Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have shown that activated partial thromboplastin time values in children are considerably longer than in adults, but the causes for this observation remained unclear. Therefore, we investigated the correlation between activated partial thromboplastin time values and concentrations of clotting factors, quotients and titers of the tissue thromboplastin inhibition test, and antiphospholipid antibodies in healthy children, children with recurrent infections, and adults. Concentrations of factors VIII, IX, and HMWK were significantly lower in children than in adults. Simple linear regression analysis failed to show a correlation between the concentration of a single clotting factor and the activated partial thromboplastin time values. No significant correlation was found between activated partial thromboplastin time and elevation of the tissue thromboplastin inhibition test quotients or titers, or antiphospholipid antibodies values. The determined activated partial thromboplastin time was best described by a function including all measured coagulation factors. Our study suggests, that no single clotting factor or lupus anticoagulants are responsible for the longer activated partial thromboplastin time in healthy children, but that activated partial thromboplastin prolongation is caused by the combination of several slightly lower clotting factors.
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PMID:Longer aPTT values in healthy children than in adults: no single cause. 1129 Dec 89

Performance characteristics of a totally synthetic activated partial thromboplastin time (APTT) reagent, recently available commercially, were evaluated and compared with a rabbit-brain extracted reagent. We found that the synthetic reagent, Synthasil, returned significantly higher normal APTT values than the brain-extracted reagent, Thrombosil. APTT ratios (APTT patients/normal mean APTT), yielded by Synthasil were higher in the majority of patients receiving heparin therapy. Synthasil also returned longer APTT values than did Thrombosil on normal plasma spiked with heparin. On patients with lupus anticoagulants, APTTs assayed with Synthasil were generally longer than with Thrombosil. However, the differences disappeared when APTT values were converted to ratios. Factors XII-, XI-, IX- and VIII-deficient plasmas supplemented with normal plasma to yield activities of 2-50%, generally gave longer APTTs with Synthasil than with Thrombosil. However, this was not always the case on plasmas from haemophilias A and B patients. No reduction in Synthasil activity was noted after the reagent had been left at 24 degrees C for 28 days.
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PMID:Performance characteristics of a new synthetic APTT reagent. 1070 16

Activated protein C (APC) is a naturally occurring anticoagulant that interacts with factor V and VIII to inhibit the clotting cascade. The prevalence of APC resistance among Korean patients with deep vein thrombosis is ill defined. The aim of the present study was to investigate the prevalence of APC resistance and factor V Leiden mutation in Korean patients with deep vein thrombosis. The presence of factor V Leiden mutation was determined in 49 patients who visited Asan Medical Center. APC ratio was performed in 33 individuals from the above 49 patients. Three patients were excluded from the analysis because their baseline aPTT was prolonged. Resistance to APC was diagnosed when the APC ratio was below 2.55. APC resistance was documented in 8 individuals, representing 27% (8/30) of the patients on whom APC resistance test was performed. The 2 patients, who showed APC resistance, were positive for lupus anticoagulant. None of the 49 patients demonstrated factor V Leiden mutation. These findings indicate that factor V Leiden mutation is rare and APC resistance is less prevalent in Korean patients with deep vein thrombosis than in Caucasians. APC resistance not caused by factor V Leiden mutation may be a risk factor for deep vein thrombosis in this population.
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PMID:Low prevalence of activated protein C resistance and coagulation factor V Arg506 to Gln mutation among Korean patients with deep vein thrombosis. 988 65

In a whole year from July 1997 to June 1998, a total of 50 patients with sonogram-proved venous thrombosis who called on our hematology clinic consecutively entered into the study. Their mean age was 59.1 +/- 17.5 years, range 18-83 years, and 29 were male. A series of examinations were performed in order to find out the cause of venous thrombosis. These examinations included antithrombin, protein C, protein S, plasminogen, heparin cofactor II, activated protein C ratio, factor V Leiden mutation, fibrinogen, factors VIII and XII, euglobulin lysis time, 677 C-->T mutation of methylenetetrahydrofolate reductase (MTHFR), prothrombin 20210 (PT 20210) A allele mutation, lupus anticoagulant, anticardiolipin antibody, and complete blood count. Five patients (10%) were found to have malignancy; an inferior vena cava thrombosis in one patient was due to venous compression by hydronephrosis; two patients had lupus anticoagulant; two had varicose veins of legs; two had protein C deficiency; four had protein S deficiency; two had plasminogen deficiency; two had antithrombin deficiency. No activated protein C resistance, elevated factor VIII level, factor V Leiden, PT 20210 A allele or heparin cofactor II deficiency was found in the present study. Homozygous MTHFR 677 C-->T gene mutation was found in 7 patients (14%); one of them also had a plasminogen deficiency. No possible risk factor of venous thrombosis could be found in 24 patients (48%). In conclusion, malignancy and protein S deficiency were the most frequent acquired and congenital causes of venous thrombosis in the Chinese, respectively.
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PMID:Causes of venous thrombosis in fifty Chinese patients. 1062 72

Venous thromboembolism (VTE) is a chronic rather than acute disease. After withdrawal of secondary thromboprophylaxis, many patients will experience a subsequent episode of thrombosis. Of these patients, approximately 5% will die from pulmonary embolism. The risk of recurrent VTE depends on the number of risk factors and their severity. High-risk patients, i.e. those with a natural coagulation inhibitor deficiency, recurrent thrombosis, active cancer, the lupus anticoagulant or compound clotting defects most probably benefit from indefinite oral anticoagulation. In these patients the risk of bleeding due to anticoagulant treatment seems to be outweighed by the risk of VTE. Patients with hyperhomocysteinemia or high factor (F) VIII plasma levels are also at an increased risk of recurrence. The optimal duration of secondary thromboprophylaxis in these patients is currently under investigation. Patients with the heterozygous F V Leiden mutation or the G20210A mutation in the F II gene do not require extended anticoagulation since their risk of recurrence is similar as in patients without the aforementioned mutations. Patients with VTE secondary to surgery or trauma have a relatively low risk of recurrence. In these patients short-term secondary thromboprophylaxis (6 to 12 weeks) is justified whereas patients with a first episode of spontaneous VTE should be treated with oral anticoagulants for a longer period of time (3 to 6 months).
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PMID:The risk of recurrent venous thromboembolism. 1223 19

Cranial dural arteriovenous fistulae (DAVF) may occur post-traumatic or sporadic. The physiopathologic mechanisms of sporadic DAVF are still unclear. A dural sinus thrombosis followed by an increase in venous pressure and/or an increased procoagulatory activity of the coagulation system are associated at least with some DAVF. The objective of this study was to investigate the coagulation profile in patients with DAVF. Thus the association of thrombophilic abnormalities, sinus thrombosis and DAVF should be analyzed. A total of 15 patients with cranial DAVF were included in this study. Blood samples were analyzed for 20210A mutation of the prothrombin gene, resistance to activated protein C and factor V Leiden mutation. Fibrinogen (Fib), Textarin time (TT), antithrombin (AT), protein C and protein S activity, von Willebrand factor antigen (vWF:Ag), Ristocetin cofactor activity (vWF:RCo), D-Dimer (DD) and coagulation factor VIII-activity (F VIII) were determined in all patients. Blood was screened for the occurrence of lupus antiphospholipid antibodies and cardiolipin antibodies. Thrombophilic risk factors were found in 5 (33%) of the 15 patients with cranial DAVF. Four patients had a heterozygote 20210A mutation of the prothrombin gene and one patient had a heterozygote FV Leiden mutation. Sinus thrombosis was detected in two patients with grade 2b DAVF and was associated with a 20210A mutation of the prothrombin gene in both patients. Additionally, one patient had deficient protein C activity and screening for cardiolipin antibodies was positive in three patients. In the current series the frequency of prothrombin Gene 20210A mutation was higher in patients with DAVF compared to the general population, whereas the incidence of Factor V Leiden mutation was not. Therefore in patients with cranial DAVF thrombophilic abnormalities should be considered in the post-operative/post-interventional management.
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PMID:Increased incidence of thrombophilic abnormalities in patients with cranial dural arteriovenous fistulae. 1457 93

Systematic evaluations of anemia, thrombocytopenia, and coagulopathy are essential to identifying and managing their causes successfully. In all cases, clinicians should evaluate RBC measurements alongside WBC and platelet counts and WBC differentials. Multiple competing factors may coexist; certain factors affect RBCs independent of those that affect WBCs or platelets. Ideally, clinicians should examine the peripheral blood smear for morphologic features of RBCs, WBCs, and platelets that provide important clues to the cause of the patient's hematologic disorder. Thrombocytopenia arises from decreased platelet production, increased platelet destruction, or dilutional or distributional causes. Drug-induced thrombocytopenias present diagnostic challenges, because many medicines can cause thrombocytopenia and critically ill patients often receive multiple medications. If they suspect type II HIT, clinicians must promptly discontinue all heparin sources, including LMWHs, without awaiting laboratory confirmation, to avoid thrombotic sequelae. Because warfarin anticoagulation induces acquired protein C deficiency, thereby exacerbating the prothrombotic state of type II HIT, warfarin should be withheld until platelet counts increase to more than 100,000/microL and type II HIT is clearly resolving. The presence of a consumptive coagulopathy in the setting of thrombocytopenia supports a diagnosis of DIC, not TTP-HUS, and is demonstrated by decreasing serum fibrinogen levels, and increasing TTs, PTs, aPTTs, and fibrin degradation products. Increasing D-dimer, levels are the most specific DIC parameter and reflect fibrinolysis of cross-linked fibrin. Elevated PTs or a PTTs can result from the absence of factors or the presence of inhibitors. Clinicians should suspect factor inhibitors when the prolonged PT or aPTT does not correct or only partially corrects following an immediate assay of a 1:1 mix of patient and normal plasma. In addition to factor inhibitors, antiphospholipid antibodies (e.g., lupus anticoagulant) can produce a prolonged aPTT that does not correct with normal plasma but is overcome by adding excess phospholipid or platelets. Paradoxically, a tendency to thrombosis, not bleeding, accompanies lupus anticoagulants and the antiphospholipid antibody syndrome. Transfusion of red blood cells, platelets, or plasma products is sometimes warranted, but clinicians must carefully weigh potential benefits against known risks. In critically ill patients, administering RBCs can enhance oxygen delivery to tissues. Among euvolemic patients who do not have ischemic heart disease, guidelines recommend a transfusion threshold of HGB levels in the range of 6.0 to 8.0 g/dL; patients who have HGB that is at least 10.0 g/dL are unlikely to benefit from blood transfusion. The use of rHuEPO to increase erythropoiesis offers an alternative to RBC transfusion, assuming normal, responsive progenitor cells and adequate iron, folate, and cobalamin stores. Future research should examine whether clinical outcomes from rHuEPO use in critically ill patients are important and cost-effective. Because platelets play an instrumental role in primary hemostasis, platelet transfusions are often important in managing patients who are bleeding or at risk of bleeding with thrombocytopenia or impaired platelet function. Platelet transfusions carry risks, and decisions to transfuse platelets must consider clinical circumstances. Most important, platelet transfusions are generally contraindicated if the underlying disorder is TTP or type II HIT, because platelet transfusion in these settings may fuel thrombosis and worsen clinical signs and symptoms. Plasma products can correct hemostasis when bleeding arises from malfunction, consumption, or underproduction of plasma coagulation proteins. Choice of plasma product for transfusion depends on clinical circumstances. FFP is the most commonly used plasma product to correct clotting factor deficiencies, particularly coagulopathies that are attributable to multiple clotting factor deficiency states as in liver disease, DIC, or warfarin anticoagulation. PCC or rFVIIa that is administered in small volumes may provide advantages over FFP when coagulopathies require quick reversal without risk of volume overload. Factor concentrates can replace specific factor deficiencies. Recombinant FVIIa bypasses inhibitors to factors VIII and IX and vWF. Use of rFVIIa in managing hemostatic abnormalities from severe liver dysfunction; extensive surgery, trauma, or bleeding; excessive warfarin anticoagulation; and certain platelet disorders requires further study to determine optimal and cost-effective dosing regimens. Recombinant activated protein C reduces mortality from severe sepsis that is associated with organ dysfunction in adults who are at high risk for death (APACHE scores of at least 25). In severe sepsis, levels of protein C decrease, as do fibrinogen and platelet levels. Because of its anticoagulant effect, however, drotrecogin alfa may induce bleeding. Guidelines for drotrecogin alfa use must take into account bleeding risks.
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PMID:Critical issues in hematology: anemia, thrombocytopenia, coagulopathy, and blood product transfusions in critically ill patients. 1471 Jun 93

Coagulopathy is a life-threatening complication of liver cirrhosis. We describe the effect of molecular adsorbent recirculating system (MARS), a cell-free dialysis technique, on the blood coagulation of cirrhotic patients. From February 2002 to July 2002, nine patients--five males (55.5%) and four females (44.4%), age 47-70 yr (median 56)--underwent 12 courses (4-7 sessions each) of MARS. Patients were treated for the following indications: six (66.6%) acute-on-chronic hepatic failure, three (33.3%) intractable pruritus. Platelet count, prothrombin time (PT), international standardized ratio and thromboelastography were measured before and after each MARS session. Coagulation factors II, V, VII, VIII, IX, X, XI, XII, XIII, von Willebrand, lupus anticoagulant, protein C, protein S, antithrombin III, plasminogen, alpha 2 antiplasmin, D-dimer, fibrin monomers, complement, and C(1) inactivator were measured before and at the end of each MARS treatment. We found a statistically significant difference (p < 0.05) in the platelet count, PT, all the thromboelastograph variables (reaction and constant time, alpha angle, and maximal amplitude), factor VIII, von Willebrand, and D-dimer, when measured before and after MARS. Previous reports have shown amelioration of blood coagulation following MARS treatments. However, we document that MARS induces coagulopathy through a platelet-mediated mechanism, whereby platelet may be mechanically destroyed during the passage of blood through the filters and lines. An alternative postulated mechanism is an immune-mediated platelet disruption - coagulopathy.
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PMID:Thromboelastography used to assess coagulation during treatment with molecular adsorbent recirculating system. 1523 11

Venous thromboembolism is a chronic disease with an annual incidence of recurrence of 5 to 10%. Patients with venous thrombosis should be treated with anticoagulants for at least 3 months. The optimal duration of anticoagulation entails balancing the risk of recurrence against the risk of treatment-associated bleeding. Candidates for extended anticoagulation are patients with a high risk of recurrence. The risk of recurrence is increased in patients with antithrombin deficiency, the lupus anticoagulant, homozygous F V Leiden, combined defects, high F VIII, high F IX, high TAFI, hyperhomocysteinemia or more than one episode of thrombosis. The risk of recurrence is low in patients with venous thrombosis secondary to surgery or trauma. Routine thrombophilia screening is aimed at identifying patients who could benefit from extended anticoagulation. This population consists of patients with venous thrombosis at a young age, an unprovoked episode of venous thrombosis, patients with a strong positive family history or patients with recurrent venous thrombosis. Screening should comprise antithrombin determination and the search for the lupus anticoagulant. Patients harbouring one of these defects are at high risk of recurrence and most likely will profit from prolonged anticoagulation. The clinical relevance of new treatment strategies such as extended low-intensity warfarin or administration of the direct thrombin inhibitor (xi-)melagatran is at present unclear.
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PMID:The optimal duration of secondary thromboprophylaxis in patients with venous thromboembolism. The importance of thrombophilia screening. 1577 39

The most common nonimmune etiology of acquired von Willebrand syndrome (AvWS) includes hypothyroidism, Wilms' tumor, thrombocythemia, or congenital heart defects, and the use of various drugs. AvWS type 1 in patients with hypothyroidism is due to decreased Willebrand factor (vWF) synthesis and is reversible by treatment with thyroxin. AvWS type 1 or 3 in children with Wilms' tumor disappears after successful chemotherapy or tumor resection but the mechanism of the vWF deficiency is unknown. The AvWS type 2 in patients with thrombocythemia of various myeloproliferative disorders is caused by increased proteolysis of large vWF multimers at increasing platelet counts to above 1000 x 10 (9)/L. Reduction of platelet counts to normal results in correction of the vWF parameters together with disappearance of the bleeding tendency. Type 2-like AvWS in children with congenital heart valve defects is caused by shear stress-induced proteolysis of large vWF multimers and is reversible after surgical correction. AvWS associated with the use of drugs disappears after discontinuation of the causative agent. Immune-mediated AvWS is associated with either systemic lupus erythematosus (SLE) or immunoglobulin G (IgG) benign monoclonal gammopathy (BMG), and usually shows a type 2 vWF deficiency. Using a simple enzyme-linked immunosorbent assay, an IgG antibody against vWF is detectable in AvWS associated with SLE and IgG BMG. The IgG-autoantibody-factor (F) vWF/VIII complex is rapidly cleared from the circulation, which explains the combined FVIII:coagulant activity (C) and vWF deficiency and the poor responses of FVIII:C and vWF parameters to intravenous desmopressin acetate and vWF/FVIII concentrates. A transient correction of both FVIII:C and vWF parameters to normal for a few weeks after high-dose intravenous immunoglobulin is seen in AvWS associated with SLE and IgG BMG. AvWS associated with SLE uniformly shows a curative response to corticosteroids. AvWS associated with IgG BMG does not respond to corticosteroids, immune suppression, or chemotherapy. AvWS associated with IgM BMG is rare and does not respond to any conventional treatment.
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PMID:Immune-mediated etiology of acquired von Willebrand syndrome in systemic lupus erythematosus and in benign monoclonal gammopathy: therapeutic implications. 1697 68


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