment of hepatic veno-occlusive disease with low-dose tissue plasminogen activator: impact on coagulation profile. 887 29

Hepatic veno-occlusive disease (VOD) is a major complication after bone marrow transplantation (BMT). Its prediction, diagnosis and treatment remain unclear. Examination was made of changes in hemostatic parameters in patients with or without VOD after BMT. Twenty-seven children were studied following BMT. Eight of them developed VOD. Tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), thrombomodulin (TM), von Willebrand factor (vWF), factor VII, fibrinogen (FBG), FDP, D-dimer (D-D), plasminogen (PLG), thrombin-antithrombin III (TAT), alpha 2-plasmin inhibitor/plasmin complex (PIC), antithrombin III (AT-III), protein C, N-terminal propeptide for type III procollagen (P-III-P), were measured weekly from pre-BMT to day 28 after BMT. In VOD patients, t-PA and PAI-1 significantly increased (P < 0.05) and FBG significantly fell during the post-transplant period (P < 0.05). Significantly low AT-III and PLG were also noted before VOD (P < 0.05). There were no changes in other hemostatic parameters. t-PA, PAI-1 and FBG would thus appear useful markers for the diagnosis of VOD, and AT-III and PLG, predictive markers for VOD. The coagulation-fibrinolysis system following endothelial cell damage may contribute to the onset of VOD.
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PMID:Changes in hemostatic parameters in hepatic veno-occlusive disease following bone marrow transplantation. 915 66

Venocclusive disease of the liver is a relatively frequent early complication of bone marrow transplantation related to pre-transplant toxic injury to the liver. Events that lead to toxicity of the liver in the pre-transplant setting are infection, anti-neoplastic and anti-infectious drug administration and radiation. The histological correlates of venocclusive disease are lesions mainly localized to structures in zone 3 of the liver acinus and in the sublobular central venules. At some point in the pathogenesis of venocclusive disease, blood clotting and inflammation occur. The first is characterized by laboratory signs of coagulation activation, by an increase in several procoagulant proteins and by a decrease in naturally occurring anticoagulants, particularly protein C, the latter being a sensitive index of liver injury. Inflammation is mediated by cytokine production, which maintains procoagulant endothelial responses and liver injury. Severe venocclusive disease is associated with multi-organ failure and elevated mortality. Attempts at finding predictive markers of the disease have succeeded in identifying some coagulation and inflammatory proteins which can be useful in predicting the occurrence of VOD in selected patient groups. The role of hemostasis in venocclusive disease is underscored also by the reports on the successful prophylaxis and management of the disease with heparin and thrombolytic agents.
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PMID:Venocclusive disease of the liver after bone marrow transplantation: the role of hemostasis. 916 34

A hypercoaguable state has been shown to follow high-dose chemotherapy for bone marrow transplantation (BMT). Deficiency of the natural anticoagulants, antithrombin III (AT-III), protein C and protein S correlate with organ dysfunction following BMT. We treated 10 patients with severe post-BMT organ dysfunction with AT-III concentrate. Indications for treatment included AT-III anticoagulant level less than 88% and life-threatening single or multiorgan dysfunction. All patients were loaded with 50 units/kg AT-III every 8 h for three doses followed by 50 units/kg/day each day for 3-12 days. Clinical improvement was seen within 1-5 days of start of therapy in all patients. Patients with veno-occlusive disease (VOD) showed a decrease in platelet consumption in nine of nine patients, resolution of hepatic tenderness in six of eight patients, and reduction of severe ascites and weight gain in four of five patients. The probability of death due to VOD and life-threatening organ dysfunction was significantly less in the AT-III-treated group when compared to a historical control group receiving the same preparative regimen (P = 0.047 and P = 0.034, respectively). Significant improvements in organ dysfunction following AT-III treatment in this small study supports a causal relationship between AT-III deficiency and post-BMT chemotherapy-induced organ dysfunction.
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PMID:Antithrombin-III for the treatment of chemotherapy-induced organ dysfunction following bone marrow transplantation. 940 29

We monitored 30 laboratory hemostatic parameters in an attempt to better comprehend alterations in coagulation and fibrinolysis in 10 patients with hematological malignancies subjected to autologous peripheral blood stem cell transplantation (APBSCT). These parameters were assessed before and just after high-dose conditioning chemotherapy, on days 1, 7, 14 and 28. Although, clinical manifestations associated with fibrino-coagulation disorders never occurred, including veno-occlusive disease, a statistically significant increase was seen in 7 of 30 parameters, compared to values seen before conditioning chemotherapy. These were subdivided into early and late phase parameters. The early phase parameters, which increased during the first day after the conditioning chemotherapy was given, then returned to baseline values, included protein C, plasma tissue factor and tissue-plasminogen activator. The late phase parameters, which increased over baseline values during days 7 to 28, included free-protein S, fibrinogen, plasmin-alpha2-plasmin inhibitor complex and soluble-thrombomodulin. The increase of early phase parameters, as produced by the liver and by endothelial cells, may reflect tissue damage by conditioning chemotherapy. Late phase parameters increased in parallel with C-reactive protein, which suggests a correlation with the degree of inflammation, such as the presence of infective disease during neutropenia. These subclinical alterations in coagulation and fibrinolysis which take on a biphasic pattern during the course of APBSCT should be kept in mind by the attending physicians during therapy.
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PMID:Subclinical alterations in coagulation and fibrinolysis in patients undergoing autologous peripheral blood stem cell transplantation. 951 13

Severe veno-occlusive disease (VOD), characterised by elevated serum bilirubin levels, is a known complication in the first 3 weeks after peripheral blood stem cell transplantation (PBSCT). Severe VOD is associated with capillary leakage and multiple organ dysfunction and leads to high mortality. We report a 17-year-old male, who developed VOD with capillary leakage (CL) after allogeneic PBSCT. The patient presented with a maximum serum bilirubin of 25.4 mg/dl, weight gain (10% of baseline weight), generalized edema, cardiovascular insufficiency, complement activation, jaundice and a decreased AT and protein C functional activity. After VOD and CL were diagnosed the patient was treated with recombinant human plasminogen activator (rt-PA) and C1 esterase-inhibitor concentrate (C1-INH-C). The clinical symptoms resolved and the patient's status stabilized. The patient was in an adequate clinical state 5 months after transplantation. We noted that the combined therapy with rt-PA and C1-INH-C in this high-risk situation led to a resolution of VOD with CL.
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PMID:Hepatic veno-occlusive disease with severe capillary leakage after peripheral stem cell transplantation: treatment with recombinant plasminogen activator and C1-esterase inhibitor concentrate. 961 90

Hepatic veno-occlusive disease (VOD) of the liver is a common complication following high-dose cytotoxic therapy for bone marrow transplantation (BMT). The major pathological changes are seen in centrilobular (zone 3) hepatocytes and adjacent endothelium. Glutathione (GSH) becomes depleted following chemotherapy and experimental evidence suggests reduced levels predispose to centrilobular hepatocyte and endothelial cell injury. Animal studies have shown that glutamine infusions can maintain GSH levels and protect against free radical injury. We have prospectively studied the effect of glutamine supplementation during BMT. Thirty-four patients undergoing BMT were randomised to receive either glycl-L-glutamine (n = 18) or an isonitrogenous mixture of non-essential amino acids (n = 16). Glutamine was shown to significantly preserve protein C (days +4 and +7, P < 0.05) and albumin levels (days 0 and +4, P < 0.02). Markers of thrombin and plasmin generation (thrombin-antithrombin, prothrombin fragment F1+2 and plasmin-antiplasmin levels) were not significantly changed between the two groups. These findings suggest that glutamine preserves hepatic function but does not alter thrombin or plasmin generation during BMT. Previous studies have shown reductions in protein C, albumin, factor X and factor VII levels post BMT. Falling protein C levels have been shown to be predictive of severe VOD. These data suggest a role for glutamine in the protection of hepatic function following BMT.
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PMID:Parenteral glutamine protects hepatic function during bone marrow transplantation. 972 Jul 43

Factors that enhance hypercoagulability following BMT may have a pathogenetic role in VOD. To investigate the relevance of hemostatic parameters for the development of VOD, we prospectively measured protein C, protein S, antithrombin III (AT III), von Willebrand factor, and factor VIII in 50 consecutive patients undergoing allogeneic BMT. Each parameter was determined before conditioning, on day 0 of BMT and weekly for 3 weeks, and patients were monitored prospectively for the occurrence of VOD. VOD occurred in 26 patients at median post-BMT day 8.5 (range, day -2 to 17). Thirteen patients had mild, 10 had moderate and three had severe VOD. No coagulation parameters were significantly different at the baseline or on day 0 of BMT between patients with no/mild VOD and moderate to severe VOD. On day 7 and thereafter, levels of protein C and AT III were significantly lower in patients with moderate to severe VOD when compared to patients with no/mild VOD. Levels of protein C and AT III decreased before the clinical onset of VOD in patients with moderate to severe VOD. Early post-BMT reduction of these parameters may indicate the development of moderate to severe VOD.
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PMID:Relevance of proteins C and S, antithrombin III, von Willebrand factor, and factor VIII for the development of hepatic veno-occlusive disease in patients undergoing allogeneic bone marrow transplantation: a prospective study. 982 16

Factor V Leiden is one of the most common genetic conditions predisposing to venous thrombosis. Diagnosis is currently made by plasma activity assay for activated protein C (APC) resistance or polymerase chain reaction (PCR)-based DNA assay. The occurrence of factor V Leiden is reported in a patient affected by acute myeloid leukaemia submitted to allogeneic bone marrow transplantation from an HLA identical sister. The donor was not affected by the factor V mutation. The patient did not develop thrombosis during induction and consolidation chemotherapy and the post-transplantation course was not complicated by thrombosis or veno-occlusive disease. At engraftment, PCR analysis showed the disappearance of factor V Leiden. Genetic tests on DNA after allogeneic marrow transplantation should be carefully interpreted as a result of donor chimerism.
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PMID:Factor V Leiden and allogeneic bone marrow transplantation: chimerism as a confounding factor in genetic test interpretation. 1067 93

The objective of the present study was to analyze whether veno-occlusive disease (VOD) is based on specific findings or whether this syndrome is the exacerbation of changes in hemostatic parameters that develop following hematopoietic stem cell transplantation (HSCT). 40 patients undergoing HSCT were enrolled (6 allogeneic bone marrow transplantation and 34 peripheral stem cell rescue-2 allogeneic, 32 autologous). Measurements of hemostatic parameters (endothelial, hypercoagulability and fibrinolytic markers) were obtained prior to chemotherapy and weekly thereafter for 3 weeks. The incidence of VOD was 15%. HSCT showed a state of moderate hypercoagulability (increase of thrombin-antithrombin complex and fibrinogen, and decrease of Factor VII, Protein C, and antithrombin-III), probably as a consequence of marked endothelial damage (increase of von Willebrand Factor and tissue plasminogen activator). All these alterations create a potentially prothrombotic state, more pronounced in VOD. The decreasing incidence of VOD and the moderate disease in all patients suggest that increasing improvements in transplant strategies have reduced the risk and severity of a syndrome that at the beginning of the transplantation era was a leading cause of morbidity/mortality.
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PMID:Is veno-occlusive disease a specific syndrome or the exacerbation of physiopathologic hemostatic changes in hematopoietic stem cell transplantation (HSCT)? 1097 71


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