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)

Ancrod is a thrombinlike enzyme from Malayan pit viper (Agkistrodon rhodostoma) venom that has a selective enzyme substrate specificity for fibrinogen. Unlike thrombin, it splits only fibrinopeptide A from the fibrinogen molecule and does not activate factor XIII. Simultaneously with the occurrence of hypofibrinogenemia there is a reduction of plasma plasminogen and a rise in fibrin degradation products, suggesting secondary recruitment of the fibrinolytic enzyme system. Ancrod was given to 18 patients with systemic lupus erythematosus and glomerular and vascular microthrombi. Before treatment vascular plasminogen activator (VPA) was low or unmeasurable in 14, an inhibitor of urokinase-induced plasminogen activation (IPA) was elevated in 18, and an inhibitor of plasmin (PI) was elevated in five. Ancrod treatment resulted in prompt normalization of IPA levels in 13 patients; they were classified as fibrinolysis responders. In five patients IPA levels remained elevated throughout treatment with ancrod; they were classified as fibrinolysis nonresponders. In these five the PI level was elevated before treatment and decreased slowly toward the normal range during ancrod administration. The PI did not appear related to the nonspecific serine protease inhibitors, and was shown to be identical with alpha 2-antiplasmin. In the fibrinolysis responders serial histologic studies showed a striking decrease of disappearance of microvascular thrombosis; in the fibrinolysis nonresponders microvascular thrombosis persisted. The action of ancrod is discussed.
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PMID:Ancrod: normalization of fibrinolytic enzyme abnormalities in patients with systemic lupus erythematosus and lupus nephritis. 387 65

Recent evidence demonstrates that coagulation plays a role in mediating glomerular damage in patients with systemic lupus erythematosus and diffuse proliferative glomerulonephritis. Because of its beneficial effect in experimental glomerulonephritis, we treated patients with systemic lupus erythematosus and diffuse proliferative glomerulonephritis with ancrod, a drug known to lower fibrinogen levels and thought to activate fibrinolysis. Our patients had unusually severe renal disease; renal function was deteriorating in many. Before ancrod, vascular plasminogen activator levels were low, and levels of an inhibitor of plasminogen activation were elevated. Some patients had elevated plasmin inhibitor levels. Results were considered in two groups. In 13 patients characterized as fibrinolysis responders, the low vascular plasminogen activator and increased plasminogen activation inhibitor levels normalized. After ancrod, striking resolution of microvascular thrombosis occurred, which was associated with some improvement in renal function and blood pressure control. In five patients characterized as fibrinolysis nonresponders and who also had an elevated plasmin inhibitor (alpha 2-antiplasmin) level, normalization of fibrinolysis did not occur. There was little change in microvascular thrombosis, renal function, or blood pressure control in the fibrinolysis nonresponders. These preliminary observations demonstrate a disorder of fibrinolysis in patients with systemic lupus erythematosus with microvascular thrombi in the kidney. Ancrod therapy reverses this disorder rapidly in patients with a normal level of plasmin inhibitor and may lead to repair of glomerular damage.
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PMID:Lupus nephritis with thrombosis and abnormal fibrinolysis: effect of ancrod. 396 67

Ancrod, which produces in vivo defibrination, has been shown to improve renal function and decrease fibrin deposition and crescents in experimental glomerulonephritis. Ancrod was given for 14 days to 5 patients with glomerulonephritis, moderate to severe renal functional impairment, crescents, and/or fibrin deposition in glomeruli. 4 patients had systemic lupus erythematosus. Ancrod treatment resulted in fibrinogen levels less than 50 mg/dl without bleeding, decrease of previously elevated factor VIII and von Willebrand factor levels, and normalization of in vitro platelet hyperaggregation. Renal function improved in all 5 patients. Serial renal biopsies showed a relatively rapid decrease of glomerular thrombi and necrosis and little increase in glomerular sclerosis. Ancrod administration appears safe, and may have a role in treatment of certain types of glomerulonephritis.
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PMID:Defibrination with ancrod in glomerulonephritis: effects on clinical and histologic findings and on blood coagulation. 681 68

Snake venoms contain a rich variety of factors affecting the haemostatic mechanism which can be broadly classified as possessing coagulatant, anticoagulant and haemorrhagic activity. Coagulant enzymes include activators of blood coagulation factors II (prothrombin), V and X; anticoagulants include protein C activators, inhibitors of prothrombin complex formation and fibrinogenases which can be further classified according to their specificity for the alpha-, beta- and gamma-chains of fibrinogen. Intermediate between true coagulants and true anticoagulants are the thrombin-like enzymes which bring about clotting in vitro but defibrination (anticoagulation) in vivo. Snake venoms also affect platelets either by inducing or inhibiting platelet aggregation and cause haemorrhage via an action on platelets or via proteolysis of the blood vessel wall. Haemorrhagins also include inter alia, the alpha-fibrinogenases. This rich diversity of snake venom components affecting haemostasis has enabled a range of practical applications to be established including therapeutic anticogulation with thrombin-like enzymes (Ancrod and Defibrase) and laboratory tests for individual haemostatic factors (protein C, prothrombin, factor X and lupus anticoagulant). This broad spectrum of materials in snake venoms suggests some evolutionary advantage to the venom producer, not only for dispatching prey but as agents which 'spread' the venom toxins throughout the body and initiate digestion.
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PMID:Snake venoms affecting the haemostatic mechanism--a consideration of their mechanisms, practical applications and biological significance. 807 11

Snake venom toxins affecting haemostasis have facilitated extensively the routine assays of haemostatic parameters in the coagulation laboratory. Snake venom thrombin-like enzymes (SVTLE) are used for fibrinogen/fibrinogen breakdown product assay and for the detection of fibrinogen dysfunction. SVTLE are not inhibited by heparin and can thus can be used for assaying antithrombin III and other haemostatic variables in heparin-containing samples. Snake venoms are a rich source of prothrombin activators and these are utilised in prothrombin assays, for studying dysprothrombinaemias and for preparing meizothrombin and non-enzymic forms of prothrombin. Russell's viper (Daboia russelli) venom (RVV) contains toxins which have been used to assay blood clotting factors V, VII, X, platelet factor 3 and, importantly, lupus anticoagulants (LA). Other prothrombin activators (from the taipan, Australian brown snake and saw-scaled viper) have now been used to assay LA. Protein C and activated protein C resistance can be measured by means of RVV and Protac, a fast acting inhibitor from Southern copperhead snake venom and von Willebrand factor can be studied with botrocetin from Bothrops jararaca venom. The disintegrins, a large family of Arg-Gly-Asp (RGD)-containing snake venom proteins, show potential for studying platelet glycoprotein receptors, notably, GPIIb/IIIa and Ib. Snake venom toxins affecting haemostasis are also used in the therapeutic setting: Ancrod (from the Malayan pit viper, Calloselasma rhodostoma), in particular, has been used as an anticoagulant to achieve 'therapeutic defibrination'. Other snake venom proteins show promise in the treatment of a range of haemostatic disorders.
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PMID:Practical applications of snake venom toxins in haemostasis. 1592 82