Complex Death Associated with Intra-Hospital Adverse Events and SARS-CoV-2 Pneumonia: Court-Appointed Medico-Legal Evaluation

Abstract

Background: Among the deaths recorded during the COVID-19 pandemic, some were caused by clinical manifestations of venous thromboembolic disease, mainly pulmonary embolism. Several litigations were settled worldwide for professional malpractice associated with COVID-19 and anticoagulant therapy management. The authors aimed to discuss, as court-appointed consultants in civil court, a case settled for compensation against a healthcare facility associated with SARS-CoV-2 infection. Case report: We described the case of an old patient in therapy with a direct oral anticoagulant for thrombotic diathesis, hospitalized for COVID-19 pneumonia, who died after two intra-hospital adverse events influencing coagulation imbalance. Discussion: Two health professionals’ malpractice hypotheses were discussed related to the adverse events’ occurrence: one related to the administration of an enema, resulting in rectal perforation, and the other related to proper anticoagulant prophylaxis and comprehensive coagulation imbalance management after the rectal perforation in a patient at high risk of venous thromboembolic disease. Intra-hospital adverse events complicated the hospitalization and then significantly reduced the concrete possibility, even uncertain in terms of time and extent, of the patient’s living longer, representing the damage of reduced possibilities of survival, also called loss-of-chance damage. Conclusions: The case discussed as court advisors, characterized by clinical and legal complexity, together with SARS-CoV-2 infection, underscores the vital role of forensic examiners in cause-of-death ascertainment and as interpreters of statistical-probabilistic data according to naturalistic, logical, and scientific criteria.

1. Introduction

Between 2020 and 2022, and subsequently in 2023, a large body of scientific literature was published on the COVID-19 pandemic and its coagulative consequences. Many studies have focused on coagulation changes, particularly those associated with vaccines, such as RNA vaccines [1,2]. During the pandemic, venous thromboembolic disease (VTE), with its clinical manifestations, particularly pulmonary embolism, represented a significant cause of death [3,4,5]. A tendency toward hypercoagulability was observed, initially attributed to the effects of disseminated intravascular coagulation and platelet activity, partly due to increased fibrinogen degradation products resulting from fibrinolysis [6,7,8]. However, the COVID-19-related increased thrombogenic tendency was associated with the activation of immune response mediators to the infection and partly to direct endothelial damage, leading to increased platelet activation and aggregation [6,7,9]. Higher levels of D-dimer were detected in most patients and were associated with increased mortality in hospitalized patients [10,11]. Additionally, increased thrombin synthesis, along with higher plasma concentrations of factors V and VIII and the von Willebrand factor, was documented [12]. Individual risk factors, such as age and patient comorbidities, as independent hospitalization-related factors, and anticoagulant prophylaxis also influenced VTE-related mortality [13,14]. Studies on thrombotic alterations come also from autopsy findings, even with several difficulties in performing them [15,16,17,18]. In addition, partly because of the high number of deaths and because of the social and media impact of the pandemic and its health management, many criminal and civil lawsuits have been filed based on health malpractice hypotheses, in particular concerning coagulation management related to COVID-19 [19,20,21].

The authors discuss the evaluation accomplished as court-appointed consultants in civil court. The lawsuit was settled for damage compensation against a healthcare facility for a patient admitted for SARS-CoV-2 pneumonia who died after two intra-hospital adverse events, questioning two health professionals’ malpractice hypotheses related to coagulation imbalance.

The case we present is of particular interest due to the medico-legal implications regarding severe intra-hospital adverse events. Moreover, it emphasizes the importance of the clear definition of factors and their contribution to the process leading to death during the COVID-19 pandemic, also for the purpose of avoiding the excessive attribution of deaths to SARS-CoV-2 infection [22,23,24].

2. Case Report and Case Law

A patient (>85 years old) was admitted in November 2020 to a university hospital in Northern Italy. This was during the second wave of the COVID-19 pandemic; vaccines had just become available for vulnerable individuals, but the vaccination campaign for the at-risk population would start in December 2020. The patient lived alone and in complete self-sufficiency at home. Following occasional contact with a positive relative, the patient exhibited high fever and dyspnea. Transported to the emergency room, bilateral SARS-CoV-2-related bronchopneumonia was diagnosed by a chest CT scan and a nasopharyngeal swab. The patient was already taking rivaroxaban, a direct oral anticoagulant (DOAC), for post-phlebitic syndrome of the lower limbs and for previous episodes of peripheral pulmonary embolism. Comorbidities were arterial hypertension, chronic obstructive pulmonary disease (COPD), and polyarthritis.

Upon admission, respiratory failure was present, with an increased alveolar–arterial oxygen gradient (A–a gradient = 47; normal value < 27) and a decreased ratio of partial pressure of arterial oxygen (PaO₂) to fraction of inspired oxygen (FiO₂) on arterial blood gas analysis. PaO₂ was 58.8 mmHg, and PaCO₂ was 35 mmHg in room air (FiO₂ = 20%). The laboratory tests for the coagulation profile are presented in

Table 1. Laboratory parameters of the coagulation profile.

	Normal Value	Day 0	Day 4	Day 5	Day 9	Day 10
Red blood cells	3.85–5.20 × 1012/L	4.35	4.01	3.69	4.26	4.32
Hemoglobin	11.8–15.8 × g/dL	12.8	13.5	12.3	13.5	13.7
Prothrombin time (PT) ratio	<1.20	1.50	1.03	1.10	1.06	1.10
Prothrombin time (PT) international normalized ratio (INR)	<1.20	1.52	1.04	1.10	1.07	1.10
Activated partial thromboplastin time (aPTT) test	0.82–1.25	2.10	1.08	1.06	0.94	1.00
Platelet count	160–370 × 109/L	145	192	262	393	405
D-dimer	<0.55 mg/L	_	_	15.75	_	_

.

After the administration of anti-inflammatory therapy (dexamethasone 6 mg and acetaminophen 1 g) and the increase in FiO₂ to 40%, the patient’s respiratory parameters improved, and she was hospitalized in the medical ward, with an oxygen blood saturation (SpO₂) of 98%. Home DOAC therapy was continued, with the prescription of dexamethasone 6 mg, pantoprazole 40 mg, broad-spectrum antibiotic ceftriaxone 2 g, and acetaminophen as needed.

Clinical improvement was observed after three days of hospitalization, until the administration of a cleansing enema on the fourth day, complicated with rectal perforation. The lesion was low and extraperitoneal and presented with rectal bleeding. In the absence of signs of peritonitis, a monitoring and wait-and-see approach was adopted, stopping the feeding and replacing the antibiotic with piperacillin and tazobactam; rivaroxaban was discontinued and replaced with a low-molecular-weight heparin, enoxaparin, at a dosage of 4000 IU twice daily, in the 60 kg patient, planned for the next day. However, due to quick clinical deterioration, enoxaparin was not administered on the fifth day, as the patient had to undergo surgery. According to clinical documentation, enoxaparin was administered on the fourth postoperative day (ninth day from admission) at a therapeutic dosage of 6000 IU twice daily, while there was no documentation regarding administration on the three postoperative days. Physical thrombosis prophylaxis measures, such as elastic stockings, were not used, and neither D-dimer monitoring nor lower-limb color Doppler ultrasound was performed in the surgically immobilized patient at high thrombotic risk. A week after surgery (twelfth day from admission), the patient died suddenly.

Clinical autopsy revealed diffuse peripheral pulmonary embolism, affecting medium- and small-caliber vessels of pulmonary circulation, with recent emboli alongside old thrombosis, with fibrotic interstitial thickening. Other relevant findings described were the consequences of recent bowel resection surgery, with colostomy and laceration of the rectum with apposition of a blood crust; mild myocardiosclerosis due to chronic ischemic heart disease was also reported.

The cause of death described by the pathologist was acute pulmonary embolism in chronic heart failure and recent intestinal resection for recent rectal perforation.

Based on these findings, the relatives initiated a civil claim against the healthcare facility, and a civil trial was settled, with the two authors (GB legal doctor and GP general surgeon) as court-appointed technical consultants. The judge ordered the healthcare facility to provide compensation based on this technical report, which examines the clinical case management, identifies the factors contributing to the death, assesses their relative impact, and defines the damage that can be attributed.

3. Discussion

3.1. Clinical Consultant’s Evaluation

Epidemiological data collected in Italy by the Health Ministry in 2023, covering the entire period of the COVID-19 pandemic, reported a mortality rate of 12.1% for individuals over 90 years old, significantly lower than the 20.2% reported in a study published in 2020 by Onder et al. [25,26]. Although higher, this rate was still lower than the peak of 29.6% reported by a Spanish group in a cumulative study that included over 600,000 cases recorded in various European countries, including Italy, as well as China and the state of New York, USA [12]. Analyzing these data showed that less than 20% of deaths occurred in individuals under 70 years old, indicating that age played a crucial role in determining the disease outcome, with 80% of the deaths occurring in individuals older than 70 years. Conversely, with a median mortality rate of 20%, the survival probability of individuals of the same age who contracted the disease at that time would have been 80% [27,28]. In other words, considering only age as a risk factor for mortality, even though the patient had already exceeded the average life expectancy in Italy [29], the patient lost the potential for recovery and an extended survival due to adverse events that occurred during hospitalization.

Considering risk factors related to comorbidities, particularly the thromboembolic condition, it is more plausible to assume that the survival rate would have decreased, with the mortality risk approaching the highest values observed during the pandemic, approximately 30%. Regardless of the outcome, looking merely at statistics, the probability of developing a pulmonary embolism during the pandemic would have ranged between 20% and 30% of patients, which would obviously have been higher in the presence of risk factors. Beyond individual factors, external adverse events unrelated to the patient’s clinical condition may have contributed to the development of pulmonary embolism and, ultimately, death. These include the iatrogenic rectal perforation caused by the enema, as well as inadequate thromboprophylaxis. In fact, for the rectal perforation and bleeding on the fourth day, a first wait-and-see phase imposed the modification of anticoagulant therapy, from rivaroxaban to the planned enoxaparin administration, on the fifth day. However, the contingent surgical indication on the fifth day necessitated the temporary discontinuation of pharmacological prophylaxis for pulmonary thromboembolism.

However, following surgery, patients are at higher risk of VTE, which is directly related to the length of surgery and the associated bed rest [30], and in this specific case, SARS-CoV-2 infection increased this risk. Clinical guidelines already available [31,32], and those published in 2020 based on the results of consensus conferences regarding the procoagulant effect of COVID-19 [33,34,35], recommended strict adherence to antithrombotic prophylaxis, through pharmacological and/or physical actions, and clinical-instrumental monitoring of the patient for the early identification of any symptoms of VTE.

In the case described the timing of prophylaxis resumption and its dosage on the following days were uncertain and, according to clinical records, absent until the ninth day. In fact, only from the third postoperative day, enoxaparin was administered, with the dose increased to 6000 IU twice daily. The interruption of the anticoagulant treatment, bed rest, the surgical approach, and the lack of alternative procedures for pulmonary thromboembolism prevention did not correspond to the clinical guidelines mentioned. In addition, no alternative physical measures to prevent thrombosis, such as intermittent compression of the lower limbs or the use of elastic stockings, were prescribed [36]. The absence of patient monitoring by repeating the D-dimer, mainly after the increased value found on the fifth after surgery, and color Doppler ultrasound of the lower limbs was also not in line with the best practice in preventing thrombotic risk in high-risk individuals.

3.2. Medico-Legal Consultant’s Evaluation

Regarding medico-legal implications, while considering age and comorbidities in this specific case, the natural course of the disease was altered by the two adverse events that occurred during hospitalization. Autopsy clearly identified the cause of death as acute pulmonary thromboembolism.

According to counterfactual reasoning, after analysis of the case, it cannot be said that death would have been avoided by diligent and prudent conduct. Even if the rectal perforation were excluded and anticoagulant therapy continued, the patient still had multiple risk factors for VTE: recent SARS-CoV-2 infection, a history of pulmonary thrombotic events, a recent surgical approach, and prolonged bed rest. Furthermore, the unpredictable and fluctuating course of COVID-19 symptoms is well documented [37,38]. As such, it can be argued that diligent behavior could have reduced the risk of pulmonary thromboembolism and thus affected only the chances of survival. It follows that no damage related to the death can be sustained.

In the discussed case, moreover, the effect of those prothrombotic factors—clinically and as a result of the malpractice—acted in a synergistic and multiplicative manner to produce the pulmonary embolism, which then led to the subject’s death. This further highlights the non-linearity of the events in the causal chain leading to death. However, it supports the difficulty in attributing to the rectal perforation—the event that changed the sequence of events in the clinical setting—the exclusive force in the determinism of death.

However, negligent conduct and superficial post-operative monitoring negatively impacted the subject’s life, squeezing the chances of better and longer survival.

Next, had the iatrogenic perforation of the rectum not occurred and had the antithromboembolic prophylaxis not been discontinued, the patient’s chances of surviving the consequences of SARS-CoV-2 infection would have been around 80%. Taking into account advanced age, along with other risk factors, such as those associated with comorbidities, and the risk for developing pulmonary embolism (even in the absence of perforation in a subject with a history of thromboembolism), this percentage should be adjusted to 70%. This significant possibility of survival—and not death, therefore—is causally attributable to the improper conduct and constitutes the harmful event.

The damage due to the reduced possibilities of survival or the loss of a chance of survival refers to the deprivation of the possibility of a hoped-for, albeit uncertain, better outcome, prolonged lifespan, or reduced suffering, resulting from the negligent conduct of healthcare professionals [39].

3.3. Clinical and Medico-Legal Synthesis

The loss of a chance of survival related to malpractice, compared to compensation for death related to the malpractice, has been recently clarified in the Italian context. Damage due to the loss of a chance of survival is the loss of a concrete and serious possibility, though uncertain in terms of time and extent, of living longer due to a health professional’s error, such as late diagnosis or improper treatment [40]. The loss of a chance of survival should be fairly compensated by the judge when there is an etiological link between the claimed inadequate conduct and the loss of the possibility of living longer. Compensation is warranted only where the lost chance is significant, logically recognizable, and realistic [39].

It follows that the task of the forensic doctor is to establish, after clarifying the death process and the presence of malpractice, a causal link with the reduction in the chances of survival. The forensic doctor must then assess whether the reduction in the chances of survival is relevant enough to be worthy of compensation.

In this type of damage, the main issue is precisely the reasoning on the naturalistic, logical, and scientific sequence of events and not simply the re-proposition of a probability percentage of survival into the probability of a causal link.

Similarly, in the most common scenario in medico-legal practice—a diagnostic and therapeutic delay in the treatment of a malignant tumor—the fact leading to death is often the progression of the neoplasm itself, while the effect of the delay due to malpractice is the negative influence on survival outcomes. Consequently, the loss of a chance of prolonged survival and the possibility of better prognosis is compared to the average survival rates observed in clinical trials to be transferred and weighed to the single case.

The iatrogenic perforation of the rectum had led to a reasonable anticipation of the patient’s death due to alteration of the functional balance (albeit fragile), to the prolonged bed rest required due to the surgical intervention with its prothrombotic effect, and, finally, to the inappropriate/lack of anticoagulant therapy and imprudent monitoring in a patient at high risk for pulmonary embolism.

The patient experienced worsening illness in the last days of her life, as well as moral damage for having spent the last days of her life with the acquired awareness of the reduction in life itself, with a more limited and suffering horizon.

4. Conclusions

The case, although single, points out the forensic medical examiner’s function, together with that of the specific specialist physician, as a translator of clinical data in court. Of particular importance was the role played in the complex reconstruction of the sequence of events and the identification of the causes associated with the negligent behavior and their influence on the death. In the Italian context, this is all the more the case when malpractice causes a reduction in the possibilities of survival rather than death.