Perioperative Heparin Research Articles

Preoperative blood donation program and postoperative Low Molecular Weight Heparine (LMWH) prophylaxis in patients undergoing radical prostatectomy

The need and timing of perioperative heparin prophylaxis is matter of debate. The aim of our work is to review the incidence of venous thromboembolism (VTE) after radical retro pubic prostatectomy (RRP) in patients undergoing preoperative blood donation, compressive stockings, haemodilution, surgical prevention of lymphocoele and postoperative low molecular weight heparin therapy as prophylaxis for thrombotic events. This is a retrospective analysis considering a series of 500 RRP performed between 1999 and 2006 by the same Surgeon (MG) at the Urological Unit, Desio, Hospital, Milan, Italy. All the patients were enrolled in an auto transfusion program and were subjected to autologous blood donation. Low molecular weight heparin (.04 ml of Calcic Nadroparin 3800 UI s.c. daily) was administrated within 24 hours following surgery until the 11th post-operative. Age, PSA, basal, preoperative and postoperative haemoglobin values were assessed in each patient. The incidence of venous thromboembolism was calculated taking into consideration occurrences of both pulmonary embolism and deep venous thrombosis. In this retrospective analysis we did not observe any major event including intra- or peri-operative deaths. There was one occurrence of pulmonary microembolism and one sural phlebitis that were treated with prolonged heparin and dicumarol therapy. Two significant haemorrhagic events occurred in the postoperative period requiring surgical revision. These data suggest that low weight heparin prophylaxis starting with 24 hours following radical prostatectomy, associated with preoperative blood donation, intra-operative haemodilution, compression stockings, surgical care to avoid lymphocoele and early mobilization in preventing venous thromboembolism.

Risk of Thromboembolism With Short-term Interruption of Warfarin Therapy

Significant uncertainty surrounds the treatment of patients who must discontinue warfarin sodium therapy before an invasive procedure. In part, the uncertainty results from the lack of published information about the risk of thromboembolism associated with short-term warfarin therapy interruption. We aimed to assess the frequency of thromboembolism and bleeding within a large cohort of patients whose warfarin therapy was temporarily withheld for an outpatient invasive procedure. This prospective, observational cohort study was performed at 101 sites (primarily community-based physician office practices) in the United States. Enrollment was conducted from April 4, 2000, to March 6, 2002. The main outcome measures were thromboembolism or clinically significant hemorrhage within 30 days of warfarin therapy interruption. A total of 1293 episodes of warfarin therapy interruption in 1024 individuals were included. The mean (SD) patient age was 71.9 (10.6) years; 438 (42.8%) were female. The most common indications for anticoagulant therapy were atrial fibrillation (n=550), venous thromboembolism (n=144), and mechanical heart valve (n=132). The most common procedures were colonoscopy and oral and ophthalmic surgery. Perioperative heparin or low-molecular-weight heparin was used in only 8.3% of cases overall. Seven patients (0.7%; 95% confidence interval [CI], 0.3%-1.4%) experienced postprocedure thromboembolism within 30 days. None of the 7 patients who experienced thromboembolism received periprocedural bridging therapy. Six patients (0.6%; 95% CI, 0.2%-1.3%) experienced major bleeding, whereas an additional 17 patients (1.7%; 95% CI, 1.0%-2.6%) experienced a clinically significant, nonmajor bleeding episode. Of these 23 patients who had bleeding episodes, 14 received periprocedural heparin or low-molecular-weight heparin. The duration of warfarin therapy interruption was variable; however, more than 80% of patients had warfarin therapy withheld for 5 days or fewer. For many patients receiving long-term anticoagulation who need to undergo a minor outpatient intervention, a brief (< or =5 days) periprocedural interruption of warfarin therapy is associated with a low risk of thromboembolism. The risk of clinically significant bleeding, even among outpatients undergoing minor procedures, should be weighed against the thromboembolic risk of an individual patient before the administration of bridging anticoagulant therapy.

Risk of Thromboembolism after Short-Term Interruption of Warfarin.

Background: Significant uncertainty exists for patients who must discontinue warfarin prior to an invasive procedure. In part, the controversy results from the lack of published information about the risk of thromboembolism associated with short-term warfarin interruption. The aim of this observational study was to assess the frequency of thromboembolism and bleeding among a large cohort of patients whose warfarin was temporarily withheld before and after an outpatient invasive procedure.Methods: A prospective cohort of patients taking warfarin was assembled from 101 sites with personnel designated as warfarin managers across the United States during the period August 2000 to December 2001; 98 sites were community-based physician office practices. All episodes of warfarin interruption among the 6,761 patients in the cohort were identified by investigator review of provider-generated progress notes. Surgical procedures (including cardiovascular interventions) that required hospitalization and cases in which follow-up INR values were not available for at least 30 days post-procedure were excluded. The primary outcomes (30 day follow-up) werethromboembolism andclinically significant hemorrhage.For each patient, the following data were also recorded: type of procedure, number of days warfarin was withheld, presence or absence of bridging therapy (e.g. low molecular weight heparin [LMWH]).Results: 1,024 unique patients (1,293 episodes of warfarin interruption) were included in our analysis. The mean age was 71.9 years; 43% were female. The most common procedures were colonoscopy (n=324), oral surgery (n=323), and ophthalmic surgery (116). Other common reasons for withholding warfarin were: epidural injection, prostate biopsy, breast biopsy, and dermatologic procedures. Perioperative heparin or LMWH was used in only 8.3% of cases. The duration of warfarin interruption was variable; however, more than 80% of patients had warfarin withheld for 5 days or fewer. Seven patients (0.7%) suffered post-procedure thromboembolism within 30 days (4 arterial, 3 venous). None of the 7 patients who experienced thromboembolism received peri-procedural bridging therapy; 3 of these thromboembolic events were associated with warfarin interruption ≥ 7 days. Twenty-three patients (2.3%) suffered clinically significant hemorrhage - of these, 14 had received peri-procedural heparin or LMWH.Conclusion: For many chronically anticoagulated patients who need to undergo a minor, outpatient intervention, a brief (5 or fewer days) peri-procedural interruption of warfarin is associated with a low risk of thromboembolism. The risk for clinically significant bleeding, even among outpatients undergoing minor procedures, should be considered prior to the administration of bridging therapy.

International multi-centre study of incidence and risk factors of symptomatic deep venous thrombosis (DVT) and or pulmonary embolism (PE) in prostate cancer patients undergoing laparoscopic radical prostatectomy (LRP)

8555 Background: There is no data regarding the incidence and variables associated with symptomatic DVT and or PE in patients undergoing LRP. Our aim was to evaluate the multi-centric incidence and risk factors for perioperative symptomatic DVT and PE after LRP. Methods: Patients with symptomatic DVT and or PE occurring within 2 months of surgery since start of the respective institutional LRP experience were included. Eight academic centers from both the United States and Europe participated. Diagnoses were made by Doppler ultrasound for DVT; and lung ventilation/perfusion scan and or chest computed tomography for PE. Associations between variables and DVT and/or PE were evaluated using Fisher’s exact test for categorical predictors and logistic regression for continuous predictors. Results: Patient reoperation (p value) (&lt;0.001), tobacco exposure (0.02), prior DVT (0.007), larger prostate size (0.02) and length of hospital stay (0.009) were significantly associated with higher risk of symptomatic DVT/PE. The nonuse of perioperative heparin was not a risk factor (1), as well as neoadjuvant therapy (1), perioperative transfusion (0.1), body mass index (0.9), surgical technique (0.3), operating time (0.2) and pathologic stage (0.5). There were no related deaths. Patients receiving preoperative heparin had significantly higher mean operative blood loss, 480cc vs 332cc (&lt;0.001) However, this did not translate into longer hospital stay (0.07); higher transfusion rates (0.09) or reoperation rates (0.3). The estimated cost of heparin prophylaxis in these patients exceeded $2.5 million. Conclusion: The incidence of symptomatic DVT or PE was similar despite different prophylactic regimens. Our data does not support the administration of prophylactic heparin in LRP to low risk patients (no prior DVT, no tobacco exposure, no prostate enlargement and or no anticipation of prolonged hospital stay). [Table: see text] No significant financial relationships to disclose.

Mesenteric Venous Thrombosis

Background and purpose: Mesenteric venous thrombosis is a rare but potentially lethal form of mesenteric ischemia. Its presentation may vary from an entirely asymptomatic clinical entity to intestinal infarction and shock. Methods: A patient with mesenteric venous thrombosis was sent to our hospital because of acute abdominal pain that had developed over a single day. The physical findings and imaging examination suggested peritonitis. Results: An emergency laparotomy revealed bowel infarction due to mesenteric venous thrombosis. Segmental resection of the involved bowel with primary anastomosis was performed and resulted in a rather smooth post-operative course with post-operative heparin administration. Conclusion: In review of the literature, the high index of suspicion of mesenteric venous thrombosis, early diagnosis, early surgical management and perioperative heparin therapy will improve the outcome of this disease.

Perioperative Management of Patients on Oral Anticoagulants: A Decision Analysis

To better inform clinicians on the optimal management of patients on oral anticoagulation who need to undergo surgery or invasive procedures, the authors performed a decision analysis examining whether a perioperative aggressive or minimalist strategy results in greater quality-adjusted survival. A decision analysis model was created comparing withholding warfarin (minimalist strategy) to withholding warfarin and administering treatment-dose subcutaneous low-molecular-weight heparin (LMWH) or intravenous heparin perioperatively (aggressive strategy). The base-case analysis examined a hypothetical 60-year-old hypertensive individual with mechanical aortic valve replacement undergoing major abdominal surgery. A probabilistic sensitivity analysis was performed using a Monte Carlo simulation with quality-adjusted life expectancy (QALE) as the outcome. Secondary analyses examined patients with a mechanical mitral valve and atrial fibrillation. Sensitivity analyses were performed for each variable. Under the base-case scenario, the minimalist strategy was preferred for 78% of trials in the Monte Carlo simulation, with a mean benefit of 0.003 years (95% confidence interval, -0.005 years to 0.011 years). Sensitivity analyses based on point estimates indicate that the aggressive strategy is preferred when the annual stroke rate is >5.6% or the increase in postoperative major bleeding induced by heparin is <2.0%; however, the benefit is small over the range of plausible values. For most patients with a mechanical aortic valve or atrial fibrillation undergoing major surgery, a minimalist strategy of simply withholding oral anticoagulation provides similar QALE as an aggressive strategy of administering perioperative subcutaneous LMWH or intravenous heparin. The aggressive therapy provides greater QALE for patients at higher risk of stroke (e.g., mechanical mitral valves), although the benefit is small.

Mesenteric venous thrombosis in a patient with congenital afibrinogenemia and diffuse peritonitis

Congenital afibrinogenemia is a rare autosomal recessive hemorrhagic disorder, and thrombotic complications occurring spontaneously or after infusion of fibrinogencontaining preparations have been reported in afibrinogenemic patients [1]. We report a case of mesenteric venous thrombosis due to fibrinogen replacement in a patient with congenital afibrinogenemia. A 19-year-old male with congenital afibrinogenemia had previously undergone uneventful surgical procedures for splenic rupture, intracranial bleeding, and mandibular abscess (2002) with preoperative supplement of fibrinogen concentrate. He was urgently admitted to the Critical Care Medical Center and diagnosed with diffuse peritonitis in 2003. After prophylactic administration of ten units of fresh-frozen plasma (FFP), resection of the small intestine was performed. Numerous thromboses were detected in the mesenteric veins of the resected specimen. The color of the remaining small intestine darkened during wound closure and mesenteric circulation worsened. Continuous infusion of unfractionated heparin (Novo Heparin 1000, Mochida Pharmaceutical Co., Japan) at 500 units/h was initiated following a 2000-unit bolus. The following day, massive resection of the small intestine, leaving only 60 cm of small intestine, was performed due to necrosis identified during a second-look operation. In 2004, emergency surgery was performed for adhesive intestinal obstruction without hemostatic complications by prophylactic administration of fibrinogen concentrate and unfractionated heparin. Perioperative laboratory data from 2002, 2003, and 2004 are shown in Table 1. In 2002, data revealed undetectable plasma fibrinogen levels by the functional assay, undetectable prothrombin time (PT) and activated partial thromboplastin time (APTT), and thrombocytosis. Supplementation with 9000 mg of fibrinogen raised fibrinogen levels to 1.91 g/l and normalized PT and APTT. In 2003, fibrinogen levels, PT, APTT, and platelet count after preoperative administration of ten units of FFP were approximately the same as in 2002. However, excessively high levels of hemostatic and inflammatory markers preoperatively indicated a hypercoagulable and inflammatory state. While perioperative heparin infusion in the first operation suppressed levels of hemostatic markers, the levels of those in the second-look operation were still above normal range. In 2004, preoperative tests again showed undetectable plasma fibrinogen level and PT, but APTT was normal. Values for all hemostatic markers, WBC, and C-reactive protein (CRP) were markedly elevated compared to reference ranges, but platelet count was normal. Supplementation with fibrinogen concentrate and intraoperative heparin administration resulted in a plasma fibrinogen concentration of 1.03 g/l and an APTT of 44.7 s. Fibrinogen level measured using both functional and immunological assays was 0.1 g/l at 5 days after administration of 1000 mg of fibrinogen concentrate. Prothrombin activation increases and increased thrombin generation has been observed in afibrinogenemia [2]. Thrombin represents a potent activator of platelets and platelet aggregation [3]. Tefferi et al. [4] reported marked thrombocytosis occurring in 22.0% of postsplenectomy patients. Furthermore, Remijn et al. [1] showed that the absence of fibrinogen results in large but loosely packed platelet aggregates and suggested that afibrinogenemic patients could be at risk for thrombosis. Thus, hypercoagulable states due to increased prothrombin activation and platelet aggregation may exist in our patient. Compensative reaction for severe intestinal inflammation and/or heparin-induced thrombocytopenia [5] may have been considerable for the reduced platelet count in 2004, Y. Takasugi (*) . Y. Shiokawa . R. Kajikawa . J. Oh . Y. Koga Department of Anesthesiology, Kinki University School of Medicine, 377-2 Ono-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan e-mail: yoshihiro.takasugi@nifty.com Tel.: +81-72-3660221 Fax: +81-72-3660206

Prospective evaluation of outcome measures in free-flap surgery.

Free-flap failure is usually caused by venous or arterial thrombosis. In many cases, lack of experience and surgical delay also contribute to flap loss. The authors prospectively analyzed the outcome of 57 free flaps over a 28-month period (January, 1999 to April, 2001). The setting was a university hospital tertiary referral center. Anastomotic technique, ischemia time, choice of anticoagulant, and the grade of surgeon were recorded. The type of flap, medications, and co-morbidities, including preoperative radiotherapy, were also documented. Ten flaps were re-explored (17 percent). There were four cases of complete flap failure (6.7 percent) and five cases of partial failure (8.5 percent). In patients who received perioperative systemic heparin or dextran, there was no evidence of flap failure (p = .08). The mean ischemia time was similar in flaps that failed (95 +/- 29 min) and in those that survived (92 +/- 34 min). Also, the number of anastomoses performed by trainees in flaps that failed (22 percent), was similar to the number in flaps that survived (28 percent). Nine patients received preoperative radiotherapy, and there was complete flap survival in each case. This study reveals that closely supervised anastomoses performed by trainees may have a similar outcome to those performed by more senior surgeons. There was no adverse effect from radiotherapy or increased ischemia time on flap survival.

Thrombophilia associated with anti-CD154 monoclonal antibody treatment and its prophylaxis in nonhuman primates.

The authors previously reported thromboembolic complications associated with anti-CD154 monoclonal antibody (mAb) treatment in nonhuman primates. The underlying mechanisms of this complication and its management have not been established. Eighty cynomolgus monkey renal allograft recipients treated with anti-CD154 mAb were studied for the incidence of thrombosis and its prophylaxis. Without anticoagulation prophylaxis, thromboembolic complications were seen in 5 of 11 recipients. With addition of perioperative heparin, the incidence was decreased to 2 of 10. No further improvement was observed by adding intraoperative prostaglandin (PG) E1. However, addition of ketorolac tromethamine to PGE1 and heparin decreased the incidence of thrombosis (one of eight). Most recently, the authors have found that ketorolac administration alone resulted in no thrombosis in 25 consecutive recipients. Ketorolac is remarkably effective in preventing thromboembolism associated with anti-CD154 mAb treatment, suggesting the mechanism underlying this complication may be related to platelet activation leading to enhanced aggregation.

Management of Thrombophilia in Renal Transplant Patients

Renal allograft recipients with thrombophilia (a hypercoagulable state) are at higher risk for early allograft loss. Following an episode of allograft renal vein thrombosis in a patient subsequently diagnosed with protein C deficiency, we adopted universal screening for hypercoagulable risk factors. Patients with a history of a thromboembolic event underwent laboratory screening for thrombophilia. Eight patients with a defined hypercoagulable disorder or a strong clinical history of thrombosis even in the absence of hematologic abnormalities were treated with anticoagulation following renal transplantation. We reviewed the outcomes of these eight patients and all renal transplant recipients at our center who developed thrombotic complications after renal transplantation. Since the introduction of universal screening for hypercoagulable risk factors, 235 consecutive transplants were performed without allograft thrombosis. Eight patients with evidence of thrombophilia, recognized before renal transplantation, received perioperative heparin and postoperative oral anticoagulation. Two of these eight patients developed perinephric hematomas requiring evacuation, blood transfusion, and temporary withholding of anticoagulation. Of interest, two of the remaining 227 patients, not identified with thrombophilia before surgery, developed thrombotic complications after renal transplantation. A hypercoagulable disorder was subsequently documented in each. Identifying patients with thrombophilia before transplantation and defining their management presents many challenges. The risk of allograft thrombosis must be weighed against the risk of perioperative bleeding and the need for long-term anticoagulation. Recommendations for managing thrombophilia in renal transplant recipients are suggested based on our experience and review of the literature.

The Efficacy and Safety of Perioperative Low Molecular Weight Heparin Substitution in Patients on Chronic Oral Anticoagulant Therapy Undergoing Transurethral Prostatectomy for Bladder Outlet Obstruction

The Efficacy and Safety of Perioperative Low Molecular Weight Heparin Substitution in Patients on Chronic Oral Anticoagulant Therapy Undergoing Transurethral Prostatectomy for Bladder Outlet Obstruction

Safety of perioperative minidose heparin in patients undergoing brain tumor surgery: a prospective, randomized double-blind study.

Safety of perioperative minidose heparin in patients undergoing brain tumor surgery: a prospective, randomized double-blind study.

The Modified Blalock-Taussig Shunt: A 6-Year Experience from a Developing Country

Since 1992 we have performed the modified Blalock-Taussig shunt (MBTS) for cyanotic children in Libya. This retrospective study reviews our results as a developing country, comparing them with those in the literature, and makes suggestions to improve our results. Between May 1992 and May 1998, 94 children (58 males and 36 females) underwent 100 MBTSs in Mesallata Cardiothoracic Centre, Libya. The age ranged from 4 days to 15 years, (median 12 months) and 25 patients were neonates. Patients' weights ranged from 3 to 31 kg (median 6.4 kg). Eighty-nine shunts were performed on the left side and 11 on the right. A 6-mm polytetrafluoroethylene graft was used in 68 children and a 4-mm graft in 32 cases. Tetralogy of Fallot (TOF) comprised the majority of cases (63; 67%), the remaining 31 (33%) included tricuspid atresia (13), pulmonary atresia (9), univentricular heart complex (6), and others (3). Acute shunt failure occurred in 3 cases (2 with 4-mm and 1 with 6-mm grafts), all of which had not received perioperative heparin. Hospital mortality was 6% (6 patients); risk factors were neonates, a diagnosis other than TOF, and emergency surgery. There were 12 late deaths, 6 of which were due to sepsis. Follow-up was achieved in 82 of 88 early survivors for a period of 2 to 60 months (median 26 months). All surviving patients had subjective and objective improvement. We conclude that MBTS is an excellent palliative procedure for children requiring a systemic-pulmonary shunt in developing as well as developed countries. This series shows an early mortality rate comparable to that of other studies, but the late mortality is higher, mainly due to sepsis, which warrants further attention.

Perioperative Anticoagulation Practices of Surgeons in a Health System

Several different management strategies for patients receiving long-term warfarin therapy who require surgery have been recommended in the literature. A recent article by Kearon and Hirsch made new recommendations based on estimating the risk of thromboembolism and bleeding from randomized trials and prospective studies. Because of the potential for variability in practice patterns, we surveyed physicians in our health system to identify their perioperative anticoagulation practices. Our results confirm variability in practice patterns. Perioperative intravenous heparin was the most frequently reported method of prophylaxis. Fifty-three percent of the surveyed physicians admitted patients to the hospital two or more days prior to surgery to receive prophylaxis. Further research is necessary to determine optimal management of perioperative anticoagulation.

Management of heparin therapy in the high-risk, chronically anticoagulated, oral surgery patient: A review and a proposed nomogram

Purpose: This study analyzes the use of a standard nomogram that can help reduce the level of anticoagulation preoperatively to effectively manage perioperative heparin therapy in chronically anticoagulated oral surgery patients who are at high risk for thromboembolism.Patients and Methods: Twenty patients with significant cardiovascular disease, ranging in age from 56 to 79 years and requiring oral surgery, were randomly divided into 2 groups. All patients were on chronic warfarin therapy, and perioperative heparinization was recommended by their cardiologist. Group A (n = 10) had their anticoagulation therapy managed with the use of a standard nomogram. The heparin therapy for group B (n = 10) was managed without the use of the nomogram. The records of all patients were analyzed for therapeutic efficacy of heparinization, number of laboratory tests required, duration of hospitalization, and complications related to heparinization.Results: Patients in group A did significantly better in all parameters when compared with group B patients. There were no complications in group A, whereas there was a 20% incidence of complications related to anticoagulation therapy in group B.Conclusions: The use of a standard nomogram to manage anticoagulation therapy in the oral surgery patient requiring heparinization is strongly recommended. This provides optimal therapeutic benefit, decreases the incidence of complications, and makes the hospitalization less costly and more comfortable for the patient.

Safety of perioperative subcutaneous heparin for prophylaxis of venous thromboembolism in patients undergoing craniotomy.

To determine whether perioperative subcutaneous heparin is safe to use for patients undergoing craniotomy and to determine the incidence of venous thromboembolism in patients undergoing craniotomy. Perioperative prophylaxis with subcutaneous heparin, 5000 U every 12 hours, was begun at induction of anesthesia for craniotomy and continued for 7 days postoperatively or until the patient was ambulating. Entry criteria to the study included patient age over 18 years and no evidence of deep vein thrombosis (DVT) preoperatively as judged by lower limb duplex ultrasound. Patients were excluded if they had duplex evidence of DVT or clinical evidence of pulmonary embolus (PE) preoperatively, had hypersensitivity to heparin or related products, had sustained a penetrating head injury, or refused informed consent. Any patient undergoing craniotomy was eligible, including patients with a ruptured aneurysm or arteriovenous malformation and those with spontaneous intracranial hemorrhage. Patients underwent duplex study 1 week after surgery and 1 month of clinical follow-up. Records were also kept on 68 nonstudy patients who refused consent. All patients were treated with lower limb pneumatic compression devices. One hundred six patients were treated. No differences were noted between study and nonstudy patients in some individual risk factors for DVT or PE, such as obesity, smoking, paralysis, infection, pregnancy or postpartum state, varicose veins, heart failure, or previous DVT or PE. Significantly more (43 of 106) patients in the study group had a history of risk factors for DVT or PE, particularly malignancy, however, compared with nonstudy patients (20 of 68 patients; chi2, P < 0.01). There were no differences between groups in intraoperative blood loss, transfusion requirements, or postoperative platelet counts. Four clinically significant hemorrhages occurred during surgery in patients receiving heparin. Three resulted from intraoperative aneurysm rupture and one from intraventricular bleeding during resection of an arteriovenous malformation. These events were believed to be related to known complications of these operations, not to heparin. Of the study patients, two developed symptomatic DVT and one developed a nonfatal PE during the 1-month postoperative period. One additional study patient developed DVT below the popliteal veins, which was not treated. Four study patients developed DVT 1 to 2 months after surgery. In nonstudy patients, three developed DVT and two developed PE (one fatal, one nonfatal). Perioperative heparin may be safe to administer to patients undergoing craniotomy, but a larger study is needed to demonstrate efficacy.

Intracerebral hemorrhage after carotid endarterectomy: Incidence, contribution to neurologic morbidity, and predictive factors

Purpose: With a diminishing rate of cardiac and neurologic events after carotid endarterectomy, intracerebral hemorrhage is gaining increasing importance as a cause of perioperative morbidity and mortality. To date, information has been largely anecdotal, and there has been no comparison with a control group of patients. Methods: The records of all patients experiencing symptomatic intracerebral hemorrhage after carotid endarterectomy were reviewed and compared with data from 50 randomly selected patients who did not experience intracranial bleeding. Univariate analyses were performed, using the Fisher exact test for dichotomous data and the Student t test for continuous data. Results: During a 6-year period, symptomatic intracranial hemorrhage developed in 11 (0.75%) of 1471 patients undergoing carotid endarterectomy, accounting for 35% of the 31 total perioperative neurologic events. Hemorrhage occurred a median of 3 days postoperatively (range, 0 to 18 days). Signs and symptoms included hypertension in all 11 patients, headache in 7 conscious patients (64%), and bradycardia in 6 patients (55%). Massive hemorrhage with herniation and death occurred in 4 patients (36%). Moderate hemorrhage developed in 5 patients (45%); 3 of these patients had partial recovery, and 2 had complete recovery. Petechial hemorrhage occurred in the remaining 2 patients (18%), 1 with partial and 1 with complete recovery. In comparison with the control group, there were no differences in respect to sex, indication for operation, smoking or diabetic history, and antiplatelet therapy or perioperative heparin management. Patients with intracranial hemorrhage were, however, younger, more frequently hypertensive, had a higher degree of ipsilateral and contralateral carotid stenosis, and had a higher rate of contralateral carotid occlusion. Conclusion: Intracranial hemorrhage occurs with notable frequency after carotid endarterectomy and accounts for a significant proportion of neurologic morbidity and mortality. Younger patients, hypertensive patients, and patients with severe cerebrovascular occlusive disease appear to be at greatest risk for the complication. (J Vasc Surg 1999;29:82-9.)

Complications of subcutaneous low-dose heparin therapy in neurosurgical patients

BACKGROUND Venous thromboembolism is a major cause of postoperative morbidity and mortality in neurosurgery. The use of low-dose unfractionated heparin therapy perioperatively for prophylaxis against deep vein thromboses and pulmonary embolism has been well demonstrated in many other surgical specialties but is less commonly used in neurosurgery because of fears of devastating postoperative hematomas. METHODS The safety of such therapy has been analyzed in 950 patients undergoing an inpatient neurosurgical procedure. 872 patients (152 cranial procedures) completed treatment with 5000 U sodium heparin subcutaneously twice a day, commencing before surgery and continuing till patients were ambulatory. RESULTS There were three minor hemorrhagic complications—two superficial wound hematomas (one requiring treatment) and one gastrointestinal hemorrhage—identified. Three clinically significant major complications developed, two epidural hematomas after spinal surgery requiring evacuation and one intraventricular hemorrhage after brain biopsy. CONCLUSION This report, along with an analysis of previously published reports of low-dose perioperative heparin therapy in neurosurgical patients, suggests that such therapy is unlikely to be associated with increased morbidity. Given the known efficacy of low-dose heparin in reducing venous thromboembolism in other surgical patients, such therapy may reduce mortality and morbidity from thromboembolic complications in neurosurgical patients with minimal risk.

Hyperviscosity syndrome in patients with ovarian carcinoma.

In patients with ovarian carcinoma, an hematocrit-independent hyperviscosity syndrome is often present. The syndrome is characterized by normal or low hematocrit and hemoglobin concentration, an elevated platelet count, and an increase in clotting factor turnover. Because deep vein thrombosis (DVT) often complicates the course of ovarian carcinoma, the aim of this study was to investigate the possible association of hyperviscosity syndrome with the development of DVT. Rheologic estimations of the blood included red blood cell (RBC) aggregation (stasis and low shear), plasma viscosity (pv), blood cell count, and fibrinogen, which were performed before primary surgery and the beginning of perioperative heparin thrombosis prophylaxis on 63 of 65 patients with Stage I-IV ovarian malignancy (according to the staging criteria of the International Federation of Gynecology and Obstetrics). Two patients who had had DVT 5-6 weeks in advance of the study were excluded from rheologic calculations. Thrombosis screening by impedance plethysmography was performed the day before primary major surgery; postoperatively on Days 1, 3, 5, 7, and 10; before each of 6 cycles of chemotherapy (once every 3 weeks); and thereafter once every 3 months during follow-up. All blood tests were also performed on 72 healthy women and 29 patients with benign ovarian tumor the day prior to surgery. All ovarian carcinoma patients, including 7 patients with tumors of low malignant potential, were eligible for surgery, and all except those with Stage IV disease (n = 12) were macroscopically tumor free after surgery. Before surgery, RBC aggregation, pv, and platelet and fibrinogen concentrations were significantly higher (P < 0.05) in cancer patients than in either of the control groups, whereas hemoglobin (hb) and hematocrit (hct) were significantly lower in cancer patients than in healthy women (P < 0.001). Platelet, leukocyte, and fibrinogen concentrations were significantly correlated to disease stage, whereas pv, RBC aggregation, hb, and hct were not. The preoperative pv was significantly higher in patients who later developed DVT (n = 17; 1.46+/-0.13 mPas; P = 0.01) than in those who did not (1.34+/-0.14 mPas). Of all estimated preoperative variables, only pv was a significant risk factor for postoperative and subsequent DVT (RR: 29.84; 95% CI: 1.076-827.16; P = 0.04). Our results confirm the presence of a hematocrit- and stage-independent hyperviscosity syndrome in untreated ovarian carcinoma patients. In addition, a high preoperative plasma viscosity was a significant risk factor for the development of DVT in the postoperative period and even thereafter.

Low molecular weight heparin: biochemistry, pharmacology, perioperative prophylaxis regimens, and guidelines for regional anesthetic management.

Low molecular weight heparin: biochemistry, pharmacology, perioperative prophylaxis regimens, and guidelines for regional anesthetic management.