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PubMed1996

IB4, a monoclonal antibody against the CD18 leukocyte adhesion protein, reduces intracranial pressure following thromboembolic stroke in the rabbit.

Neutrophil activation and accumulation as a consequence of cerebral ischemia-reperfusion has been suggested to exacerbate tissue injury. The current study is designed to examine the effect of IB4, a monoclonal antibody directed against the neutrophil adhesion protein, CD18, in a rabbit model of thromboembolic stroke. New Zealand rabbits (3-3.5 kg n=8 each group), were given an autologous clot embolus, delivered to the anterior circulation of the brain via the internal carotid artery. Immediately following thromboembolism, the mean arterial pressure in all animals was reduced to 30 mmHg by controlled exsanguination for a period of 45 min. All animals were mechanically ventilated and following parameters were monitored hourly: arterial blood gases, intracranial pressure, regional cerebral blood flow, hematocrit, and core temperature. Rabbits were given either IB4 (1 mg kg(-1)), or vehicle (1 percent albumin, IV) 30 min following the thromboembolic event. The mean arterial pressure of all animals was restored to the baseline value of 50-60 mmHg for the remainder of the 4-h experiment. Following the thromboembolic event, the intracranial pressure rose in both groups, although this was significantly less in the IB4-treated group, with the final values being 195.9 +/- 38.3 vs. 135.5 +/- 26.0 percent of baseline (mean +/- SEM, p < 0.05). However, regional cerebral blood flow and infarct size (TTC staining) were virtually identical in both groups. It is concluded that blockade of the neutrophil adhesion protein, CD18, may contribute to a reduction in the intracranial pressure following cerebral ischemia and reperfusion, providing further evidence that activated neutrophils may contribute to cerebral edema.

Animals↗
PubMed1995

Prophylaxis against thromboembolism in neurosurgical patients: a survey of current practice in the United Kingdom.

Venous thromboembolism is a life threatening, but preventable complication of major surgery. Many neurosurgical patients are at high risk of developing thromboembolic disease. A postal survey was undertaken of 44 UK neurosurgical centres to assess the use of physical and pharmacological methods of prophylaxis against thromboembolism. Thirty-five replies were received from 31 centres. Seventy-seven per cent of units used antiembolism stockings (TEDs) for elective surgery and 37% for emergency surgery; in approximately two-thirds of these units TEDs constituted the sole method of prophylaxis used during both elective and emergency surgery. Intermittent pneumatic compression (IPC) was utilized in 37 and 11% of units for elective and emergency surgery, respectively. Subcutaneous heparin was used in 32% of units perioperatively including 6% of emergency cases. These findings suggest that neurosurgical patients, who are at moderate to high risk of developing thromboembolic complications, may not receive effective prophylaxis; those undergoing emergency neurosurgery are less likely to receive any form of prophylaxis.

Brain↗
PubMed2001

Use of venous thromboembolism prophylaxis for surgical patients: a multicentre analysis of practice in Spain.

OBJECTIVE: To assess the use of venous thromboembolism prophylaxis in surgical patients. DESIGN: Retrospective multicentre study. SETTING: Eight acute-care teaching hospitals with more than 400 beds, Spain. PATIENTS: Medical records of all consecutive patients undergoing operations in the general surgical and trauma and orthopaedic services during the month of April, 1997, were randomly selected. INTERVENTION: The sample size for each type of operation (general, trauma-orthopaedic) was calculated from the number of operations done at each hospital (with an absolute precision of 5%, and an alpha error of 5%) and the prevalence of the use of venous thromboembolism prophylaxis obtained from a random sample of 50 records (25 from patients in general surgery and 25 from patients in orthopaedic surgery) from each centre. MAIN OUTCOME MEASURES: Appropriate and inappropriate pharmacological prophylaxis defined according to a combination of risk categories for venous thromboembolism, doses of antithrombotic agents given, time of starting prophylaxis, and its duration. RESULTS: A total of 1848 medical records (general surgery, n = 1025; trauma-orthopaedic surgery, n = 823) were included. Physical methods (elastic stockings, intermittent pneumatic compression) were used in only 0.3% of patients. Pharmacological prophylaxis consisted of low molecular weight heparin in 99% of cases. The percentage given heparin-based prophylaxis was 54%. Overall, appropriate prophylaxis was given in 1175 patients (64%). Use of thromboprophylaxis ranged from 27% to 70% among the participating hospitals. Prophylaxis was more likely to be appropriate in orthopaedic patients (577, 70%) than in general surgical patients (598, 58%) in both the high and moderate risk categories. CONCLUSIONS: Given the large variability between the participating hospitals, more specific protocols and recommendations about prophylaxis of thromboembolism in surgical patients are needed.

Adolescent↗
PubMed1993

Perioperative prophylaxis of venous thromboembolism.

Venous thromboembolism is an important cause of morbidity and mortality in hospitalized patients, causing 100,000 to 200,000 deaths per year in the United States. Patients undergoing surgery are at the highest risk of venous thromboembolism. The magnitude of this risk in a patient depends on the surgical procedure performed and the presence of other risk factors that predispose to venous thromboembolism. The clinical diagnosis of both deep vein thrombosis and pulmonary embolism is notoriously inaccurate. Furthermore, two thirds of all fatal pulmonary emboli cause death within 30 minutes of the embolic episode, leaving little time for diagnostic work-up and effective treatment. Prophylactic treatment for prevention of venous thromboembolism is therefore important in these patients, and several effective mechanical and chemical methods for this purpose are available. The pathogenesis of deep vein thrombosis in the surgical patients, the predisposing risk factors, and the available prophylactic modalities are discussed in this article. Recommendations for the use of various approaches in different risk categories are provided.

Humans↗
PubMed2001

The acute management of venous thromboembolism in pregnancy.

Pulmonary thromboembolism is the leading cause of maternal death in the UK. Optimal management of deep venous thrombosis and pulmonary thromboembolism requires an appreciation of risk factors, particularly thrombophilia, and signs or symptoms suggestive of venous thromboembolism, along with objective diagnosis and treatment with anticoagulants. Low molecular weight heparins are now replacing unfractionated heparin for the treatment of deep venous thrombosis and pulmonary thromboembolism in pregnancy because of the lower risk of side effects, ease of administration and reduced need for monitoring.

Anticoagulants↗
PubMed1989

Diagnosis of thrombosis of the deep veins of the lower extremities and pelvis and pulmonary thromboembolism using 99Tcm human serum albumin macroaggregates.

Radionuclide phlebography of the lower extremities, pelvis and pulmonary scintigraphy was performed using 99Tcm human serum albumin macroaggregates (MAA) in 90 patients aged 20 to 80 years, 13 (14%) in post-operative period and 77 (85%) with suspected deep venous thrombosis or pulmonary thromboembolism. The aim of the study was to evaluate the diagnosis of thrombosis of the deep veins of the lower extremities and pelvis and pulmonary thromboembolism using a refined technique. Deep venous thrombosis (DVT) was detected in all surgical patients and in 59 patients with systemic diseases. Perfusion scintigraphic defects characteristic of pulmonary thromboembolism (PE) were discovered in 12 of the surgical patients and in 38 of the medical patients. The results of the examinations have again shown that patients after surgery are exposed to high risks of DVT and pulmonary thromboembolism, while a relatively high percentage of normal findings in patients with suspected DVT have indicated unreliability of clinical symptoms and signs in diagnosing this disease.

Adolescent↗
PubMed1999

Venous thromboembolism: risk factors in the craniotomy patient population.

PURPOSE: The purpose of the study was to determine risk factors for the development of venous thromboembolism in the craniotomy population. Four hundred forty-three patients who under went craniotomy surgery were enrolled in the study. Patients were assessed daily during their postoperative recovery and at the 6-week return postoperative visit for signs and symptoms of thromboembolism. Those not returning for a checkup received a call which asked about the occurrence of signs and symptoms. Chart audits were completed to gather data on risk factors and thromboembolism characteristics. Risk factors included demographic, clinical history, lab, medications, intraoperative and postoperative variables. Deep venous thrombosis and pulmonary embolus symptomatology were also evaluated. Forty-four patients (10%) developed a thrombosis during hospitalization or during the 6 week recovery. The diagnosis was confirmed by duplex scan or venogram. Multiple vessels were the most frequent site. Only 22.7% of the patients had symptoms. Significant risk factors included: presence of leg weakness (p = 0.05), longer LOS (p = 0.0001), more postoperative ICU days (p = 0.001), more preoperative ICU days (p = 0.01), longer recovery time in PACU (p = 0.03), and a longer postoperative period to initiate all activities, ROM, chair, BRP, and ambulating in hall (p = < 0.01). Venous thromboembolism increases morbidity, mortality and health care costs. A risk profile can assist nurses in targeting patients for additional preventive interventions.

Adult↗
PubMed2006

Bosentan in Eisenmenger syndrome and chronic thromboembolic pulmonary hypertension.

BACKGROUND: Bosentan, a dual endothelin receptor antagonist, has been used for symptomatic improvement of patients with idiopathic pulmonary arterial hypertension (PAH) and specific types of secondary (e.g. scleroderma and human immunodeficiency virus infection) PAH, but its efficacy in patients with congenital heart disease and chronic thromboembolic pulmonary hypertension is still under evaluation. In this study two patients are presented, one with common atrioventricular canal and pulmonary hypertension and the other with recurrent pulmonary thromboembolism; both improved significantly after bosentan administration. MATERIALS AND METHODS: The first patient was a 38-year-old female with trisomy 21, common atrioventricular canal and pulmonary hypertension (Eisenmenger syndrome). The second patient was a 57-year-old male, who was on anticoagulant therapy owing to an episode of pulmonary embolism that had been diagnosed 3 years earlier. Recurrent pulmonary thromboembolism was considered the most probable diagnosis. Chest spiral computed tomography examination excluded pulmonary endarterectomy as a therapeutic approach. At admission, the two patients were on New York Heart Association class IV, diagnosed by progressive rest dyspnea. Bosentan was administered to patients 1 and 2 for 6 and 9 months, respectively (62.5 mg b.i.d. for 4 weeks, then 125 mg b.i.d.). RESULTS: Bosentan therapy resulted in significant clinical improvement in both patients. No hepatic dysfunction nor any other side-effect was observed. CONCLUSIONS: Bosentan could be an effective therapy for pulmonary hypertension owing to congenital heart disease and chronic thromboembolic disease.

Administration, Oral↗
PubMed2004

A thromboembolic predisposition and the effect of anticoagulants on migraine.

OBJECTIVE: To investigate the presence of thromboembolic risk factors and the effect of low-dose acenocoumarol therapy on migraine in patients who spontaneously reported a reduction of their migraine attacks during previous therapeutic use of anticoagulants. BACKGROUND: The positive effect of anticoagulants on migraine has been described in case reports and observational studies. It remains unclear whether this concerns only a select group of migraineurs with certain common characteristics. METHODS: In 4 migraineurs with a self-reported reduction of attack frequency during previous use of anticoagulants (international normalization ratio [INR], 2.5:4.0), the presence of thromboembolic risk factors and the effect of low-dose acenocoumarol therapy (INR, 1.5:2.0) on migraine attacks were prospectively investigated in an open study. RESULTS: All patients had one or more thromboembolic risk factors. Two patients, both with factor V Leiden heterozygosity, experienced a clear improvement of migraine during low-dose acenocoumarol therapy. CONCLUSIONS: Our findings support the hypothesis that migraine, as a phenotype, has different underlying mechanisms, amongst which a thromboembolic tendency. In this group of patients, oral anticoagulants may be a suitable form of migraine prophylaxis, but this needs further clinical investigation.

Acenocoumarol↗
PubMed1998

Should Transesophageal Echocardiography Become a Routine Test in Patients with Suspected Pulmonary Thromboembolism?

Pulmonary thromboembolism presents in two clinical subsets: acute pulmonary embolism (PE) with or without right heart thrombi or paradoxical embolism and chronic thromboembolic pulmonary hypertension (CTEPH). Both PE and CTEPH have been underdiagnosed and carry high mortality rates. Acute massive PE is a hemodynamic entity leading to right ventricular overload readily identified with the use of transthoracic echocardiography. Transesophageal echocardiography (TEE) is a noninvasive bedside technique that has high diagnostic accuracy for the detection of central pulmonary thromboembolism. Due to the high prevalence of central pulmonary thromboembolism in acute PE, TEE is a useful method to provide the necessary proof for the institution of thrombolytic therapy. In the subset of patients with acute PE combined with right heart thrombi or paradoxical embolism, TEE is the technique of choice to guide surgery. CTEPH presents as primary pulmonary hypertension, but it has become a surgically curable disease. TEE is a fast, fairly sensitive, and highly specific diagnostic bedside modality to select surgical candidates with CTEPH. TEE should become a routine test in patients with suspected massive acute PE, suspected right heart thrombi, or paradoxical embolism associated with acute pulmonary embolism and in patients with primary pulmonary hypertension to select those having CTEPH who are suitable for surgery.

Journal Article↗
PubMed2002

Oral beraprost sodium improves exercise capacity and ventilatory efficiency in patients with primary or thromboembolic pulmonary hypertension.

OBJECTIVE: To investigate the effect of beraprost sodium, an orally active prostacyclin analogue, on exercise capacity and ventilatory efficiency in patients with primary pulmonary hypertension and chronic thromboembolic pulmonary hypertension. PATIENTS AND DESIGN: Symptom limited cardiopulmonary exercise testing was performed before and 3 (1) months (mean (SEM)) after beraprost treatment in 30 patients with precapillary pulmonary hypertension (14 with primary pulmonary hypertension and 16 with chronic thromboembolic pulmonary hypertension). RESULTS: Long term treatment with beraprost resulted in significant increases (mean (SEM)) in peak workload (87 (4) W to 97 (5) W, p < 0.001) and peak oxygen consumption (peak VO2, 14.9 (0.7) ml/kg/min to 16.8 (0.7) ml/kg/min, p < 0.001). Beraprost decreased the ventilatory response to carbon dioxide production during exercise (VE-VCO2 slope, 42 (2) to 37 (1), p < 0.001). No significant difference in the responses of these variables to beraprost treatment was observed between patients with primary pulmonary hypertension and chronic thromboembolic pulmonary hypertension. CONCLUSIONS: Oral administration of beraprost sodium may improve exercise capacity and ventilatory efficiency in patients with both primary and chronic thromboembolic pulmonary hypertension.

Administration, Oral↗
PubMed1997

Chronic thromboembolism: diagnosis with helical CT and MR imaging with angiographic and surgical correlation.

PURPOSE: To evaluate the accuracy of identification of central and segmental chronic thromboembolic disease on helical computed tomographic (CT) scans and on magnetic resonance (MR) images. MATERIALS AND METHODS: Radiologic findings in 55 patients suspected of having chronic thromboembolic pulmonary hypertension were analyzed; these included findings from angiography (n = 55), helical CT (n = 47), and MR imaging (n = 26). Forty patients underwent thromboendarterectomy. CT and MR images were independently interpreted by two readers for the presence of thromboembolic material in central and segmental vessels. Surgical findings and angiographic findings were the reference standards for disease in central and segmental vessels, respectively. RESULTS: Central vessel disease was determined more accurately with helical CT scans (accuracy of 0.79 for each of the two readers) than with angiograms (accuracy of 0.74) or with MR images (accuracy of 0.39 and 0.46 for two readers). Segmental vessel disease was also more accurately determined with CT scans (accuracy of 0.75 and 0.76 for two readers) than with MR images (accuracy of 0.61 and 0.57 for two readers). CONCLUSION: Helical CT is a useful alternative to conventional angiography for diagnosis of chronic thromboembolism but may not be sufficient for selecting candidates for surgery in all cases.

Aged↗
PubMed1999

Should patients with venous thromboembolism and cancer be treated differently?

Patients with malignant disease constitute a significant subgroup among patients with venous thromboembolism. Current results suggest that cancer patients are not only at an increased risk for thromboembolic events, particularly during chemotherapy treatment or after surgery, they also have an increased risk for bleeding complications while receiving oral anticoagulant treatment. The exact incidences of venous thromboembolic complications for the various types of cancer, however, are not well determined. Recent studies have indicated that subcutaneous low-molecular-weight heparin (LMWH) is as safe and effective as intravenous unfractionated heparin (UFH) in the initial treatment of venous thromboembolism. Moreover, a meta-analysis has provided preliminary evidence that, compared with UFH, LMWH treatment may prolong survival in cancer patients. Initiation of LMWH treatment in these patients is, therefore, recommended. Prospective randomized clinical trials to assess the optimum dose and duration of therapy are called for.

Anticoagulants↗
PubMed2005

Tissue plasminogen activator extravasated through the cerebral vessels: evaluation using a rat thromboembolic stroke model.

Neurotoxic effects of endogenous tissue plasminogen activator (tPA) have recently been reported. Employing a rat model of thromboembolic stroke, we evaluated the extent and degree of extravasation of exogenous tPA administered for the purpose of fibrinolysis. In a thromboembolic model using Sprague-Dawley rats, focal cerebral ischemia was induced at the territory of the middle cerebral artery (MCA). Early reperfusion was induced by administering tPA (10 mg/kg) intravenously at 30 minutes after the onset of ischemia. Extravasated tPA was evaluated by immunohistochemistry, and the concentration of tPA in the brain tissue was quantified by enzyme-linked immunosorbent assay methods. The integrity of the blood-brain barrier (BBB) was examined electronmicroscopically. In a thread model of transient ischemia, reperfusion was induced without tPA administration at 30 minutes or 2 hours after the onset of ischemia, and the tPA content of the brain was quantified. In the rats with thromboembolic stroke, extravasation of tPA was observed at the territory of the MCA. Both the endogenous and exogenous tPA contents were 3.5 +/- 1.6 ng/ml of homogenized brain in saline. Electronmicroscopically, mild ischemic changes were observed, although the integrity of the BBB was preserved. In the thread model rats, the endogenous tPA contents of the ischemic hemisphere were 0.9 +/- 0.1 and 1.0 +/- 0.2 ng/ml in the 30-minute and 2-hour ischemia groups, respectively, and were significantly lower than the tPA contents in the thromboembolic stroke rats (p<0.01). The present findings indicate that significant extravasation of exogenous tPA occurs through the cerebral vessels even though early reperfusion is induced.

Animals↗
PubMed1997

Thromboembolism prophylaxis in chronic atrial fibrillation. Practice patterns in community and tertiary-care hospitals.

BACKGROUND AND PURPOSE: By 1992, several prospective trials established the efficacy of anticoagulation (AC) and to some extent antiplatelet (AP) agents in the prevention of stroke in the setting of atrial fibrillation (AF). The objective of this study was to determine whether practice patterns in AF stroke prophylaxis reflect the findings of clinical trials and whether stroke prophylaxis in AF differs between community hospitals and tertiary teaching hospitals. METHODS: Retrospectively, 1250 hospital charts were reviewed. After patients who had undergone recent surgery, received treatment for malignancy, or were not in chronic AF on discharge were eliminated, 651 remaining records were analyzed for the presence of 26 clinical factors influencing the selection of thromboembolism prophylaxis. Descriptive statistics and logistic regression were used to analyze the association between clinical and demographic factors and the decision to treat with AC, AP, or no specific antiembolic therapy. RESULTS: Of the 651 patients in AF, 273 (42%) received noemboli prophylaxis while 219 (34%) were treated with AC (warfarin), 146 (22%) were treated with AP, and 13 (2%) received both agents. Patients discharged in AF from community hospitals were significantly less likely to be treated with either AC or AP agents than patients discharged from tertiary centers. A strong bias against thromboembolism prophylaxis with either AC or AP agents in AF existed with age over 45 years. Multivariate logistic regression indicated that the decision to treat was associated only with the presence of prosthetic valve, history of prior stroke, mitral disease, and absence of a recent gastrointestinal bleed or occult blood in stool. Even after adjustment for these factors, a significant bias against treatment with either AC or AP agents with advancing age and discharge from community hospitals remained. CONCLUSIONS: Thromboembolism prophylaxis with either AC or AP agents is underutilized in the setting of AF. Furthermore, factors known to increase the risk of embolization in AF such as age, hypertension, diabetes, and heart disease were not associated with decisions to treat with either AP or AC agents. This study suggests that the use of clinical guidelines suggested by trials of thromboembolism prophylaxis in AF could reduce the incidence of stroke.

Aged↗
PubMed2000

Advances in Therapy and the Management of Antithrombotic Drugs for Venous Thromboembolism.

This review focuses on antithrombotic therapy for venous thromboembolism and covers a diverse range of topics including a discussion of emerging anticoagulant drugs, a renewed focus on thrombolytic agents for selected patients, and an analysis of the factors leading to adverse events in patients on warfarin, and how to optimize therapy. In Section I Dr. Weitz discusses new anticoagulant drugs focusing on those that are in the advanced stages of development. These will include drugs that (a) target factor VIIa/tissue factor, including tissue factor pathway inhibitor and NAPc2; (b) block factor Xa, including the synthetic pentasaccharide and DX9065a; (c) inhibit factors Va and VIIIa, i.e., activated protein C; and (d) block thrombin, including hirudin, argatroban, bivalirudin and H376/95. Oral formulations of heparin will also be reviewed. In Section II, Dr. Comerota will discuss the use of thrombolysis for selected patients with venous thromboembolism. Fibrinolytic therapy, which has suffered from a high risk/benefit ratio for routine deep venous thrombosis, may have an important role to play in patients with iliofemoral venous thrombosis. Dr. Comerota presents his own results with catheter-directed thrombolytic therapy and the results from a large national registry showing long-term outcomes and the impact on quality of life. In Section III, Dr. Ansell presents a critical analysis of the factors responsible for adverse events with oral anticoagulants and the optimum means of improving outcomes. The poor status of present day anticoagulant management is reviewed and the importance of achieving a high rate of "time in therapeutic range," is emphasized. Models of care to optimize outcomes are described, with an emphasis on models that utilize patient self-testing and patient self-management of oral anticoagulation which are considered to be the ultimate in anticoagulation care. The treatment of venous and arterial thromboembolism is undergoing rapid change with respect to the development of new antithrombotic agents, an expanding list of new indications, and new methods of drug delivery and management. In spite of these changes, many of the traditional therapeutics are still with us and continue to play a vital role in the treatment of thromboembolic disease. The following discussion touches on a wide range of therapeutic interventions, from old to new, exploring the status of anticoagulant drug development, describing a new intervention for iliofemoral venous thrombosis, and analyzing the critical factors for safe and effective therapy with oral anticoagulants.

Journal Article↗
PubMed2002

The role of thrombophilic risk factors in the severity of pulmonary thromboembolism.

High plasma factor-VIIIc concentration, presence of factor-V 1691 G-A (FVL) and prothrombin20210A (PT20210A) mutations were shown to be significant risk factors for venous thromboembolism (VTE) and recurrent VTE. The objective of this study was to investigate the role of these thrombotic risk factors in the severity of pulmonary thromboembolism (PTE). The plasma concentrations of factor VIIIc, presence of FVL and PT20210A mutations were studied in 32 patients with PTE. Eleven of the patients had documented recurrent VTE. Lung perfusion scans were scored according to the percentage of vascular obstruction. Patients who had a pulmonary vascular obstruction score (PVOs) >50% were compared to those with PVOs <50%. There was no significant difference between the patients with PVOs >50% and those with PVOs <50%, with regard to the presence of FVL and PT20210A mutation. However, patients with PVOs >50% had a significantly higher factor-VIIIc concentration than those with PVOs <50% (factor-VIIIc levels were 253.3 +/- 29.1 International Units (IU) x dL(-1) and 138.5 +/- 16.2 IU x dL(-1), respectively; p<0.005). Factor-VIIIc concentrations were significantly correlated with PVOs (r=0.52, p<0.005). Patients with recurrent VTE had significantly higher factor-VIIIc concentrations than those in which it occurred for the first time (factor-VIIIc concentrations were 232.6 +/- 30.9 IU x dL(-1) and 158.3 +/- 20.6 IU x dL(-1), respectively; p<0.05). The authors conclude that in addition to being a risk factor for venous thromboembolism, high factor-VIIIc concentration is an important factor in the severity of pulmonary thromboembolism.

Factor V↗
PubMed2005

Four cases of cardiopulmonary thromboembolism during liver transplantation without the use of antifibrinolytic drugs.

Orthotopic liver transplantation (OLT) is one of the most demanding surgical procedures performed. Intraoperative bleeding can be substantial and related to both surgical and nonsurgical causes. A less common but previously reported phenomenon is intraoperative cardiopulmonary thromboembolism precipitating major patient morbidity and mortality. In this paper, we present four cases of intraoperative thromboembolism during OLT. These cases were performed without the concomitant use of antifibrinolytic drugs. We performed a review and analysis of previously reported cases of intraoperative thromboembolism during OLT. Possible causes of thromboembolism, clinical management, use of thromboelastography, and the role of antifibrinolytic drugs are discussed.

Adult↗