Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For rehabilitation training it is recommended that the intensity of exercise should be clearly below the individual anaerobic threshold (IAT). We investigated blood coagulation, particularly endogenous thrombin potential (ETP) and fibrinolysis following a standardized treadmill (TR) ergometer test at 90% IAT for 60-120 min. Sixteen healthy male non-smokers underwent the TR test. Blood samples were taken after a 30-min rest, immediately after exercise, and 2 h after exercise completion. Extrinsic and intrinsic total (TTP(ex+in)) and endogenous (ETP(ex+in)) thrombin potential, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), plasmin-alpha2-antiplasmin complex (PAP), D-dimer, tissue plasminogen activator antigen and activity (tPA-AG and tPA-ACT) and plasminogen activator inhibitor type 1 antigen and activity (PAI-1-AG and PAI-1-ACT) were measured. Immediately after TR, F1+2, TAT and TTP(ex+in) were increased ( P<0.05) while ETP(ex+in) remained unchanged. In contrast, PAP, D-dimer, tPA-AG, tPA-ACT ( P<0.05) were distinctly enhanced while PAI-1-ACT was decreased ( P<0.05) immediately after exercise. The changes in tPA-AG, tPA-ACT, and PAI-1-ACT were reversed to nearly baseline while the enhancement in PAP and D-dimer was prolonged by more than 2 h after exercise. Long-duration exercise between 60 and 120 min controlled by IAT (90%) on a TR ergometer only implicates a small increase in thrombin generation markers and total (free and alpha(2)-macroglubulin-bound thrombin), but not in endogenous (free) thrombin potential alone. In contrast, fibrinolysis is distinctly increased after this type of exercise. Endurance exercise with an intensity below 90% IAT and a duration below 2 h generates a more favourable condition for fibrinolysis than for blood coagulation in healthy young subjects. Data are given as mean (SD).
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PMID:Blood coagulation and fibrinolysis after long-duration treadmill exercise controlled by individual anaerobic threshold. 1288 4

Immune thrombotic thrombocytopenic purpura (iTTP) is a chronically relapsing, humorally-mediated autoimmune disorder characterized by unpredictable episodes of microangiopathic hemolytic anemia and thrombocytopenia, commonly associated with neurologic dysfunction, kidney injury, and fever. Episodes are caused by immune destruction or inhibition of the von Willebrand Factor (vWF) cleaving protease ADAMTS13. Currently, the standard of care is therapeutic plasma exchange (TPE), and most add immunosuppression with corticosteroids - a standard that is unchanged for nearly 30 years. There are multiple strategies for adding corticosteroids to TPE and the limited data available suggests that corticosteroids reduce the duration of ADAMTS13 deficiency in iTTP. Rituximab is also frequently used in the treatment of iTTP and evidence suggests that while it may not reduce the number TPE procedures required to induce remission, it likely increases relapse-free survival. Novel approaches to immunosuppression that have been reported include low-dose rituximab (also currently in clinical trials) and proteasome inhibition. A more targeted approach includes the anti-vWF nanobody, caplacizumab, recently approved for iTTP in Europe and United States, which in two large randomized controlled trials significantly shortened the time to normalization of platelet count, appreciably lowered the 30-day recurrence rate, and decreased the rate of the composite endpoint of death, recurrence, and major thromboembolic events. Recombinant ADAMTS13 has been tested in congenital TTP and could be tested in iTTP as well, along with novel approaches of modifying the enzyme to avoid the immune response or leveraging other vWF cleaving proteases such as plasmin to bypass ADAMTS13. Also, therapies that target preformed antibodies that are currently being tested in other humorally-mediated disorders could cross over to iTTP. Finally, progress has long been hampered in iTTP due to difficulty with accrual and disagreement about trial design. A good surrogate endpoint for relapse-free survival is also needed. Despite these challenges, a new era of precision medicine is likely soon emerging for treatment of iTTP, and with it comes the opportunity to further improve outcomes in this rare and deadly disease.
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PMID:Taking Empiricism out of Immune Thrombotic Thrombocytopenic Purpura: Current and Future Treatment Strategies. 3164 75