Coagulation factor V Leiden mutation in sudden fatal pulmonary embolism and in a general northern European population sample

The R506Q point mutation in the gene coding for coagulation factor V (Leiden mutation) is the major underlying defect in resistance to activated protein C (APC), which predisposes to venous thrombosis. The risk of deep vein thrombosis is clearly elevated in carriers of the mutation, but the risk for pulmonary embolism has not been demonstrated to be as high. The aim of our study was to determine the frequency of the Leiden mutation in an autopsy series of sudden fatal pulmonary embolism cases. PCR and subsequent restriction enzyme digestion were applied for genotyping 164 cases of pulmonary embolism. According to our data, the allele frequency of the Leiden mutation is not higher in sudden fatal pulmonary embolism cases (0.8%, 95% CI 0-1.9%) than in the general Finnish population (1.5%, 95% CI 0-3.3%). In addition to the 97 Finns, we determined the frequency of the Leiden mutation in 255 individuals from the neighbouring populations (Saami, Komi, and Karelians from Russia and Estonians), and found the Saami to have the highest frequency of the Leiden mutation (6.3%, 95% CI 3.2-9.2) in the general northern European population sample studied here.     

Prothrombin G20210A mutation and sudden death

The authors present a case of sudden death in a previously healthy 36-year-old male. At autopsy there were bilateral pulmonary thromboemboli and right ventricular dilatation. Histologic findings in the lungs included recanalized, old thrombi and evidence of pulmonary hypertension. Genetic analysis for hereditary risk factors was heterozygous positive for the prothrombin G20210A mutation. Implications of this finding, its history and the diagnostic technique shall be discussed. The authors recommend that all cases of deep venous thromboses and pulmonary thromboemboli lacking known risk factors be evaluated for newly described genetic variations associated with an increased risk for venous thrombosis.     

肺动脉栓塞致死23例法医学分析

目的总结分析肺动脉栓塞致死的一般特点,探讨法医病理学鉴定要点及注意事项。方法对2001~2011年在中山大学法医鉴定中心鉴定的23例肺动脉栓塞案例进行回顾性分析。结果肺动脉栓塞致死以男性多见;发病年龄主要集中在31～70岁之间;主要诱因是严重外伤、长期卧床后运动,以下肢静脉系统血栓形成并脱落致肺动脉栓塞最为常见。结论对肺动脉栓塞致死案例法医病理学鉴定要点进行了总结。     

Lower extremity deep venous thrombosis with fatal pulmonary thromboembolism caused by benign pelvic space-occupying lesions--an overview

Venous stasis predisposes to thrombosis. One hundred and sixty cases of fatal pulmonary thromboembolism were reviewed to determine how many cases had deep venous thromboses associated with venous blood flow reduction caused by external pressure from benign pelvic masses. Three cases were identified, representing 2% of cases overall (3/160): a 44-year-old woman with a large uterine leiomyoma (1048 g); a 74-year-old man with prostatomegaly and bladder distension (containing 1 L of urine); and a 70-year-old man with prostatomegaly and bladder distension (containing 3 L of urine). Although a rare cause of fatal deep venous thrombosis and pulmonary thromboembolism, space-occupying pelvic lesions can lead to extrinsic pressure on adjacent veins reducing blood flow and causing stasis and thrombosis. Individuals with large pelvic masses may, therefore, be at increased risk of pulmonary thromboembolism from deep venous thrombosis, particularly in the presence of concurrent risk factors such as immobility, thrombophilias, malignancy, and significant cardiopulmonary disease.     

Saddle Pulmonary Embolism with Paradoxical Coronary Artery Embolism through a Patent Foramen Ovale

A 35‐year‐old male patient was found in cardiac arrest in his vehicle, with no apparent injuries after a minor motor vehicle collision. The decedent was found to have a saddle pulmonary embolus with a thromboembolus impacted across a patent foramen ovale and a paradoxical embolism in the circumflex coronary artery, as well as significant clotting in the deep veins of both lower extremities. There were no risk factors in his history to explain the deep venous thrombosis; family history suggested the possibility of an unrecognized clotting disorder.     

Fatal pulmonary cement embolism following percutaneous vertebroplasty (PVP)

A case of fatal pulmonary embolism with acrylic cement occuring during a percutaneous vertebroplasty on account of a fracture of L1 is described. Autopsy confirmed the presence of large amounts of surgical cement in the paravertebral venous system and in the pulmonary arteries. This rare complication occurred because perivertebral venous cement migration was not recognized during vertebroplasty. To our knowledge, this is the first case of fatal pulmonary embolism caused by surgical cement following a percutaneous vertebroplasty.     

Is There a Relationship Between Bladder Outlet Obstruction due to Benign Prostatic Hyperplasia and Pulmonary Thromboembolism?

Benign prostatic hyperplasia with chronic bladder outlet obstruction has been associated with deep venous thrombosis (DVT) and fatal pulmonary thromboembolism (PTE). To evaluate this further, 60 autopsy cases of men with PTE were compared with 60 age-matched controls. The criteria for outlet obstruction were macroscopic prostatic enlargement with bladder trabeculation and benign prostatic hyperplasia on microscopy. Ten of the 60 men (16.7%) with fatal PTE had evidence of bladder outlet obstruction (age 57-78 years; mean 71.4 years). Of the 60 controls, 12 had evidence of bladder outlet obstruction (20%) (age 67-86 years; mean 75.5 years). No significant relationship could be demonstrated between bladder outlet obstruction and fatal PTE cases (p = 0.8). Given reports of this association, however, it is possible that bladder distension with venous compression may act as a risk modifier in certain individuals in association with other significant comorbidities, but this risk appears low.     

Sudden death from secondary massive pulmonary embolism derived from marrow emboli trapped by Chiari's network.

We report a case of fatal massive pulmonary embolism in an 86-year-old woman. The embolus occurred as a result of embolic bone marrow particles from a fractured femur becoming trapped by a Chiari's network which then acted as a source for propagation of a large thrombus which detached and caused sudden death from massive pulmonary embolism. To our knowledge this is the first report of such a case.     

Etiology of pulmonary thromboembolism in the absence of commonly recognized risk factors

Pulmonary thromboembolism is an often fatal complication of venous thrombosis. Any component or combination of the components composing Virchow's triad (venostasis, hypercoagulability, and endothelial damage) increases the propensity for a thrombophilic state. Hypercoagulable states may be inherited or acquired. While the etiology in many cases may be evident either on physical examination or on evaluation of the decedent's medical history, this is often not the case. We conducted a retrospective study of cases presenting to the Jefferson County Coroner/Medical Examiner's Office in Birmingham, Alabama, who were given a diagnosis of pulmonary embolism. A search of cases within the past 23 years yielded 81 cases. An underlying cause was determined in 70 cases (86%). The remaining 11 (14%) cases had no identifiable cause. We believe that a number of these cases may represent an underlying thrombophilic disorder. Since these disorders may be of an inherited or acquired nature, the determination of an etiology may be relevant to the decedent's family. Postmortem blood analyses may in selected cases be useful and appropriate for the detection of some of these disorders. However, such analyses are not practical in all cases, with each case having to be evaluated on its own merits.     

Fatal Acute Hemorrhagic Bowel Infarction Caused by Mesenteric Venous Thrombosis

Acute mesenteric venous thrombosis (MVT) is a rare, but life‐threatening medical phenomenon. MVT is normally characterized by insidious onset, with nonspecific signs and symptoms. A high index of clinical suspicion is required for diagnosis, and emergency surgery is necessary to optimize the chances of patient survival, especially in the people aged more than 70 years. Surprisingly, based on my review of the literature, no fatal acute MVT case has been reported in the forensic literature. All reported such cases have been documented in medical literature, and most of them have been associated with underlying risk factors for venous thrombosis, such as hypercoagulable state, certain cancers, and stasis of the blood flow. Here, I report the case of a sudden unexpected death due to extensive intestinal ischemia and infarction with massive abdominal hemorrhage caused by acute MVT in a 72‐year‐old man without known underlying risk factors.     

Assessment of the stability of 30 antipsychotic drugs in stored blood specimens

The accuracy of antemortem diagnosis of pulmonary embolism is within the range of just 10-30%, so representing one of the most frequent missed diagnosis in sudden, unexpected death. We describe 43 fatal cases of pulmonary embolism as confirmed by post-mortem examination. The aim of our study was to verify the systematic search for the most common genetic thrombophilias (Factor V Leiden (G1691A) and FII (G20210A) gene variants) and dating the thrombus. As a whole, 41 patients (95.3%) had at least one risk factor. Pre-existing symptoms are described just before fatal embolism in 18 (41.9%) out 43 patients. In 18 out of 43 (41.9%) it was not possible to find the thrombotic site. In 24 out of the remaining 25 cases the involvement of the deep veins of one leg was shown; in 1 case the thrombus was localised in the inferior caval vein. 10 (41.7%) were iliac vein thromboses, 7 (29.1%) femoral, 2 (8.3%) popliteal, 3 (12.6%) posterior-tibial, 1 (4.1%) anterior-tibial and 1 (4.1%) peroneal vein thromboses. In our cohort of patients, 4 (10%) out of 40 cases carried the 20210A prothrombin gene variant in heterozygosis. One (2.5%) out of 40 carried the Factor V Leiden (G1691A) gene variant in heterozygosis. Patients carrying these gene variants in homozygosis or carrying both were not present in our case-series. We strongly underline the relevance of a complete methodological approach, integrating clinical data by means of autopsy findings and histological study. On the contrary, investigating common inherited thrombophilia is not warranted.     

Forensic Considerations in Cases of Myotonic Dystrophy at Autopsy

Myotonic dystrophy (DM) is a chronic, slowly progressive, autosomal‐dominant disorder with delayed muscle relaxation after contraction, distal skeletal muscle weakness, and atrophy. It has a reduced life expectancy due predominantly to respiratory failure or sudden cardiac death. The mortality rate is approximately 7.3 times greater than the general population with a mean age at death of 53 years. Degeneration of the cardiac conduction system causes atrioventricular block, arrhythmias, and ventricular failure. A case of sudden death in a 44‐year‐old woman with DM type 1 is reported to demonstrate an alternative lethal mechanism. At autopsy, there was extensive infiltration of skeletal muscles with adipose tissue. The heart was structurally normal. A deep venous thrombosis of the right calf was identified with a large saddle pulmonary thromboembolus and bilateral peripheral thromboemboli. DM1‐related thrombosis had most likely occurred because of the decedent's impaired mobility, possible hypercoagulable state, and serum changes from muscle necrosis.     

Traumatic venous aneurysm of the popliteal vein with outcome: a case report and review of the literature.

A case of sudden death due to recurrent pulmonary thromboembolism is described. The fatality took place three and a half weeks following blunt trauma to the left popliteal region. The patient died unexpectedly. Autopsy revealed the source of the emboli as a sacciform venous aneurysm of the popliteal vein, an entity seldom described, but important to consider in cases of soft tissue popliteal masses or unexplained pulmonary embolism, especially in otherwise healthy individuals.     

Sickle cell lung disease and sudden death: a retrospective/prospective study of 21 autopsy cases and literature review

Sudden death in the setting of sickle cell lung disease (SCLD), is periodically seen in the practice of medical examiners. The goal of the present study was to identify the most common pathologic findings of SCLD associated with sudden or unexpected death. A retrospective/prospective review of 21 autopsy cases from sickle cell patients between 1990 and 2004 was performed. Review of medical records, autopsy reports, and H&E-stained slides of lung tissue was performed. Oil-Red-O and elastic staining of lung tissue were evaluated. All cases were screened for both acute and chronic forms of SCLD. Patients admitted for sickle cell pain crisis ranged in age from 8 months to 65 years. Fifteen out of 21 cases (71.4%) showed significant pulmonary pathology. The most frequent lung findings included pulmonary edema (47.6%), pulmonary thromboembolism (38.1%), fat emboli (33.3%), pulmonary hypertension, grades I-IV (33.3%), and microvascular occlusive thrombi (28.5%). Our study demonstrates higher-than-expected percentages of acute and chronic sickle cell-related lung injury such as fat embolism (33.3%) and pulmonary hypertension (33.3%), with right ventricular hypertrophy (33.3%). Therefore, we propose a simple and high-yield autopsy algorithm of ancillary procedures that should be applied on all known and suspected autopsy cases of sickle cell disease.     

Lethal manifestations of systemic lupus erythematosus in a forensic context

Systemic lupus erythematosus is an autoimmune connective tissue disorder that affects multiple organs. While the clinical manifestations may vary in intensity over time and be associated with chronic disease, occasional cases occur where sudden and unexpected death has occurred. Cardiovascular disease is common, with accelerated atherosclerosis, intravascular thrombosis associated with antiphospholipid syndrome, and hypertensive cardiomegaly. Vasculitis with superimposed thrombosis may result in critical reduction in blood to vital organs, such as the heart and brain with infarction. Mesenteric ischemia may be caused by vasculitis, thrombosis, and accelerated atherosclerosis and may result in lethal intestinal infarction. Other diverse causes of sudden death include myocarditis, epilepsy, pulmonary hypertension, pulmonary thromboembolism, and sepsis. The autopsy evaluation of such cases requires careful examination of all organs with extensive histological sampling to include blood vessels, and microbiological sampling for bacteria, viruses, and fungi.     

An autopsy case of intraoperative death due to pulmonary fat embolism—possibly caused by release of tourniquet after multiple muscle-release and tenotomy of the bilateral lower limbs

We report a case of a juvenile male with muscle rigidity caused by cerebral palsy who experienced intraoperative sudden death due to pulmonary fat embolism after multiple muscle-release and tenotomy of the bilateral lower limbs. Data were obtained through review of the surgical and anesthesia records, as well as from autopsy and histopathological examination. All surgical procedures were performed within the same operation, beginning with the right lower limb and then proceeding with the left lower limb, with application of a pneumatic tourniquet to avoid intraoperative hemorrhage. Slight changes in the hemodynamics were noticed after release of the right tourniquet. Further, sudden onset of hypotension, severe bradycardia, and a marked decrease in percutaneously monitored oxygen saturation occurred just after release of the left tourniquet when the left limb was raised for casting. The patient died despite immediate and vigorous cardiopulmonary resuscitation. At autopsy performed 20 h after death, examination of the lungs revealed a pale surface, slight edema, and obvious fat droplets in the vessels at the cut surfaces. Histopathological examination with fat staining was notable for the presence of pulmonary fat embolism. These results suggest that restoration of venous return after removal of the tourniquet combined with massive fat embolism from dead spaces was the likely cause of death.     

Pulmonary embolism: a rare cause of sudden infant death

Pulmonary embolism can be observed at any age, but it occurs very rarely in the infant. The authors report the case of a 12-month-old boy who suddenly died during clinical improvement of gastroenteritis associated with otitis. Autopsy showed signs of dehydration and acute left pulmonary embolism, which was the cause of death. Thrombosis of the inferior vena cava extending into renal veins was seen. In this case, plasma hyperosmolality caused by dehydration might have favored the formation of venous thromboses. The various risk factors of pulmonary embolism in the child are discussed, including genetic factors.     

Sudden and Unexpected Death in Three Cases of Ehlers‐Danlos Syndrome Type IV*

Abstract: Ehlers–Danlos syndrome (EDS) type IV is a connective tissue disorder characterized by the inability to produce sufficient amounts of collagen or a defect in the structure of collagen. The most serious complications include a rupture of a viscus or vascular rupture with or without mural dissection. Death may result from internal hemorrhage. This report describes three cases of sudden and unexpected death caused by EDS type IV. Two cases involved hemothorax as a result of dissection of the subclavian artery and aorta, respectively. The third case represented spontaneous pulmonary rupture and hemorrhage. A detailed family history should be sought, and additional specimens collected to confirm the diagnosis, including skin fibroblasts for collagen testing and blood for DNA testing. The forensic pathologist should consider the possibility of EDS type IV upon discovery of spontaneous visceral or arterial rupture and should alert the family members of this hereditary and potentially fatal condition.     

脂肪栓塞中苏丹Ⅲ染色的定量分析

目的探讨苏丹Ⅲ染色如何定量应用于脂肪栓塞的法医学鉴定。方法应用苏丹Ⅲ对11例肺脂肪栓塞猝死的案例和11例其他原因致死的案例进行染色,并结合统计学方法对脂肪栓塞的阳性面积百分率及脂肪栓子数进行定量分析。结果脂肪栓塞致死者肺内苏丹Ⅲ染色阳性面积百分率为（5±1．7）％、脂肪栓子数为（9±2．4）％,均远大于其他原因致死的案例（P〈0．01）。结论苏丹Ⅲ染色法定量分析在脂肪栓塞中的法医学鉴定上结果可靠。     

Unexpected sudden death from coronary sinus thrombosis. An unusual complication of central venous catheterization

Coronary sinus thrombosis is an unusual but potentially serious complication of the use of central venous devices. We report a fatal case of coronary sinus thrombosis in relation to a malpositioned central venous catheter. The death occurred very soon following the beginning of symptoms and the cause could not be suspected. Direct trauma of the catheter on the coronary sinus endothelium seems the most probable cause of the thrombosis.