Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In patients on chronic dialysis, unfractionated heparin (UFH) is the most commonly used agent for anticoagulation of the hemodialysis extracorporeal circuit, for hemodialysis catheter "locking" between dialysis treatments, and for nondialysis indications such as venous thromboembolic disease, peripheral vascular disease, and acute coronary artery disease. Potentially serious complications of UFH, such as hemorrhage, osteoporosis, and thrombocytopenia, have led to consideration of other options for anticoagulation, including low molecular weight heparin (LMWH) and direct thrombin inhibitors (DTIs). LMWH can be used for anticoagulation of the hemodialysis circuit, but whether this has significant benefit compared to UFH remains to be proven. Because of the somewhat unpredictable risk of severe bleeding complications when LMWH is used for other indications in dialysis patients, UFH rather than LMWH is preferred for treatment of thromboembolic disease in these patients. DTIs have been used for anticoagulation in dialysis patients with heparin-induced thrombocytopenia (HIT), with argatroban being the preferred agent if heparin-free hemodialysis cannot be performed. UFH still remains the preferred anticoagulant in the vast majority of dialysis patients requiring systemic anticoagulation and for anticoagulation of the extracorporeal hemodialysis circuit.
Semin Dial
PMID:The safety of heparins in end-stage renal disease. 1689 8

The factors contributing to platelet dysfunction in hemodialysis patients are still not completely known. We explored whether the fibrinolytic system influences platelet function in hemodialysis patients. We measured standard fibrinolytic parameters and markers of fibrinolysis/coagulation activation, and correlated them to platelet aggregation in 15 hemodialysis patients. Fifteen healthy age-matched volunteers served as controls. Hemodialysis patients had significantly decreased levels of plasminogen (0.76 [0.64-0.86] vs. 0.98 [0.87-1.08] rel, P < 0.001), and increased levels of fibrinogen (4.6 [3.9-5.5] vs. 4.0 [3.4-4.6] g/L, P < 0.05), whereas tissue-type plasminogen activator antigen and plasminogen activator inhibitor (PAI)-1 antigen and PAI activity were comparable to controls. Furthermore, elevated levels of markers of fibrinolysis/coagulation were found in hemodialysis patients: D-dimer (280 [170-460] vs. 135 [120-150] ng/mL, P < 0.01), prothrombin fragments 1 + 2 (1.7 [1.4-1.9] vs. 1.1 [1.0-1.2] nmol/L, P < 0.001), and thrombin-antithrombin complexes (5.2 [4.2-17.7] vs. 0 [0-4.2]microg/L, P < 0.01). The aggregation of platelets (induced by adenosine diphosphate) was slightly impaired in patients compared to controls (72 [43-79] vs. 83 [73-88]%, P = 0.08). Analysis showed that platelet aggregation positively correlated with plasminogen levels (r = 0.48, P < 0.01). No correlation with other fibrinolytic parameters or markers of activation was found. In hemodialysis patients platelet (dys)function appears to be associated with both the fibrinolytic and coagulation systems. We found that platelet aggregation significantly correlates with plasma plasminogen levels. This relation, which has not been hitherto described, seems to be causal and clinically important. Further exploration of this may help us to better understand the mechanisms of platelet dysfunction in hemodialysis patients.
Ther Apher Dial 2008 Apr
PMID:Platelet (dys)function and plasma plasminogen levels in hemodialysis patients. 1838 61

Vascular access for hemodialysis remains a challenge for nephrologists, vascular surgeons, and interventional radiologists alike. Arteriovenous fistula and synthetic grafts remain the access of choice for long-term hemodialysis; however, they are subject to complications from infection and repeated needle cannulation. Pseudoaneurysms are an increasingly recognized adverse event. At present, there are many minimally invasive methods to repair these wall defects. We present a graft pseudoaneurysm, which required a combination of endovascular stent graft placement and percutaneous thrombin injection for successful occlusion.
Semin Dial
PMID:Successful endovascular treatment of a hemodialysis graft pseudoaneurysm by covered stent and direct percutaneous thrombin injection. 1876 89

Continuous renal replacement therapy (CRRT) has emerged as the preferred dialysis modality for critically ill patients with acute kidney injury, particularly those with hemodynamic instability. Anticoagulation is necessary for effective delivery of CRRT, but this requirement can also present challenges, as many critically ill patients with sepsis and inflammation already have a higher risk of bleeding as well as clotting. Without anticoagulation, CRRT filter and circuit survival are diminished, and therapy becomes less helpful. Heparins are presently the most commonly used anticoagulants worldwide for CRRT. They are widely available and can be easily monitored, but disadvantages include risks of hemorrhage, heparin resistance, and heparin-induced thrombocytopenia (HIT). Because of the potential side effects of heparin, alternative methods of anticoagulation have been investigated, including regional heparin/protamine, low molecular weight heparins, heparinoids, thrombin antagonists (hirudin and argatroban), regional citrate, and platelet inhibiting agents (prostacyclin and nafamostat). Each of these techniques has unique advantages and disadvantages, and anticoagulation for CRRT should be adapted to the patient's characteristics and institution's experience. Of the alternative methods, citrate anticoagulation is gaining wider acceptance with the development of simplified and safer protocols.
Semin Dial
PMID:Anticoagulation for continuous renal replacement therapy. 1942 17

We investigated whether hemoperfusion with a polymyxin B column (DHP-PMX) was able to improve coagulation abnormalities in patients with sepsis. Sixteen patients with sepsis were enrolled in the study. They all had signs of systemic inflammatory response syndrome due to infection and a mean arterial blood pressure > or =65mm Hg (irrespective of the use of catecholamines). A thermodilution catheter was inserted prior to DHP-PMX for intravenous infusion, and DHP-PMX was performed twice within 24 h for 3 h each time. Circulating levels of thrombin-antithrombin complex (TAT), plasmin-alpha2 plasmin inhibitor complex (PIC), the TAT/PIC ratio, and plasminogen activator inhibitor-1 (PAI-1) were measured six times. Before DHP-PMX, the TAT level was 24.5 +/- 8.3 ng/mL, the PIC level was 2.5 +/- 1.1 microg/mL, the TAT/PIC ratio was 13.9 +/- 3.5, and the PAI-1 level was 143.0 +/- 24.4 ng/L. The TAT level, TAT/PIC ratio, and PAI-1 were all significantly lower (P < 0.05) after 48 hr compared with before DHP-PMX, but no significant change of PIC was observed. In these patients with sepsis, fibrinolysis was inhibited by PAI-1, whereas clotting activity was significantly increased. This coagulation/fibrinolysis imbalance was improved by DHP-PMX. The present results suggest that indirect inhibition of clotting activity can be achieved in patients with sepsis through adsorption of lipopolysaccharide by DHP-PMX.
Ther Apher Dial 2009 Dec
PMID:Hemoperfusion with a polymyxin B fiber column decreases clotting activity. 1995 77

Unfractionated heparin (UFH) is the anticoagulant of choice for most maintenance hemodialysis units in the United States. Low molecular weight heparin (LMWH) is the norm in Western Europe, but is not approved for this indication in the United States. UFH is likely to remain the agent of choice in the United States because of its relative ease of use, safety, and low cost. Coating tubing and dialyzers with heparin is now possible, but systemic anticoagulation with heparin is usually still required. The additional cost of this innovation does not yet justify its use. Side effects of both UFH and LMWH include heparin-induced thrombocytopenia, hypertriglyceridemia, and hyperkalemia. It is uncertain whether osteoporosis is an important side effect, as vitamin D deficiency, secondary hyperparathyroidism, age, and debility are confounding factors. When UFH poses a risk or its use is contraindicated, e.g., after development of heparin-induced thrombocytopenia, the use of direct thrombin inhibitors, regional citrate anticoagulation, citrate dialysate, and heparin-free dialysis may be appropriate.
Semin Dial
PMID:Unfractionated heparin for hemodialysis: still the best option. 2103 76

To clarify the influence of neutral dialysate (ND) on peritoneum, we examined changes in peritoneal permeability and in various markers of the coagulation and fibrinolytic system in effluent and the correlations between peritoneal permeability and those markers in peritoneal dialysis (PD) patients using ND. We evaluated 14 patients (8 men, 6 women; mean age: 58.6 +/- 12.0 years) who started PD using ND. The peritoneal equilibration test (PET) was performed to assess dialysate-to-plasma ratio for creatinine (D/P Cr) as peritoneal permeability. Coagulation markers [thrombin-antithrombin complex, fibrin monomer (FM), prothrombin fragment 1+2 (F1 + 2)] and fibrinolytic markers (fibrin degradation products, D-dimer) in effluent were also measured. At 2 years, FM in effluent was significantly lower (p = 0.006). The other markers and the D/P Cr did not change significantly. At the initiation of PD and at 2 years, D/P Cr was significantly correlated with F1 + 2 (r = 0.70 and 0.76 respectively, p < 0.01). Furthermore, multiple regression analysis showed that only F1 + 2 was correlated with D/P Cr at 2 years (r = 0.79, p = 0.004). These results suggest that ND has little influence on coagulation and fibrinolytic markers in effluent. In addition, F1 + 2 is a useful marker for peritoneal permeability in PD patients using ND.
Adv Perit Dial 2011
PMID:Prothrombin fragment 1 + 2 (F1 + 2) in effluent is a useful marker for peritoneal permeability in peritoneal dialysis patients using neutral dialysate. 2207 19

End-stage renal disease (ESRD) patients exhibit an increased risk of bleeding compared with non-chronic kidney disease (CKD) patients due to uraemic platelet dysfunction, altered vessel architecture and other factors. This renders any long-term oral anticoagulation potentially difficult. While there is little doubt that ESRD patients with recurrent thromboembolism or a mechanical cardiac valve should receive vitamin K antagonists (coumarins), the use of coumarins in ESRD patients with atrial fibrillation is a matter of debate. In non-CKD patients, current guidelines strongly recommend the use of oral anticoagulants for stroke prophylaxis in atrial fibrillation if certain risk factors are present (CHA2DS2-VASc score). This recommendation is often extrapolated to patients with advanced CKD or ESRD but data supporting this practice are weak to absent. Besides an increased bleeding risk in ESRD patients, coumarins will also accelerate cardiovascular calcification and are potent risk factors for the development of calcific uraemic arteriolopathy (calciphylaxis). Novel coumarin alternatives such as direct thrombin inhibitors are promising but none is currently approved for use in ESRD patients. Whether interventional treatment strategies such as atrial appendage occlusion are safe and effective options in advanced CKD is also as yet unresolved. This review attempts to balance the potential risks and benefits of coumarin usage in ESRD patients and to give the best possible recommendations for everyday patient care.
Nephrol Dial Transplant 2013 Mar
PMID:Sailing between Scylla and Charybdis: oral long-term anticoagulation in dialysis patients. 2318 Aug 80

Warfarin is the most widely used oral anticoagulant in clinical use today. Indications range from prosthetic valve replacement to recurrent thromboembolic events due to antiphospholipid syndrome. In hemodialysis (HD) patients, warfarin use is even more frequent than in the nonrenal population due to increased cardiovascular comorbidities. The use of warfarin in dialysis patients with atrial fibrillation requires particular caution because side effects may outweigh the assumed benefit of reduced stroke rates. Besides increased bleeding risk, coumarins exert side effects which are not in the focus of clinical routine, yet they deserve special consideration in dialysis patients and should influence the decision of whether or not to prescribe vitamin K antagonists in cases lacking clear guidelines. Issues to be taken into consideration in HD patients are the induction or acceleration of cardiovascular calcifications, a 10-fold increased risk of calciphylaxis and problems related to maintaining a target INR range. New anticoagulants like direct thrombin inhibitors are promising but have not yet been approved for ESRD patients. Here, we summarize the nontraditional side effects of coumarins and give recommendations about the use of vitamin K antagonists in ESRD patients.
Semin Dial
PMID:Vitamin K antagonists: beyond bleeding. 2440 Aug 2

In the setting of end-stage kidney disease, the incidence and risk for thrombotic events are increased and use of anticoagulants is common. The incidence of bleeding, however, is also a frequent issue and creates additional challenges in the management of anticoagulation therapy. Patients with end-stage renal disease are typically excluded from large clinical trials exploring the use of anticoagulants, which limits our knowledge of optimal management approaches. Furthermore, varying degrees of renal failure in addition to conditions that alter the pharmacokinetics of various anticoagulants or pharmacodynamic response may warrant alternative approaches to dosing. This review will explore systemic chronic anticoagulation therapy in the setting of chronic kidney disease where hemodialysis is required. Agents discussed include vitamin K antagonists, low-molecular-weight heparins, fondaparinux, oral factor Xa antagonists, and direct thrombin inhibitors. Clinical challenges, approaches to dosing regimens, and tools for measuring responses and reversal will be explored.
Semin Dial
PMID:Considerations for Systemic Anticoagulation in ESRD. 2595 1


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