Massive intrathoracic haemorrhage as a complication of pulmonary parenchymal haemorrhage and anticoagulant treatment of lung embolization during COVID-19 – two case reports

Overview

Introduction: The medical and social interest in the SARS-CoV-2 infection is currently high. This infection can, in severe cases, be accompanied by a series of complications, such as thromboembolic disease or pulmonary parenchymal haemorrhage.

Case reports: The paper presents two rare cases of massive intrathoracic haemorrhage caused by pulmonary parenchymal haemorrhage and exacerbated by full anticoagulant treatment of thromboembolic disease.

Results: In both cases, the haemorrhage originated in the left lower lobe and was life threatening, requiring urgent anatomical lung resection – left lower lobectomy.

Conclusions: The combinaion of anticoagulant therapy and thromboembolic events related to COVID-19 can cause, in rare cases, massive pulmonary haemorrhage. This rare complication proved lethal in one out of two of the cases described in this paper. An imminent and adequate reaction is necessary when the first signs of haemorrhage appear.

Keywords:

Lobectomy – COVID-19 – diffuse alveolar haemorrhage – thromboembolic disease – haemothorax

INTRODUCTION

The many complications which can develop as a consequence of a SARS-CoV-2 infection, as well as post- COVID, have been described in recent publications. Barotrauma and, to a lesser extent, pulmonary parenchymal haemorrhage (PPH), including pulmonary impairment, with the exception of inflammatory affection and the impairment of pulmonary functions, have been recorded. Pulmonary haemorrhage is usually caused by vascular pathology, such as capillary endothelium damageand vasculopathy [1]. PPH and thromboembolic disease are both severe and potentially life-threatening complications that may develop during COVID-19 [2–4]. Here, we present two cases of patients with COVID-19 whose conditions were further complicated by massive intrathoracic haemorrhage caused by PPH and exacerbated by anticoagulant treatment in combination with thromboembolic disease, for which both patients required an urgent surgical intervention.

CASE REPORT 1

A 64-year-old man, morbidly obese (BMI 41.6), with COVID-19 but no comorbidities, was admitted to the Faculty Hospital Pilsen on 18. 11. 2020, to the internal ward. The reasons for admission were progressive shortness of breath, high fever, an unflagging cough and worsening of his overall condition. Upon admission, a lung examination using computed tomography (CT) was carried out. The examination revealed tiny emboli in the sub-segmental branches of the pulmonary trunk in the upper right lobe and both lower lobes, as well as inflammatory infiltrates of viral origin in both lungs. The patient was started on standard therapy for viral pneumonia. High-flow oxygen therapy was indicated when SpO₂ was 85%, as well as the application of low molecular weight heparin, which was prescribed (Clexane 1.4 mL s.c. every 12 hours with AntiXa activity checks every 4 hours after administration within the range 0.5–0.9) in an attempt to achieve full anticoagulation due to the aforementioned pulmonary embolization. The condition of the patient deteriorated on the morning of the fifth day of hospitalization. Haemoptysis and hypotension occurred, alongside a significant decrease in haemoglobin levels (from 119 g/L to 72 g/L) and an increase in leukocytosis (to 50.3×10⁹/L). The patinet was therefore transfered to ICU. A follow-up CT examination of the lungs detected the progression of the pulmonary infiltrates and a massive left-sided pleural effusion (see Fig 1). The radiologist evaluated the finding as being primarily a complicated pulmonary abscess with para-pneumonic effusion, or empyema. However, the above-mentioned haemoptysis and the important decrease in haemoglobin levels indicated possible intrathoracic haemorrhage. As a result, the anticoagulant therapy was restricted; the coagulation parameters were corrected and transfusion products applied repeatedly. The patient’s condition continued to deteriorate rapidly, resulting in shock caused by a combination of hypovolemia from the haemorrhage and left-sided hemithorax tension. The patient was therefore intubated; artificial pulmonary ventilation was used, pharmacological support of the circulation started, and his chest was drained on the left side on the same day around 9 o’clock PM. The chest tube drained almost 3000 mL of dark blood in a short period of time, but the haemorrhage continued. The patient subsequently underwent an urgent left-side thoracotomy as “ultimum refugium” in the early hours of the morning of 24. 11. 2021, almost twelve hours after the CT scan.

The posterolateral thoracotomy revealed approximately 1500 mL of dark blood and approximately the same number of blood clots in the pleural cavity. This was caused by a massive haemorrhage in the lower left lobe and was accompanied by a massive subpleural haematoma that flowed through the ruptured visceral pleura into the pleural cavity. The lower left lobectomy was performed as the only possible procedure when taking into consideration this finding. The haemorrhage into the pleural cavity stopped as a consequence. The upper lobe was largely infected by many rigid inflammatory infiltrates. However, at the end of surgery, the lobe fully expanded and completely filled the pleural cavity.

The gradual stabilization of the patient´s circulation was achieved after the massive haemorrhage, coagulation disorder and respiratory failure were addressed by means of surgery. The patient´s dependence on artificial pulmonary ventilation continued due to the combination of viral pneumonia, the restriction caused by pulmonary resection, and the condition of unresected areas after pulmonary embolization. Anticoagulant therapy continued: non-fractionator heparin was administered due to the risk of haemorrhage. There were no other surgical complications. Chest tubes were left in the pleural cavity longer than usual, with the last one removed only on the 17^th day after surgery.

The underlying pulmonary disease required the continuation of artificial pulmonary ventilation with limited parameters. The patient´s condition did not improve. On the contrary, nosocomial pneumonia caused by a resistant strain of Enterococcus faecalis developed. On the 25^th day of hospitalization, the already exhausted patient suffered circulatory failure and as a result required increased pharmacological support of his circulation; up to resuscitation doses. Oxygenation was untenable in spite of the aggressive artificial pulmonary ventilation. The patient´s condition deteriorated rapidly and they died on 15. 12. 2020.

A histological examination of the removed lower left lobe revealed a massive new intra-alveolar haemorrhage and intra-alveolar edema, mild fibrous extension of the interstitium and lymphocytic infiltration, as well as leukostasis in the vessels. Blood was also present in some mildly expanded bronchioles.

CASE REPORT 2

A 54-year-old man, slighty obese (BMI 30.9), with COVID-19 but no comorbidities was in home care from the 5. 1. 2021. He was admitted to the Department of Internal Medicine of the regional hospital on the 20. 1. 2021 due to a deterioration in his condition (dyspnea, tickling cough, chest pain). He was diagnosed with bilateral viral pneumonia and right pulmonary embolization caused by phlebothrombosis of the right lower extremity. The patient was administered the standard treatment for viral pneumonia and was prescribed anticoagulant treatment with Clexane 1 mL s.c. once a day. The patient´s condition was complicated by the development of left-side pneumothorax, which was drained from the left pleural cavity. The patient was subsequently transferred to our department on 01. 02. 2021 in order to perform the drainage and treat the severe complication of his COVID infection.

During admission to our department, the patient was: conscious; haemodynamically stable; without dyspnea; SpO₂ 83–87% with oxygen therapy 10 L O2/min; breathing was auscultatory significantly weakened on the left; haemoglobin 97 g/L; leukocytosis 26×10⁹/L; C-reactive protein 52 mg/L. The patient was indicated for resuscitative thoracotomy based on a CT scan that revealed a massive haemothorax on the left (see Fig 2). A left posterolateral thoracotomy was performed. There were approximately 2000 mL of liquid blood and almost 1000 mL of coagulated blood in the pleural cavity. This was caused by a massive haemorrhage of almost all the left lower lobe parenchyma, which created a massive subpleural haematoma that flowed into the pleural cavity after the perforation of the visceral pleura, as was the case in the previous patient. The condition was resolved with a left lower lobectomy. Many rigid inflammatory infiltrates were also seen in the left upper lobe.

The patient´s condition was without significant complications after surgery. The chest tube was removed on the 6^th day after surgery and the patient was discharged on the 9^th day after surgery. He continued the anticoagulant treatment: Clexane 1 mL s.c., every 12 hours, after discharge. After one week, the medication was changed to Eliquis Tab. 5 mg every 12 hours. Throughout, the patient remained in the care of an angiologist and pneumologist. During a check-up on 27. 04. 2021, he was without difficulties and in good condition. A spirometry examination did not show respiratory failure and only slightly reduced vital capacity (VC 71% of propriate value). On 06. 05. 2021, a duplex ultrasonography examination of the lower extremities showed partial recanalization of popliteal-crural phlebothrombosis on the right.

Areas of aerial pulmonary parenchyma, with signs of mild chronic vesicular emphysema, congestion and intra-alveolar haemorrhage were found during a histological examination of the pulmonary lobe resection sample. There was also massive fibrosis of the pulmonary parenchyma; in some areas with signs of intra-parenchymatous haemorrhage. Histological findings confirmed the clinical diagnosis of intra-parenchymatous, or subpleural haematoma, of the left lower lobe which showed signs of previous viral pneumonia.

DISCUSSION

Of our region’s 884,000 inhabitants, 142,826 tested positive for SARS-CoV-2 infection in one year of the pandemic (up to 12. 05. 2021). In total, 12,498 people were hospitalized due to a more severe course of the disease, of which 2,407 were admitted into intensive care. The two cases of severe intrathoracic haemorrhage presented here represent 0.001% of the COVID-positive individuals , and only 0.02% of those hospitalized with COVID-19.

SARS-CoV-2 affects haemostasis by directly infecting the endothelium through angiotensin converting enzyme 2 (ACE2), which can consequently lead to damage of the microcirculation and other organ complications [5]. Inflammatory response and activation of the coagulation system can occur on several levels during a SARS-CoV-2 infection. This can lead to the creation of microthrombus and increase the risk of arterial and venous thrombosis and embolic events [6]. Factors which negatively affect the course of COVID-19 include age, obesity, associated comorbidities and lymphocytopenia. Both the patients described in thispaper were healthy before their COVID-19 infection; their risk factors were obesity and age. Pulmonary microcirculation damage and capillary endothelium damage, haemorrhage and vasculopathies are among the serious and more frequent complications of viral SARS-CoV-2 infection [1]. Intra-parenchymal pulmonary haemorrhage needen’t be connected to the acute stage of the disease: it can occur in the post-covid period, an increasingly common occurrence. This manifests itself primarily through increased breathing difficulties and haemoptysis, haemothorax during the rupture of the visceral pleura and in the most extreme cases, we may encounter haemorrhagic shock along with life-threating haemorrhaging [2]. Thromboembolic events are among the most severe complications of COVID-19. This is when most patients, including adolescents, experience vascular complications [3,4]. Thromboembolic complications occur in almost 25% of patients with viral pneumonia caused by SARS-CoV-2 who did not use anticoagulant treatment, with lethality reaching 40%. Immobility that is the result of hospitalization contributes to the risk of thromboembolic illness. Current studies indicate that the application of low molecular weight heparin correlates with significantly lower mortality. Haematological associations worldwide therefore agree on the suitability of its application. Most authors recommend the application of a medium dose (between prophylactic and full treatment), with only a minority recommending the usage of a full treatment dose [3,7].

However, the application of low molecular weight heparin itself can cause a severe complication in the form of spontaneous soft tissue hematoma (SSTH) [8]. The risk of this occurring is connected to higher doses of anticoagulant treatment. The occurrence of haemorrhage complications during anticoagulant treatment is 1–17% in the general population [8, 9]. SSTH is usually found in retroperitoneum or in the abdominal wall; pulmonary hematoma as a complication of anticoagulant treatment has not been noted in our department. Most cases of SSTH do not require surgical intervention because of tamponade by surrounding structures and spontaneous absorption. However, in some situations, such as excessive anticoagulant treatment of pulmonary embolization in our two cases of morbidly obese patients, the increase of hematoma does not have to stop, which can result in a massive haemorrhage, respectively a life threating haemorrhage after overcoming bordering structures.

We think that in both presented cases it concerned the accumulation of the aforementioned complications with parenchymal pulmonary haemorrhage at the beginning (potentially originated from tissue damaged by barotrauma or from the area of pulmonary infarction during embolization), which was then potentiated by excessive anticoagulant treatment of thromboembolic disease. This subpleural hematoma, which increased due to the pressure on visceral pleura, caused it to rupture, resulting in a massive haemorrhage into the pleural cavity. There is also some kind of analogy with the mechanism associated with a twophase spleen rupture. However, it is not clear why haemorrhage occurred in the left lower lobe in both cases. It is interesting, that although cases of PPH are not so rare, and thromboembolic complications affect a quarter of patients with COVID-19 infection, the described complication is rare, at least in our region.

CONCLUSION

Although the pandemic in Europe seems to be receding, the medical and social interest in the SARS-CoV-2 infection remains high. This is because new complications are being detected. The views on the treatment of COVID-19, respectively the complications arising from it, is changing because of deepening experience. Experience has shown that significant numbers of patients with COVID-19 suffer from thromboembolic events and that related therapeutic anticoagulation can cocause, in rare cases, massive pulmonary haemorrhage, respectively intrathoracic haemorrhage. It is therefore necessary to bear this risk in mind and to react on time and adequately when the first signs of haemorrhage appear.

This work was supported by the Charles University Research Fund (Progres Q39) and by project No. CZ.02.1.01 /0.0/0.0/16_019/0000787 „Fighting Infectious Diseases“, awarded by the MEYS CR, financed from EFRR.

Conflict of interests 

The authors declare that they have not conflict of interest in connection with this paper and that the article has not been published in any other journal, except congress abstracts and clinical guidelines.

Jakub Šebek, M.D.

Department of Surgery,

University Hospital Pilsen

Faculty of Medicine Charles University in Pilsen,

e-mail: sebekj@fnplzen.cz