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1.
PURPOSE: To describe the perioperative management in a heparin-induced thrombocytopenia (HIT) positive patient who had prosthetic valve endocarditis and an aortic root abscess. The patient underwent high-risk cardiac re-operation with the use of the alternative anticoagulant, bivalirudin. CLINICAL FEATURES: A 62-yr-old patient who underwent stentless tissue aortic valve replacement with a Toronto-SPV valve in 1998, was admitted to hospital with symptoms of stroke. A heparin infusion was started and further investigation revealed positive blood cultures. The patient developed HIT which was confirmed by laboratory tests. Echocardiographic examination performed one month later showed vegetations on the aortic tissue valve and a small aortic root abscess. The patient still tested positively for the presence of HIT antibodies and was treated conservatively with antibiotics. A repeat echocardiographic examination showed progression of the aortic root abscess and it was decided to proceed with urgent redo aortic valve surgery. Anticoagulation for cardiopulmonary bypass (CPB) was achieved with the use of a direct thrombin inhibitor (DTI), bivalirudin. Following an uneventful wean from CPB, hemostasis was achieved within 40 min. The postoperative course was uncomplicated and the patient was discharged from hospital on the seventh postoperative day. CONCLUSION: Bivalirudin is a DTI, which can be used as an alternative anticoagulant for CPB in HIT positive patients. This case report showed a favourable outcome with bivalirudin for urgent complex redo cardiac surgery requiring CPB.  相似文献   

2.
An 81-year-old man with previous syncopal episodes, progressive shortness of breath, pulmonary edema, severe calcific aortic stenosis, and a history of heparin-induced thrombocytopenia required aortic valve replacement. Bivalirudin, a thrombin-specific anticoagulant, was used in place of heparin. The patient received a 50 mg bivalirudin bolus followed by an infusion between 1.5 mg x kg(-1) x h(-1) and 1.75 mg x kg(-1) x h(-1). Adequate anticoagulation was readily obtained resulting in an uneventful cardiopulmonary bypass. Activated clotting time (ACT) values steadily declined after discontinuation of the bivalirudin infusion. Bivalirudin is a practical alternative to heparin during cardiac surgical procedures.  相似文献   

3.
Unfractionated heparin has been a near universal anticoagulant for cardiac surgery; however it is contraindicated in heparin-induced thrombocytopenia type II. Alternative anticoagulants such as bivalirudin (a direct thrombin inhibitor) are being utilized. Bivalirudin was successfully used in an immunologically complex patient (diagnoses of heparin-induced thrombocytopenia type II, systemic lupus erythematosus, antiphospholipid syndrome, and dialysis-dependent renal failure) requiring cardiopulmonary bypass. Thrombotic events are common in antiphospholipid syndrome patients undergoing cardiac surgery utilizing high-dose heparin. This may represent unrecognized heparin-induced thrombocytopenia type II. Our patient did not experience perioperative thrombotic or bleeding complications. The possible cross-reactivity between heparin induced thrombocytopenia type II and antiphospholipid syndrome has not been investigated.  相似文献   

4.
Heparin-induced thrombocytopenia and cardiac surgery   总被引:3,自引:0,他引:3  
Unfractionated heparin given during cardiopulmonary bypass is remarkably immunogenic, as 25% to 50% of postcardiac surgery patients develop heparin-dependent antibodies during the next 5 to 10 days. Sometimes, these antibodies strongly activate platelets and coagulation, thereby causing the prothrombotic disorder, heparin-induced thrombocytopenia. The risk of heparin-induced thrombocytopenia is 1% to 3% if unfractionated heparin is continued throughout the postoperative period. When cardiac surgery is urgently needed for a patient with acute or subacute heparin-induced thrombocytopenia, options include an alternative anticoagulant (bivalirudin, lepirudin, or danaparoid) or combining unfractionated heparin with a platelet antagonist (epoprostenol or tirofiban). As heparin-induced thrombocytopenia antibodies are transient, unfractionated heparin alone is appropriate in a patient with previous heparin-induced thrombocytopenia whose antibodies have disappeared.  相似文献   

5.
Unfractionated heparin given during cardiopulmonary bypass is remarkably immunogenic, as 25% to 50% of postcardiac surgery patients develop heparin-dependent antibodies during the next 5 to 10 days. Sometimes, these antibodies strongly activate platelets and coagulation, thereby causing the prothrombotic disorder, heparin-induced thrombocytopenia. The risk of heparin-induced thrombocytopenia is 1% to 3% if unfractionated heparin is continued beyond the first postoperative week. When cardiac surgery is urgently needed for a patient with acute or subacute heparin-induced thrombocytopenia, options include an alternative anticoagulant (bivalirudin, lepirudin, or danaparoid) or combining unfractionated heparin with a platelet antagonist (epoprostenol or tirofiban). As heparin-induced thrombocytopenia antibodies are transient, unfractionated heparin alone is appropriate in a patient with previous heparin-induced thrombocytopenia whose antibodies have disappeared.  相似文献   

6.
Infants with heparin‐induced thrombocytopenia (HIT) represent a challenging and high‐risk group of patients when they require cardiopulmonary bypass (CPB). Bivalirudin offers many potential pharmacologic advantages over other nonheparin anticoagulants for such patients. We describe our protocol for the use of bivalirudin in a 5‐month‐old infant undergoing stage 2 Norwood for hypoplastic left heart syndrome. The patient was a 5‐ month‐old, 6‐kg infant who developed HIT after a bowel resection complicating initial Norwood stage 1. After sternotomy and dissection had been redone, the child received an initial dose of bivalirudin of 1.0 mg/kg and 0.5 mg/kg 5 min later. The CPB circuit was primed with 50 mg/kg bivalirudn/400 cc volume. With the initiation of CPB, a continuous infusion of 2.5 mg/kg bivalirudin was begun. Activated clotting time (ACT) was targeted for over 400 s, with an examination prior to bypass and each 15 min thereafter. Bivalirudin was discontinued with separation from bypass and during modified ultrafiltration (MUF). The ACT was 286 s after the initial 1 mg/kg bolus and 597 s after the second 0.5 mg/kg bolus and initiation of CPB. At a rate of 2.5 mg/kg/min, ACT ranged between 461 and 597 s. At the completion of MUF, the ACT was 316 s. The ACT was 214 s 20 min after MUF. No clots were noted in the CPB circuit, and good hemostasis was achieved within 10 min after MUF was completed. Incision to closure time was 160 min; time from completion of MUF to sternal closure was 30 min. Post‐MUF, 60 cc of processed cell saver blood was reinfused, and no clotting factors were required. Chest tube output was 10, 10, 3, and 4 ccs, respectively, at hours 1–4 post operation. Bivalirudin provides effective anticoagulation in infants requiring CPB in the presence of HIT. Bivalirudin's efficacy is effectively monitored by ACT, and, after CPB, its short half‐life and ability to be ultrafiltered facilitate the ability to achieve hemostasis in a timely fashion.  相似文献   

7.
Heparin is widely used as the anticoagulant of choice for cardiopulmonary bypass. However, some patients exposed to heparin therapies develop heparin-induced thrombocytopenia (HIT). Severe complications of HIT-induced thrombosis may lead to end-organ dysfunction and death. Bivalirudin, a hirudin analog, is an alternative anticoagulant that may be used in the patient with HIT without inducing thrombotic disorders. This case report provides a look at the successful use of bivalirudin as the sole anticoagulant in a patient diagnosed with HIT undergoing minimally invasive cardiothoracic surgery requiring cardiopulmonary bypass for severe mitral insufficiency. An 80-year-old male presented to the operating room for a minimally invasive mitral valve repair. Past medical history included mitral valve prolapse, atrial fibrillation, hypertension, and congestive heart failure. Preoperative evaluation noted the existence of HIT with heparin exposure 2 months prior. The decision was made to use bivalirudin as the sole anticoagulant for the operative procedure. Anticoagulation evaluation was performed with both high-does thrombin time (HiTT) and Celite activated clotting time tubes for comparison using a Hemochron device. Cardiopulmonary bypass was initiated, and the patient's mitral valve was repaired using a 34-mm annuloplasty ring. The patient was successfully weaned from bypass. No complications or evidence of HIT exacerbation were noted in the postoperative course.  相似文献   

8.
BACKGROUND: Despite high-dose heparin anticoagulation, cardiopulmonary bypass (CPB) is still associated with marked hemostatic activation. The purpose of this study was to determine whether a reduced dose of bivalirudin, added as an adjunct to heparin, would reduce thrombin generation and circulating markers of inflammatory system activation during CPB as effectively as full-dose bivalirudin, without adversely affecting postoperative hemostasis. METHODS: Using a model of normothermic CPB in rats, the authors prospectively compared markers of thrombin generation (thrombin-antithrombin complexes) and inflammatory markers (tumor necrosis factor alpha, interleukin 1beta, interleukin 6, and interleukin 10) in three groups: conventional high-dose heparin (H), full-dose bivalirudin (B), and a combined group (standard high-dose heparin with the addition of reduced dose bivalirudin or H&B), at baseline, after 60 min of CPB, and 60 min after CPB. Postoperative hemostasis was also assessed. RESULTS: Groups H&B and B showed reduced thrombin-antithrombin complex formation during CPB compared with group H (P = 0.0003), and this persisted after CPB for group B (P = 0.009). Perioperative increases in interleukin 6 and interleukin 10 showed a trend toward being reduced in animals receiving bivalirudin (P = 0.06). Evidence of residual anticoagulation was found in group H&B as measured by activated clotting time (P = 0.04) and activated partial thromboplastin time (P = 0.02), but no intergroup difference in primary hemostasis was found. CONCLUSIONS: Bivalirudin attenuates hemostatic activation during experimental CPB with potential effects on markers of the inflammatory response. However, with this dosing regimen, the combination of heparin and bivalirudin does not seem to confer any measurable advantages over full-dose bivalirudin anticoagulation.  相似文献   

9.
PURPOSE: To report three patients who developed heparin resistance during cardiac surgery which was successfully managed with 1000 U Antithrombin III (AT III). CLINICAL FEATURES: We observed heparin resistance prior to cardiopulmonary bypass (CPB) in one patient and during the CPB in two patients. In the first patient who was scheduled for mitral valve replacement, although heparin was administered sequentially up to 500 U x kg(-1) prior the CPB, the ACT value was 354 sec. After 1,000 U ATIII were administered the ACT was 395 sec and CPB was initiated. The ACT remained between 496 and 599 sec throughout CPB and a total of 260 mg protamine sulfate was given. In the other two patients following 300 U x kg(-1) heparin, the ACT was up to 400 sec and CPB was initiated. During CPB, ACT were decreased 360 sec and 295 sec in patients II and III respectively. Although heparin was added 1,500 U, ACT increased to > or = 400 sec could not be achieved. In the second patient ATIII activity was found 10%. After the administration of 1,000 U ATIII, ATIII activity was found to be 67% 40 min later and ACT were increased up to 400 sec. There was no thrombosis within the extracorporeal circuit, additional heparin was not required, less protamine was administered (< or = 3 mg x kg(-1)) and no excessive postoperative bleeding was observed in all patients. CONCLUSION: We recommend that AT III supplementation should be considered to manage heparin resistance prior or during CPB in patients undergoing open heart surgery.  相似文献   

10.
BACKGROUND: Patients with heparin-induced thrombocytopenia II (HIT II) need an alternative nonheparin-based method of anticoagulation for cardiopulmonary bypass (CPB) to prevent thrombosis and thrombosis related complications. METHODS: Bivalirudin was used during CPB and deep hypothermic circulatory arrest (DHCA) for resection of multiple right atrial masses in a patient with HIT II and antiphospholipid antibodies syndrome (APS). Anticoagulation was monitored with the activated clotting time (ACT) and a target ACT of 450 seconds or greater was maintained. RESULTS: Surgical removal of multiple right atrial masses was successful and there was no evidence of thromboembolic events. Clot was noticed in the cardiotomy and venous reservoir after CPB was discontinued and the system flushed. The postoperative course was uneventful. CONCLUSIONS: Anticoagulation was successfully managed with bivalirudin, a new short-acting, and direct thrombin inhibitor. Further studies are necessary to evaluate the safety of bivalirudin during DHCA.  相似文献   

11.

Purpose

Bivalirudin use for anticoagulating patients undergoing cardiac surgery, particularly those with or at risk for heparin-induced thrombocytopenia, has expanded over the past several years. The purpose of this review is to provide a summary of the following: the differences between indirect and direct thrombin inhibition, unfractionated heparin’s limitations (i.e., heparin-induced thrombocytopenia), bivalirudin’s pharmacology, recent cardiac surgery trials comparing bivalirudin and unfractionated heparin as anticoagulants, the growing role of bivalirudin-mediated anticoagulation for various surgical procedures, and the potential of bivalirudin-mediated vascular graft patency.

Source

A systematic search of the English literature was performed using PubMed from the United States National Library of Medicine. Pertinent articles from 1992-2010 were obtained from this search, and their reference lists were used to retrieve additional relevant articles.

Principal findings

In small studies in the cardiac surgery arena, bivalirudin has demonstrated a similar safety and efficacy profile compared with unfractionated heparin. Bivalirudin’s role as an anticoagulant in various cardiac surgical procedures (i.e., heart transplant) and vascular surgical procedures is growing and reviewed. Additionally, the molecular basis for the potential for bivalirudin-mediated improvement in vascular graft patency after coronary artery bypass graft procedures is discussed.

Conclusion

Although bivalirudin is not approved for cardiac surgery in the United States, it can be used in this setting in Canada as an anticoagulant in patients with heparin-induced thrombocytopenia provided the cardiac anesthesiologist is knowledgeable about potential complications from its use and knows how to manage or mitigate their incidence appropriately. During cardiopulmonary bypass, bivalirudin anticoagulation protocols must be thoroughly followed to attain optimal clinical outcomes. Additionally, further studies with bivalirudin are needed to determine the best monitoring modality and dosing regimen.  相似文献   

12.
OBJECTIVE: Bivalirudin has been successfully used as a replacement for heparin during on-pump coronary artery bypass grafting. This study was conducted to assess the effects of the currently suggested protocol for bivalirudin on hemostatic activation during cardiopulmonary bypass with and without cardiotomy suction. METHODS: Ten patients scheduled for coronary artery bypass grafting were enrolled. Bivalirudin was given with a bolus of 50 mg in the priming solution and 1.0 mg/kg for the patient, followed by an infusion of 2.5 mg . kg(-1) . h(-1) until 15 minutes before the conclusion of cardiopulmonary bypass. Cardiopulmonary bypass was performed with a closed system in 5 patients with and in 5 patients without the use of cardiotomy suction. Blood samples were obtained before and after cardiopulmonary bypass. D-dimers, fibrinopeptide A, prothrombin 1 and 2 fragments, thrombin-antithrombin, and factor XIIa were determined. RESULTS: Values for factor XIIa remained almost unchanged in both groups, indicating a minor effect of contact activation. In patients without cardiotomy suction, post-cardiopulmonary bypass values for D-dimers, fibrinopeptide A, prothrombin 1 and 2 fragments, and thrombin-antithrombin were not significantly increased compared with pre-cardiopulmonary bypass values. In patients with cardiotomy suction, values obtained for these parameters had significantly increased compared with pre-cardiopulmonary bypass values and the values obtained in the group without cardiotomy suction after cardiopulmonary bypass. CONCLUSIONS: With this protocol, hemostatic activation during cardiopulmonary bypass was almost completely attenuated when cardiotomy suction was avoided. Cardiotomy suction results in considerable activation of the coagulation system and should therefore be restricted and replaced by cell saving whenever possible.  相似文献   

13.
OBJECTIVES: The endotoxemia associated with cardiac surgery is thought to be dominantly influenced by the use of cardiopulmonary bypass. The objectives of this study were to assess the relative contribution of cardiopulmonary bypass on endotoxemia apart from cardiac surgical access and to improve our understanding of the potential benefits of off-pump procedures. METHODS: Thirty patients undergoing coronary artery bypass grafting were followed up prospectively. The patients were divided into 2 equal groups: those who underwent bypass grafting through a sternotomy incision without cardiopulmonary bypass (off-pump group) and those who underwent bypass grafting through a sternotomy incision with cardiopulmonary bypass (CPB group). Blood sampling for endotoxin, lactate, and cardiac index measurements were performed during the following time points: (1) after sternotomy; (2) during the coronary occlusion period in the off-pump group and during aortic clamping in the CPB group; (3) after removal of the coronary occlusion sutures in the off-pump group and after removal of the aortic clamp in the CPB group; (4) 30 minutes after the completion of all distal anastomoses in the off-pump group and immediately after weaning from cardiopulmonary bypass in the CPB group; (5) 1 hour postoperatively; and (6) 12 hours postoperatively. RESULTS: Endotoxin and lactate levels were significantly (P <.05) lower in the off-pump group at all sampling time points, except after sternotomy. CONCLUSIONS: In conclusion, this study has shown that endotoxemia during coronary artery bypass surgery seems mainly to be associated with cardiopulmonary bypass procedure. The relatively lower endotoxin levels observed in off-pump surgery might contribute to improved postoperative recovery.  相似文献   

14.
Open-heart surgery is a relatively high-risk procedure when performed in patients with Child-Pugh class C cirrhosis. Even though they can tolerate cardiac surgery with cardiopulmonary bypass (CPB), most of them suffer major postoperative complications and prolonged hospital stay. The present report describes a case of a patient with Child-Pugh class C cirrhosis who developed severe heart failure secondary to aortic valve stenosis. The patient underwent successful aortic valve replacement with the use of dilutional ultrafiltration during CPB to reduce adverse effects of CPB. He recovered smoothly after the operation without major postoperative complications. Thus, the use of dilutional ultrafiltration (DUF) during CPB appears to produce beneficial effects for improving outcomes in patients with decompensated cirrhosis who require open-heart surgery.  相似文献   

15.
OBJECTIVE: To report the incidence, severity, and possible risk factors for early and delayed cerebral complications. DESIGN: Retrospective study. SETTING: Link?ping University Hospital, Sweden. PARTICIPANTS: Consecutive patients who underwent cardiac surgery in the period July 1996 through June 2000 (n = 3,282). INTERVENTIONS: A standard cardiopulmonary bypass (CPB) technique was used for most patients. Postoperative anticoagulant treatment included heparin or anti-Xa dalteparin. Patients undergoing coronary artery bypass graft surgery received acetylsalicylic acid, and patients undergoing valve surgery received warfarin. MEASUREMENTS AND MAIN RESULTS: Cerebral complications occurred in 107 patients (3.3%). Of these, 60 (1.8%) were early, and 33 (1.0%) were delayed, and in 14 (0.4%) patients the onset was unknown. There were 37 variables in univariate analysis (p < 0.15) and 14 variables in multivariate analysis (p < 0.05) associated with cerebral complications. Predictors of early cerebral complications were older age, preoperative hypertension, aortic aneurysm surgery, prolonged CPB time, hypotension at CPB completion and soon after CPB, and postoperative arrhythmia and supraventricular tachyarrhythmia. Predictors of delayed cerebral complications were female gender, diabetes, previous cerebrovascular disease, combined valve surgery and coronary artery bypass graft surgery, postoperative supraventricular tachyarrhythmia, and prolonged ventilator support. Early cerebral complications seem to be more serious, with more permanent deficits and a higher overall mortality (35.0% v 18.2%). CONCLUSION: Most cerebral complications had an early onset. The results of this study suggest that aggressive antiarrhythmic treatment and blood pressure control may imfurther prove the cerebral outcome after cardiac surgery.  相似文献   

16.
Unfractionated heparin (UFH) is the gold standard for anticoagulation during cardiopulmonary bypass (CPB). Of patients undergoing CPB operations, 25% to 50% develop heparin-dependent antibodies during the postoperative period, typically between day 5 and 10, if UFH is continued during the postoperative course. In 1% to 3% of all patients undergoing CPB operation with UFH anticoagulation, these antibodies activate platelets causing a prothrombotic disorder, known as heparin-induced thrombocytopenia (HIT), which can lead to life-threatening thromboembolic complications. If urgent cardiac operation with the use of CPB in patients with positive antibody titer is required, different anticoagulatory approaches are available, such as lepirudin, bivalirudin, and danaparoid or UFH in combination with platelet antagonists, such as epoprostenol or tirofiban. In patients with previous HIT but no detectable antibodies, UFH alone can be used only during CPB, but alternative anticoagulation has to be used pre- and postoperatively.  相似文献   

17.
Assessment of anticoagulation status during cardiac surgery can be valuable for novel therapeutics, including direct thrombin inhibitors. The ecarin clotting time (ECT) has been reported to be sensitive for monitoring of bivalirudin in cardiac surgery but is not commercially available. The activated clotting time (ACT), commonly used for heparin monitoring, may display a lack of sensitivity to alternative anticoagulants when used in on-pump cardiac surgery. Both the ACT and ECT have been successfully used for monitoring bivalirudin anticoagulation in off-pump cardiac surgery. A new ACT, the ACTT, was developed to increase the linearity of the clotting time response to bivalirudin at higher concentrations. After Ethics Committee approval, a pilot study was performed to evaluate the feasibility of using bivalirudin for on-pump cardiac surgery and to evaluate dosing of bivalirudin in terms of the pharmacokinetic and safety profile in patients undergoing coronary artery bypass graft (CABG) surgery. Secondary objectives included an assessment of the anticoagulation profile and correlation of the response seen with various ACTs and the ECT with the plasma bivalirudin concentration in the patients' blood. After informed consent, 10 sequential patients presenting for elective cardiac surgery requiring cardiopulmonary bypass received bivalirudin anticoagulation in lieu of heparin. Dosing was fixed (1.0 mg/kg bolus followed by a 2.5 mg/kg/h infusion) and not titrated on the basis of coagulation test results. At baseline and 15-minute intervals, blood samples were collected for ACT (ACTT, Celite, kaolin, ACT+), ECT, and bivalirudin plasma level measurements. Over the range of bivalirudin plasma concentrations in this study, all clot-based systems examined were prolonged according to concentration and showed good correlation with bivalirudin plasma levels. The ACTT and the ECT showed greater sensitivity to bivalirudin (-28.5 sec/microg/ml bivalirudin) compared with the other ACTs evaluated (approximately 14 sec/microg/ml). This difference in sensitivity was also evident at low concentrations of bivalirudin (<10 microg/ ml), with the ECT and ACTT showing slopes near 40, and the ACT slopes varying from 18 to 27 sec/microg/ml. The ACTT assay is sensitive to levels of bivalirudin and may offer a simple method for monitoring bivalirudin during cardiac surgery.  相似文献   

18.
Heparin-induced thrombocytopenia with thrombosis (HITT) type II is a life-threatening complication of heparin therapy that most often occurs after 5-10 days of exposure to heparin. Anticoagulation is a significant concern for patients with HITT type II being prepared for cardiac surgery requiring cardiopulmonary bypass (CPB). We report a case series of 12 patients with a history HITT type II who underwent CPB and cardiac surgery. Six patients did not express the antibody that mediates HITT type II immediately before surgery. Heparin was used as the anticoagulant for the duration of CPB only, and all these patients did well without thrombotic complications. Six patients expressed the antibody that mediates HITT type II immediately before surgery. Hirudin was used as the anticoagulant for CPB in these patients. The ecarin clotting time was used to guide hirudin therapy during CPB. The patients receiving hirudin did well, but they had a large amount of bleeding, required transfusions of multiple allogeneic blood products, and had a frequent rate of reexploration of the mediastinum after CPB.  相似文献   

19.
Bivalirudin is a short-acting direct thrombin inhibitor that has been used in cardiac surgical patients with heparin-induced thrombocytopenia (HIT) or suspected HIT. Although no direct thrombin inhibitor is indicated for anticoagulation during cardiac surgery in patients with heparin-induced thrombocytopenia (HIT) or suspected HIT, use of heparin-alternatives are increasing as the awareness of HIT increases. Reports of anticoagulation with bivalirudin are sporadic, however, with variable dosing and management strategies. In this report, we describe our management techniques for cardiopulmonary bypass with bivalirudin based upon our personal experience. Although the reported clinical experience with bivalirudin in cardiac surgery is reviewed, operative techniques for the perfusionist/surgeon team are discussed in detail. We recognize that the use of bivalirudin during cardiopulmonary bypass is evolving and modifications of technique will undoubtedly occur as further data and experience accumulate.  相似文献   

20.
Heparin-induced thrombopenia is a common autoimmune complication. It is a prothrombotic state due to the formation of antibodies against heparin/platelet factor 4 complexes. In this situation drugs other than heparin must be used for anticoagulation during extracorporeal circulation (bypass) surgery.Two cases of heart transplantation are presented in whom bivalirudin was used as an anticoagulant during the cardiopulmonary bypass. Severe bleeding complications were observed in both patients.The diagnosis of heparin-induced thrombopenia needs to be improved, as well as the development of protocols for using new drugs other than heparin. For this reason, we have reviewed current protocols and alternative therapies to heparin.  相似文献   

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