Potential pitfalls in diagnostic and therapeutic decision-making in pulmonary embolism-related obstructive shock in patients with cancer: a case report

Abstract

Background

Pulmonary embolism (PE) is a potentially life-threatening condition and represents the third most common cardiovascular syndrome. Patients with cancer are at markedly increased risk of PE and often present with complex metabolic and haemodynamic alterations. Risk stratification in acute PE relies on clinical parameters, biomarkers, and imaging findings to guide therapeutic decisions. However, elevated lactate levels may have alternative aetiologies in oncologic patients, potentially leading to overtreatment of patients.

Case summary

We report the case of a 60-year-old woman presenting with high-risk bilateral pulmonary embolism complicated by obstructive shock. Initial findings included hypotension, tachycardia, right ventricular dysfunction, elevated troponin, and severe hyperlactatemia. Systemic thrombolysis was administered following multidisciplinary discussion within a Pulmonary embolism response team. Despite rapid clinical and haemodynamic improvement, serum lactate levels remained persistently elevated without evidence of metabolic acidosis. Imaging revealed a large soft-tissue mass of the right leg, subsequently diagnosed as high-grade B-cell lymphoma. After exclusion or treatment of other possible explanations, the persistent hyperlactatemia was attributed to tumour-related aerobic glycolysis, consistent with the Warburg effect. Given the favourable clinical evolution, further invasive PE therapies were avoided. The patient was transitioned to anticoagulation and oncologic treatment, with a favourable long-term outcome.

Discussion

This case illustrates how malignancy-associated metabolic alterations, such as the Warburg effect, can interfere with therapy in acute pulmonary embolism. Awareness of alternative causes of hyperlactatemia is essential to avoid unnecessary invasive interventions and to optimize individualized treatment strategies in cancer-associated PE.

Learning points.

• Persistently elevated lactate levels in acute pulmonary embolism may not necessarily indicate ongoing circulatory failure.

• Awareness of the malignancy-associated aerobic glycolysis (Warburg effect) needs to be increased to avoid over-treating the patient.

• Careful integration of all available data within a multidisciplinary team is essential in cancer-associated pulmonary embolism.

Introduction

Pulmonary embolism is a potentially life-threatening condition with an annual incidence estimated to be about 39–115 cases per 100 000 people in the general population, making it the third most frequent cardiovascular syndrome behind myocardial infarction and stroke.¹ Patients with cancer have a higher incidence of pulmonary embolism (odds ratio 2–9), with studies showing rates between 15–20% in patients with specific types of cancers (e.g. haematological malignancies, pancreatic, lung, or brain cancer).^1,2 A broad scale of therapies exists, ranging from low molecular weight heparins to thrombolysis or mechanical thrombectomy. Swift and targeted treatment without provoking serious adverse effects is crucial in saving lives. The ESC guidelines on acute pulmonary embolism provide treatment strategies based on risk stratification incorporating clinical parameters, biomarkers, and imaging findings.¹

The Warburg effect, first described by Otto Warburg in 1924, is the metabolization of glucose to lactate through glycolysis, even when there is sufficient oxygen (called ‘aerobic glycolysis’), especially observed in cancer cells (Figure 1).^3,4 Although less efficient, this leads to a faster production of adenosine 5′-triphosphate (ATP) compared to mitochondrial oxidative phosphorylation, which supports biosynthesis and rapid proliferation. Furthermore, it increases lactate levels and acidifies the area surrounding the tumour, which facilitates tumour metastasis, angiogenesis, and immunosuppression.^5–8 To this day, the exact underlying mechanisms of the Warburg effect remain insufficiently understood and open to debate.

Figure 1.

Explanatory image of the Warburg phenomenon.

Summary figure

(A) Transthoracic ultrasound showing dilated right ventricle. (B) CT angio thorax showing bilateral segmental pulmonary embolism (blue arrows). (C) MRI scan (T1 TSE transverse + gadolinium) of mass in the right upper leg (blue asterisk). (D) Evolution of heart rate (b.p.m.), blood pressure (mmHg), troponin I (ng/L), and lactate (mmol/L).

Case presentation

A 60-year-old female patient with an elevated cardiovascular risk profile (former smoker, arterial hypertension, and hypercholesterolaemia) was transferred to our hospital after she was diagnosed with bilateral pulmonary embolism. She presented herself in the referring hospital with progressive dyspnoea, thoracic pain on inspiration, and reduced exercise tolerance. She also experienced a syncope with minimal prodromal symptoms on the day of presentation.

In the past 2 months, the patient developed a swelling of her right leg. When she first reported it to her family doctor, a few weeks before presentation, an ultrasound suspected a haematoma. She was reassured, and although the volume increased significantly over time, she assumed this was a normal evolution and ultimately believed it would resolve spontaneously.

The initial work up in the referring hospital showed bilateral pulmonary embolism with signs suggestive for obstructive shock with hypotension (87/59 mmHg), tachycardia (106 bpm), elevated lactate level (9.6 mmol/L; normal 0.5–1.6 mmol/L) and elevated troponin I (82.5 ng/L; normal <15.6 ng/L), pulmonary hypertension (systolic pulmonary artery pressure 44 mmHg), inferolateral ST depression on ECG, and D-shaping on the transthoracic echocardiography Figure 2. The right ventricular systolic function remained intact. The Pulmonary Embolism Severity Index score was 110 (Class IV, high risk).

Figure 2.

ECG upon admission showing a sinus rhythm with inferolateral ST depression.

A magnetic resonance imaging scan of the leg revealed a voluminous, vascularized, soft tissue mass surrounding the right femur (14 × 15 × 24 cm), with associated malignant permeative bone involvement and periosteal reaction of the femoral diaphysis (Summary figure).

Given the signs of obstructive shock, the pulmonary embolism response team (PERT) was consulted and the decision to treat the patient with thrombolysis using alteplase (10 mg in bolus, followed by 90 mg over 1 hour) was made. The interventional radiologist, who was part of the PERT team, was able to exclude active bleeding in the leg and was ready to intervene if necessary. The patient was admitted to the cardiac intensive care unit. Heparin via continuous intravenous administration, titrated according to the activated partial thromboplastin time, was initiated after thrombolysis. After the initial treatment, haemodynamic improvement over the following hours was observed with a rise in the blood pressure to 106/58 mmHg and a reduction of the heart rate to 95 bpm. However, blood lactate levels remained unexpectedly high (around 6 mmol/L). Furthermore, blood gas analysis showed an acute respiratory alkalosis, not acidosis, with a persistent alveolar-arterial (A-a) gradient (atmospheric pressure 760 mmHg (sea level), FiO₂ 29%, pH 7.46 (7.35–7.45), pCO₂ 33 mmHg (36–44), pO₂ 70 mmHg (75–100), HCO3- 23 mmol/L (22–26), and A-a oxygen gradient 95.5 mmHg (19 mmHg expected for age—suggestive of V/Q mismatch due to pulmonary embolism)). In view of the persistent but stable lactate, other therapeutic options (e.g. surgical embolectomy or catheter-directed thrombolysis) were discussed in the PERT team. Given the favourable clinical evolution, a further conservative approach was adopted.

In the following days, the clinical condition further improved and the signs of right heart overload on ultrasound disappeared. The patient was discharged from our ward to the Oncology department on Day 5. Lactate remained elevated around 5–6 mmol/L, without systemic metabolic acidosis (Summary figure).

Alternative aetiologies for the unexpected persistently elevated lactate were explored. The patient had fever at presentation (38.3°C) but not during hospitalization. Upon presentation, there was a slightly elevated white blood cell count of 11.4 × 10^9/L (normal 4–11 × 10^9/L) and C-reactive protein of 17.8 mg/L (normal <5 mg/L) which rose gradually to a maximum of 190 mg/L on Day 4. Cultures (i.e. multiple haemo-, urine-, and sputum cultures) were negative. Procalcitonin was not measured. There was a mild acute kidney failure (creatinine 1.22 mg/dL (normal 0.55–0.95 mg/dL), eGFR 46 mL/min (CKD-EPI, normal >90 mL/min)) during hospitalization with a full recovery to baseline at discharge. A drop in haemoglobin from 12.2 g/dL to 9.1 g/dL (normal 11.7–16 g/dL) on Day 4 was observed. Clinically, the patient developed a large haematoma at her right leg due to the traumatic syncope at home and the thrombolysis Figure 3. One unit of packed cells was given on Day 4. Liver function tests were normal. The patient did not take any medication, nor did she experience a seizure explanatory for the elevated lactate. During her admission on the cardiac intensive care, there was only a short need for vasopressors (noradrenaline, max infusion rate 0.1 µg/kg/min). IV fluid (plasmalyte at a continuous infusion rate of 41 ml/h) was administered only shortly. Despite resolution of the inflammatory parameters, the acute kidney failure, and the anaemia, and the cessation of vasopressors, the lactate persisted (Summary figure).

Figure 3.

Legs upon admission. The right leg was significantly thicker than the left leg.

Further work up of the mass showed a high-grade B-cell lymphoma with diffuse large B-cell lymphoma morphology, of germinal centre type (GCB) for which six cycles of Pola-R-CHP (polatuzumab vedotin—rituximab—cyclophosphamide—doxorubicin—prednisone) was initiated on day 13.

On Day 18, the patient was discharged from the Oncology ward with therapeutic low molecular weight heparin, and the further clinical course was favourable up to six months after the initial presentation (Figure 4).

Figure 4.

Timeline indicating key clinical events. US, ultrasound; Pola-R-CHP, polatuzumab vedotin–rituximab–cyclophosphamide–doxorubicin–prednisone.

Discussion

In this case, there was a clear discrepancy between the clinical evolution, imaging, and biochemical findings. According to the 2019 ESC Guidelines on the Diagnosis and Management of Acute Pulmonary Embolism, the patient was classified as high-risk upon presentation and treated with thrombolysis.¹ Although clinical and imaging parameters improved after thrombolysis and heparin infusion, lactate levels remained elevated, which made us consider alternative treatments (e.g. thrombectomy or surgical interventions, both associated with considerable morbidity and mortality).^1,9 However, we explored alternative causes of serum lactate elevation and suspected the Warburg effect, especially given the clinical course, the persistence of lactate although alternative aetiologies were treated, together with the confirmation of a high-grade B-cell lymphoma. Subsequently, we chose to carefully monitor the patient.

Even though the Warburg effect is a well-known phenomenon in patients with cancer^10,11, and pulmonary embolism is more common in cancer, its potential confounding effect in patients with pulmonary embolism is not frequently described in the literature. Our case illustrates that keeping an overview and exploring alternative explanations for elevated lactate, together with the awareness of the Warburg effect may profoundly influence clinical decision-making in the treatment of acute pulmonary embolism and may affect patient outcomes by potentially avoiding unnecessary invasive interventions with intrinsic procedural risks.

Lead author biography

Dr. Tom Van den Hoek is a sixth-year Cardiology Resident at the University of Antwerp, Belgium, currently working at Jessa Ziekenhuis, Hasselt, Belgium. His clinical interests include Interventional Cardiology, Acute Cardiovascular and Intensive Care and Sports Cardiology. Dr Van den Hoek is involved in clinical research and case-based education, with a focus on translating guideline-directed management into individualized patient care.

Supplementary material

Supplementary material is available at European Heart Journal – Case Reports online.

Author contributions

Tom Van Den Hoek (Conceptualization, Data curation, Formal analysis, Project administration, Visualization, Writing—original draft, Writing—review & editing [lead]), Peter Kayaert (Conceptualization, Writing—original draft, Writing—review & editing [supporting], Supervision [equal]), Eva De Caluwé (Conceptualization, Visualization, Writing—original draft, Writing—review & editing [supporting], Supervision [equal]), and Philippe Timmermans (Conceptualization, Writing—original draft, Writing—review & editing [supporting], Supervision [equal])

Consent: Approval from the hospital’s ethics committee was obtained, and a written informed consent was discussed with and signed by the patient.

Funding

This case report is not funded.

Data availability

The data underlying this article are available in the article and in its online supplementary material.