Wesley K. Lew

Clinical use of topical thrombin as a surgical hemostat

When surgical ligation of bleeding fails, or is not possible, surgeons rely on a number of hemostatic aids, including thrombin. This review discusses the history, pharmacology and clinical application of thrombin as a surgical hemostat. The initial thrombin was bovine in origin, but its use has been complicated by the formation of antibodies that cross react with human coagulation factors. This has been associated with life threatening bleeding and in some circumstances anaphylaxis and death. Human thrombin, isolated from pooled plasma of donors, has been developed in an effort to minimize these risks, but its downside is the potential of transmitting blood-borne pathogens and limited availability. Recently a recombinant thrombin has been developed and approved for use by the FDA. It has the advantage of being minimally antigenic and devoid of the risk if viral transmission. Thrombin is often used in conjunction with other hemostatic aids, including absorbable agents (like gelfoam, collagen, and cellulose), and with fibrinogen in fibrin glues. The last part of this review will discuss these agents in detail, and review their clinical applications.

A comparison of recombinant thrombin to bovine thrombin as a hemostatic ancillary in patients undergoing peripheral arterial bypass and arteriovenous graft procedures

OBJECTIVES Recombinant thrombin (rThrombin) is a potential hemostatic alternative to bovine and human plasma-derived thrombin. This report examines the clinical results for the vascular surgery subgroup of patients enrolled in a larger double-blind, randomized, multicenter trial, which evaluated the comparative safety and efficacy of rThrombin and bovine plasma-derived thrombin (bThrombin) when used as adjuncts to surgical hemostasis. METHODS Data from the 164 vascular patients who underwent either a peripheral arterial bypass (PAB) or arteriovenous graft (AV) procedure are included in this analysis. Time to hemostasis at proximal and distal anastomotic sites at 1.5-, 3-, 6-, and 10-minute intervals was determined by procedure (PAB or AV) and overall (PAB + AV). Baseline and day 29 immunologic sera were analyzed. The incidences of postoperative adverse events were compared between treatment groups. Categorical adverse events were evaluated in relation to thrombin product antibody formation. RESULTS Patients were randomized to either bThrombin (n = 82) or rThrombin (n = 82). Procedures included PAB (n = 88) and AV (n = 76). The bThrombin and rThrombin groups were well matched for demographics and baseline characteristics. A comparable incidence of anastomotic hemostasis was observed in both treatment groups at 10 minutes (94% bThrombin, 91% rThrombin). The incidence of hemostasis was lower at all time points for PAB procedures compared with AV procedures. In the PAB group, a significantly greater proportion of patients receiving rThrombin (55%) achieved hemostasis at 3 minutes compared with bThrombin (39%; P < .05). Adverse event profiles and laboratory findings were similar between groups. No patients in the rThrombin group developed anti-rThrombin product antibodies at day 29, whereas 27% of patients in the bThrombin group developed antibodies to bThrombin product (P < .0001). CONCLUSIONS rThrombin or bThrombin used as a hemostatic ancillary for anastomotic bleeding was equally effective at 10 minutes; however, rThrombin compared with bThrombin may provide a more rapid onset of hemostasis at 3 minutes in PAB procedures. Adverse events were similar between the two thrombins. In patients undergoing vascular surgery, both treatments were similarly well tolerated, although rThrombin demonstrated a superior immunogenicity profile.

Endovascular Management of Mycotic Aortic Aneurysms and Associated Aortoaerodigestive Fistulas

We evaluated the short- and intermediate-term results of endovascular aneurysm repair (EVAR) for mycotic aneurysms. We reviewed all patients undergoing EVAR for mycotic aneurysms at our institution. To be consistent with the existing literature, patients with associated aortoaerodigestive fistulas were included. Aneurysm location, demographics, clinical findings, EVAR success, morbidity, and short- (<30 days) and long-term mortality were reviewed. From 2000 to 2007, 326 patients underwent EVAR. Nine of these (3%) had treatment of a mycotic aneurysm. The average age was 72 years (range 53-86), and seven patients were male. Four of the aneurysms were located in the thoracic aorta, two in the abdominal aorta, and three in the thoracoabdominal aorta. Four patients presented with gastrointestinal bleeding, two with hemoptysis, one with hemothorax, and two with fever. Etiologies included bacteremia from endocarditis and central catheter infection, erosion of anastomotic aneurysms from a previous aortic repair or endograft, erosion of a penetrating ulcer with pseudoaneurysm, infected aortic repair, left chest empyema, and unknown in one patient. Methicillin-resistant Staphylococcus aureus was the only bacteria isolated in 56% of the patients. EVAR successfully excluded the aneurysm or fistula in all nine patients; however, five patients experienced at least one postoperative complication. Two patients expired within 30 days. After 30 days, four additional patients expired; three of these deaths were procedure/aneurysm-related. Of the three survivors, over a mean follow-up of 257 days (range 60-417), one has required excision of an infected endograft with extra-anatomic bypass grafting but is now alive and well. All three surviving patients and two out of four patients expiring after 30 days had received long-term postoperative antibiotics. Despite an in-hospital mortality of 22.2%, EVAR can be used to treat acute complications from mycotic aneurysms and associated aortoaerodigestive fistulas, such as gastrointestinal bleeding, hemoptysis, or hemodynamic instability. As a definitive treatment, EVAR remains suspect and therefore should be considered a bridge to open surgical repair.

Thrombin use in surgery: an evidence-based review of its clinical use

When surgical ligation of bleeding fails, or is not possible, surgeons rely on a number of hemostatic aids, including thrombin. This review discusses the history, pharmacology and clinical application of thrombin as a surgical hemostat. The initial thrombin was bovine in origin, but its use has been complicated by the formation of antibodies that cross-react with human coagulation factors. This has been associated with life-threatening bleeding and in some circumstances anaphylaxis and death. Human thrombin, isolated from pooled plasma of donors, was developed in an effort to minimize these risks, but its downsides are its limited availability and the potential for transmitting blood-borne pathogens. Recently a recombinant thrombin has been developed, and approved for use by the FDA. It has the advantage of being minimally antigenic and devoid of the risk of viral transmission. Thrombin is often used in conjunction with other hemostatic aids, including absorbable agents such as Gelfoam, and with fibrinogen in fibrin glues. The last part of this review will discuss these agents in detail, and review their clinical applications.

Use of thrombolytics in vascular and endovascular surgery.

Until recently, acute arterial or venous thromboses were routinely managed with surgical intervention. With the development of effective thrombolytic pharmacologic agents and improved modes of delivery of these agents to the target site, surgery is no longer the only option. Greater understanding and knowledge about the finely orchestrated, counterbalanced processes of coagulation and fibrinolysis/thrombolysis have enabled development of agents and strategies for pharmacologic restoration of vascular patency while reducing or eliminating the need for surgery. An evidence-based rationale now exists for the use of thrombolysis in acute limb ischemia, deep venous thrombosis, stroke, and arteriovenous vascular access thromboses. Thrombolytic agents are valuable ancillary agents that allow a less invasive solution to a variety of thrombotic vascular conditions. Strategies that combine thrombolytic agents with endovascular techniques provide precise delivery of these drugs to the target thrombus. A more widespread adoption of this strategy has been limited primarily owing to problems with the currently available pharmacologic agents. The future of thrombolysis therapy is discussed in terms of data obtained from ongoing and recently completed clinical trials. Efforts to develop and study new thrombolytic agents that act directly on the thrombus without activation of intermediary biochemical steps will provide the next major step forward, as well as the rational basis for expansion of currently accepted indications for the treatment of acute arterial and venous thromboses.This study evaluated the value of computed tomographic angiography (CTA) early after an endovascular aneurysm repair (EVAR) in relation to CTA 3 months after EVAR. We retrospectively reviewed all elective EVAR patients with available postprocedural and 3-month follow-up CTAs who were treated between 1996 and 2006. CTAs were analyzed for EVAR-related complications in terms of endoleaks, migration, and stent graft thrombosis. Secondary procedures and other complications within a 4-month time interval after EVAR were noted and analyzed for any association with the postprocedural CTA. During the study period, 291 patients (275 men), with a mean age of 71 years, underwent elective EVAR. All had postprocedural and 3-month follow-up CTAs, which detected 93 (32%) endoleaks (8 type I, 84 type II, 1 type III) and 1 stent graft thrombosis. These findings resulted in four secondary interventions (one interposition cuff, two extension cuffs, one conversion). All reinterventions were successfully done in an elective setting. During the first 3 postoperative months, five other reinterventions were required for acute ischemia in four patients (three Fogarty procedures, one femorofemoral crossover bypass) or groin infection in one patient. Eight patients died, but none of the deaths were related to abdominal aortic aneurysm or EVAR (four cardiac, two pulmonary, one gastric bleeding, one carcinoma). At 3 months, 43 endoleaks (3 type I, 40 type II), 3 stent graft thromboses, and 1 stent graft migration were seen. In two patients (0.7%), a new endoleak was diagnosed compared with the postprocedural CTAs. In 287 (99%) of 291 patients, the postprocedural CTA did not influence our treatment policy in the first 3 months after EVAR. More than half of the early endoleaks were self-limiting, and new endoleaks were seen in only two patients (< 1%) at the 3-month follow-up CTA. After an uneventful EVAR procedure, it is safe to leave out the early postprocedural CTA.

Endovascular Management of Hoarseness Due to a Thoracic Aneurysm: Case Report and Review of the Literature

Although uncommon, hoarseness can be a presenting symptom of a thoracic aneurysm. We present a case of a 67-year-old man with hoarseness, subsequently found to have left vocal paralysis. On workup, a computed tomography scan demonstrated a saccular thoracic aneurysm compressing the recurrent laryngeal nerve at the aortopulmonary window. About 6 months after treatment with an endovascular stent graft, the aneurysm sac decreased in size and hoarseness resolved without further surgical intervention. Although uncommonly mentioned as an indication for surgery, hoarseness from a thoracic aneurysm can be successfully managed with endovascular stent grafting.

The Role of Endovascular Therapy in Contemporary Management of Mycotic Aortic Aneurysms and Asscociated Aortoaerodigestive Fistulas.

variables but retaining the frailty domains (nutrition, social, physical function) performed just as well (AUC 1⁄4 0.76; Fig). Addition of procedure-specific mortality risk further improved model performance (AUC 1⁄4 0.77). The final model showed that open aortic procedures, thoracic endovascular aortic repair, and renal insufficiency carried the greatest risk for 9-month mortality. A nomogram summing points for each frailty element and procedure-based risk allows estimation of 9-month mortality (Fig). Conclusions: A model using only seven VQI frailty-related data elements and procedure-based risk estimates 9-month mortality after arterial reconstruction. Frailty assessment may improve preoperative decision-making, especially in considering risk/benefit of procedures for claudication or asymptomatic disease.