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Clinical Recognition of Pulmonary Embolism: Problem of Unrecognized and Asymptomatic Cases

      Dyspnea, pleuritic chest pain, and tachypnea are widely appreciated as common initial features of pulmonary embolism (PE). This knowledge is derived primarily from prospective studies evaluating diagnostic tests or therapeutic interventions in which the study patients are suspected to have PE based on their initial symptoms. Autopsy studies, however, continue to show that most cases of fatal PE are unrecognized and undiagnosed. Data from studies screening for PE in patients with deep venous thrombosis and in postoperative patients suggest that many patients with PE are asymptomatic and that PE is unrecognized. We believe that the current concepts regarding the initial clinical features of PE are too narrow and biased toward symptomatic cases. High clinical suspicion may be insufficient in recognizing PE. Herein we summarize the available data and explore the implications for clinical practice.
      DVT (deep venous thrombosis), PE (pulmonary embolism)
      Pulmonary embolism (PE) is a common cause of morbidity and mortality.
      • Moser KM
      Venous thromboembolism.
      • Ryu JH
      • Rooke TW
      • Rosenow III, EC
      Venous thromboembolism.
      It is a complication of deep venous thrombosis (DVT) with thromboemboli usually originating from the deep veins of the lower extremities.
      • Moser KM
      Venous thromboembolism.
      • Ryu JH
      • Rooke TW
      • Rosenow III, EC
      Venous thromboembolism.
      Although the actual incidence and case fatality rates of PE are difficult to ascertain, an estimated 500,000 to 600,000 patients suffer from PE each year in the United States, and PE is the cause of death in 50,000 to 200,000 patients.
      • Moser KM
      Venous thromboembolism.
      • Ryu JH
      • Rooke TW
      • Rosenow III, EC
      Venous thromboembolism.
      • Alpert JS
      • Dalen JE
      Epidemiology and natural history of venous thromboembolism.
      It is the most common medical cause of maternal deaths associated with live births.
      • Goldhaber SZ
      • Morpurgo M
      Diagnosis, treatment, and prevention of pulmonary embolism: report of the WHO/lnternational Society and Federation of Cardiology Task Force.
      The incidence and mortality rates of PE increase with advancing age, but no age-group, including infants, is immune from this disorder.
      • Alpert JS
      • Dalen JE
      Epidemiology and natural history of venous thromboembolism.
      • Andrew M
      • David M
      • Adams M
      • Ali K
      • Anderson R
      • Barnard D
      • et al.
      Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE.
      When promptly diagnosed and appropriately treated, PE rarely causes death. Despite advances in diagnostic methods, treatment, and prophylaxis, the incidence and mortality rates of acute PE seem to have changed little during the past 30 years.
      • Alpert JS
      • Dalen JE
      Epidemiology and natural history of venous thromboembolism.
      • Karwlnski B
      • Svendsen E
      Comparison of clinical and postmortem diagnosis of pulmonary embolism.
      • Lindblad B
      • Sternby NH
      • Bergqvist D
      Incidence of venous thromboembolism verified by necropsy over 30 years.
      The diagnosis of PE necessitates confirmation by objective testing. This diagnostic evaluation for possible PE is initiated by the clinician's suspicion based on the patient's initial symptoms and signs. Thus, diagnostic algorithms usually begin with “clinical suspicion” of PE or “suspected” PE.
      • Hyers TM
      Integrated management of venous thromboembolism.
      • Rosenow III, EC
      Venous and pulmonary thromboembolism: an algorithmic approach to diagnosis and management.
      • Ginsberg JS
      Management of venous thromboembolism.
      Typically, the clinician expects to encounter acute onset of dyspnea, pleuritic chest pain, or tachypnea. This expectation has been reinforced by recent studies emphasizing the high sensitivity (more than 95%) of these symptoms in identifying patients with PE.
      • Stein PD
      • Saitzman HA
      • Weg JG
      Clinical characteristics of patients with acute pulmonary embolism.
      • Stein PD
      • Terrin ML
      • Hales CA
      • Palevsky HI
      • Saltiman HA
      • Thompson BT
      • et al.
      Clinical, laboratory, roentgenographic and electrocardiographs findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease.
      • Paila A
      • Petruzzelli S
      • Donnamaria V
      • Guntini C
      The role of suspicion in the diagnosis of pulmonary embolism.
      In contrast, some investigators have acknowledged that a substantial number of cases of asymptomatic PE may exist.
      • Ryu JH
      • Rooke TW
      • Rosenow III, EC
      Venous thromboembolism.
      • Alpert JS
      • Dalen JE
      Epidemiology and natural history of venous thromboembolism.
      • Moser KM
      • Fedullo PF
      • LitteJohn JK
      • Crawford R
      Frequent asymptomatic pulmonary embolism in patients with deep venous thrombosis [published erratum appears in JAMA 1994:271:1908].
      These diverse viewpoints likely result from the differences in the design of the studies used in supporting the respective conclusions. In this article, we summarize the available data and review the current concepts regarding the clinical features of acute PE, with an emphasis on the problem of unrecognized and asymptomatic cases.

      PROSPECTIVE DIAGNOSTIC AND TREATMENT STUDIES OF PE

      Most of our inferences regarding the clinical features of acute PE are based on data from large prospective studies evaluating the diagnostic accuracy of ventilation-perfusion lung scans and the therapeutic efficacy of thrombolytic agents.
      • Stein PD
      • Saitzman HA
      • Weg JG
      Clinical characteristics of patients with acute pulmonary embolism.
      • Stein PD
      • Terrin ML
      • Hales CA
      • Palevsky HI
      • Saltiman HA
      • Thompson BT
      • et al.
      Clinical, laboratory, roentgenographic and electrocardiographs findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease.
      • Urokinase Pulmonary Embolism Trial Study Group
      Urokinase Pulmonary Embolism Trial: phase 1 results; a cooperative study.
      • Uroklnase Pulmonary Embolism Trial Study Group
      Urokinase-Strep-tokinase Embolism Trial: phase 2 results; a cooperative study.
      • PIOPED Investigators
      Value of the ventilation/perfusion scan in acute pulmonary embolism: results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPEDI).
      • Bell WR
      • Simon TL
      • DeMete DL
      The clinical features of submassive and massive pulmonary emboli.
      • Stein PD
      • Willis III, PW
      • DeMets DL
      History and physical examination in acute pulmonary embolism in patients without preexisting cardiac or pulmonary disease.
      • Bell WR
      Pulmonary embolism: progress and problems.
      The frequency of the most common symptoms and signs encountered in patients in whom PE is eventually proved by pulmonary angiography is summarized in Table 1. Common initial symptoms include dyspnea, pleuritic chest pain, and cough. Apprehension, leg swelling, leg pain, diaphoresis, hemoptysis, nonpleuritic chest pain, palpitations, wheezing, and syncope occur less often.
      • Stein PD
      • Saitzman HA
      • Weg JG
      Clinical characteristics of patients with acute pulmonary embolism.
      • Stein PD
      • Terrin ML
      • Hales CA
      • Palevsky HI
      • Saltiman HA
      • Thompson BT
      • et al.
      Clinical, laboratory, roentgenographic and electrocardiographs findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease.
      • Bell WR
      • Simon TL
      • DeMete DL
      The clinical features of submassive and massive pulmonary emboli.
      Hemoptysis and pleuritic chest pain are associated with pulmonary infarctions and hemorrhage that are caused by thromboembolic obstruction of a medium-sized artery.
      • Bell WR
      • Simon TL
      • DeMete DL
      The clinical features of submassive and massive pulmonary emboli.
      • Wagenvoort CA
      Pathology of pulmonary thromboembolism.
      Syncope is associated with massive emboli.
      • Bell WR
      • Simon TL
      • DeMete DL
      The clinical features of submassive and massive pulmonary emboli.
      Table 1Common Symptoms and Signs in Patients With Pulmonary Embolism, Proved by Pulmonary Angiography
      HR = heart rate; PIOPED = Prospective Investigation of Pulmonary Embolism Diagnosis; RR = respiratory rate; S2P = pul-monic component of the second heart sound; UPET = Urokinase Pulmonary Embolism Trial; USPET = Urokinase-Streptokinase Pulmonary Embolism Trial.
      Symptom or signUPET/USPET
      Data from Stein and associates.19
      (%)
      PIOPED
      Data from Stein and associates.12
      (%)
      Dyspnea8473
      Pleuritic chest pain7466
      Cough5037
      Leg pain3926
      Hemoptysis2813
      Tachypnea (RR >20/min)8570
      Rales5651
      Tachycardia (HR>100beats/min)5830
      Increased S2P5723
      Pleural friction rub183
      * HR = heart rate; PIOPED = Prospective Investigation of Pulmonary Embolism Diagnosis; RR = respiratory rate; S2P = pul-monic component of the second heart sound; UPET = Urokinase Pulmonary Embolism Trial; USPET = Urokinase-Streptokinase Pulmonary Embolism Trial.
      Data from Stein and associates.
      • Stein PD
      • Willis III, PW
      • DeMets DL
      History and physical examination in acute pulmonary embolism in patients without preexisting cardiac or pulmonary disease.
      Data from Stein and associates.
      • Stein PD
      • Terrin ML
      • Hales CA
      • Palevsky HI
      • Saltiman HA
      • Thompson BT
      • et al.
      Clinical, laboratory, roentgenographic and electrocardiographs findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease.
      The initial symptoms have been grouped into manifesting syndromes: pulmonary infarction, isolated dyspnea, and circulatory collapse.
      • Stein PD
      • Henry JW
      Clinical characteristics of patients with acute pulmonary embolism stratified according to their presenting syndromes.
      In one study, patients with pulmonary infarction syndrome accounted for about threefourths of patients with proven PE, and their initial symptoms were pleuritic chest pain and dyspnea. Those with isolated dyspnea accounted for one-fifth of patients with PE. The remaining small percentage of patients had circulatory collapse (shock or syncope). PE was thought to be mild in those with pulmonary infarction syndrome, moderate in those with isolated dyspnea, and severe in those with circulatory collapse.
      • Stein PD
      • Henry JW
      Clinical characteristics of patients with acute pulmonary embolism stratified according to their presenting syndromes.
      The most common physical signs in patients with acute PE have been tachypnea, rales, and tachycardia, all of which are nonspecific. Other signs present in a minority of patients have included increased pulmonic component of the second heart sound, diaphoresis, fever, wheezes, Homans' sign, right ventricular lift, pleural friction rub, third or fourth heart sound, cyanosis, hepatomegaly, and hepatojugular reflux.
      • Stein PD
      • Saitzman HA
      • Weg JG
      Clinical characteristics of patients with acute pulmonary embolism.
      • Stein PD
      • Terrin ML
      • Hales CA
      • Palevsky HI
      • Saltiman HA
      • Thompson BT
      • et al.
      Clinical, laboratory, roentgenographic and electrocardiographs findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease.
      • Bell WR
      • Simon TL
      • DeMete DL
      The clinical features of submassive and massive pulmonary emboli.
      • Stein PD
      • Willis III, PW
      • DeMets DL
      History and physical examination in acute pulmonary embolism in patients without preexisting cardiac or pulmonary disease.
      • Bell WR
      Pulmonary embolism: progress and problems.
      On the basis of these data, the diagnosis of PE is extremely unlikely in the absence of dyspnea, pleuritic chest pain, or tachypnea.
      • Hyers TM
      Integrated management of venous thromboembolism.
      • Stein PD
      • Saitzman HA
      • Weg JG
      Clinical characteristics of patients with acute pulmonary embolism.
      • Stein PD
      • Terrin ML
      • Hales CA
      • Palevsky HI
      • Saltiman HA
      • Thompson BT
      • et al.
      Clinical, laboratory, roentgenographic and electrocardiographs findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease.
      • Bell WR
      Pulmonary embolism: progress and problems.
      Analysis of the data from the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study of patients with no prior cardiac or pulmonary disease showed dyspnea, tachypnea, or chest pain to be present in 97% of patients with proven PE
      • Stein PD
      • Terrin ML
      • Hales CA
      • Palevsky HI
      • Saltiman HA
      • Thompson BT
      • et al.
      Clinical, laboratory, roentgenographic and electrocardiographs findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease.
      Thus, these clinical features, although nonspecific, seem to be very sensitive in identifying patients with PE. The differential diagnoses of a patient with these symptoms commonly include pneumonia, myocardial infarction, pneumothorax, and viral pleurisy. These features are less helpful in patients with preexisting heart or lung disease.
      Of importance, however, the patients enrolled in these studies had symptoms suggestive of PE. Therefore, these studies likely limit the clinical spectrum of patients to those with symptomatic embolism and exclude asymptomatic patients and those with atypical features. This dilemma is illustrated in the recent data from the French Registry of venous thromboembolic diseases that includes 387 patients with PE.
      • Ferrari E
      • Baudouy M
      • Cerboni P
      • Tibi T
      • Guigner A
      • Leonetti J
      • et al.
      Clinical epidemiology of venous thromboembolic disease: results of a French Multicentre Registry.
      In symptomatic patients, 87% had dyspnea, a prevalence similar to that noted in previous studies (Table 1); however, 34% of patients were asymptomatic.

      AUTOPSY STUDIES OF PE

      In routine autopsies of adult patients, grossly recognizable emboli are found in 1.5 to 30% of cases.
      • Lindblad B
      • Sternby NH
      • Bergqvist D
      Incidence of venous thromboembolism verified by necropsy over 30 years.
      • Wagenvoort CA
      Pathology of pulmonary thromboembolism.
      • Modan B
      • Sharon E
      • Jelin N
      Factors contributing to the incorrect diagnosis of pulmonary embolic disease.
      • Rossman I
      • Rodstein M
      • Bomstein A
      Undiagnosed diseases in an aging population”, pulmonary embolism and bronchopneumonia.
      • Dalen JE
      • Alpert JS
      Natural history of pulmonary embolism.
      • Coon WW
      The spectrum of pulmonary embolism: twenty years later.
      • Goldhaber SZ
      • Hennekens CH
      • Evans DA
      • Newton EC
      • Godleski JJ
      Factors associated with correct antemortem diagnosis of major pulmonary embolism.
      • Landefeld CS
      • Chren MM
      • Myers A
      • Geller R
      • Robbins S
      • Goldman L
      Diagnostic yield of the autopsy in a university hospital and a community hospital.
      • Lindblad B
      • Eriksson A
      • Bergqvist D
      Autopsy-verified pulmonary embolism in a surgical department: analysis of the period from 1951 to 1988.
      • Dlebold J
      • Lohrs U
      Venous thrombosis and pulmonary embolism: a study of 5039 autopsies.
      • Saeger W
      • Genzkow M
      Venous thromboses and pulmonary embolism in post-mortem series: probable causes by correlations of clinical data and basic diseases.
      • Morgenthaler TL
      • Ryu JH
      Clinical characteristics of fatal embolism in a referral hospital.
      • Stein PD
      • Henry JW
      Prevalence of acute pulmonary embolism among patients in a general hospital and at autopsy.
      • Cohen AT
      • Edmondson RA
      • Phillips MJ
      • Ward VP
      • Kakkar VV
      The changing pattern of venous thromboembolic disease.
      • Baglin TP
      • White K
      • Charles A
      Fatal pulmonary embolism in hospitalized medical patients.
      With careful dissection and microscopic examination, the percentage of autopsy cases showing recent or old thromboemboli increases to 51 to 69%.
      • Frelman DG
      • Suyemoto J
      • Wessler S
      Frequency of pulmonary thromboembolism in man.
      • Morrell MT
      • Dunnill MS
      The post-mortem incidence of pulmonary embolism in a hospital population.
      • Havig O
      Pulmonary thromboembolism: gross and microscopical findings in 508 randomized autopsies, with special reference to the relationship between central and peripheral emboli.
      PE is the primary cause of death in 3 to 10% of all hospital deaths and is a contributing cause in another 10%.
      • Lindblad B
      • Sternby NH
      • Bergqvist D
      Incidence of venous thromboembolism verified by necropsy over 30 years.
      • Modan B
      • Sharon E
      • Jelin N
      Factors contributing to the incorrect diagnosis of pulmonary embolic disease.
      • Dalen JE
      • Alpert JS
      Natural history of pulmonary embolism.
      • Coon WW
      The spectrum of pulmonary embolism: twenty years later.
      • Goldhaber SZ
      • Hennekens CH
      • Evans DA
      • Newton EC
      • Godleski JJ
      Factors associated with correct antemortem diagnosis of major pulmonary embolism.
      • Landefeld CS
      • Chren MM
      • Myers A
      • Geller R
      • Robbins S
      • Goldman L
      Diagnostic yield of the autopsy in a university hospital and a community hospital.
      • Dlebold J
      • Lohrs U
      Venous thrombosis and pulmonary embolism: a study of 5039 autopsies.
      • Morgenthaler TL
      • Ryu JH
      Clinical characteristics of fatal embolism in a referral hospital.
      • Stein PD
      • Henry JW
      Prevalence of acute pulmonary embolism among patients in a general hospital and at autopsy.
      • Dismuke SE
      • Wagner EH
      Pulmonary embolism as a cause of death: the changing mortality in hospitalized patients.
      • Rubinstein I
      • Murray D
      • Hoffstein V
      Fatal pulmonary emboli in hospitalized patients: an autopsy study.
      • Hauch O
      • Jorgensen LN
      • Khattar SC
      • Tegibjaerg CS
      • Wahiln AB
      • Rathenborg P
      • et al.
      Fatal pulmonary embolism associated with surgery: an autopsy study.
      • Anderson Jr, FA
      • Wheeler HB
      • Goldberg RJ
      • Hosmer DW
      • Patwandhan NA
      • Jovanovic B
      • et al.
      A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism: the Worchester DVT Study.
      • Rao MG
      • Rangwala AF
      Diagnostic yield from 231 autopsies in a community hospital.
      • McKelvie PA
      Autopsy evidence of pulmonary thromboembolism.
      • Rasmussen MS
      • Wille-Jorgensen P
      • Jorgensen LN
      Postoperative fatal pulmonary embolism in a general surgical department.
      • Goldman L
      • Sayson R
      • Robbins S
      • Cohn LH
      • Bettman M
      • Weisberg M
      The value of the autopsy in three medical eras.
      Thus, PE is the primary cause or a substantial contributor in more than 10% of all hospital deaths. At autopsy, PE is one of the most commonly overlooked major diagnoses.
      • Landefeld CS
      • Chren MM
      • Myers A
      • Geller R
      • Robbins S
      • Goldman L
      Diagnostic yield of the autopsy in a university hospital and a community hospital.
      • Goldman L
      • Sayson R
      • Robbins S
      • Cohn LH
      • Bettman M
      • Weisberg M
      The value of the autopsy in three medical eras.
      In many of these cases, premortem diagnosis could have led to a change in management that may have resulted in cure or improved survivaL
      • Landefeld CS
      • Chren MM
      • Myers A
      • Geller R
      • Robbins S
      • Goldman L
      Diagnostic yield of the autopsy in a university hospital and a community hospital.
      • Goldman L
      • Sayson R
      • Robbins S
      • Cohn LH
      • Bettman M
      • Weisberg M
      The value of the autopsy in three medical eras.
      Despite its relatively common occurrence at autopsy, PE is diagnosed before death in only a minority of patients (Table 2). In most large autopsy series; 60 to 80% of fatal PE cases are clinically unsuspected and undiagnosed.
      • Modan B
      • Sharon E
      • Jelin N
      Factors contributing to the incorrect diagnosis of pulmonary embolic disease.
      • Rossman I
      • Rodstein M
      • Bomstein A
      Undiagnosed diseases in an aging population”, pulmonary embolism and bronchopneumonia.
      • Goldhaber SZ
      • Hennekens CH
      • Evans DA
      • Newton EC
      • Godleski JJ
      Factors associated with correct antemortem diagnosis of major pulmonary embolism.
      • Landefeld CS
      • Chren MM
      • Myers A
      • Geller R
      • Robbins S
      • Goldman L
      Diagnostic yield of the autopsy in a university hospital and a community hospital.
      • Rubinstein I
      • Murray D
      • Hoffstein V
      Fatal pulmonary emboli in hospitalized patients: an autopsy study.
      • Hauch O
      • Jorgensen LN
      • Khattar SC
      • Tegibjaerg CS
      • Wahiln AB
      • Rathenborg P
      • et al.
      Fatal pulmonary embolism associated with surgery: an autopsy study.
      • Anderson Jr, FA
      • Wheeler HB
      • Goldberg RJ
      • Hosmer DW
      • Patwandhan NA
      • Jovanovic B
      • et al.
      A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism: the Worchester DVT Study.
      • McKelvie PA
      Autopsy evidence of pulmonary thromboembolism.
      • Gross JS
      • Neufeld RR
      • Libow LS
      • Gerber I
      • Rodstein M
      Autopsy study of the elderly institutionalized patient: review of 234 autopsies.
      • Alpert JS
      • Smith R
      • Carison J
      • Ockene IS
      • Dexter L
      • Dalen JE
      Mortality in patients treated for pulmonary embolism.
      This is despite the fact that, at autopsy, 50 to 55% of patients with fatal PE have evidence of old or recent emboli.
      • Morgenthaler TL
      • Ryu JH
      Clinical characteristics of fatal embolism in a referral hospital.
      • Havig O
      Pulmonary thromboembolism: gross and microscopical findings in 508 randomized autopsies, with special reference to the relationship between central and peripheral emboli.
      In these fatal cases, underdiagnosis of PE is partly attributable to underlying medical illnesses, such as pneumonia, congestive heart failure, and myocardial infarction, that may obscure the presence of PE.
      • Goldhaber SZ
      • Hennekens CH
      • Evans DA
      • Newton EC
      • Godleski JJ
      Factors associated with correct antemortem diagnosis of major pulmonary embolism.
      • Morgenthaler TL
      • Ryu JH
      Clinical characteristics of fatal embolism in a referral hospital.
      Other contributing factors include sudden death due to initial massive embolism and impaired ability to communicate, as in patients who are intubated on mechanical ventilation and those with stroke.
      • Morgenthaler TL
      • Ryu JH
      Clinical characteristics of fatal embolism in a referral hospital.
      Nevertheless, in some of these unrecognized cases of fatal PE, the patients may actually have been asymptomatic.
      Table 2Autopsy Studies of Pulmonary Embolism
      PE = pulmonary embolism; NS = not stated.
      ReferenceNo. of patientsPatients with autopsy-proven PEPatients with PE unsus pected or undiagnosed before death
      No.%No.%
      Freiman et al,
      • Frelman DG
      • Suyemoto J
      • Wessler S
      Frequency of pulmonary thromboembolism in man.
      1965
      6139643692
      Morrell & Dunnill,
      • Morrell MT
      • Dunnill MS
      The post-mortem incidence of pulmonary embolism in a hospital population.
      1968
      26313652NSNS
      Modan et al,
      • Modan B
      • Sharon E
      • Jelin N
      Factors contributing to the incorrect diagnosis of pulmonary embolic disease.
      1972
      2,1073531723567
      Rossman et al,
      • Rossman I
      • Rodstein M
      • Bomstein A
      Undiagnosed diseases in an aging population”, pulmonary embolism and bronchopneumonia.
      1974
      25016
      Fatal pulmonary embolism only—that is, pulmonary embolism was the primary cause of death.
      6.4850
      Coon,
      • Coon WW
      The spectrum of pulmonary embolism: twenty years later.
      1976
      4,6005671251491
      Havig,
      • Havig O
      Pulmonary thromboembolism: gross and microscopical findings in 508 randomized autopsies, with special reference to the relationship between central and peripheral emboli.
      1977
      50835269NSNS
      Goldhaber et al,
      • Goldhaber SZ
      • Hennekens CH
      • Evans DA
      • Newton EC
      • Godleski JJ
      Factors associated with correct antemortem diagnosis of major pulmonary embolism.
      1982
      1,45554
      Fatal pulmonary embolism only—that is, pulmonary embolism was the primary cause of death.
      3.73870
      Goldman et al,
      • Goldman L
      • Sayson R
      • Robbins S
      • Cohn LH
      • Bettman M
      • Weisberg M
      The value of the autopsy in three medical eras.
      1983
      30024
      Fatal pulmonary embolism only—that is, pulmonary embolism was the primary cause of death.
      8.01563
      Rubinstein et al,
      • Rubinstein I
      • Murray D
      • Hoffstein V
      Fatal pulmonary emboli in hospitalized patients: an autopsy study.
      1988
      1,27644
      Fatal pulmonary embolism only—that is, pulmonary embolism was the primary cause of death.
      3.43068
      Landefeld et al,
      • Landefeld CS
      • Chren MM
      • Myers A
      • Geller R
      • Robbins S
      • Goldman L
      Diagnostic yield of the autopsy in a university hospital and a community hospital.
      1988
      23315
      Fatal pulmonary embolism only—that is, pulmonary embolism was the primary cause of death.
      6.41173
      Karwinski & Svendsen,
      • Karwlnski B
      • Svendsen E
      Comparison of clinical and postmortem diagnosis of pulmonary embolism.
      1989
      21,52967
      Fatal pulmonary embolism only—that is, pulmonary embolism was the primary cause of death.
      0.35988
      Rao & Rangwala,
      • Rao MG
      • Rangwala AF
      Diagnostic yield from 231 autopsies in a community hospital.
      1990
      23118
      Fatal pulmonary embolism only—that is, pulmonary embolism was the primary cause of death.
      7.81161
      Hauch et al,
      • Hauch O
      • Jorgensen LN
      • Khattar SC
      • Tegibjaerg CS
      • Wahiln AB
      • Rathenborg P
      • et al.
      Fatal pulmonary embolism associated with surgery: an autopsy study.
      1990
      13116
      Fatal pulmonary embolism only—that is, pulmonary embolism was the primary cause of death.
      121063
      Lindblad et al,
      • Lindblad B
      • Eriksson A
      • Bergqvist D
      Autopsy-verified pulmonary embolism in a surgical department: analysis of the period from 1951 to 1988.
      1991
      1,23439132NSNS
      Lindblad et al,
      • Lindblad B
      • Sternby NH
      • Bergqvist D
      Incidence of venous thromboembolism verified by necropsy over 30 years.
      1991
      99434535NSNS
      Diebold & Lohrs,
      • Dlebold J
      • Lohrs U
      Venous thrombosis and pulmonary embolism: a study of 5039 autopsies.
      1991
      5,0391,50030NSNS
      McKelvie,
      • McKelvie PA
      Autopsy evidence of pulmonary thromboembolism.
      1994
      13216121381
      Saeger & Genzkow,
      • Saeger W
      • Genzkow M
      Venous thromboses and pulmonary embolism in post-mortem series: probable causes by correlations of clinical data and basic diseases.
      1994
      4,07775819NSNS
      Rasmussen et al,
      • Rasmussen MS
      • Wille-Jorgensen P
      • Jorgensen LN
      Postoperative fatal pulmonary embolism in a general surgical department.
      1995
      18717
      Fatal pulmonary embolism only—that is, pulmonary embolism was the primary cause of death.
      9.1NSNS
      Morgenthaler & Ryu,
      • Morgenthaler TL
      • Ryu JH
      Clinical characteristics of fatal embolism in a referral hospital.
      1995
      2,42792
      Fatal pulmonary embolism only—that is, pulmonary embolism was the primary cause of death.
      3.86368
      Stein & Henry,
      • Stein PD
      • Henry JW
      Prevalence of acute pulmonary embolism among patients in a general hospital and at autopsy.
      1995
      40420
      Fatal pulmonary embolism only—that is, pulmonary embolism was the primary cause of death.
      5.01470
      Cohen et al,
      • Cohen AT
      • Edmondson RA
      • Phillips MJ
      • Ward VP
      • Kakkar VV
      The changing pattern of venous thromboembolic disease.
      1996
      14,667615
      Fatal pulmonary embolism only—that is, pulmonary embolism was the primary cause of death.
      4.2NSNS
      Baglin et al,
      • Baglin TP
      • White K
      • Charles A
      Fatal pulmonary embolism in hospitalized medical patients.
      1997
      4004511NSNS
      * PE = pulmonary embolism; NS = not stated.
      Fatal pulmonary embolism only—that is, pulmonary embolism was the primary cause of death.
      Major embolism including bilateral, central thromboemboli may occasionally be asymptomatic.
      • Browse NL
      • Clemenson G
      • Bateman NT
      • Gaunt JI
      • Croft DN
      Effect of intravenous dextran 70 and pneumatic leg compression on incidence of postoperative pulmonary embolism.
      • Harris WH
      • McKusick K
      • Athanasoulis CA
      • Waltman AC
      • Strauss HW
      Detection of pulmonary emboli after total hip replacement using serial C15O2 pulmonary scans.
      This issue was addressed in a Mayo Clinic study in which the clinical records of patients with fatal PE were retrospectively reviewed.
      • Morgenthaler TL
      • Ryu JH
      Clinical characteristics of fatal embolism in a referral hospital.
      Despite the presence of older organizing emboli in one-half of these patients, classic symptoms of PE were often absent before death. For example, dyspnea was noted in 59% of these patients, pleuritic chest pain in 8%, cough in 3%, and hemoptysis in 3%.
      • Morgenthaler TL
      • Ryu JH
      Clinical characteristics of fatal embolism in a referral hospital.
      Similarly, Modan and associates
      • Modan B
      • Sharon E
      • Jelin N
      Factors contributing to the incorrect diagnosis of pulmonary embolic disease.
      reported dyspnea in only 28% and chest pain in 19.5% of patients with PE confirmed at autopsy. Other studies have reported absence of symptoms in 63 to 85% of patients with PE detected at autopsy.
      • Frelman DG
      • Suyemoto J
      • Wessler S
      Frequency of pulmonary thromboembolism in man.
      • McKelvie PA
      Autopsy evidence of pulmonary thromboembolism.
      In approximately one-half of patients with fatal PE, life expectancies were relatively short due to underlying diseases such as cancer, congestive heart failure, stroke, and advanced chronic lung disease.
      • Coon WW
      The spectrum of pulmonary embolism: twenty years later.
      • Landefeld CS
      • Chren MM
      • Myers A
      • Geller R
      • Robbins S
      • Goldman L
      Diagnostic yield of the autopsy in a university hospital and a community hospital.
      • Morgenthaler TL
      • Ryu JH
      Clinical characteristics of fatal embolism in a referral hospital.
      • Morrell MT
      • Dunnill MS
      The post-mortem incidence of pulmonary embolism in a hospital population.
      • Goldman L
      • Sayson R
      • Robbins S
      • Cohn LH
      • Bettman M
      • Weisberg M
      The value of the autopsy in three medical eras.
      In the remaining patients, however, with prompt diagnosis and treatment of venous thromboembolism, the disastrous outcome may have been avoided.

      CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION

      In patients who survive an episode of PE, the prognosis is generally good when appropriate therapy is administered.
      • Alpert JS
      • Dalen JE
      Epidemiology and natural history of venous thromboembolism.
      • Ferrari E
      • Baudouy M
      • Cerboni P
      • Tibi T
      • Guigner A
      • Leonetti J
      • et al.
      Clinical epidemiology of venous thromboembolic disease: results of a French Multicentre Registry.
      • Alpert JS
      • Smith R
      • Carison J
      • Ockene IS
      • Dexter L
      • Dalen JE
      Mortality in patients treated for pulmonary embolism.
      • Carson JL
      • Kelley MA
      • Duff A
      • Weg JG
      • Fulkerson WJ
      • Palevsky HI
      • et al.
      The clinical course of pulmonary embolism.
      • van Beek EJ
      • Kuijer PM
      • Buller HR
      • Brandjes DP
      • Bossuyt PM
      • ten Cate JW
      The clinical course of patients with suspected pulmonary embolism.
      The pulmonary emboli primarily resolve, and residual respiratory symptoms are uncommon.
      • Alpert JS
      • Dalen JE
      Epidemiology and natural history of venous thromboembolism.
      • Riedel M
      • Stanek V
      • Wldlmsky J
      • Prerovsky I
      Longterm follow-up of patients with pulmonary thromboembolism: late prognosis and evolution of hemodynamic and respiratory data.
      Long-term mortality is related to underlying diseases such as cancer, congestive heart failure, infections, or chronic lung disease.
      • Carson JL
      • Kelley MA
      • Duff A
      • Weg JG
      • Fulkerson WJ
      • Palevsky HI
      • et al.
      The clinical course of pulmonary embolism.
      • van Beek EJ
      • Kuijer PM
      • Buller HR
      • Brandjes DP
      • Bossuyt PM
      • ten Cate JW
      The clinical course of patients with suspected pulmonary embolism.
      Some long-term survivors have development of chronic thromboembolic pulmonary hypertension related to inadequate resolution of large pulmonary thromboemboli or recurrent embolism. This is estimated to occur in only 0.1 to 0.5% of patients with acute PE.
      • Fedullo PF
      • Auger WR
      • Channlck RN
      • Moser KM
      • Jamieson SW
      Chronic thromboembolic pulmonary hypertension.
      In patients who eventually have development of chronic thromboembolic pulmonary hypertension, an asymptomatic “honeymoon” period is thought to last months to years after the initial episode of PE. This is followed by gradual symptomatic decline with worsening exertional dyspnea and hypoxemia.
      • Fedullo PF
      • Auger WR
      • Channlck RN
      • Moser KM
      • Jamieson SW
      Chronic thromboembolic pulmonary hypertension.
      Despite the presence of extensive lesions in the pulmonary vascular tree, a history compatible with a prior episode of venous thromboembolism could not be elicited in about one-half of these patients, even with retrospective questioning.
      • Moser KM
      • Auger WR
      • Fedullo PF
      • Jamieson SW
      Chronic thromboembolic pulmonary hypertension: clinical picture and surgical treatment.
      • Simonneau G
      • Azarlan R
      • Brenot F
      • Dartevelle PG
      • Musset D
      • Duroux P
      Surgical management of unresolved pulmonary embolism: a personal series of 72 patients.

      SCREENING FOR PE IN PATIENTS WITH DVT

      Although prospective studies evaluating diagnostic tests and therapeutic agents for PE have suggested that almost all patients with PE are symptomatic, a different perspective is provided by screening studies of patients at risk for PE. Monreal and colleagues
      • Monreal M
      • Rulz J
      • Olazabal A
      • Arias A
      • Roca J
      Deep venous thrombosis and the risk of pulmonary embolism: a systematic study.
      performed ventilationperfusion lung scanning in 434 consecutive patients with venographic ally proven DVT; in 164 (38%), scans showed high probability for PE. Of those 164 patients, 54% had symptoms or signs consistent with PE, and 46% did not. Similarly, Moser and associates
      • Moser KM
      • Auger WR
      • Fedullo PF
      • Jamieson SW
      Chronic thromboembolic pulmonary hypertension: clinical picture and surgical treatment.
      described 44 patients with venographically proven DVT, in whom 52% had high probability of PE as noted on lung scans. Less than one-half of these patients with high probability of PE on lung scans had symptoms that were suggestive of PE. The data regarding the occurrence of asymptomatic PE in patients with DVT are summarized in Table 3.
      • Monreal M
      • Rulz J
      • Olazabal A
      • Arias A
      • Roca J
      Deep venous thrombosis and the risk of pulmonary embolism: a systematic study.
      • Kistner RL
      • Ball JJ
      • Nordyke RA
      • Freeman GC
      Incidence of pulmonary embolism in the course of thrombophlebitis of the lower extremities.
      • Moreno-Cabral R
      • Kistner RL
      • Nordyke RA
      Importance of calf vein thrombophlebitls.
      • Moser KM
      • leMoine JR
      Is embolic risk conditioned by location of deep venous thrombosis?.
      • Plate G
      • Ohlin P
      • Eklof B
      Pulmonary embolism in acute iliofemoral venous thrombosis.
      • Dorfman GS
      • Cronan JJ
      • Tupper TB
      • Messersmith RN
      • Denny DF
      • Lee CH
      Occult pulmonary embolism: a common occurrence in deep venous thrombosis.
      • Huisman MV
      • Buller HR
      • ten Cate JW
      • van Royen EA
      • Vreeken J
      • Kersten MJ
      • et al.
      Unexpected high prevalence of silent pulmonary embolism in patients with deep venous thrombosis.
      • Hirsch JF
      • Demllly P
      Depistage des embolies pulmonaires asymptomatiques par la scintigraphie systematique au cours des phlebites apparemment non compliquees.
      • Prandonl P
      • Polistena P
      • Bernardi E
      • Cogo A
      • Casara D
      • Verlato F
      • et al.
      Upper-extremity deep vein thrombosis: risk factors, diagnosis, and complications.
      • Decousus H
      • Lelzorovlcz A
      • Parent F
      • Page Y
      • Tardy B
      • Girard P
      • Prevention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group
      • et al.
      A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis.
      These data suggest that most PE occurring in patients with DVT is asymptomatic. Distal DVT is associated with smaller pulmonary thromboemboli and is less likely to cause symptoms.
      Table 3Incidence of Symptomatic and Asymptomatic Pulmonary Embolism in Patients With Deep Venous Thrombosis Confirmed by Venography
      DVT = deep venous thrombosis; PE = pulmonary embolism.
      Patients with PE
      Pulmonary embolism was diagnosed by ventilation-perfusion lung scanning or pulmonary angiography (or both).
      Patients with PE who were asymptomatic
      ReferenceSite of DVTNo. of patientsNo.%No.%
      462452
      Moreno-Cabral et al,
      • Moreno-Cabral R
      • Kistner RL
      • Nordyke RA
      Importance of calf vein thrombophlebitls.
      1976
      Proximal271867739
      Distal27933556
      Moser & LeMoine,
      • Moser KM
      • leMoine JR
      Is embolic risk conditioned by location of deep venous thrombosis?.
      1981
      Proximal15853788
      Distal2100
      Plate et al,
      • Plate G
      • Ohlin P
      • Eklof B
      Pulmonary embolism in acute iliofemoral venous thrombosis.
      1985
      Proximal4922451673
      Dorfman et al,
      • Dorfman GS
      • Cronan JJ
      • Tupper TB
      • Messersmith RN
      • Denny DF
      • Lee CH
      Occult pulmonary embolism: a common occurrence in deep venous thrombosis.
      1987
      Proximal49173517
      DVT = deep venous thrombosis; PE = pulmonary embolism.
      100
      Distal900
      Huisman et al,
      • Huisman MV
      • Buller HR
      • ten Cate JW
      • van Royen EA
      • Vreeken J
      • Kersten MJ
      • et al.
      Unexpected high prevalence of silent pulmonary embolism in patients with deep venous thrombosis.
      1989
      Proximal-distal894551454100
      Hirsch & Demilly,
      • Hirsch JF
      • Demllly P
      Depistage des embolies pulmonaires asymptomatiques par la scintigraphie systematique au cours des phlebites apparemment non compliquees.
      1991
      Proximal-distal218388
      These studies included only patients without symptoms suggestive of pulmonary embolism.
      100
      Monreal et al,
      • Monreal M
      • Rulz J
      • Olazabal A
      • Arias A
      • Roca J
      Deep venous thrombosis and the risk of pulmonary embolism: a systematic study.
      1992
      Proximal
      Information not given for 70 study patients with indeterminate results on lung scans.
      292132457255
      Distal
      Information not given for 70 study patients with indeterminate results on lung scans.
      723244413
      Moser et al,
      • Moser KM
      • Auger WR
      • Fedullo PF
      • Jamieson SW
      Chronic thromboembolic pulmonary hypertension: clinical picture and surgical treatment.
      1992
      Proximal-distal4423521670
      Prandoni et al,
      • Prandonl P
      • Polistena P
      • Bernardi E
      • Cogo A
      • Casara D
      • Verlato F
      • et al.
      Upper-extremity deep vein thrombosis: risk factors, diagnosis, and complications.
      1997
      Upper extremity22836563
      Decousus et al,
      • Decousus H
      • Lelzorovlcz A
      • Parent F
      • Page Y
      • Tardy B
      • Girard P
      • Prevention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group
      • et al.
      A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis.
      1998
      Proximal400197495226
      * DVT = deep venous thrombosis; PE = pulmonary embolism.
      Pulmonary embolism was diagnosed by ventilation-perfusion lung scanning or pulmonary angiography (or both).
      These studies included only patients without symptoms suggestive of pulmonary embolism.
      § Information not given for 70 study patients with indeterminate results on lung scans.
      In most of these studies, ventilation-perfusion lung scanning was used to screen for PE. It is likely that some of the patients with lung scans showing high probability for PE did not have PE. Nevertheless, reversibility of the defects with anticoagulant therapy and angiographic confirmation employed in some of these studies suggest that most patients with high probability of PE on lung scans indeed did have PE.
      • Harris WH
      • McKusick K
      • Athanasoulis CA
      • Waltman AC
      • Strauss HW
      Detection of pulmonary emboli after total hip replacement using serial C15O2 pulmonary scans.
      • Kistner RL
      • Ball JJ
      • Nordyke RA
      • Freeman GC
      Incidence of pulmonary embolism in the course of thrombophlebitis of the lower extremities.
      • Moreno-Cabral R
      • Kistner RL
      • Nordyke RA
      Importance of calf vein thrombophlebitls.
      • Huisman MV
      • Buller HR
      • ten Cate JW
      • van Royen EA
      • Vreeken J
      • Kersten MJ
      • et al.
      Unexpected high prevalence of silent pulmonary embolism in patients with deep venous thrombosis.
      • Hirsch JF
      • Demllly P
      Depistage des embolies pulmonaires asymptomatiques par la scintigraphie systematique au cours des phlebites apparemment non compliquees.
      • Dorr LD
      • Sakimura I
      • Mohler JG
      Pulmonary emboli following total hip arthroplasty: incidence study.
      • Williams JW
      • Elkman EA
      • Greenberg S
      Asymptomatic pulmonary embolism: a common event in high risk patients.
      • Foley M
      • Maslack MM
      • Rothman RH
      • Casey MP
      • Lugano EM
      • Parry CE
      • et al.
      Pulmonary embolism after hip or knee replacement: postoperative changes on pulmonary scintigrams in asymptomatic patients.

      SCREENING FOR PE IN POSTOPERATIVE PATIENTS

      Surgical patients, particularly those undergoing an orthopedic operation, are at high risk for venous thromboembolism.
      • Clagett GP
      • Anderson Jr, FA
      • Helt J
      • Levine MN
      • Wheeler HB
      Prevention of venous thromboembolism.
      During the past 30 years, multiple screening studies have documented the incidence of DVT and PE in high-risk patients. Pertinent studies regarding the occurrenee of asymptomatic PE are summarized in Table 4.
      • Browse NL
      • Clemenson G
      • Bateman NT
      • Gaunt JI
      • Croft DN
      Effect of intravenous dextran 70 and pneumatic leg compression on incidence of postoperative pulmonary embolism.
      • Harris WH
      • McKusick K
      • Athanasoulis CA
      • Waltman AC
      • Strauss HW
      Detection of pulmonary emboli after total hip replacement using serial C15O2 pulmonary scans.
      • Dorr LD
      • Sakimura I
      • Mohler JG
      Pulmonary emboli following total hip arthroplasty: incidence study.
      • Williams JW
      • Elkman EA
      • Greenberg S
      Asymptomatic pulmonary embolism: a common event in high risk patients.
      • Foley M
      • Maslack MM
      • Rothman RH
      • Casey MP
      • Lugano EM
      • Parry CE
      • et al.
      Pulmonary embolism after hip or knee replacement: postoperative changes on pulmonary scintigrams in asymptomatic patients.
      • Rissanen V
      • Suomalalnen O
      • Karajalalnen P
      • Kettunen K
      • Karkkalnen A
      • Lanslmles E
      • et al.
      Screening for postoperative pulmonary embolism on the basis of clinical symptomatology. routine electrocardiography and plain chest radiography.
      In the postoperative patient, asymptomatic PE occurred 4 times as often as did symptomatic PE. For example, Rissanen and colleagues
      • Rissanen V
      • Suomalalnen O
      • Karajalalnen P
      • Kettunen K
      • Karkkalnen A
      • Lanslmles E
      • et al.
      Screening for postoperative pulmonary embolism on the basis of clinical symptomatology. routine electrocardiography and plain chest radiography.
      used ventilation-perfusion lung scanning to screen 108 patients undergoing an elective hip operation and found that 20 (19%) had high probability for PE. Of these 20 patients, only 6 had symptoms of PE—that is, 70% with high probability for PE were asymptomatic. Similarly, Williams and coworkers
      • Williams JW
      • Elkman EA
      • Greenberg S
      Asymptomatic pulmonary embolism: a common event in high risk patients.
      used weekly ventilation-perfusion lung scanning to screen 158 patients undergoing a hip operation or major lower extremity amputation; 48 (30%) had evidence of postoperative PE, of whom 44 (92%) had no symptoms suggestive of PE. Harris and associates
      • Harris WH
      • McKusick K
      • Athanasoulis CA
      • Waltman AC
      • Strauss HW
      Detection of pulmonary emboli after total hip replacement using serial C15O2 pulmonary scans.
      studied 73 patients undergoing total hip replacement, of whom 17 had development of PE, which was confirmed by pulmonary angiography in almost all cases. Of these 17 patients 14 (82%) were asymptomatic. Although many of these asymptomatic emboli were small and peripheral, some were large and central.
      • Harris WH
      • McKusick K
      • Athanasoulis CA
      • Waltman AC
      • Strauss HW
      Detection of pulmonary emboli after total hip replacement using serial C15O2 pulmonary scans.
      Table 4Screening for Pulmonary Embolism in Postoperative Patients
      PE = pulmonary embolism.
      Patients with PE
      Pulmonary embolism was diagnosed by ventilation-perfusion lung scanning or pulmonary angiography (or both).
      Patients with PE who were asympi tomatic
      Reference
      Most studies were prophylaxis trials comparing patients receiving prophylaxis versus control subjects.
      Type of operationNo. of patientsNo.%No.%
      Browse et al,
      • Browse NL
      • Clemenson G
      • Bateman NT
      • Gaunt JI
      • Croft DN
      Effect of intravenous dextran 70 and pneumatic leg compression on incidence of postoperative pulmonary embolism.
      1976
      General surgery10016161275
      Dorretal,
      • Dorr LD
      • Sakimura I
      • Mohler JG
      Pulmonary emboli following total hip arthroplasty: incidence study.
      1979
      Total hip arthroplasty, amputations, debridements49363100
      Williams et al,
      • Williams JW
      • Elkman EA
      • Greenberg S
      Asymptomatic pulmonary embolism: a common event in high risk patients.
      1982
      Hip surgery, amputations15848304492
      Rissanen et al,
      • Rissanen V
      • Suomalalnen O
      • Karajalalnen P
      • Kettunen K
      • Karkkalnen A
      • Lanslmles E
      • et al.
      Screening for postoperative pulmonary embolism on the basis of clinical symptomatology. routine electrocardiography and plain chest radiography.
      1984
      Elective hip surgery10820191470
      Harris et al,
      • Harris WH
      • McKusick K
      • Athanasoulis CA
      • Waltman AC
      • Strauss HW
      Detection of pulmonary emboli after total hip replacement using serial C15O2 pulmonary scans.
      1984
      Total hip replacement7317231482
      Foley et al,™ 1989Total hip or knee replacement4031741376
      * PE = pulmonary embolism.
      Most studies were prophylaxis trials comparing patients receiving prophylaxis versus control subjects.
      Pulmonary embolism was diagnosed by ventilation-perfusion lung scanning or pulmonary angiography (or both).

      CONCLUSION

      The evidence summarized herein suggests that many episodes of PE are unrecognized and undiagnosed, especially in postoperative patients. Some patients with undiagnosed and untreated PE suffer unexpected death or chronic thromboembolic pulmonary hypertension (Fig. 1); however, it is likely that many of these overlooked cases have no recognizable clinical sequelae and are never identified. Although most clinicians realize that the common initial features of PE including dyspnea, pleuritic chest pain, and tachypnea are nonspecific, it is not widely appreciated that these symptoms and signs may be relatively insensitive in identifying patients with PE.
      Figure thumbnail gr1
      Fig. 1Schema of relationship between suspected and actual cases of pulmonary embolism (PE). Only a third of suspected PE cases are actually PE. Conversely, many cases of PE, including fatal ones, are unrecognized or undiagnosed.
      During the past 30 years, we have come to realize that symptoms of myocardial infarction are absent or atypical and therefore unrecognized in 20 to 60% of all cases.
      • Kannel WB
      • Cupples LA
      • Gagnon DR
      Incidence, precursors and prognosis of unrecognized myocardial infarction.
      • Sigurdsson E
      • Thorgelrsson G
      • Slgvaldason H
      • Sigfusson N
      Unrecognized myocardial infarction: epidemiology, clinical characteristics, and the prognostic role of angina pectoris; the Reykjavik Study.
      In most cases, these unrecognized episodes of myocardial infarction are eventually diagnosed by routine electrocardiography.
      • Kannel WB
      • Cupples LA
      • Gagnon DR
      Incidence, precursors and prognosis of unrecognized myocardial infarction.
      • Sigurdsson E
      • Thorgelrsson G
      • Slgvaldason H
      • Sigfusson N
      Unrecognized myocardial infarction: epidemiology, clinical characteristics, and the prognostic role of angina pectoris; the Reykjavik Study.
      Unfortunately, no accurate screening test is available for PE. Thus, many uncertainties remain regarding the prevalence, natural history, and mortality of this disorder.
      • Egerrnayer P
      • Town GI
      The clinical significance of pulmonary embolism: uncertainties and implications for treatment-a debate [published erratum appears in J Intern Med 1997;241:341J.
      For patients who have survived an unrecognized episode of PE, the prognostic implications may not be as serious as those for silent myocardial infarction if no persistent risk factor exists for recurrence of venous thromboembolism.
      If many cases of PE are indeed clinically silent, “high clinical suspicion” is inadequate in diagnosing PE. Furthermore, clinical suspicion is not only nonspecific but also insensitive in identifying patients with venous thromboembolism. This partly explains the persistently high prevalence of undiagnosed fatal PE, even with the availability of advanced imaging techniques. Possibly, some of the overlooked cases of PE represent small emboli that are not “clinically significant,” particularly if recurrence is not a risk. More studies are needed in determining whether and how often cases of clinically insignificant PE may occur.
      In the meantime, more effort is needed in the area of prevention for patients at risk. Currently available methods of prophylaxis reduce the incidence of venous thromboembolism by about two-thirds.
      • Clagett GP
      • Anderson Jr, FA
      • Helt J
      • Levine MN
      • Wheeler HB
      Prevention of venous thromboembolism.
      Advances are being made in improving the efficacy of these methods in preventing venous thromboembolism; however, several studies have shown that prophylaxis for venous thromboembolism is underused, even in patients with obvious risk factors.
      • Morgenthaler TL
      • Ryu JH
      Clinical characteristics of fatal embolism in a referral hospital.
      • Clagett GP
      • Anderson Jr, FA
      • Helt J
      • Levine MN
      • Wheeler HB
      Prevention of venous thromboembolism.
      • Anderson Jr, FA
      • Wheeler HB
      • Goldberg RJ
      • Hosmer DW
      • Forcier A
      • Patwardhan NA
      Physician practices in the prevention of venous thromboembolism.
      Clearly, we must be more vigilant in identifying patients at risk and in using appropriate means of prophylaxis.

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