Radiographic aspects of occult pulmonary haemorrhage

Clin. Radiol. (1978) 29, 139-143 RADIOGRAPHIC ASPECTS OF OCCULT PULMONARY HAEMORRHAGE P. E. S. PALMER, T. N. FINLEY, W. L. DREW and D. W. GOLDE*

From the Department of Radiology, U.C Davis School of Medicine, Davis, California; Department of Medicine, Veterans Administration Hospital, Martinez, California; Mount Zion Hospital, San Francisco, California; and Department of Medicine, University of California, Los Angeles, California

Patients with leukaemia, on anticoagulant therapy, or with disseminated intravascular coagulation may develop occult pulmonary haemorrhage; it will mimic pulmonary oedema, pulmonary hemosiderosis or opportunistic infections. It can be diagnosed by bronchopulmonary lavage. The radiographic changes are described and the differential diagnosis discussed in a series of 12 such patients.

INTRODUCTION We previously described groups of leukaemic patients with thrombocytopenia and anticoagulated patients who developed unexplained dyspnoea, anaemia, and densities on their chest films (Golde et al., 1975; Finley et al., 1975). Bronchopulmonary lavage was helpful in establishing that the cause of their abnormal radiographic findings was pulmonary haemorrhage. The haemorrhages occurred in an occult manner, without a haemoptysis. Recognition of this syndrome (occult pulmonary haemorrhage) is important because platelet transfusion or cessation of anticoagulation can be lifesaving. Also, biopsy procedures are particularly dangerous in patients with bleeding diathesis. Little has been written about such occult pulmonary haemorrhage. However, in a recent review of the radiographic findings in immunocompromised patients, Blank et al. (1973) found that 15 of 246 cases with leukaemia, malignant lymphoma, or Hodgkins disease had biopsy proven haemorrhage. The lesions developed rapidly and were often extensive. They noted that haemoptysis was uncommon. We have collected our radiographic data on patients with this syndrome. MATERIAL AND METHODS

There were 12 patients with evidence of occult pulmonary haemorrhage: nine patients with thrombocytopenia, and three anticoagulated patients. The pertinent clinical data are summarised in Table 1 and * Supported in part by N.I.H. Grant 1 E01 HC 17495. Request for reprints should be addressed to Dr T. N. Finley, Professor of Medicine, U.C. Davis, Veterans Administration Hospital, 150 Muir Road, Martinez, California 94553.

the case histories are in previous publications (Golde etal., 1975; Finley etal., 1975). The bronchopulmonary lavage technique has been described previously (Finley et al., 1967; Golde et al., 1975). Aliquots of the lavage fluid were submitted for smears (Gram, acid-fast, and methenamine silver stains), wet mount, and viral, bacteriological, and fungal culture. Some of the material was processed for cytological and histological examination. The remainder was centrifuged at 150g for 7rain. The cell pellet was resuspended in Hank's balanced salt solution with 15% foetal calf serum. Cytocentrifuge preparations were made and stained for haemosiderin with the ferrocyanide reagent and for haemoglobin with benzidine. Differential counts were performed on Giemsa-stained slides. The haemosiderin content o f pulmonary macrophages was measured as previously described (Finley et al., 1975). Seven healthy volunteers, five of them cigarette smokers, served as controls, together with two thrombocytopenic patients with leukaemia and lymphoma, in w h o m the diagnosis of Pneumocystis carinii pneumonia was made by bronchopulmonary lavage. The haemosiderin content of the alveolar macrophages was greatly increased in all patients. Also, many of the cells contained haemoglobin which had not yet been degraded. A presumptive diagnosis of pulmonary haemorrhage was based on these findings.

RADIOLOGY

There was no distinctive radiological pattern: the changes on the chest radiographs were progressive but variable (see Table 1). The process may begin with a fine granular appearance (similar to many cases of pulmonary haemosiderosis) and progress to more

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CLINICAL RADIOLOGY

Table 1 - Case summaries

Prothrombin/time (s)

Chest X-ray

F/69

Thrombophlebitis

24

Bilateral lower lobe nodular densities

M/42

Mitral prosthesis

54

Diffuse nodular densities

M/70

Lupus erythematous

6 M/12

Acute myelogenous leukaemia

7 M/54

Acute myelogenous leukaemia

14 000

Diffuse bilateral interstitial to nodular densities for five months

8 F/50

Acute myelogenous leukaemia

38 000

Diffuse bilateral nodular densities

9 M/56

Chronic lymphocytic leukaemia

45 000

Left lower lobe densities for five days

0 M/39

Renal transplant

50 000

Diffuse densities both lower lobes

1 F/40

Multiple myeloma

1 100

Diffuse, bilateral densities for one month

2 M/60

Chronic lymphocytic leukaemia

95 000

Bilateral lower lobe densities

3 M/13

Acute myelogenous leukaemia

20 000

Right lower lobe densities

4 F/69

Acute lymphocytic leukaemia (ALL)

30 000

Bilateral intersititial densities

On heparin Platelet count/ram 3 15 000

marked and more definite nodulation (Fig. la, b, c). The nodulation may be confluent (Fig. 2) or develop into a picture of pulmonary oedema (Fig. 3a), which is often migratory and may vary from day to day. The radiographic appearance may also mimic consolidation (Fig. 4). The majority of patient s is whom this diagnosis is first considered will have bilateral alveolar exudates, which m a y not be symmetrical (Fig. 5). There will probably be some interstitial oedema, and in many, there will be peribronchial thickening and clearly defined air bronchograms (Fig. lc, 6). Only one case in our series showed septal (Kerley's) lines. There was no consistent distribution, the apices being as often involved as the bases. In the majority, the heart size was normal and there was no evidence of congestive failure.

Upper lobe confluent densities Bilateral upper lobe densities.

DISCUSSION There is no way in which a confident radiological diagnosis can be made to the exclusion of all others, but the possibility of pulmonary haemorrhage must be considered in the differential diagnosis of any patient with leukaemia, of patients on anticoagulant therapy or with disseminated intravascular coagulation. Immunocompromised patients frequently develop pulmonary disorders which are difficult to diagnose. The chest radiographs exhibit shadows which are o f equal concern to the radiologist and the clinician because of the difficulty in determining the nature of the pulmonary process and its aetiology. Infection, particularly by 'opportunistic pathogens', is usually the first and most important consideration. Direct

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141

Fig. 1 - (a) Fine bilateral granula_t densities progressing to (b) more marked nodulafion. (c) The nodulation becomes more definite and there are air bronchograms.

infiltration of the lung parenchyma by neoplastic cells is also an important possibility. Occult pulmonary haemorrhage is anotKer significant cause of the abnormal chest radiograph in this setting. Patients taking anticoagulants may also develop intrapulmonary bleeding. Occult pulmonary haemorrhage is seldom recognised as a complication of anticoagulation. It has been found at necropsy in patients dying from bishydroxycoumarin (Dicoumarol) intoxication and has been confirmed experimentally in animals. A similar type of pulmonary haemorrhage can occur in disseminated intravascular coagulation, but in both of these conditions, haemoptysis is common. In leukaemia associated with thrombocytopenia bleeding into lung parenchyma may be responsible for considerable morbidity and mortality. The same general group of patients with haemostatic abnormalities may include idiopathic pulmonary haemosiderosis, in the majority of whom neither the radiological nor the clinical diagnosis is very difficult: almost all have haemoptysis.

The chest radiographs in occult pulmonary haemorrhage may be indistinguishable from pulmonary oedema or from idiopathic pulmonary haemosiderosis: if a fine granular pattern can be distinguished, towards the periphery beyond the oedema the possibility of haemorrhage should be strongly considered. Similarly, extensive 'oedema' in the absence of congestive heart failure may suggest bleeding in such patients. When pulmonary haemorrhage is massive, the patient may be dyspnoeic, and often acutely anaemic. A diagnosis of occult pulmonary haemorrhage may be established by bronchopulmonary lavage. The presence of blood in the lavage fluid can be suggestive but is not in itself diagnostic, because such bleeding could be related to the trauma of the procedure. In pulmonary haemorrhage, there should be a large increase in the haemosiderin content of alveolar macrophages. The macrophage ingests erythrocytes in the alveolar spaces and converts haemoglobin into haemosiderin. If the bleeding is recent, the haemosiderin score may not be greatly raised, but the pulmonary macrophages may be filled with haemoglobin or intact red cells: there may be insufficient time for the release of the iron from haeme. Bronchopulmonary lavage is safe, and it has the added advantage that if there is also infection, the lavage may allow identification of its cause. CONCLUSION The chest radiographs of patients with leukaemia can be extremely difficult to interpret. The patients are often febrile and their immunological and microbicidal defences are impaired. The possibility of

142

CLINICAL RADIOLOGY

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Fig. 2 - The nodules axe m o r e confluent. Fig. 3 - (a) Bilateral p u l m o n a r y haemorrhage, indistinguishable from p u l m o n a r y oedema. (b) from right lower lobe pneumonia. Fig. 4 - Bilateral alveolar exudates, with areas suggesting central necrosis. Easily mistaken for an opportunistic infection. Fig. 5 - Well-defined air bronchograms (left upper and right upper and lower lobes) in p u l m o n a r y haemorrhage.

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143

aspects in pulmonary infection patients with altered immunity. Radiologic Clinics of North America, 11, 175-190. Brown, O. L., Garvey, J. M. & Stern, C. A. (1965). Diffuse intrapulmonary haemorrhage caused by coumadin intoxication. Diseases of the Chest, 48,525-526. Finley, T. N., Aronow, A., Cosentino, A. M., & Golde, D. W. (1975). Occult pulmonary haemorrhage in anticoagulated patients. American Review Of Respiratory Disease, 112, 23-29. Finley, T. N., Swenson, E. W., Curran, W. S., Huber, G. L. & Ladman, A. J. (1967). Bronchopulmonary lavage in normal subjects and patients with obstructive lung disease, Annals of Internal Medicine, 66, 651-658. Golde, D. W., Drew, W. L. Klein, H. Z., Finley, T. N. & Cline, REFERENCES M. J. (1975). Occult pulmonary haemorrhage in Leukaemia. British Medical Journal, 2, 166-168. Blank, N,, Castellino, R. A. & Shah, V. (1973). Radiographic

Gram-negative bacterial pneumonia, opportunistic fungal viral diseases, and of Pneumocystis carinii infection, must be considered. We suspect that pulmonary haemorrhage occurs more frequently in leukaemic patients than has previously been noted. The diagnosis o f occult pulmonary haemorrhage should be suspected in the clinical situation of haemostatic defect with abnormal chest radiographs and can be supported b y identifying iron and haemoglobin in macrophages obtained at pulmonary lavage,