Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monocytes and endothelial cells were stimulated in co-culture with allogeneic lymphocytes to produce thromboplastin (TPL). The induction was biphasic, an early response (8-24 h) was greatly augmented by cyclosporin A (CS) (0.5-5 micrograms/ml) whereas the late response (day 3-4) was inhibited. Prednisolone inhibited both responses. Both drugs inhibited lymphocyte proliferation. Interferon-gamma decreased MLC TPL activity but increased thymidine incorporation. CD4+ cells were instrumental in inducing the early TPL peak in monocytes, whereas CD8+ cells decreased the TPL effect. With endothelial cells both T cell classes were equally effective. Conditioned medium from MLC as well as from co-cultures of endothelial cells and lymphocytes induced early TPL synthesis in endothelial cells. Upon allogeneic stimulation monocytes, but not endothelial cells, produced a significant amount of F-VII, most of which was apparently undercarboxylated.
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PMID:Allogenic induction of thromboplastin synthesis in monocytes and endothelial cells. Biphasic effect of cyclosporin A. 252

A 81-year-old man who had been healthy without any history of abnormal bleeding, developed ecchymosis and hematuria in November, 1992 and was hospitalized in December, 1992. On admission, he developed widespread ecchymosis in his trunk and extremities, and subsequently ecchymosis of his cheek and neck, and also oral and pharyngeal hematoma. The laboratory data were as follows: whole blood clotting time, > 20 minutes; activated partial thromboplastin time (APTT), 108.6 seconds; Factor VIII activity, 4%. The level of Factor VIII inhibitor was high, 65.0 Bethesda Unit/ml. This inhibitor was a IgG type immunoglobulin, which had both kappa and lambda light chain. His serological and blood biochemical data of the blood were normal, and tests for autoantibodies were negative. The patient was treated with plasma exchange therapy, Prednisolone (PSL), Cyclophosphamide and Factor VIII concentrate. The hemorrhagic symptoms were improved, the inhibitor disappeared and the activity of Factor VIII returned to normal after one month. Follow-up was continued in the outpatient clinic for 5 months. After the dose of PSL was decreased, he developed bloody sputum and hematuria, and was readmitted in August, 1994. Factor VIII activity was 21% and the titer of Factor VIII inhibitor was 3.0 BU/ml. The hemorrhagic symptoms disappeared soon after increasing the dose of PSL, and the Factor VIII activity was normalized and the inhibitor could not be detected. These treatments appeared to offer effective control on severe hemorrhage in a patient with Factor VIII inhibitor.
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PMID:[Elderly non-hemophiliac patient with factor VIII inhibitor presenting various type hemorrhages]. 773 44

Renal artery infarction is a very rare complication in patients with systemic lupus erythematosus (SLE), even in patients with antiphospholipid syndrome which often causes thromboembolism: Renal infarctions have only been reported in 4 SLE patients with antiphospholipid antibodies (aPL). Here we report a case of SLE without aPL who accompanied by renal and cerebral infarctions. A 42-year old Japanese woman with 8 year history of SLE manifested by arthralgia, central nervous system symptoms, positive-antinuclear and anti-DNA antibodies was admitted to our hospital for the treatment of progressive lupus nephritis. Physical examinations revealed hypertension (130-160/80-110 mmHg) without pitting pretibial edema. Laboratory evaluations showed proteinuria (3.7 g/day), normal serum creatinine level (0.9 mg/dl), low serum albumin level (2.3 g/dl) and high cholesterol level (317 mg/dl). Old cerebral infarctions were recognized by magnetic resonance imaging. However, hematological and immunological studies revealed that this case has neither a prolonged activated partial thromboplastin time, lupus anticoagulant nor anticardiolipin antibodies. Prednisolone was increased from 30 mg/every other day to 30 mg/day, and oral azathioprine, 50 mg/day, was started for the treatment of lupus nephritis. On the 11th day, she suddenly complained severe abdominal pain, which gradually localized on the right side. Computed tomography of the kidney suggested right renal infarctions, and arteriography of right renal artery confirmed both an obstruction of the ventral branch and a narrowing of the dorsal branch of right renal artery. No intra-cardiac thrombus was demonstrated by echocardiography. Following to the treatment with fibrinolytic agent and anticoagulant, her symptoms have improved.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Renal and cerebral infarctions in a patient with systemic lupus erythematosus without antiphospholipid antibodies]. 823 16

Acquired inhibitors to factor VIII (FVIII) are rare, but life-threatening in up to 22% of cases. The optimal therapy for suppression of these inhibitors remains unclear. Prednisolone is the mainstay of therapy, producing responses in approximately 30% of cases. Intravenous immunoglobulin (IVIg) has a similar response rate, but a more rapid effect. We report the results of prednisolone 1 mg kg(-1) combined with IVIg 2 g kg(-1) in divided doses as first-line therapy in seven consecutive patients with acquired FVIII inhibitors. All patients were bleeding at the time of diagnosis with prolonged activated partial thromboplastin time. There were four complete responses, one partial response, one nonresponse and one with an inadequate follow-up for assessment of response, giving an overall response rate of 71%. In all complete responders the inhibitor declined rapidly and was undetectable by day 21 from start of treatment. Therapy was well tolerated and responses have been maintained off treatment for 2-8 months. This is a safe, well-tolerated rapidly acting regimen with good response rates.
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PMID:Combined prednisolone and intravenous immunoglobulin treatment for acquired factor VIII inhibitors: a 2-year review. 1126 Feb 75

Acquired von Willebrand syndrome (AVWS) associated with hypothyroidism is of type I, results from a decreased synthesis of factor VIII and von Willebrand factor (VWF), responds to desmopressin with normal half-life times for factor VIII and VWF parameters, and disappears after treatment with I-thyroxine. AVWS type I or III, which occurs in a minority of patients with Wilms' tumour in the complete absence of an inhibitor against VWF and no absorption of factor VIII or VWF onto nephroblastoma cells, responds to chemotherapy and/or tumour resection. Hyaluronic acid produced by nephroblastoma cells may be the causative factor in atypical AVWS in Wilms' tumour. AVWS associated with thrombocythaemia of various myeloproliferative disorders is characterized by normal factor VIII and von Willebrand factor antigen (VWF: Ag) levels and a selective deficiency of functional ristocetin co-factor activity (VWF: RCo) and collagen-binding activity (VWF: CBA). AVWS type II in thrombocythaemia is caused by a platelet-dependent proteolysis of large VWF multimers, given the inverse relationship between platelet count and large VWF multimers in plasma and specific increases in the number of proteolytic VWF fragments in plasma. The laboratory findings of AVWS associated with systemic lupus erythematosus or IgG benign monoclonal gammopathy are characterized by a prolonged bleeding time and activated partial thromboplastin time, decreased or absent ristocetin-induced platelet activity, low to very low levels of factor VIII coagulant activity (mean 15%), VWF: Ag (mean 10.7%) and VWF: RCo (mean 6.2%), and a type II multimeric pattern of VWF. Neutralizing and non-neutralizing anti-VWF autoantibodies, usually IgG, have been detected in patient plasma either free or tightly bound to the intermediate and high molecular weight VWF factor VIII particles. The bound auto antibody-antigen complex is rapidly cleared from the circulation, resulting in low levels of factor VIII, VWF parameters as documented by a poor response to desmopressin and VWF factor VIII concentrate. High-dose intravenous immunoglobulin transiently corrects the factor VIII coagulant and VWF levels, lasting for a few weeks in AVWS type II associated with systemic lupus erythematosus or IgG benign monoclonal gammopathy. Prednisolone is effective in AVWS associated with autoimmune disorder. Prednisolone and chemotherapy will not affect AVWS associated with IgG benign monoclonal gammopathy because the monoclonal IgG protein remains to act as an anti-VWF autoantibody. An absorption of VWF to malignant cells has been documented in a few patients with various lymphoproliferative disorders or adrenal carcinoma and suggested to result in a depletion of VWF. The clinical picture of AVWS associated with early-stage IgG multiple myeloma, chronic lymphocytic leukaemia or non-Hodgkin's lymphoma without a paraprotein or no detectable underlying disorder is similar to that of AVWS type II in IgG benign monoclonal gammopathy but poorly documented with regard to the underlying immune mechanism of AVWS. The mechanical destruction of large VWF multimers may be of relevance in conditions in which the shear rate of flowing blood is increased, as may occur in cases of aortic stenosis, other heart valve defects or stenosed vessels. Drug-induced AVWS has been described in association with the use of pesticides valproic acid, ciprofloxacin, griseofulvin, tetracycline, thrombolytic agents and hydroxyethyl starch.
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PMID:Acquired von Willebrand syndromes: clinical features, aetiology, pathophysiology, classification and management. 1168 7

A 56-year-old woman was referred to our hospital with symptoms of swelling, purpura, and pain in her limbs. Prior to referral, bleeding in her limbs had spontaneously appeared and disappeared several times. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were prolonged, and the factor II level was 17%. The plasma-mixing test indicated lupus anticoagulant (LA), which was confirmed using aPTT-LA and dilute Russell's viper venom time (dRVVT). Therefore, she was diagnosed with lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS). During screening for underlying disorders, chest computed tomography (CT) revealed a retrosternal mass. Biopsy was not performed because the administration of freshly frozen plasma failed to correct her coagulopathy. Prednisolone (PSL) treatment (1 mg/kg) was initiated, which normalized the coagulation tests. The retrosternal mass also disappeared. PSL was tapered without LAHPS recurrence; however, the follow-up CT revealed systemic lymphadenopathy. Follicular lymphoma was diagnosed using lymph-node biopsy. Considering the subsequent LAHPS recurrence, six cycles of bendamustine + rituximab were administered. Complete response with no LAHPS recurrence was observed at the time of drafting this report. LAHPS is rare and distinct from antiphospholipid syndrome because it can cause severe bleeding. Underlying disorders should be evaluated in cases of LAHPS.
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PMID:[Lupus anticoagulant-hypoprothrombinemia syndrome associated with follicular lymphoma]. 3275 60

Since acquired factor V inhibitor (FV-INH) has been first reported in Germany in 1955, about 200 cases have been recorded globally. The incidence of FV-INH is extremely low, with a rate of 0.023-0.09 per million persons per year. FV-INH formation is caused by infection, use of antibiotics and other drugs, surgery, and diseases, including malignancy and autoimmune disorder. Some patients with FV-INH present with abnormal clinical laboratory test results but have no hemorrhagic symptoms. Others experience life-threatening bleeding. Moreover, thrombosis can sometimes occur. The diagnosis is based on prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT), an inhibitor pattern shown by a cross-mixing test of PT and APTT, decreased factor V activity, and detection of FV-INH. Treatment includes hemostatic and immunosuppressive therapy. However, in some cases, the monitoring of progression alone is appropriate. In terms of hemostatic therapies, infusion of platelet concentrates and administration of recombinant factor VIIa are highly useful. However, no definitive treatment strategy has been established. In about 50% of cases, FV-INH is eliminated spontaneously. Therefore, immunosuppressive therapy is recommended only for hemorrhagic patients or those at high risk of hemorrhage. Prednisolone is generally used for the management of immunosuppression. However, some reports have shown that the administration of rituximab, cyclophosphamide, and intravenous immunoglobulin and plasma-exchange can be utilized as treatments.
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PMID:[Acquired factor V inhibitor]. 3275 67