Secondary Logo

Journal Logo

Multiple myeloma with pulmonary embolism: a case report

YING, Ke-jing; ZHOU, Yong; JIANG, Hao; CHEN, En-guo; ZHOU, Pan

Section Editor(s): WANG, Mou-yue; Shen, Xi-bin

Case report

Edited by

Department of Respiratory Medicine (Ying KJ, Zhou Y, Chen EG and Zhou Pan), Department of Hematology (Jiang H), Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou 310016, China

Correspondence to: Dr. ZHOU Yong, Department of Respiratory Medicine, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou 310016, China (Email:

(Received April 26, 2006)

We report a rare case of a patient who died suddenly, in whom bilateral pulmonary artery thrombosis with multiple myeloma was found at autopsy. An estimate of the incidence of pulmonary embolism in myeloma patients based on postmortem examinations is about 3.2%. Hypercoagulability and decreased fibrinolytic capacity due to multiple myeloma were the probable causes of multiple thromboses.

Back to Top | Article Outline


A 63-year-old woman was admitted to the hospital on November 5, 2005 due to chest pain, cough and fever for one week.

The patient had been well until one week before admission, when she developed sudden left thoracic pain accompanied by nonproductive cough while she was doing some housework, and worsened with deep breathing. She also complained of mild shortness of breath and poor appetite. The next day, her pain subsided, and a low grade fever developed with a little bloody sputum. Her temperature was 38°C. In a local hospital, thoracic CT scan suggested a mass in the right pleural cavity, and right lung cancer was suspected. Antipyretic treatment was given but was not effective. She was then transferred to our hospital.

The temperature was 38.5°C, the pulse was 106 per minute, the blood pressure was 120/80 mmHg, and respirations were 24 per minute. Physical examination revealed that the patient was moderately well nourished. No jaundice, skin rashes, or petechiae were present. She had no jugular vein dilation. No superficial lymph nodes were palpated. She had no thoracic malformations or tenderness, and both lungs were clear. She had normal heart size, regular heart rhythm, and no murmur was heard. Her abdomen was soft without tenderness. No hepatosplenomegaly was palpated. The vertebral column and joints of the extremities were normal. No positive nervous system signs were found.

The white-cell count was 12.4 × 109/L, with 86 percent neutrophils, 10 percent lymphocytes, and 2 percent monocytes. The red cell count was 3.45×1012/L, Hb was 101 g/L, and platelet count was 303 × 109/L. Erythrocyte sedimentation rate (ESR) was 26 mm/1h. The bleeding time and coagulation time were 2 minutes. Urine analysis revealed the presence of protein. Liver enzymes were within the normal range, serum total protein was 57 g/L, albumin was 24 g/L, globulin was 33 g/L, A/G was 0.75, serum cholesterol was 870 mg/L, and creatine phosphokinase was 21 IU. An electrocardiogram showed tachycardia with increased left ventricular voltage (Fig. 1).

Fig. 1.

Fig. 1.

She was diagnosed right lower lobe pneumonia upon admission. And then she was given cefotaxime sodium for the first two days. After that, a thoracic CT scan, compared with the former CT scan from the local hospital, showed that no mass was present, but rather a progressive infiltration in the right lower lung and lamellar infiltrations in the left lung with a little pleural effusion (Fig. 2). Cefotaxime sodium treatment continued for 5 days, and the temperature dropped from 39.4°C to 37.4°C. Cough and shortness of breath subsided. At 11:30 a.m. on November 11, 2005, the patient suffered sudden shortness of breath and orthopnea. The respirations were 41 per minute, the heart rate was 165 per minute, the blood pressure was 100/49 mmHg. She had an irregular heart rhythm and decreased breath sounds in both lungs with a few moist rales. The arterial blood gas showed a pH of 7.396, PaCO2 of 32.2 mmHg, PaO2 of 66.5 mmHg, HCO3 of 19.9 mmol/L, and the SaO2 was 93%. She was transferred to the ICU immediately and intubated followed by mechanical ventilation. Dopamine was used to maintain the blood pressure. Thirty minutes later, the heart rate was 64 per minute, the blood pressure was 71/48 mmHg, SaO2 was 88%, and respirations were 26 per minute. An electrocardiogram showed ventricular premature beats, with coupled rhythm. Shortly after that, spontaneous rhythm and blood pressure were not detectable. Atropine, epinephrine and lidocaine were given intravenously, and cardiac massage was carried out immediately. However, the patient died after a 30-minute unsuccessful effort at resuscitation.

Fig. 2.

Fig. 2.

An autopsy was performed. Thrombosis of the bilateral main pulmonary arteries and their branches, renal arterioles, right common iliac vein, and left external iliac vein were identified, causing bilateral multiple pulmonary infarctions, left pleural effusion, interstitial nephritis with protein cast and hemorrhage in the renal portal fascia, with bilateral pneumonia and compensatory emphysema. We found that both lungs appeared dark red in color with congestion, especially the lower lobes. There were five infarction lesions in the right lobe, and three of which were triangle-shaped. A columnar grey-colored embolus was found in the main artery of the right lung. On the back side of the left lower lobe, several scattered triangle-shaped infarction lesions could be identified. There were three emboli in the main artery of the left lung; one was dark red and the other two were pale yellow. Microscopy findings were consistent with infarction with diffuse white and red blood cells. Intraluminal thromboemboli were found in the pulmonary artery, vein and arterioles near the borders of the infarctions.

Atherosclerotic lesions were identified in the left anterior descending and right coronary arteries. Old myocardial infarction scars and degeneration with fat infiltration were found. Microscopy findings showed a 50%—70% occlusion in the left anterior descending coronary artery and a 25%—50% occlusion in the right coronary artery.

Multiple myeloma lesions in the skull and ribs were detected and evaluated. Three discrete osteolytic skull and ribs defects were found in the patient. Microscopy findings showed diffuse abnormal plasma cells in the skull lesions and sternum with little remaining red marrow. These abnormal plasma cells could also be found in her spleen (Fig. 3).

Fig. 3.

Fig. 3.

Back to Top | Article Outline


The patient was an elderly woman who presented with chest pain, cough and fever. She also had bloody sputum with increased serum white blood cells and neutrophils. In the local hospital, computed tomography showed right lower lung infiltrations, hence bacterial pneumonia with pleurisy should be considered. Furthermore antibiotic therapy was partially effective. However, her chest CT scan could not be interpreted completely by inflammation. Lung cancer could be ruled out as the rechecked CT scan showed no mass and the infiltrations changed rapidly. Cefotaxime allergy could be ruled out because of discrepant clinical manifestations and poor responses to sufficient treatments.

The fourth likely diagnosis is acute myocardial infarction. The patient had sudden dyspnea that was immediately followed by a blood pressure drop, but no obvious chest pain with the sudden onset. Her EKG revealed premature ventricular contractions without T wave and ST segment changes. Her myocardial enzymes were normal. So, together with lung lesions, acute myocardial infarction can be ruled out.

The final most likely diagnosis is pulmonary embolism. Clinical presentations of pulmonary embolism vary dramatically. Pulmonary embolism can present either without symptoms or it can be life-threatening, and is usually obscured by another coexisting disease. The majority of preventable deaths associated with pulmonary embolism can be ascribed to a missed diagnosis rather than to a failure of existing therapies.1

However, this patient had no past medical history suggesting a high risk of pulmonary embolism. Pneumonia was first considered, and antibiotic therapy was partially effective. These facts decreased suspicion of pulmonary embolism. However, her second chest CT scan showed enlarged infiltrations, suggestive of a progressive disease despite antibiotic treatment. The lung infiltrations were triangle-shaped with its top aiming at the hila, which is consistent with pulmonary embolism (Fig. 2). Therefore, further evaluations were needed to determine whether she had pulmonary embolism and to determine the nature of the possible thrombogenic disease.

The typical manifestations of multiple myeloma are anemia, high serum globulin, typical bony pain, evidence of renal damage, and hypercalcemia. However, the patient only exhibited positive urine protein, pleuritic pain and pulmonary infiltrates, which could be accounted for by pneumonia and fever. Her chest X-ray did not indicate rib lesions. Hence, it was very difficult to consider the diagnosis of multiple myeloma.

Multiple myeloma may present as diffuse bony disease (myelomatosis), as solitary plasmacytoma of bone, or as extramedullary (extraosseous) plasmacytomas (EMPs).2 Whereas the most common thoracic disorders associated with myeloma are bone involvement or pulmonary infiltrates secondary to a complicating infectious process, primary thoracic involvement by myeloma occurs in less than 1% of cases.3

This patient developed another indirect thoracic manifestation of multiple myeloma, that of pulmonary thromboembolism. An estimate of the incidence of pulmonary embolism in myeloma patients based on postmortem examinations is about 3.2%.4

Thrombosis is recognized as the most frequent complication of malignant diseases. Patients with multiple myeloma are also predisposed to an increased incidence of venothromboembolic disease,5 and often have additional risk factors from prolonged bed rest, back pain, the presence of amyloidosis and hyperviscosity, all of which cause hypercoagulability.

There are at least four basic mechanisms of hypercoagulability specifically related to multiple myeloma. First, the high level of immunoglobulins decreases the efficacy of the fibrinolytic pathway. Immunoglobulins change the structure of fibrinogen, and compete with factor XIII, which is required for clot retraction and plasmin-induced lysis. Second, the abnormal immunoglobulin may act as an autoantibody directed against phospholipids or critical natural anticoagulants. Third, multiple myeloma has an inflammatory component caused by abnormal cytokine production and acute phase reactants, including high levels of C-reactive protein, IL-6, and tumor necrosis factor which have procoagulant activity. Fourth, non-factor V Leiden resistance to activated protein C (APC) has been recently demonstrated in patients with multiple myeloma.6

Multiple myeloma patients also have decreased fibrinolytic activity because of increased PAI-1 (plasminogen activator inhibitor-1) activity, which is positively related to elevated IL-6 levels.7 The risk of DVT is greater in those receiving multiagent chemotherapy (e.g., thalidomide or doxorubicin)8 and antiangiogenic drugs.9

In conclusion, multiple myeloma should be considered as a hypercoagulable state as a result of both increased procoagulant activity and decreased fibrinolytic capacity, and thus causes DVT and PTE. IL-6 may play a key role not only in survival and proliferation of plasma cells, but also in thrombogenesis. In multiple myeloma patients, especially with chemotherapy, prophylactic use of anticoagulants should be considered.

Back to Top | Article Outline


We thank Dr. Welch for his assistance with the preparation of this manuscript.

Back to Top | Article Outline


1. Fedullo PF, Tapson VF. Clinical practice. The evaluation of suspected pulmonary embolism. N Engl J Med. 2003; 349:1247-1256.
2. Kapadia SB. Multiple myeloma: a clinicopathologic study of 62 consecutively autopsied cases. Medicine 1980; 59: 380-392.
3. Shin MS, Carcelen MF, Ho KJ. Diverse roentgenographic manifestations of the rare pulmonary involvement in myeloma. Chest 1992; 102: 946-948.
4. Sakuma M, Fukui S, Nakamura M, Takahashi T, Kitamukai O, Yazu T, et al. Cancer and pulmonary embolism: thrombotic embolism, tumor embolism, and tumor invasion into a large vein. Circ J 2006; 70:744-749.
5. Srkalovic G, Cameron MG, Rybicki L, Deitcher SR, Kattke-Marchant K, Hussein MA. Monoclonal gammopathy of undetermined significance and multiple myeloma are associated with an increased incidence of venothromboembolic disease. Cancer 2004;101: 558-566.
6. Zangari M, Saghafifar F, Mehta P, Barlogie B, Fink L, Tricot G. The blood coagulation mechanism in multiple myeloma. Semin Thromb Hemost 2003;29: 275-282.
7. Yagci M, Sucak GT, Haznedar R.Fibrinolytic activity in multiple myeloma. Am J Hematol 2003;74: 231-237.
8. Zangari M, Anaissie E, Barlogie B, Badros A, Desikan R, Gopal AV, et al. Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy. Blood 2001;98:1614-1615.
9. Gabriel DA, Muga K, Boothroyd EM. The effect of fibrin structure on fibrinolysis. J Biol Chem 1992; 2367: 24259-24263.

pulmonary embolism;; multiple myeloma;; hypercoagulability;; autopsy

© 2006 Chinese Medical Association