Acute Cor Pulmonale Caused by Pulmonary Tumor Thrombotic Microangiopathy as the Initial Presentation of Multiple Myeloma: A Case Report

ABSTRACT

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare cause of acute cor pulmonale, typically associated with advanced solid tumors; its occurrence as the initial presentation of multiple myeloma (MM) has not been described. A 45‐year‐old woman developed acute right heart failure on postoperative day 1 after uterine myomectomy. Echocardiography showed a pulmonary artery systolic pressure of 86 mmHg with a d‐shaped left ventricle and right ventricular dysfunction (TAPSE 10 mm); CTPA excluded pulmonary embolism but revealed bilateral ground‐glass opacities. Platelet count fell from 115 × 10⁹/L preoperatively to 30 × 10⁹/L. An overlooked preoperative globulin of 67 g/L prompted serum protein electrophoresis and immunofixation, which identified an IgG κ M‐protein; bone marrow aspiration revealed 14% morphologically abnormal plasma cells. Presumed MM‐associated PTTM was treated with heparin and sildenafil. The platelet count recovered, and a follow‐up echocardiogram on day 7 showed normalized cardiac structure and function. The patient self‐discontinued rivaroxaban 1 week after discharge and died 3 months later from progression of untreated MM. In CTPA‐negative acute cor pulmonale with unexplained thrombocytopenia, an elevated globulin on routine biochemistry may be the only early clue to a plasma cell disorder, and timely anticoagulation with pulmonary vasodilation may buy time for definitive therapy.

1. Introduction

Acute cor pulmonale in the ICU is usually from massive pulmonary embolism or ARDS [1]. When CTPA is negative and thrombocytopenia is present, pulmonary tumor thrombotic microangiopathy (PTTM) enters the differential. In PTTM, tumor microemboli occlude pulmonary arterioles and trigger intimal fibrocellular proliferation, causing progressive pulmonary hypertension and right heart failure [2, 3]. PTTM is most often linked to gastric, breast, and lung cancers [2].

2. Case Description

A 45‐year‐old woman with no significant past medical history was admitted for elective uterine myomectomy. Preoperative blood tests revealed globulin 67 g/L, albumin 35 g/L, and total protein 100 g/L; a full blood count showed borderline thrombocytopenia (platelets 115 → 101 × 10⁹/L by admission) with macrocytosis (MCV 104.4 fL). None of these abnormalities was investigated. Laparoscopic myomectomy was performed uneventfully 2 days after admission.

On postoperative day (POD) 1, she developed acute dyspnea with SpO₂ 87%. Morning blood tests now showed albumin 24 g/L and globulin 52 g/L; after ICU transfer, lactate dehydrogenase (LDH) was 627 U/L with a normal creatine kinase (125 U/L), and calcium was 1.73 mmol/L. Platelet count was 36 → 30 × 10⁹/L from the morning draw to ICU admission. Echocardiography showed right ventricular enlargement with septal flattening (d‐sign), a pulmonary artery systolic pressure of 86 mmHg, TAPSE 10 mm, and left ventricular ejection fraction 58% (Figure 1). CTPA showed a dilated pulmonary trunk (26 mm) without filling defects, together with bilateral patchy ground‐glass opacities and bilateral pleural effusion. Acute cor pulmonale was diagnosed, and she was transferred to the ICU.

Figure 1.

Imaging findings at ICU admission. (A) Parasternal short‐axis view: interventricular septal flattening (d‐sign, arrow). (B) Apical four‐chamber view: right ventricular enlargement. (C) CTPA (mediastinal window): patent pulmonary arteries without filling defects. (D) CTPA (lung window): patent peripheral pulmonary vessels.

On ICU admission, temperature 36.2°C, heart rate 114 bpm, blood pressure 105/62 mmHg; bilateral crackles and a systolic murmur at the tricuspid area were noted, without lower extremity edema. High‐flow nasal cannula (50 L/min, FiO₂ 50%) maintained SpO₂ at 98%. Arterial blood gas (FiO₂ 100%): pH 7.21, PCO₂ 27 mmHg, PaO₂/FiO₂ 99 mmHg, lactate 6.4 mmol/L, base excess −15.6 mmol/L. Coagulation: PT 16.0 s, APTT 29.2 s, fibrinogen 1.51 g/L, D‐dimer 1.76 mg/L FEU, antithrombin III 57%, protein C 44%. Immunofixation identified a monoclonal IgG κ component; serum IgG was 45.31 g/L with suppressed IgA (0.59 g/L) and IgM (0.37 g/L). Antinuclear, antiphospholipid, and vasculitis antibody panels were negative. Serum tumor markers were within normal limits. Serum protein electrophoresis revealed an M‐protein of 39.5% on admission, still present at 34.6% 2 days later.

The differential was addressed as follows. Thrombotic thrombocytopenic purpura was unlikely: no schistocytes on smear, normal indirect bilirubin and creatinine, no neurologic involvement, a PLASMIC score of 4 of 7 [4], and platelet recovery without plasma exchange; ADAMTS13 activity and reticulocyte count were not measured. Heparin‐induced thrombocytopenia did not fit the timing of the platelet decline relative to heparin exposure. For disseminated intravascular coagulation, the ISTH overt‐DIC score was 5, at the threshold for overt DIC [5]; the coagulopathy was interpreted as consumptive, which is not mutually exclusive with PTTM, as tumor microembolism is a recognized trigger of consumptive coagulopathy. The combination of CTPA‐negative acute cor pulmonale, consumptive thrombocytopenia, and diffuse ground‐glass opacities suggested PTTM, and the elevated globulin directed the workup toward a plasma cell disorder. Bone marrow aspiration showed 3.5% plasma cells on differential count with 14% morphologically abnormal plasma cells, reported as “cannot exclude multiple myeloma.” Lung biopsy was declined by the family; with a PaO₂/FiO₂ of 99 mmHg and a pulmonary artery systolic pressure of 86 mmHg, an invasive procedure was prohibitive, so a presumed diagnosis of MM‐associated PTTM was established.

Treatment comprised unfractionated heparin (APTT target 45–70 s), sildenafil 50 mg three times daily, HFNC, and diuresis. The platelet count trajectory was 97 → 21 → 99 × 10⁹/L on POD 2, 4, and 10. A follow‐up echocardiogram on POD 7 showed normalized cardiac structure and function (ejection fraction 75%). She was discharged with improved dyspnea on rivaroxaban and sildenafil. Follow‐up at Peking University People's Hospital included repeat bone marrow examination and PET‐CT, which revealed osteolytic skull lesions, consistent with active MM; anti‐myeloma chemotherapy was nonetheless not initiated. One week after discharge, she self‐discontinued rivaroxaban while continuing sildenafil. Nearly 3 months after surgery, she was readmitted to Peking University People's Hospital with worsening dyspnea; emergency endotracheal intubation was performed, and she died 6 days after readmission despite resuscitation.

3. Discussion

To our knowledge, this is the first report of PTTM as the presenting manifestation of multiple myeloma (MM). PTTM is almost always a complication of advanced solid tumors [2], and MM‐associated PTTM is vanishingly rare, although thrombotic microangiopathy complicating plasma cell disorders is documented [6]. The diagnosis of active MM followed the IMWG criteria [7]: a monoclonal IgG κ protein with suppressed IgA and IgM, marrow plasma cells with atypia, osteolytic skull lesions as the only positive CRAB item, and an LDH of 627 U/L as a tumor‐burden marker.

Acute cor pulmonale with a dilated pulmonary trunk demands a structured differential. Massive pulmonary embolism was excluded by CTPA, left‐heart and congenital heart disease by echocardiography, connective‐tissue disease and vasculitis by the negative antibody panels, and chronic thromboembolic hypertension by the acute onset and the absence of organized thrombus. HIV and liver disease were not screened. The remaining diagnosis was PTTM, in which tumor microemboli sit below CTPA resolution [3].

The prognosis of PTTM is grim: median survival is approximately 9.5 weeks [3], and rapid death even without a previously known malignancy is described [8]. Our patient survived about 3 months after surgery. She stopped rivaroxaban 1 week after discharge and deteriorated weeks later; untreated active MM is the more parsimonious explanation for her death, and self‐discontinuation, though temporally associated, cannot be established as causal in a single case.

We preferred HFNC over invasive ventilation because positive pressure further increases right ventricular afterload, and perioperative PTTM‐induced cardiac arrest has been reported [9]. Anticoagulation in PTTM is controversial because the obstruction is fibrocellular rather than thrombotic [3]. This patient had consumptive coagulopathy, and the temporal association of heparin with platelet recovery and echocardiographic normalization is hypothesis‐generating at best; a single case cannot establish a treatment effect. Sildenafil was given as a pulmonary vasodilator bridge: the approved dose for pulmonary arterial hypertension is 20 mg three times daily [10], and 50 mg three times daily was an off‐label choice for rapid afterload reduction at a pulmonary artery systolic pressure of 86 mmHg; no dose‐finding data exist for PTTM.

Three limitations exist. First, PTTM was diagnosed clinically without histology; other microvascular processes cannot be fully excluded, and ground‐glass opacities are not pathognomonic. Second, ADAMTS13 and reticulocyte count were not measured; the LDH elevation reflects tissue ischemia and tumor burden rather than hemolysis. HIV and liver disease were not screened. Third, the anticoagulation response and the consequence of self‐discontinued rivaroxaban are subject to the limits of a single case.

When a patient shows up with CTPA‐negative acute cor pulmonale and thrombocytopenia, think past solid tumors. Plasma cell disorders like MM can cause PTTM, and an elevated globulin on routine labs might be the only warning. Anticoagulation and pulmonary vasodilators can buy a window for definitive therapy, even though the ultimate prognosis depends on controlling the underlying disease.

Author Contributions

J.C. collected clinical data, drafted the manuscript, and participated in ICU management. B.Z. contributed to clinical decision‐making and critical revision. X.D. supervised study design, contributed to diagnostic reasoning, revised the manuscript, and served as corresponding author. All authors read and approved the final version.

Ethics Statement

This case report was approved by the Ethics Committee of Liangxiang Hospital, Fangshan District, Beijing. Written informed consent was obtained from the patient's family.

Conflicts of Interest

The authors declare no conflicts of interest.

Cui J, Zhao B, Ding X, “Acute Cor Pulmonale Caused by Pulmonary Tumor Thrombotic Microangiopathy as the Initial Presentation of Multiple Myeloma: A Case Report,” Pulmonary Circulation 16 (2026): e70425. 10.1002/pul2.70425.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.