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.     

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.     

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.     

An unusual case of fatal gas embolism.

We describe an unusual case of fatal gas embolism, in which a man died by connecting an extension tube supplying oxygen to an indwelling catheter that was inserted into the left cephalic vein.     

Fatal pulmonary thromboembolism and hereditary thrombophilias

Pulmonary thromboembolism (PE) is found commonly in forensic pathology practice, as it typically causes sudden death. It is attributed to a wide variety of predominantly acquired etiologies. Although likely etiologically multifactorial, some common proximate causes include: surgery, pregnancy, injury, inactivity of any cause, cancer, obesity, or serum hyperviscosity. On occasion, no apparent predisposing condition is identified. In these instances, occult hereditary thrombophilias may play a causal role. Deaths referred to the Office of Chief Medical Examiner (OCME) of New York City between December, 2000 and September, 2003 and due to PE were retrospectively reviewed. Molecular analysis (FRET) was performed on selected cases for three common hereditary thrombophilias: mutations in factor V Leiden (FVL), prothrombin G20210A (PT), and methylenetetrahydrofolate reductase (MTHFR).During the study period, 124 of 15,280 deaths were primarily attributable to PE. Of those, 34 were selected for molecular analysis. One or more mutations were detected in 35% of those, five of which were clearly causally related to death. Given the potential benefits to surviving family members, our data indicate that postmortem molecular testing for the common hereditary thrombophilias is warranted in at least selected cases.     

Medical devices; hematology and pathology devices; classification of the Factor V Leiden DNA mutation detection systems devices. Final rule

The Food and Drug Administration (FDA) is classifying the Factor V Leiden deoxyribonucleic acid (DNA) mutation detections systems device into class II (special controls). The special control that will apply to the device is the guidance document entitled "Class II Special Controls Guidance Document: Factor V Leiden DNA Mutation Detection Systems." The agency is taking this action in response to a petition submitted under the Federal Food, Drug, and Cosmetic Act (the act) as amended by the Medical Device Amendments of 1976 (the 1976 amendments), the Safe Medical Devices Act of 1990 (SMDA), the Food and Drug Administration Modernization Act of 1997 (FDAMA), and the Medical Device User Fee and Modernization Act of 2002. The agency is classifying this device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device. Elsewhere in this issue of the Federal Register, FDA is publishing a notice of availability of a guidance document that is the special control for this device.     

Fatal intoxications in a Swedish forensic autopsy material during 1992-2002

Compilations of substances detected in fatal intoxications are important in order to observe changes in intoxication patterns, to monitor effects of preventive work and to discover new trends in drug usage. The aim of the present study was to describe the current pattern of substances detected in fatal intoxications in Sweden. Fatal intoxications investigated at the Department of Forensic Chemistry, Link?ping, Sweden, during 1992-2002, were analysed. All suicides, uncertain cases and accidents where the cause of death were fatal intoxications (ICD-9: E950, E980 and E859) were included and substances detected in more than 50 fatal intoxications (in femoral blood) were listed. For each substance, a cut off value was set, above which concentrations were considered toxic. Fatal intoxications were detected by forensic-chemical analyses in 12% (6998/60,314) of the forensic autopsies during the study period. Among the suicides, an average of 3.8 substances were detected per case, the corresponding figure for uncertain cases and accidents were 3.5 and 4.1 substances, respectively. Ethanol was by far the most frequently detected substance, detected in 43% (3039) of the fatal intoxications, of which 32% (960) had toxic concentrations, followed by propoxyphene, detected in 27% (1863) of the fatal intoxications of which 74% (1370) had toxic concentrations. The number of cases where ethanol and propoxyphene were detected decreased during the study period. Moreover, other CNS-active drugs such as antidepressants, analgesics and anxiolytics were also frequently detected. The drugs with high proportions of cases with toxic concentrations detected were propoxyphene, amitriptyline, zolpidem, carisoprodol, alprazolam, thioridazine, methadone and ketobemidone. Selective serotonin reuptake inhibitors (SSRI) and tricyclic antidepressants (TCA) were detected in 12% (833) and 10% (665), respectively. A significantly (P <0.001) higher proportion of cases where TCA were detected had toxic concentrations when compared with cases where SSRI were detected (64% versus 31%).     

Massive systemic silicone embolism: a case report and review of literature

Subcutaneous injections of inert or quasi-inert plastic material designed to smooth out wrinkled skin or to create a more esthetically sought appearance have become very popular with the American public in general, and, in particular, with certain groups highly focused on their physical image. The case of the injection procedure has attracted into the field of plastic medicine a substantial number of illegal, incompetent, and unscrupulous operators. Their ignorance of involved medical risks and procedures not uncommonly results in severe complications, disfigurement, and death of patients. We report the typical pathological and chemical findings of a systemic fatal silicone embolism in a 53-year-old heterosexual woman following illegal chronic injections of silicone in her hips and buttocks. The injected subcutaneous silicone apparently migrated rapidly from the interstitial subcutaneous tissue into the general blood stream resulting in a fatal systemic silicone embolism. An analysis of the presented case in conjunction with a review of the pertinent medical literature, including a recent article, revealed a marked similarity in the clinicopathologic findings between silicone embolism and fat embolism.     

Widespread myocardial and pulmonary bone marrow embolism following cardiac massage.

Widespread fatal massive bone marrow embolism of the coronary and the pulmonary arteries are described in a 71-year-old man with a respiratory disease. Cardiac massage was carried out during the cardiac arrest. In autopsy findings there were no fractures of the ribs or the sternum. The authors suggested that the cardiac massage was the most important predisposing factor for the bone marrow embolism.     

肺动脉栓塞猝死的法医病理学检验

对５０例肺动脉栓塞猝死案例分析,结果显示：引起肺动脉栓塞猝死的主要原因为创伤（４２％）,心脏疾病（３２％）,外科手术（２０％）等。血栓栓子多来源于下肢静脉（８０％）;其次为心腔内附壁血栓（２０％）。发生猝死高峰季节为１０～１２月;低峰季节为４～６月。猝死场所多见于医院内。最后提出了该病的法医学鉴定注意事项     

Air embolism following arthroscopy--autopsy findings and forensic medicine aspects

An iatrogenic cause of air embolism with a fatal outcome is reported that occurred in a case in which arthroscopy of the knee had been carried out. Even after worldwide use of arthroscopy for many years, this complication has never been seen until now. At autopsy, when air bubbles were observed in the right heart chamber and in the vena cava inferior, only the knee joint was taken into consideration as the air-access route. The access of air was detected by means of arthroscopy on the corpse, combined with a special autopsy technique and shown experimentally. Insufflated air had entered via a fracture of the tibial articular surface and then passed through the spongiosa into the femoral vein. These findings are of far-reaching clinical consequence because the indication for arthroscopy by gas insufflation must be reconsidered again. Finally, the medicolegal aspects of such an incident are discussed.     

Activated protein C resistance is uncommon in sudden death due to pulmonary embolism

Activated protein C resistance (APC-R) is the most common inherited defect of the coagulation system known to date, affecting 3-5% of Americans. It is an autosomal dominant disorder associated with an increased risk of venous thrombosis and is reportedly found in 21% of individuals with deep venous thrombosis. Medical examiners are in a unique position to make the diagnosis since a fatal pulmonary embolism may be the first manifestation of the disorder. This study examines the prevalence of APC-R in individuals who die suddenly of pulmonary embolism to help medical examiners decide if routine testing is indicated. We examined 66 cases of sudden death due to pulmonary embolism seen at the Bexar County Forensic Science Center in San Antonio, Texas, from 1993-1997. The median age was 46 years with a range of 14 to 93 years. Fifty-three percent were Caucasian, 24% were African-American, and 23% were Hispanic. Twenty-seven percent had no known risk factors for pulmonary embolism. Whole blood was tested for the factor V codon 506Q mutation responsible for APC-R using polymerase chain reaction. The prevalence of APC-R was 4.5%, which is similar to the prevalence of APC-R in the general American population. These data imply that individuals with APC-R are not in increased risk for sudden death due to pulmonary embolism, or, conversely, that most fatal pulmonary emboli seen in the medical examiner setting are not induced by APC-R. Routine postmortem testing for the factor V 506Q mutation does not appear indicated at this time, given the low prevalence and high cost of testing.     

α-纤维蛋白原基因多态性与肺动脉栓塞相关性初探

目的探讨α-纤维蛋白原Thr312Ala基因的多态性分布与肺动脉栓塞的相关性。方法选取尸检已确诊的肺动脉栓塞病例的甲醛固定心肌组织14例和正常健康人群外周血56例,采用改良酚-氯仿法和Chelex100法分别提取心肌组织和外周静脉血基因组DNA,用PCR-RFLP法检测α-纤维蛋白原基因Thr312Ala多态性,并分析其与肺动脉栓塞的关联性。结果α-纤维蛋白原Thr312Ala基因的各基因型在肺动脉栓塞组与对照组比较差异具有显著性意义（P〈0.05）;各等位基因在两组间比较差异具有显著性意义（P〈0.05）;A等位基因与PE呈负相关（RR=0.475,P〈0.05）;G等位基因与PE呈正相关（RR=5.818,P〈0.05）。结论α-纤维蛋白原基因Thr312Ala位点G等位基因与肺动脉栓塞有正关联,肺动脉栓塞死亡者中GA、GG基因型分布频率较高,本文数据可为相关研究提供参考。     

新疆地区66例多类型栓塞死亡法医学尸检分析

总结分析不同类型的栓子(血栓、脂肪、空气、羊水)栓塞致死的一般特点,探讨其法医病理学鉴定要点及注意事项.对2015～2021年在新疆医科大学司法鉴定所鉴定的66例栓塞致死案例进行回顾分析.经过研究分析,导致患者出现栓塞的因素较多,栓塞致死以肺动脉血栓栓塞多见,另外空气栓塞、羊水栓塞和脂肪栓塞也不容忽视,其均能导致呼吸、...     

An Autopsy Case of Acute Massive Hematochezia Caused by Superior Mesenteric Vein Thrombosis: A First Report in Forensic Medicine

Superior mesenteric vein thrombosis (SMVT) is an uncommon cause of intestinal ischemia and massive gastrointestinal bleeding. This report describes a man with alcoholic liver cirrhosis, who died of massive hematochezia due to SMVT. A medicolegal autopsy disclosed a thrombus at the superior mesenteric vein and hemorrhagic infarction of the bowel wall, an area also within the territory of the superior mesenteric vein. Liver cirrhosis, an enlarged spleen, and esophageal varices without rupture were also observed, but ulcers and variceal bleeding were not. Other organs showed no significant findings. His blood alcohol level was 0.14% w/v. Thus, this man died from severe hematochezia associated with SMVT due to liver cirrhosis and alcohol dehydration, which can lead to coagulopathy and rapid progress of thrombus formation. This is the first report on an alternate cause for massive gastrointestinal hemorrhage with a cirrhotic patient in a forensic autopsy.     

中国北方汉族人群FUT6基因3个SNPs遗传多态性

目的对中国北方汉族人群FUT6基因编码区序列特征及等位基因多态性进行调查。方法测序分析30例中国北方汉族人FUT6基因整个编码区序列并鉴定其单倍型,采用复合PCR与复合限制性内切酶结合的RFLP法分析FUT6基因rs778805（C370T）、G855A及rs61147939（C907G）3个SNPs遗传多态性;应用Haploview4.1软件进行相关统计分析。结果 30例测序样本中共检出8个SNPs和6种单倍型,149例中国北方汉族个体C370T、G855A、C907G基因型分布均符合Hardy-Weinberg平衡。杂合度分别为0.544、0.416、0.510;多态信息含量为0.375、0.372、0.367;个人识别能力为0.600、0.651、0.603;非父排除率为0.187、0.186、0.183。PCR-RFLPs检出13种基因型,单倍型变异度为0.646。Haploview4.1软件分析表明3个SNPs处于连锁不平衡状态。结论中国北方汉族人群FUT6基因编码区序列呈现出高度多态性;C370T、G855A、C907G位点多态性分布良好,但处于连锁不平衡状态。     

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.     

Fat Transfer and Fatal Macroembolization

Fat embolism is usually associated with long bone fractures or other trauma. The diagnosis is usually clinical, and in most cases, emboli are not fatal and not usually seen on gross examination. At the Los Angeles County Coroner's Office, we autopsied the victim of fatal macroscopic fat embolization to the lungs. The patient died during buttock enhancement surgery when fat from liposuction was injected into her buttocks. Fat embolism from liposuction and fat injection is reportedly rare, and macroscopic embolization is rarer still. Varicose veins can occur in the area of the sciatic notch and are known to cause painful sciatica symptoms. We suggest them as a potential conduit for macroscopic fat to reach the lungs. Simple pre‐operative questioning for sciatica symptoms and possible radiologic study to rule out sciatic varices seem prudent before undertaking buttock‐enhancing surgery. Careful fat injection with pre‐aspiration is always advised.     

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.