Mallory-Weiss syndrome

A Study of 45 Medicolegal Autopsy Cases

* Context.-Some autopsy studies have dealt with histologic features of esophageal varices after different therapeutic procedures. However, to the best of our knowledge, no reports have been published describing outpatient characteristics that are associated with fatal esophageal variceal hemorrhage in a medicolegal autopsy population.

Objectives.-To (1) assess the incidence of sudden deaths from esophageal variceal hemorrhage in an unselected medicolegal autopsy population and (2) determine demographics of outpatients dying from esophageal variceal hemorrhage with special reference to blood alcohol concentrations at the time of death.

Design.-We performed a retrospective study of all autopsy cases of sudden death from esophageal variceal hemorrhage from a total of 6038 medicolegal autopsies performed over a 5-year period (1997-2001). We analyzed individual cases to determine gender, age, location and histology of bleeding esophageal varices, pathogenic mechanism for esophageal varices, concomitant underlying diseases contributing to fatal outcome, body mass index, circumstances at the death scene, and blood alcohol levels at the time of death. We reviewed the results of toxicologic analyses of alcohol concentrations in samples of femoral venous blood and urine obtained at autopsy; concentrations had been determined by gas chromatography with mass spectroscopy and enzymatic assays.

Results.-We identified 45 cases of fatal esophageal variceal hemorrhage that occurred out of hospital and presented as sudden death; the corresponding 5-year inci

dence in this autopsy population was 0.75%. All of the deceased were white; the male-female ratio was 1.61, and the mean age was 50.6 years. Ruptured esophageal varices were located in the lower third of the esophagus in 44 cases. Cirrhosis of the liver was present in all cases (alcoholic cirrhosis of the liver in 42 cases), and a hepatocellular carcinoma was present in 3 cases. Alcohol-induced pancreatic tissue alterations were frequently found. The results of toxicologic analysis were positive for alcohol in femoral venous blood and urine in 30 cases. Blood alcohol levels at the time of death were less than 100 mg/dL (21.7 mmol/L) in 15 cases, between 100 and 200 mg/dL (21.7 and 43.4 mmol/L) in 8 cases, and greater than 200 mg/dL (43.4 mmol/L) in the remaining 7 cases.

Conclusions.-,Apart from abnormalities in coagulation due to poor liver function in long-term alcohol users, acute alcohol intake may represent an important factor influencing mortality in individuals with esophageal variceal hemorrhage. Acute alcohol intake has transient effects on blood clotting time caused by ethanol and its main metabolites. In the present study, bloodstains at the death scene and unusual body positions of the deceased that aroused suspicion of a violent death were leading reasons for conducting a medicolegal autopsy. Apart from aspects of forensic pathology, the demographics of our study population are also noteworthy from the viewpoint of social medicine. The data we present stress the importance of fatal esophageal variceal hemorrhage as a relevant cause of sudden death occurring outside the hospital in socially isolated, alcohol-addicted individuals.

(Arch Pathol Lab Med. 2002;126:1197-1200)

Esophageal variceal hemorrhage is a life-threatening complication of portal hypertension associated with a mortality rate significantly higher than that of other causes of gastrointestinal bleeding. Although a large number of clinical studies have dealt with the clinical management, prognosis, and prophylaxis of bleeding esophageal varices, a paucity of autopsy studies have addressed the topic. These studies have focused primarily on the chronologic sequence of pathomorphologic and angioarchitectural changes of the esophageal wall after endoscopic injection sclerotherapy or band ligation of esophageal varices in inpatients.2-6

To the best of our knowledge, no reports have been published regarding the medicolegal aspects of fatal esophageal variceal hemorrhage in outpatients. Therefore, the present study was conducted (1) to assess the number of sudden, unexpected deaths from esophageal variceal hemorrhage in an unselected medicolegal autopsy population and (2) to determine the demographics of outpatients dying from esophageal variceal hemorrhage with special reference to blood alcohol levels at the time of death.

MATERIALS AND METHODS

We retrospectively reviewed charts for 6038 autopsies performed at the Institute of Legal Medicine, University of Hamburg, Germany, for the years 1997-2001 to identify outpatient deaths due to esophageal variceal hemorrhage presenting as sudden, unexpected death. We analyzed individual cases to determine gender, age, location and histology of bleeding esophageal varices, pathogenic mechanism of esophageal varices, concomitant underlying diseases contributing to the fatal outcome, body mass index (BMI), blood alcohol levels at the time of death, findings on external examination of the deceased (eg, blood smears resulting from hematemesis or melena), and circumstances at the death scene.

A microscopic examination of the esophageal variceal rupture site was performed in each case to rule out potential differential diagnoses or concomitant underlying disorders as the source of esophageal hemorrhage.

We calculated BMI using the formula BMI = weight/height^sup 2^, where weight is expressed in kilograms, and height is expressed in meters.7,8 The subjects were classified as underweight (BMI, 30 kg/m^sup 2^).9

In each case, samples of femoral venous blood and urine obtained at autopsy were toxicologically analyzed to determine alcohol concentrations. The samples were stored refrigerated in plastic tubes without preservatives until further processing within 24 hours. The samples were analyzed using a full complement of analytic methods for determination of alcohol concentrations, including gas chromatography with mass spectroscopy and enzymatic (alcohol dehydrogenase-specific) assays.

In addition, we performed a MEDLINE search of the literature published from 1995 to 2001 using the keywords sudden death, gastrointestinal hemorrhage, exsanguination, alcoholism, and coagulation alone and in combination. We procured any article considered relevant to the subject. Bibliographies in the articles provided further references. In this article, we discuss only studies with more than 20 cases.

RESULTS

Study Population

We identified 45 cases of fatal hemorrhage from esophageal varices presenting as sudden, unexpected death; the corresponding 5-year incidence in our medicolegal autopsy population was 0.75%. All 45 individuals were white. There were 28 men and 17 women (male-female ratio, 1.6: 1), and the age of the deceased ranged between 24 and 72 years (mean age overall, 50.6 years; mean age of men and women, 48.7 and 53.7 years, respectively). All 45 deaths occurred outside of a hospital; therefore, data on the previous medical history or medication use before death were limited in the majority of cases. Based on information obtained from family members and witness reports from police files, we were able to establish a history of chronic alcohol use in 42 cases (93%); in 1 case, acute alcohol use just before death was witnessed by a family member. According to the available official reports, at least 31 persons (69%) had lived socially isolated and had no close contact with family or neighbors.

External Examination of the Deceased and Circumstances at the Death Scene

At external examination, blood smears on the body surface resulting from hematemesis or melena were present in 40 cases. At the death scene, blood stains on furniture, carpets (Figure 1), or personal belongings were documented in 13 cases, and body positions arousing suspicion (Figure 2) were seen in 9 cases.

Autopsy Findings

In the overwhelming majority of cases (44 cases), the ruptured esophageal varices were located in the lower third of the esophagus or in the esophagogastric junction. In 1 case, the rupture site was located in the middle third of the esophagus. Mallory-Weiss syndrome was ruled out macroscopically.

Cirrhosis of the liver was present in all cases. Alcoholic cirrhosis of the liver was present in the 42 cases with a known history of chronic alcohol consumption. Other forms of cirrhosis were present in 3 cases (hepatitis, 2 cases; unknown origin, 1 case). A hepatocellular carcinoma was found in 3 cases, and splenomegaly was found in 11 cases. Fibrosis of the pancreas was present in 13 cases, chronic pancreatitis was present in 4 cases, and acute pancreatitis was present in 3 cases.

Death was attributed to hemorrhagic shock due to ruptured esophageal varices in 37 cases. In 8 cases (5 men, 3 women; age, 26-66 years), death was attributed to a combination of exsanguination and other concomitant diseases contributing to the fatal outcome. The concomitant diseases were decompensated diabetes (5 cases), bronchopneumonia (1 case), dilated cardiomyopathy (1 case), and acute hemorrhagic pancreatitis (1 case).

Histology

Esophageal varicosis, indicated by an excessive number of dilated submucosal veins, was present in all cases. Apart from mild to moderate autolysis of the esophageal mucosa, we detected no pathologic mucosal conditions such as peptic ulceration, esophagitis, inflammation at the rupture sites, atrophy-related alterations, vascular malformations, or tumorous lesions as the source of esophageal hemorrhage. In a large number of cases, the rupture sites were predominantly located subepithelially and could be identified by means of serial sections of the esophageal wall (Figure 3).

Body Mass Index

We were able to calculate BMI for 42 cases. Two subjects were classified as underweight, 28 subjects were of normal weight, 9 subjects were overweight, and 3 subjects were obese.

Blood and Urine Alcohol Levels

The results of toxicologic analysis were positive for alcohol in femoral venous blood and urine in 30 cases (67%). Blood alcohol levels at the time of death were less than 100 mg/dL (21.7 mmol/L) in 15 cases, between 100 and 200 mg/dL (21.7 and 43.4 mmol/L) in 8 cases, and greater than 200 mg/dL (43.4 mmol/L) in the remaining 7 cases.

COMMENT

In this study, we retrospectively investigated 45 medicolegal autopsy cases of sudden death from esophageal variceal hemorrhage occurring out of hospital. Esophageal varices represent the most important complication of portal hypertension and arise from the opening of portosystemic collaterals as an adaptation to decompress the portal venous system. It is well established that alcoholic liver cirrhosis is the primary factor in the pathophysiology of portal hypertension. Cirrhosis was present in all 45 cases in this study. Alcoholic cirrhosis of the liver was present in 42 cases, and a hepatocellular carcinoma was found in 3 cases. These findings support the current clinical concepts that alcoholic liver cirrhosis is associated with a significantly higher risk of variceal bleeding than is cirrhosis arising from other causes,10 and that the prognosis for an individual patient, depending on the severity of the bleeding episode and underlying liver function, is generally poor in patients with established cirrhosis and hepatocellular carcinoma.11

In clinical studies, controversy exists about the percentage of upper gastrointestinal hemorrhages that result from esophageal variceal bleeding. Although some reports indicate that variceal bleeding accounts for 11% to 20% of all upper gastrointestinal bleedings,12-14 other studies suggest that ruptured esophageal varices are responsible for 50% to 80% of upper gastrointestinal bleeding episodes.15,16 With the observed frequency of 0.75% of all deaths encountered in a medicolegal autopsy population over a 5-year period, fatal esophageal variceal bleeding accounts for a larger proportion of out-of-hospital deaths than previously assumed.17,18

In a recent study, we showed that the number of fatal gastrointestinal hemorrhages in younger individuals occurring out of hospital is likely to be underestimated from the clinical viewpoint due to the underrepresentation of such cases in the field of clinical pathology.19 The present results clearly support this assumption. With a mean age of 50.6 years, the outpatients that we studied are substantially younger than the inpatients presenting with acute esophageal variceal hemorrhage, since a recent clinical cohort study found that the mean age of inpatients was 56 years.20 These disparate results can in fact be explained by a selection bias, since the deaths of younger individuals taking place out of hospital are more often subjected to a medicolegal autopsy than are the deaths of older individuals that occur more often inside hospital.

Several factors may promote bleeding from esophageal varices, including clinical factors, such as endoscopic, hemodynamic, and sonographic factors, and physical factors, such as intravariceal pressure and elastic properties of the varices.1,21 Clinical factors associated with an increased risk of variceal bleeding include poor liver function and continuing alcohol abuse.2,7,22,23 Poor liver function contributes to abnormalities in coagulation via chronic inadequate hepatic synthesis of coagulation factors; continuing alcohol abuse leads to progressive liver cirrhosis, with progressively increasing portal hypertension on the one hand, and further deterioration of liver function on the other.

In this study, we documented the presence at autopsy of morphologic alterations of internal organs induced by chronic alcohol consumption, such as alcoholic cirrhosis and pancreatic tissue alterations. However, we also focused on individual blood alcohol levels at the time of death. Traces of alcohol were detected in femoral venous blood and urine in 30 cases (67%). Blood alcohol levels at the time of death were less than 100 mg/dL (21.7 mmol/ L) in 15 cases, between 100 and 200 mg/dL (21.7 and 43.4 mmol/L) in 8 cases, and greater than 200 mg/dL (43.4 mmol/L) in 7 cases. We assume that apart from the wellestablished abnormalities in coagulation in chronic alcohol abusers (namely an increased risk of bleeding episodes due to inadequate hepatic synthesis of coagulation factors), our data raise the possibility that the transient effects of acute alcohol intake (eg, thrombocytopenia, increased whole blood clotting time, and inhibition of collagen-induced platelet aggregation caused by ethanol and its main metabolites24-27) may be important factors influencing mortality. Notwithstanding the fact that this assumption is derived from a postmortem study, we theorize that in some of the cases investigated in this study, the acute influence of alcohol additionally altered coagulation and promoted the fatal outcome of esophageal variceal hemorrhage.

From the medicolegal point of view, we emphasize that blood stains at the death scene (Figure 1) and unusual body positions of the deceased (Figure 2) that arouse suspicion of a violent death (eg, preceding blunt force) were one of the leading causes for conducting a medicolegal autopsy in the present series of fatal esophageal variceal hemorrhage. Apart from aspects of forensic pathology, the demographics of our study population are also noteworthy from the viewpoint of social medicine, since at least 31 individuals (69%) lived in social isolation, and 42 individuals (93%) had a history of chronic alcohol consumption confirmed by autopsy findings. In bringing such deaths and the social setting to light, the field of legal medicine reflects the society of a special region.

By nature, medicolegal autopsy studies analyzing sudden death in outpatients often lack detailed information about the clinical picture preceding death; therefore, conclusions of these studies are based mainly on autopsy findings and police reports. We are unable to comment on the study subjects' medical histories and symptoms before death, and many new therapeutic options established during the last decades are able to control variceal bleeding with primary success rates of up to 97%.28-34 Nonetheless, the data presented here stress the importance of fatal esophageal variceal hemorrhage as a relevant cause of sudden death occurring outside the hospital in socially isolated, alcohol-addicted individuals.

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M. Tsokos, MD; E E. Turk, MD

Accepted for publication May 20, 2002.

From the Institute of Legal Medicine, University of Hamburg, Hamburg, Germany.

Reprints: M. Tsokos, MD, Institute of Legal Medicine, University of Hamburg, Butenfeld 34, 22529 Hamburg, Germany (e-mail: mtsokos@web.de).

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