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1.  Deep Vein Thrombosis Prophylaxis in Trauma Patients 
Thrombosis  2011;2011:505373.
Deep vein thrombosis (DVT) and pulmonary embolism (PE) are known collectively as venous thromboembolism (VTE). Venous thromboembolic events are common and potentially life-threatening complications following trauma with an incidence of 5 to 63%. DVT prophylaxis is essential in the management of trauma patients. Currently, the optimal VTE prophylaxis strategy for trauma patients is unknown. Traditionally, pelvic and lower extremity fractures, head injury, and prolonged immobilization have been considered risk factors for VTE; however it is unclear which combination of risk factors defines a high-risk group. Modalities available for trauma patient thromboprophylaxis are classified into pharmacologic anticoagulation, mechanical prophylaxis, and inferior vena cava (IVC) filters. The available pharmacologic agents include low-dose heparin (LDH), low molecular weight heparin (LMWH), and factor Xa inhibitors. Mechanical prophylaxis methods include graduated compression stockings (GCSs), pneumatic compression devices (PCDs), and A-V foot pumps. IVCs are traditionally used in high risk patients in whom pharmacological prophylaxis is contraindicated. Both EAST and ACCP guidelines recommend primary use of LMWHs in trauma patients; however there are still controversies regarding the definitive VTE prophylaxis in trauma patients. Large randomized prospective clinical studies would be required to provide level I evidence to define the optimal VTE prophylaxis in trauma patients.
PMCID: PMC3195354  PMID: 22084663
2.  New oral antithrombotics: focus on dabigatran, an oral, reversible direct thrombin inhibitor for the prevention and treatment of venous and arterial thromboembolic disorders 
Venous thromboembolism, presenting as deep vein thrombosis or pulmonary embolism, is a major challenge for health care systems. It is the third most common vascular disease after coronary heart disease and stroke, and many hospitalized patients have at least one risk factor. In particular, patients undergoing hip or knee replacement are at risk, with an incidence of asymptomatic deep vein thrombosis of 40%–60% without thromboprophylaxis. Venous thromboembolism is associated with significant mortality and morbidity, with patients being at risk of recurrence, post-thrombotic syndrome, and chronic thromboembolic pulmonary hypertension. Arterial thromboembolism is even more frequent, and atrial fibrillation, the most common embolic source (cardiac arrhythmia), is associated with a five-fold increase in the risk of stroke. Strokes due to atrial fibrillation tend to be more severe and disabling and are more often fatal than strokes due to other causes. Currently, recommended management of both venous and arterial thromboembolism involves the use of anticoagulants such as coumarin and heparin derivatives. These agents are effective, although have characteristics that prevent them from providing optimal anticoagulation and convenience. Hence, new improved oral anticoagulants are being investigated. Dabigatran is a reversible, direct thrombin inhibitor, which is administered as dabigatran etexilate, the oral prodrug. Because it is the first new oral anticoagulant that has been licensed in many countries worldwide for thromboprophylaxis following orthopedic surgery and for stroke prevention in patients with atrial fibrillation, this compound will be the main focus of this review. Dabigatran has been investigated for the treatment of established venous thromboembolism and prevention of recurrence in patients undergoing hip or knee replacement, as well as for stroke prevention in atrial fibrillation patients with a moderate and high risk of stroke.
PMCID: PMC3273411  PMID: 22323896
dabigatran etexilate; venous thromboembolism; stroke; prevention; treatment
3.  Fatal pulmonary embolism in hospitalised medical patients. 
Journal of Clinical Pathology  1997;50(7):609-610.
This study aimed to determine the frequency of fatal pulmonary emboli in hospitalised medical patients by a retrospective necropsy review and prospective non-interventional patient follow up study. The main outcome measure, necropsy proven fatal pulmonary embolism, was determined from 400 consecutive necropsy records and 200 consecutive medical inpatient episodes. Fatal pulmonary embolism was recorded in 29 of 400 necropsies; 17 were medical patients. Thirty one of 200 consecutive medical patients died. Fourteen necropsies were performed and revealed pulmonary embolism as the cause of death in five patients. The incidence of necropsy proven fatal pulmonary embolism was therefore 2.5% (95% confidence intervals 0.8% to 5.7%). Therefore, one in 40 medical patients had pulmonary embolism recorded as the cause of death at necropsy. As the necropsy rate was only 45% the incidence of fatal pulmonary embolism may be greater. There is, therefore, a need to perform more large prospective studies to confirm the incidence of fatal pulmonary embolism in medical patients and to identify risk factors and effective antithrombotic prophylaxis.
PMCID: PMC500077  PMID: 9306945
4.  Fatal pulmonary embolism following shoulder arthroplasty: a case report 
Fatal pulmonary embolism following a shoulder joint replacement is a rare event. The exact prevalence of shoulder arthroplasties is not clear. Unlike hip and knee joint replacements where some form of thromboprophylaxis is routinely prescribed, no such guidelines and practice exist for shoulder replacements. Other case reports have confirmed fatal and non-fatal pulmonary embolisms following shoulder replacements, but particular risk factors were identifiable in those patients.
Case presentation
We report the case of a 73-year-old Caucasian woman with fatal pulmonary embolism secondary to a calf deep vein thrombosis following a shoulder joint replacement procedure. The patient was otherwise healthy; there were no other risk factors directly contributing to deep vein thrombosis and pulmonary embolism except for a body mass index of 34. Post-mortem examination confirmed that the patient had a thrombus in the calf and a pulmonary embolus.
Fatal deep vein thrombosis and pulmonary embolism can occur following shoulder joint replacements in otherwise normal patients. A high degree of suspicion should therefore be maintained in susceptible individuals. Thromboprophylaxis needs careful consideration in shoulder replacements in susceptible individuals.
PMCID: PMC2737754  PMID: 19830239
5.  Heparin prophylaxis for deep venous thrombosis in a patient with multiple injuries: an evidence-based approach to a clinical problem 
Canadian Journal of Surgery  2002;45(4):282-287.
To demonstrate a clinical decision-making process by which to determine if heparin prophylaxis for deep venous thrombosis (DVT) is appropriate in a specific patient with multiple injuries.
Data sources
A Medline search of the literature. Search terms included trauma, heparin, deep venous thrombosis, thrombophlebitis, phlebitis, and trauma.
Study selection
Eleven studies were selected from 789 publications using published criteria. Incidence, risk and potential for prophylaxis were established through a structured review process.
Data extraction
After the structured review, a small number of studies were available for the consideration of incidence (2), natural history (4) and prophylactic therapy (2).
Data synthesis
The incidence of DVT in a patient with such multiple injuries is significant (58%–63%). The resulting risk of pulmonary embolism was 4.3% with an associated 20% death rate. Prophylaxis with low molecular weight heparin is associated with a statistically and clinically significant risk reduction for DVT when compared with unfractionated heparin and untreated controls.
Few of the multiple available studies concerning trauma, DVT and pulmonary embolism meet reasonable standards to establish clinical validity. Available guidelines for literature evaluation allow surgeons to select relevant articles for consideration. Patients with multiple trauma appear to be at significant risk for DVT. The death rate associated with subsequent pulmonary embolism is significant. There is reasonably good evidence to suggest that low molecular weight heparin will reduce this likelihood without a significant risk of treatment complications.
PMCID: PMC3684683  PMID: 12174986
6.  Prevention of venous thromboembolism in medically ill patients: a clinical update 
Postgraduate Medical Journal  2006;82(974):806-809.
The risk of venous thromboembolism (VTE) in hospitalised medically ill patients is often underestimated, despite the fact that it remains a major cause of preventable morbidity and mortality in this group. It is not well recognised that the risk of VTE in many hospitalised medically ill patients is at least as high as in populations after surgery. This may partly be attributed to the clinically silent nature of VTE in many patients, and the difficulty in predicting which patients might develop symptoms or fatal pulmonary embolism. Two large studies, Prospective Evaluation of Dalteparin Efficacy for Prevention of VTE in Immobilized Patients Trial and prophylaxis in MEDical patients with ENOXaparin, have shown that low‐molecular‐weight heparins provide effective thromboprophylaxis in medically ill patients, without increasing bleeding risk. Recent guidelines from the American College of Chest Physicians recommend that acutely medically ill patients admitted with congestive heart failure or severe respiratory disease, or those who are confined to bed and have at least one additional risk factor for VTE, should receive thromboprophylaxis.
PMCID: PMC2653926  PMID: 17148703
low molecular weight heparin; internal medicine; prophylaxis; venous thrombosis
7.  Fatal pulmonary embolism in hospitalized patients: a large autopsy-based matched case-control study 
Clinics  2013;68(5):679-685.
Pulmonary embolism is an underdiagnosed major cause of death for hospitalized patients. The objective of this study was to identify the conditions associated with fatal pulmonary embolism in this population.
A total of 13,074 autopsy records were evaluated in a case-control study. Patients were matched by age, sex, and year of death, and factors potentially associated with fatal pulmonary embolism were analyzed using univariate and multivariate conditional logistic regression.
Pulmonary embolism was considered fatal in 328 (2.5%) patients. In the multivariate analysis, conditions that were more common in patients who died of pulmonary embolism were atherosclerosis, congestive heart failure, and neurological surgery. Some conditions were negatively associated with fatal pulmonary embolism, including hemorrhagic stroke, aortic aneurism, cirrhosis, acquired immune deficiency syndrome, and pneumonia. In the control group, patients with hemorrhagic stroke and aortic aneurism had short hospital stays (8.5 and 8.8 days, respectively), and the hemorrhage itself was the main cause of death in most of them (90.6% and 68.4%, respectively), which may have prevented the development of pulmonary embolism. Cirrhotic patients in the control group also had short hospital stays (7 days), and 50% died from bleeding complications.
In this large autopsy study, atherosclerosis, congestive heart failure, and neurological surgery were diagnoses associated with fatal pulmonary embolism.
PMCID: PMC3654296  PMID: 23778403
Atherosclerosis; Heart Failure; Neurosurgery; Pulmonary Embolism; Venous Thromboembolism
8.  Failure of low-dose heparin to prevent significant thromboembolic complications in high-risk surgical patients: interim report of prospective trial. Groote Schuur Hospital Thromboembolus Study Group. 
British Medical Journal  1979;1(6176):1447-1450.
The efficacy of low-dose subcutaneous heparin (5000 IU eight-hourly) is being studied in a single-centre, prospective randomised trial of patients aged over 40 submitted to major elective intra-abdominal surgery. The trial end-points are the objectively defined incidence and extent of deep vein thrombosis (as seen on uptake of 125I-labelled fibrinogen, Doppler ultrasonography, and bilateral ascending phlebography) and non-fatal pulmonary embolus (as measured by preoperative spirometry and preoperative and postoperative chest radiography and perfusion lung scanning performed on a routine, unselected basis). An interim analysis of the first 200 patients indicates that low-dose heparin significantly reduces the incidence of calf-vein thrombosis but does not reduce the incidence of proximal segment thrombosis or non-fatal pulmonary embolism. Thus the routine use of low-dose heparin prophylaxis in all major surgical procedures in patients aged over 40 may not be advisable.
PMCID: PMC1599102  PMID: 380742
9.  Venous thromboembolism prophylaxis for hospitalized medical patients, current status and strategies to improve 
Annals of Thoracic Medicine  2010;5(4):195-200.
Venous thromboembolism (VTE), comprising life-threatening pulmonary embolism (PE) and its precursor deep-vein thrombosis (DVT), is commonly encountered problem. Although most patients survive DVT, they often develop serious and costly long-term complications. Both unfractionated heparin and low molecular weight heparins significantly reduce the incidence of VTE and its associated complications. Despite the evidence demonstrating significant benefit of VTE prophylaxis in acutely ill medical patients, several registries have shown significant underutilization. This underutilization indicates the need for educational and audit programs in order to increase the number of medical patients receiving appropriate prophylaxis. Many health advocacy groups and policy makers are paying more attention to VTE prophylaxis; the National Quality Forum and the Joint Commission recently endorsed strict VTE risk assessment evaluation for each patient upon admission and regularly thereafter. In the article, all major studies addressing this issue in medical patients have been reviewed from the PubMed. The current status of VTE prophylaxis in hospitalized medical patients is addressed and some improvement strategies are discussed.
PMCID: PMC2954373  PMID: 20981179
Deep vein thrombosis; heparin; low molecular weight heparin; pulmonary embolism; thromboprophylaxis
10.  Rivaroxaban and other non-vitamin K antagonist oral anticoagulants in the emergency treatment of thromboembolism 
Pulmonary embolism (PE) is potentially fatal and often requires emergency management. Because PE associated with shock and/or hypotension carries a high risk of sudden death, emergency clinicians must rapidly make a diagnosis and initiate appropriate therapeutic strategies, usually involving anticoagulant treatment. Traditional anticoagulants, such as heparins and vitamin K antagonists, although effective and recommended by guidelines, are associated with limitations. Several targeted, orally administered anticoagulants that may overcome some of these constraints have been developed recently and undergone analysis in randomised, phase III clinical trials. Rivaroxaban, a direct factor Xa inhibitor, was non-inferior to standard therapy with enoxaparin plus a vitamin K antagonist for the prevention of recurrent, symptomatic venous thromboembolism (VTE) in patients with acute PE and led to a 50% reduction in major bleeding. Dabigatran, a direct thrombin inhibitor, was also non-inferior to standard therapy for the prevention of recurrent VTE or VTE-related death when given after a parenteral anticoagulant and had a similar incidence of major bleeding. The results of a phase III study of apixaban, another direct factor Xa inhibitor, for the acute treatment of VTE are expected in the near future. Rivaroxaban is now approved in Europe and the US for the treatment of acute PE and prevention of recurrent VTE. This article reviews the current guidance on the treatment of PE with special focus on the emergency setting, and considers data regarding rivaroxaban and the other non-vitamin K antagonist oral anticoagulants and their potential role, including patients who are and are not appropriate for treatment with these agents. Issues such as drug interactions, reversal of anticoagulant effect and coagulation monitoring are also discussed.
PMCID: PMC3717133  PMID: 23866080
Acute thrombosis; Emergency setting; Oral anticoagulant; Pulmonary embolism
11.  Low-dose heparin prophylaxis against fatal pulmonary embolism. 
British Medical Journal  1975;4(5991):257-259.
A prospective randomised controlled trial in 500 patients over the age of 50 who were undergoing major surgery showed that low-dose subcutaneous heparin was an effective prophylactic measure against fatal pulmonary embolism. None of the 252 patients who received perioperative heparin cover died of fatal pulmonary embolism while eight of the 236 who did not receive heparin prophylaxis died of fatal pulmonary embolism. These results were statiscally significant (P less than 0.01).
PMCID: PMC1675117  PMID: 1104060
12.  Optional Inferior Vena Cava Filters in the Trauma Patient 
Trauma patients are at exceedingly high risk of development of venous thromboembolism (VTE) including deep venous thrombosis and pulmonary embolism (PE). The epidemiology of VTE in trauma patients is reviewed. PE is thought to be the third major cause of death after trauma in those patients who survive longer than 24 hours after onset of injury. In fact, patients recovering from trauma have the highest rate of VTE among all subgroups of hospitalized patients. Various prophylactic and surveillance methods have been evaluated and found helpful in certain situations, but VTE complications can occur despite such measures. Therapeutic and prophylactic uses of inferior vena cava (IVC) filters in trauma patients are reviewed. Prophylactic IVC filter use is revealed to be a controversial subject with valid arguments on both sides of the issue. With the lack of prospective randomized trials of IVC filter use in trauma, it is impossible to make evidence-based recommendations. Unfortunately, two sets of guidelines are available for insertion of filters in trauma patients, with conflicting recommendations. The introduction of retrievable IVC filters seems to offer a unique solution for VTE protection in the trauma patient population, which often consists of younger members of our population. Lastly, current generations of FDA-approved retrieval filters are discussed.
PMCID: PMC3036500  PMID: 21359016
Venous thromboembolism; inferior vena cava filter; trauma
13.  A study of pulmonary embolism after abdominal surgery in patients undergoing prophylaxis 
AIM: To determine risk factors for pulmonary embolism and estimate effects and benefits of prophylaxis.
METHODS: We included 78 patients who died subsequently to a pulmonary embolism after major abdominal surgery from 1985 to 2003. A first, retrospective analysis involved 41 patients who underwent elective surgery between 1985 and 1990 without receiving any prophylaxis. In the prospectively evaluated subgroup, 37 patients undergoing major surgery between 1991 and 2003 were enrolled: all of them had received a prophylaxis consisting in low-molecular weight heparin, given subcutaneously at a dose of 2850 IU AXa/0.3 mL (body weight < 50 kg) or 5700 IU AXa/0.6 mL (body weight ≥ 50 kg).
RESULTS: A higher incidence of thromboembolism (43.9% and 46.34% in the two groups, respectively) was found in older patients (> 60 years). The incidence of pulmonary embolism after major abdominal surgery in patients who had received the prophylaxis was significantly lower compared to the subjects with the same condition who had not received any prophylaxis (P < 0.001, OR = 2.825; 95% CI, 1.811-4.408). Furthermore, the incidence of pulmonary embolism after colorectal cancer surgery was significantly higher compared to incidence of pulmonary embolism after other abdominal surgical procedures. Finally, the incidence of pulmonary embolism after colorectal cancer surgery among the patients who had received the prophylaxis (11/4316, 0.26%) was significantly lower compared to subjects undergoing a surgical procedure for the same indication but without prophylaxis (10/1562, 0.64%) (P < 0.05, OR = 2.522; 95% CI, 1.069-5.949).
CONCLUSION: Prophylaxis with low molecular weight heparin is highly recommended during the preoperative period in patients with diagnosis of colorectal cancer due to high risk of pulmonary embolism after elective surgery.
PMCID: PMC2653332  PMID: 19140235
Pulmonary embolism; Surgery; Colorectal cancer; Risk factor; Prevention
14.  Thrombo-prophylaxis in pelvic and acetabular trauma patients: a UK consensus? 
International Orthopaedics  2011;36(1):165-169.
The incidence of deep vein thrombosis, non-fatal pulmonary embolism and fatal pulmonary embolism may be as high as 61%, 10% and 2%, respectively, in patients with pelvic and acetabular injuries. A survey of the pelvic and acetabular units across the United Kingdom was performed to ascertain the thrombo-prophylaxis policy for these patients. In particular, questions were asked about different regimes on post-operative patients, conservatively managed patients and those simply discussed over the telephone. We enquired about their known rates of DVT and PE and their methods of data collection.
Postal questionnaires were sent to 22 pelvic and acetabular trauma centres around the United Kingdom.
Replies from 18 units were received in which a total of 837 operations are performed per year. Forty-five percent of pelvic and acetabular units do not routinely prescribe chemical prophylaxis for post-operative patients and 56% do not prescribe prophylaxis for conservatively managed patients. The policy of the remaining units showed no consistency in duration or agent. Fifty-three percent of units use a database to collect information related to the numbers of patients operated up on. Forty-seven percent have no defined method for collecting DVT and PE numbers. For this reason, reported rates of proximal DVT, non-fatal PE and fatal PE were below that expected at 2.5%, 0.8% and 0.1%, respectively.
Despite high rates of thrombo-embolic complications in patients with pelvic and acetabular injuries there is no UK consensus on prescribing prophylaxis.
PMCID: PMC3251659  PMID: 21614603
15.  Statin treatment and risk of recurrent venous thromboembolism: a nationwide cohort study 
BMJ Open  2013;3(11):e003135.
Statins may decrease the risk of primary venous thromboembolism (VTE), that is, deep vein thrombosis (DVT) and pulmonary embolism (PE) but the effect of statins in preventing recurrent VTE is less clear. The aim of this study was therefore to investigate the association between statin therapy and risk of recurrent VTE.
A prospective cohort study.
All hospitals in Denmark.
All patients with a hospital diagnosis of VTE in Denmark during 1997–2009 associated with a warfarin or heparin prescription were identified.
Main outcome measures
Adjusted HR of recurrent hospitalised VTE (ie, fatal or non-fatal DVT or PE) associated with use of statins.
44 330 patients with VTE were included in the study. Of these 3914 were receiving statin therapy at baseline. Patients receiving statins were older (68±11 compared to 62±18 years), had more comorbidity and used more medications. The incidence rate for recurrent VTE was 24.4 (95% CI 22.8 to 26.2) per 1000 person-years among statin users and 48.5 (95% CI 47.4 to 49.7) per 1000 person-years among non-statin users. Statin use was associated with a significantly lower risk of a recurrent VTE, adjusted HR 0.74 (95% CI 0.68 to 0.80), compared with no statin use. The association between statin use and risk of recurrent VTE was significantly affected by age. Among younger individuals (≤80 years), statin use was associated with lower risk of recurrent VTE, HR 0.70 (95% CI 0.65 to 0.76) whereas in older individuals (>80 years) statin use was significantly associated with higher risk of recurrent VTE, HR 1.28 (95% CI 1.02 to 1.60), p for interaction=<0.0001.
Statin use was associated with a decreased risk of recurrent VTE.
PMCID: PMC3822311  PMID: 24202053
16.  Benefit–risk assessment of rivaroxaban versus enoxaparin for the prevention of venous thromboembolism after total hip or knee arthroplasty 
Venous thromboembolism is a common complication after major orthopedic surgery. When prescribing anticoagulant prophylaxis, clinicians weigh the benefits of thromboprophylaxis against bleeding risk and other adverse events. Previous benefit–risk analyses of the REgulation of Coagulation in ORthopaedic surgery to prevent Deep vein thrombosis and pulmonary embolism (RECORD) randomized clinical studies of rivaroxaban versus enoxaparin after total hip (THA) or knee (TKA) arthroplasty generally used pooled THA and TKA results, counted fatal bleeding as both an efficacy and a safety event, and included the active and placebo-controlled portions of RECORD2, which might confound benefit–risk assessments. We conducted a post hoc analysis without these constraints to assess benefit–risk for rivaroxaban versus enoxaparin in the RECORD studies.
Patients and methods
Data from the safety population of the two THA and two TKA studies were pooled separately. The primary analysis compared the temporal course of event rates and rate differences between rivaroxaban and enoxaparin prophylaxis for symptomatic venous thromboembolism plus all-cause mortality (efficacy events) versus nonfatal major bleeding (safety events). Additionally, these rates were used to derive measures of net clinical benefit, number needed to treat (NNT), and number needed to harm (NNH) for these two end points.
After THA or TKA, and compared with enoxaparin, rivaroxaban therapy resulted in more efficacy events prevented than safety events caused, with benefits exceeding harms early and throughout treatment and follow-up. Relative to enoxaparin, rivaroxaban treatment prevented six efficacy events per harm event caused for THA, with NNT =262/NNH =1,711. For TKA, rivaroxaban treatment prevented four to five efficacy events per harm event caused, with NNT =102/NNH =442. Sensitivity analysis that included surgical-site bleeding resulted in NNH =345 for THA and NNH =208 for TKA.
In the RECORD studies, considering death, symptomatic venous thromboembolism, and major bleeding, rivaroxaban resulted in greater benefits than harms compared with enoxaparin. When incorporating surgical-site bleeding, rivaroxaban also results in greater benefit than harm for TKA and is balanced with enoxaparin for THA.
PMCID: PMC3971939
VTE; DVT; PE; thromboprophylaxis; total hip arthroplasty; total knee arthroplasty
17.  Deep Venous Thrombosis and Pulmonary Embolism are Uncommon in East Asian Patients after Total Hip Arthroplasty 
In Western countries, deep vein thrombosis (DVT) and pulmonary embolism (PE), are relatively common after THA and many surgeons recommend routine pharmacologic thromboprophylaxis. There is some suggestion in the literature that the incidences of DVT and PE may be lower in East Asian patients. Therefore, it would be important to establish the incidences in a large number of East Asian patients who did not receive pharmacologic thromboprophylaxis.
We therefore determined the incidence of DVT and PE and evaluated the associated risk factors in a series of East Asian patients who underwent primary THA without pharmacologic prophylaxis.
We retrospectively evaluated all 861 patients who underwent 992 elective primary THAs from May 2003 to December 2009. We identified patients with symptomatic DVT, symptomatic PE, and fatal PE. For potential risk factors we considered age, gender, body mass index (BMI), administration of aspirin, type of anesthesia, operation time, approach, simultaneous bilateral THAs, and duration of immobilization between symptomatic and asymptomatic patients.
We identified eight patients with symptomatic DVT, one of whom also had a symptomatic PE; there were no cases of fatal PE. The incidences of fatal PE, symptomatic PE, and symptomatic DVT were 0 %, 0.1 %, and 0.8 %, respectively. Longer duration of immobilization predicted symptomatic DVT or PE.
East Asian patients have a low incidence of symptomatic DVT and PE and virtually no fatal PEs after primary THA. The incidences and risk factors should be taken into consideration when deciding whether to prophylactically treat these patients with pharmacologic agents.
Level of Evidence
Level IV, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.
PMCID: PMC3210292  PMID: 21748508
18.  Identifying future ‘unexpected’ survivors: a retrospective cohort study of fatal injury patterns in victims of improvised explosive devices 
BMJ Open  2013;3(8):e003130.
To identify potentially fatal injury patterns in explosive blast fatalities in order to focus research and mitigation strategies, to further improve survival rates from blast trauma.
Retrospective cohort study.
UK military personnel killed by improvised explosive device (IED) blasts in Afghanistan, November 2007–August 2010.
UK military deployment, through NATO, in support of the International Security Assistance Force (ISAF) mission in Afghanistan.
Data sources
UK military postmortem CT records, UK Joint Theatre Trauma Registry and associated incident data.
Main outcome measures
Potentially fatal injuries attributable to IEDs.
We identified 121 cases, 42 mounted (in-vehicle) and 79 dismounted (on foot), at a point of wounding. There were 354 potentially fatal injuries in total. Leading causes of death were traumatic brain injury (50%, 62/124 fatal injuries), followed by intracavity haemorrhage (20.2%, 25/124) in the mounted group, and extremity haemorrhage (42.6%, 98/230 fatal injuries), junctional haemorrhage (22.2%, 51/230 fatal injuries) and traumatic brain injury (18.7%, 43/230 fatal injuries) in the dismounted group.
Head trauma severity in both mounted and dismounted IED fatalities indicated prevention and mitigation as the most effective strategies to decrease resultant mortality. Two-thirds of dismounted fatalities had haemorrhage implicated as a cause of death that may have been anatomically amenable to prehospital intervention. One-fifth of the mounted fatalities had haemorrhagic trauma which currently could only be addressed surgically. Maintaining the drive to improve all haemostatic techniques for blast casualties, from point of wounding to definitive surgical proximal vascular control, alongside the development and application of novel haemostatic interventions could yield a significant survival benefit. Prospective studies in this field are indicated.
PMCID: PMC3733302  PMID: 23906957
Cause of Death; Battlefield Trauma; IED
19.  Tuberculosis in the intensive care unit: A retrospective descriptive cohort study with determination of a predictive fatality score 
Despite effective treatments, tuberculosis-related mortality remains high among patients requiring admission to the intensive care unit (ICU).
To determine prognostic factors of death in tuberculosis patients admitted to the ICU, and to develop a simple predictive scoring system.
A 10-year, retrospective study of 53 patients admitted consecutively to the Hôpitaux de Paris, Hôpital Lariboisière (Paris, France) ICU with confirmed tuberculosis, was conducted. A multivariate analysis was performed to identify risk factors for death. A predictive fatality score was determined.
Diagnoses included pulmonary tuberculosis (96%) and tuberculous encephalomeningitis (26%). Patients required mechanical ventilation (45%) and vasopressor infusion (28%) on admission. Twenty patients (38%) died, related to direct tuberculosis-induced organ failure (n=5), pulmonary bacterial coinfections (n=14) and pulmonary embolism (n=1). Using a multivariate analysis, three independent factors on ICU admission were predictive of fatality: miliary pulmonary tuberculosis (OR 9.04 [95% CI 1.25 to 65.30]), mechanical ventilation (OR 11.36 [95% CI 1.55 to 83.48]) and vasopressor requirement (OR 8.45 [95% CI 1.29 to 55.18]). A score generated by summing these three independent variables was effective at predicting fatality with an area under the ROC curve of 0.92 (95% CI 0.85 to 0.98).
Fatalities remain high in patients admitted to the ICU with tuberculosis. Miliary pulmonary tuberculosis, mechanical ventilation and vasopressor requirement on admission were predictive of death.
PMCID: PMC3597393  PMID: 24294270
Death; Intensive care unit; Mycobacterium tuberculosis; Miliary; Predictive factor; Tuberculosis
20.  Trends in incidence and case fatality rates of acute myocardial infarction in Denmark and Sweden 
Heart  2003;89(5):507-511.
Objective: To compare the incidence and case fatality of acute myocardial infarction in Denmark and Sweden.
Design: A cohort study, linking the national registries of hospital admissions and causes of death in the two countries.
Patients: All admissions and deaths with acute myocardial infarction as primary or secondary diagnosis were extracted (Denmark, 1978 to 1998; Sweden, 1987 to 1999).
Main outcome measures: The incidence was estimated using the first acute myocardial infarct for each patient. Case fatality was estimated in the first 28 days after acute myocardial infarction, including prehospital deaths. All rates were adjusted for age.
Results: The incidence of myocardial infarction and the case fatality declined significantly among all subgroups of patients. Case fatality was higher in Denmark early in the study period (1987–1990) than in Sweden. The odds ratios (OR) ranged from 1.28 to 1.50 in the four age groups. In 1994–1999, the prognosis of patients younger than 75 years did not differ. Patients aged 75–94 years still fared worse in Denmark (OR 1.21, 95% confidence interval 1.17 to 1.27). Women aged 30–54 years had a worse prognosis than men in both Denmark and Sweden (OR associated with male sex 0.85 and 0.90, respectively). In contrast, for patients older than 65 years, women had a better prognosis than men. This difference in the effect of sex with age was significant (p < 0.0001) and did not change over time.
Conclusions: Case fatality after acute myocardial infarction was notably higher in Denmark than in Sweden in 1987–1991, but in the later periods the prognosis was comparable in the two countries.
PMCID: PMC1767620  PMID: 12695453
acute myocardial infarction; secular trend; Denmark; Sweden
21.  Heparin Prophylaxis against Fatal Postoperative Pulmonary Embolism * 
British Medical Journal  1974;2(5911):153-155.
Low-dose heparin prophylaxis against fatal pulmonary embolism has been studied in a random and prospective trial in 300 patients over the age of 50 who underwent major surgery. A dose of 5,000 IU mucous heparin sodium given two hours preoperatively and for five days post operatively prevented fatal pulmonary embolism in all 156 patients so treated, whereas out of 144 patients in the unheparinized group 6 (4·2%) died of pulmonary embolism. This difference is statistically significant. There was no increase in operative or post-operative bleeding or in the formation of wound haematomas in the heparinized group.
PMCID: PMC1610370  PMID: 4825114
22.  Comparison of efficacy and safety of low molecular weight heparins and unfractionated heparin in initial treatment of deep venous thrombosis: a meta-analysis. 
BMJ : British Medical Journal  1994;309(6950):299-304.
OBJECTIVE--To compare the efficacy and safety of low molecular weight heparins and unfractionated heparin in the initial treatment of deep venous thrombosis for the reduction of recurrent thromboembolic events, death, extension of thrombus, and haemorrhages. DESIGN--Meta-analysis of results from 16 randomised controlled clinical studies. SUBJECTS--2045 patients with established deep venous thrombosis. INTERVENTION--Treatment with low molecular weight heparins or unfractionated heparin. MAIN OUTCOME MEASURES--Incidences of thromboembolic events (deep venous thrombosis or pulmonary embolism, or both); major haemorrhages; total mortality; and extension of thrombus. RESULTS--A significant reduction in the incidence of thrombus extension (common odds ratio 0.51, 95% confidence interval 0.32 to 0.83; P = 0.006) in favour of low molecular weight heparin was observed. Non-significant trends also in favour of the low molecular weight heparins were observed for the recurrence of thromboembolic events (0.66, 0.41 to 1.07; P = 0.09), major haemorrhages (0.65, 0.36 to 1.16; P = 0.15), and total mortality (0.72, 0.46 to 1.4; P = 0.16). CONCLUSIONS--Low molecular weight heparins seem to have a higher benefit to risk ratio than unfractionated heparin in the treatment of venous thrombosis. These results, however, remain to be confirmed by using clinical outcomes in suitably powered clinical trials.
PMCID: PMC2540865  PMID: 8086867
23.  Incidences of fatal postoperative pulmonary embolism after prophylaxis with dextran 70 and low-dose heparin: an international multicentre study. 
British Medical Journal  1980;280(6207):69-72.
A total of 4352 patients were admitted to a prospective' randomised multicentre trial comparing the prophylactic efficacy of dextran 70 and low-dose heparin against fatal pulmonary embolism after elective operations for general, orthopaedic, urological, and gynaecological conditions. Out of 3984 patients correctly admitted, 1993 were allocated to receive dextran 70 and 1991 to receive low-dose heparin. Withdrawal of prophylaxis because of bleeding or technical difficulties occurred more often in the heparin group, but allergic reactions were more common in the dextran group. Of the 75 patients who died within 30 days after operation, 38 had been given dextran and 37 low-dose heparin. Necropsy was performed in 33 and 32 of these cases respectively. In six patients in each group pulmonary embolism was the sole or a contributory cause of death. Of these, five patients in the dextran group and two in the heparin group had received a full course of prophylaxis. There was no statistically significant difference between the two treatment groups in the incidence of fatal pulmonary embolism after a full course of prophylaxis.
PMCID: PMC1600226  PMID: 7353128
24.  Fatal Pulmonary Embolism following Achilles Tendon Repair: A Case Report and a Review of the Literature 
Case Reports in Orthopedics  2013;2013:401968.
Deep venous thrombosis (DVT) is a significant source of morbidity in orthopaedic surgery. It can progress to a pulmonary embolism, a significant source of mortality. Up to date, patients with Achilles tendon rupture routinely do not receive DVT chemical prophylaxis. We are presenting a case of fatal pulmonary embolism after a surgically treated Achilles tendon rupture in a forty-two-year-old male healthy patient. In the current body of the literature, the reported incidence of DVT after Achilles tendon rupture is highly variable ranging from less than 1% to 34%, and there is a disagreement in the international guidelines regarding the need of chemical DVT prophylaxis with this type of injury. Further research needs to be conducted to investigate the risks and benefits of chemical DVT prophylaxis following Achilles tendon rupture. For low-risk patients, the use of milder forms of prophylaxis such as aspirin should also be explored.
PMCID: PMC3683453  PMID: 23819088
25.  Acute management of vascular air embolism 
Vascular air embolism (VAE) is known since early nineteenth century. It is the entrainment of air or gas from operative field or other communications into the venous or arterial vasculature. Exact incidence of VAE is difficult to estimate. High risk surgeries for VAE are sitting position and posterior fossa neurosurgeries, cesarean section, laparoscopic, orthopedic, surgeries invasive procedures, pulmonary overpressure syndrome, and decompression syndrome. Risk factors for VAE are operative site 5 cm above the heart, creation of pressure gradient which will facilitate entry of air into the circulation, orogenital sex during pregnancy, rapid ascent in scuba (self contained underwater breathing apparatus) divers and barotrauma or chest trauma. Large bolus of air can lead to right ventricular air lock and immediate fatality. In up to 35% patient, the foramen ovale is patent which can cause paradoxical arterial air embolism. VAE affects cardiovascular, pulmonary and central nervous system. High index of clinical suspicion is must to diagnose VAE. The transesophgeal echocardiography is the most sensitive device which will detect smallest amount of air in the circulation. Treatment of VAE is to prevent further entrainment of air, reduce the volume of air entrained and haemodynamic support. Mortality of VAE ranges from 48 to 80%. VAE can be prevented significantly by proper positioning during surgery, optimal hydration, avoiding use of nitrous oxide, meticulous care during insertion, removal of central venous catheter, proper guidance, and training of scuba divers.
PMCID: PMC2776366  PMID: 20009308
Vascular air embolism; high risk surgeries; pressure gradient; decompression syndrome; transesopageal echocardiogram; hyperbaric oxygen; dysbarism

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