Abstract
Background
Patients treated with oral or targeted therapies for hematologic malignancies represent a growing population among candidates for thoracic surgery. These treatments, along with the underlying hematologic disorders, can impair hemostasis and increase perioperative bleeding risk. However, no specific recommendations currently exist for their perioperative management. The aim of this review is to explore potential factors contributing to perioperative bleeding in patients with hematologic malignancies receiving oral or targeted therapies who underwent anatomical lung resection.
Methods
We conducted a retrospective monocentric case series of seven patients with hematologic malignancies receiving oral chemotherapy who underwent major lung resection for lung cancer at the University Hospital of Nancy between 2024 and 2025. Data regarding intraoperative blood loss, postoperative drainage, occurrence of hemothorax, transfusion, and need for surgical revision were collected.
Results
Postoperative hemothorax occurred in 71.4% (5/7) of patients, and 42.9% required blood transfusion. Two patients (28.6%) required surgical revision for postoperative bleeding. Median intraoperative blood loss was 100 mL (80–1,000 mL), and median postoperative day-1 drainage was 1,040 mL (130–2,000 mL). Notably, the two patients who discontinued oral chemotherapy before surgery did not experience postoperative bleeding.
Conclusions
An unexpectedly high incidence of postoperative hemorrhagic complications was observed in this small cohort of patients receiving oral or targeted therapies for hematologic malignancies. Although causality cannot be established, these findings support careful multidisciplinary perioperative assessment and warrant further investigation in larger studies.
Keywords: Lung cancer, hematological malignancy, oral chemotherapy, thoracic surgery, bleeding complications
Highlight box.
Key findings
• Patients receiving oral or targeted therapies for hematologic malignancies undergoing anatomical lung resection experienced a high incidence of postoperative hemorrhagic complications in this small retrospective series.
What is known and what is new?
• Postoperative bleeding after anatomical lung resection is uncommon in the general thoracic surgical population.
• This study highlights that patients with hematologic malignancies receiving targeted or oral therapies may represent a particularly challenging population because of the coexistence of disease-related and treatment-related hemostatic abnormalities.
What is the implication, and what should change now?
• These findings should be considered hypothesis-generating rather than evidence of a causal relationship.
• Careful multidisciplinary perioperative planning involving thoracic surgeons, anesthesiologists, and hematologists is warranted, and larger prospective studies are needed to define optimal perioperative management of targeted therapies.
Introduction
Thoracic surgery is the cornerstone of the treatment for localized stage non-small cell lung carcinoma (NSCLC) (1). Anatomical lung resections represent a major surgery with a risk of several complications.
One of them is the occurrence of postoperative hemothorax, a rare complication but associated with high mortality. This complication occurs in 0.6% to 4.6% of patients and with a mortality of 5.1% to 17.8% (2). The frequency of reoperation required in patients with postoperative hemorrhage is considered to be 1% to 3% (3). Bleeding may originate from bronchial or intercostal vessels, although the source is often unidentified at reoperation.
The risk of a bleeding complication is even greater in patients receiving oral chemotherapy for hematological malignancy due to a combination of treatment-related platelet dysfunction and disease-related hemostatic abnormalities, including acquired von Willebrand syndrome in selected hematologic malignancies (4). Minor procedures such as port implantation or appendicectomy can become complicated (5). The consequences of these treatments on hemorrhagic risk during thoracic surgery for lung cancer is unpredictable and requires appropriate perioperative management in agreement with the anesthesia team. There are currently no specific perioperative management recommendations. The objective of this original article is to retrospectively evaluate the incidence of bleeding complications of all the patients treated with oral chemotherapies for hematologic malignancies who underwent thoracic surgery for lung cancer in the departement of thoracic surgery at University Hospital of Nancy. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1307/rc).
Methods
Ethical statement
The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The Société Française de Chirurgie Thoracique et Cardio-Vasculaire (SFCTCV) committee approved the conduct of this study (No. IRB00012919). All patients had signed a consent form allowing their data to be used for scientific purposes.
Study design
A retrospective mono-centric study was conducted at the University Hospital of Nancy (France) from 2024 to 2025. Adult patients treated with oral chemotherapies for hematologic malignancies who benefited from major lung resection for NSCLC were included.
Major lung resection included pneumonectomy, bilobectomy, lobectomy, or segmentectomy with lymph node dissection.
Oral chemotherapies included Bruton tyrosine kinase (BTK) inhibitors (i.e., ibrutinib), Janus kinase (JAK) inhibitors (i.e., ruxolitinib) and hydroxyurea. High bleeding-risk hematologic malignancies included Waldenström macroglobulinemia and essential thrombocythemia.
The primary endpoint was the occurrence of postoperative hemorrhagic complications, defined by postoperative bloody pleural drainage associated with a significant decrease in hemoglobin level, increased chest tube output, hemodynamic deterioration, blood transfusion, and/or surgical re-exploration. Clinically significant postoperative bleeding was defined as bleeding requiring blood transfusion and/or surgical re-exploration (6).
Secondary outcomes included intraoperative blood loss in milliliters, the amount of fluid produced on the chest drain on D1 postoperatively and the total amount of fluid on the chest drain in milliliters, the rate of surgical revision, transfusion, duration of chest drainage and hospital stay. Blood transfusion was performed according to institutional practice, based on the combination of hemoglobin level, ongoing blood loss, hemodynamic status, and clinical signs of inadequate oxygen delivery, rather than on a fixed hemoglobin threshold alone.
Statistical analysis
The continuous data were presented as the median with minimum-maximum values in parentheses. The categorical data were presented as the patient number with percentage in parentheses. No missing data were identified for the analyzed variables.
Results
Between January 1, 2024, and March 31, 2025, in all patient operated in the departement of thoracic surgery at University Hospital of Nancy, a total of seven adult patients treated with oral chemotherapy for a hematologic malignancy and undergoing major lung resection were included in the study. All data were collected from patients’ electronic medical records. The characteristics of these seven patients are shown in Table 1.
Table 1. Characteristics of patients with hematological treatment.
| Variable | Value (n=7) |
|---|---|
| Age (years) | 71 [60–77] |
| Sex | |
| Male | 6 (85.7) |
| Female | 1 (14.3) |
| Charlson’s score | 5 [4–8] |
| Preoperative underlying comorbidities | |
| Cardiac pathologies | 2 (28.5) |
| Pulmonary pathologies | 3 (42.9) |
| Previous contralateral lung resection | 2 (28.5) |
| Hematologic pathologies | |
| CML | 1 (14.3) |
| CLL | 1 (14.3) |
| Myelofibrosis | 1 (14.3) |
| Essential thrombocythemia | 3 (42.8) |
| Waldenstrom macroglobulinemia | 1 (14.3) |
| Smoking history | 6 (85.7) |
| Surgery | |
| RUL | 1 (14.3) |
| MLL | 1 (14.3) |
| RLL | 1 (14.3) |
| LUL | 1 (14.3) |
| Left S1–S2–S3 segmentectomy | 1 (14.3) |
| Right S1 segmentectomy | 1 (14.3) |
| Right S1–S2 segmentectomy | 1 (14.3) |
| Surgical approach | |
| Thoracotomy | 3 (42.9) |
| VATS | 4 (57.1) |
| Hematological treatment | |
| Ibrutinib | 2 |
| Ruxolitinib | 3 |
| Hydroxyurea | 3 |
| Anticoagulant treatment | |
| Fluindione | 1 |
| Antiaggregant treatment | |
| Aspirin | 2 |
Data are presented as n (%) or median (min–max). CLL, chronic lymphocytic leukaemia; CML, chronic myeloid leukemia; LUL, left upper lobectomy; MLL, middle lobe lobectomy; RLL, right lower lobectomy; RUL, right upper lobectomy; VATS, video-assisted thoracoscopic surgery.
The choice of surgical approach [thoracotomy or video-assisted thoracoscopic surgery (VATS)] depended on the operating surgeon’s routine practice. Three resections were planned as primary thoracotomies because they were performed by a senior surgeon who routinely performs anatomical lung resections through an open approach. None of these procedures represented a conversion from VATS.
The hematological, anticoagulant, antiaggregant treatments and preoperative hemostasis tests for each patient are detailed in Table 2. Patient 4 stopped ruxolitinib one month before surgery and then aspirin 75 mg was introduced in relay in prevention of thrombocytemia, continued pre- and post-operatively. Patient 5 had anticoagulant and antiaggregant treatments in addition to the hematological treatment for a history of pulmonary embolism and peripheral obliterative arteriopathy respectively. Fluindione was discontinued 5 days before surgery and bridged with low-molecular-weight heparin according to institutional practice while aspirin was continued before and after surgery.
Table 2. Characteristics and outcomes of the patients with hematological treatment.
| Characteristics | Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | Patient 7 |
|---|---|---|---|---|---|---|---|
| Hemathological malignancy | Myelofibrosis | CLL | Essential thrombocytemia | Essential thrombocytemia | Essential thrombocytemia | CML | Waldenström macroglobulinemia |
| Hematological treatment | Ruxolitinib; hydroxyurea; not stopped | Ibrutinib; not stopped | Ruxolitinib; not stopped | Ruxolitinib stopped a month before surgery | Hydroxyurea; not stopped | Hydroxyurea; not stopped | Ibrutinib; stopped 5 days before surgery |
| Anticoagulant treatment | – | – | – | – | Fluindione stopped 5 days before operation with a LMWH relay | – | – |
| Antiaggregant treatment | – | – | – | Pre- and post-operative aspirin 75 mg (relaying ruxolitinib) | Pre- and post-operative aspirin 75 mg | – | – |
| Preoperative hemostasis test | Plat: 388 G/L; PT: 83%; APPT: 1.06 | Plat: 134 G/L; PT: 96%; APPT: 1.05 | Plat: 118 G/L; PT: 72%; APPT: 0.87; Fibri: 2.6 g/L | Plat: 255 G/L; PT: 82%; APPT: 0.93 | Plat: 506 G/L; PT: 95%; APPT: 1.1% | Plat: 112 G/L; PT: 69%; APTT: 1.3 | Plat: 172 G/L; PT: 86%; APTT: 1.06 |
| Tumor characteristics | Peripheral, right upper lobe S2 segment, 31 mm | Peripheral, middle lobe S4 segment, 34 mm | Peripheral, left upper lobe S3 segment, 12 mm | Peripheral, right upper lobe S1 segment, 6 mm | Peripheral, right lower lobe S8 segment, 36 mm | Central, left upper lobe S3 segment, 39 mm | Peripheral, right upper lobe S1 segment, 12 mm |
| Surgery | RUL | MLL† | Left S1 S2 S3 segmentectomy | Right S1 segmentectomy | RLL | LUL | Right S1–S2 segmentectomy |
| Surgical approach | Thoracotomy | VATS | VATS | VATS | Thoracotomy | Thoracotomy | VATS |
| Intraoperative blood loss (mL) | 1,000 | 500 | Minimal (<100) | Minimal (<100) | 500 | Minimal (<100) | 100 |
| Fluid amount at D1 or surgical revision (mL) | 1,040 | 440 | 2,000 | 170 | 1,350 | 1,390 | 130 |
| Surgical revision required‡ | No | No | Yes (D0) | No | Yes (D0) | No | No |
| Blood loss at surgical revision (mL) | – | – | 500 | – | 1,000 | – | – |
| Total fluid amount§ (mL) | 1,380 | 610 | 2,700 | 680 | 3,010 | 2,830 | 130 |
| Transfusion | Yes | No | Yes | No | Yes | No | No |
| Total transfusion during hospital stay | 4 pRBC units | – | 4 pRBC units; 1 platelet unit | 3 pRBC units | – | – | |
| Chest tube drainage time (days) | 5 | 2 | 3 | 2 | 5 | 7 | 1 |
| Hospital stay (days) | 7 | 6 | 6 | 4 | 15 | 7 | 2 |
| Final pathology | Adenocarcinoma; pT2aN0 | Adenocarcinoma; pT1cN0 | Adenocarcinoma; pT1bN0 | Adenocarcinoma; pT1bN0 | Adenocarcinoma; pT2aN0 | Adenocarcinoma; pT2bN0 | Adenocarcinoma; pT1a(mi)N0 |
†, without lymph node dissection. ‡, decision based on the rate of bleeding into the chest tube, and clinical and biological data. §, corresponds to intraoperative blood loss, fluid amount at D1 or surgical revision, blood loss at surgical revision (if it has occurred) and fluid amount from D1 until the drain is removed. APPT, activated partial thromboplastin time; CLL, chronic lymphocytic leukaemia; CML, chronic myeloid leukaemia; D0, day 0; D1, day 1; Fibri, fibrinogen; LMWH, low molecular weight heparin; LUL, left upper lobectomy; MLL, middle lobe lobectomy; N, node; Plat, platelets; pRBC, packed red blood cells; PT, prothrombin time; RLL, right lower lobectomy; RUL, right upper lobectomy; T, tumor; VATS, video-assisted thoracoscopic surgery.
The lymph node dissection could not be performed in one patient because of the large amount of per-operative blood loss before to start the lymph node dissection.
Regarding the primary endpoint, the rate of a postoperative hemothorax was 71.4% (5/7).
Regarding the secondary endpoints, the intraoperative blood loss was 100 mL (80–1,000 mL). The fluid production of the chest drain on D1 postoperative or until surgical revision when it occurred at D0 of the operation, was 1,040 mL (130–2,000 mL).
The surgical revision rate was 28.6% (2/7, patients 3 and 5). Among the two patients requiring surgical revision, no active bleeding from a major vessel, bronchial artery, intercostal artery, or vascular stump was identified. Revision surgery demonstrated diffuse pleural oozing. No computed tomography (CT) angiography was performed prior to revision because of the urgency of the clinical situation. No significant pleural adhesions, vascular anomalies, or major technical difficulties were reported in the operative records. The other three patients (patients 1, 2 and 6) with hemothorax did not require a surgical revision, and appropriate medical and resuscitation management was sufficient. A transfusion occurred in 42.9% (3/7) of patients [1 with 4 packed red blood cell (pRBC) units, 1 with 3 pRBC units and 1 with 4 pRBC units and 1 platelet unit]. Finally, the chest tube drainage time was 3 days (1–7 days) and the hospital stay was 6 days (2–15 days). Peri-operative outcomes are available in Table 2.
Discussion
Perioperative management of patients receiving oral or targeted therapies for hematologic malignancies is poorly documented. This study reports the bleeding risk associated with hematological malignancies and oral chemotherapies during thoracic surgery for lung cancer. By retrospectively analyzing perioperative data from seven patients, we identified a notably high incidence of bleeding complications in those receiving oral chemotherapy.
A high rate of postoperative hemothorax (71.4%) was observed. Because our definition of postoperative hemorrhagic complications was broader than the definitions commonly used in thoracic surgical series, direct numerical comparison with published hemothorax rates is not appropriate. Nevertheless, the frequency of clinically relevant bleeding requiring transfusion (43%) and surgical re-exploration (29%) observed in our cohort remained notable and warrants further investigation.
The median of volume of liquid evacuated in the drain on postoperative D1 was 1,040 mL in our study and was clearly hematic in 5 patients (patients 1, 2, 3, 5 and 6 in Table 2). Interestingly, the two patients who did not experience postoperative bleeding had discontinued their hematologic therapy before surgery (patients 4 and 7). However, both also underwent VATS sublobar resections, which are associated with less extensive surgical dissection. Therefore, the respective contributions of treatment interruption, surgical approach, and extent of resection cannot be distinguished in this small cohort. These patients produced 170 mL and 130 mL of serous fluid, respectively, which aligns with findings in the general population (7).
A surgical revision must be performed in 28.6% (n=2). Usually, the frequency of reoperation required in patients with postoperative hemorrhage is considered to be 1% to 3% (3). There are no data in the literature on blood loss in thoracic surgery in patients with oral chemotherapy for hematological malignancies, but a trend towards increased bleeding has been described in other surgeries, particularly in digestive surgery (5). The high rate of surgical revision observed in our cohort likely reflects the unique hemorrhagic profile of patients receiving targeted therapies for hematologic malignancies. Although our study cannot demonstrate a causal relationship, the absence of a clearly identifiable surgical bleeding source, together with the lack of significant technical difficulties or anatomical abnormalities, supports the hypothesis that treatment-related platelet dysfunction and/or the underlying hematologic disorder may have contributed to the diffuse hemorrhagic pattern observed in these patients. Importantly, none of the patients underwent vascular reconstruction, sleeve resection, or other procedures requiring unusually extensive hilar vascular dissection. Therefore, although the influence of tumor location and surgical complexity cannot be completely excluded in this small series, these factors alone are unlikely to account for the high incidence of postoperative bleeding. About 40% of our patients required transfusion, compared with 11.6% reported by Tai et al. after surgery (7).
The mechanisms underlying the increased bleeding risk in this population are probably multifactorial. In addition to treatment-related platelet dysfunction, particularly with BTK inhibitors, disease-related hemostatic abnormalities should also be considered. Patients with essential thrombocythemia and Waldenström macroglobulinemia may develop acquired von Willebrand syndrome despite normal or elevated platelet counts, which may further impair primary hemostasis. Because no platelet function assays or von Willebrand factor studies were performed in the present study, the relative contribution of these mechanisms cannot be determined. Future prospective studies should incorporate comprehensive perioperative hemostatic assessment, including platelet function testing and von Willebrand factor evaluation when appropriate.
During the study period, 779 anatomical lung resections for NSCLC were performed in the departement of thoracic surgery at University Hospital of Nancy, including 560 lobectomies and 219 segmentectomies. In the overall institutional cohort, postoperative bleeding occurred in 21 cases (2.7%), surgical re-exploration for bleeding in 16 cases (2.1%), and blood transfusion was required in 68 cases (8.7%). These rates were substantially lower than those observed in the present series. Although only descriptive, comparison with in the departement of thoracic surgery at University Hospital of Nancy experience suggests that the bleeding rates observed in this cohort substantially exceeded those usually encountered after anatomical lung resection for NSCLC, supporting the hypothesis that hematologic disease and/or targeted therapies may contribute to an increased hemorrhagic risk.
This study has several limitations, including its retrospective, non-randomized, absence of a matched control group and single-center design, as well as the very small number of patients included and short inclusion period. The involvement of three different surgeons may also introduce bias. Additionally, the duration of drainage could be influenced by various factors, such as persistent air leakage, while the length of hospital stay may be affected by other postoperative complications, including cardiac arrhythmias or pneumonia.
Our results describe a high incidence of hemorrhagic complications in this small cohort. However, because of the retrospective design, the heterogeneity of treatments and hematologic diseases, concomitant antithrombotic therapy in some patients, and surgical confounding factors, the relative contribution of each factor cannot be determined. Nevertheless, the two patients who discontinued hematological treatment preoperatively did not experience such complications. This observation is based on very few patients and should be considered hypothesis-generating. With the acceleration in the development of targeted therapies/oral chemotherapies and the increase in number of patients receiving these therapies, it is crucial to establish a preoperative strategy in collaboration with the anesthesia team and referring hematologists to balance thrombotic and hemorrhagic risks (8).
Conclusions
Our findings support careful preoperative multidisciplinary assessment of patients receiving targeted or oral therapies for hematologic malignancies. When clinically feasible and in accordance with hematology recommendations, temporary interruption of therapies known to impair platelet function—particularly BTK inhibitors—may be considered according to the anticipated surgical bleeding risk. However, decisions should remain individualized after balancing the risk of hemorrhagic complications against the risk of hematologic disease progression. Therefore, the present study should be viewed as exploratory and hypothesis-generating. A larger multicenter matched study is currently being considered to further investigate this question.
Supplementary
The article’s supplementary files as
Acknowledgments
None.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Société Française de Chirurgie Thoracique et Cardio-Vasculaire (SFCTCV) committee (No. IRB00012919) and informed consent was taken from all individual patients.
Footnotes
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1307/rc
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1307/coif). The authors have no conflicts of interest to declare.
Data Sharing Statement
Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1307/dss
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