Diffuse Alveolar Hemorrhage

Chapter 78

Diffuse Alveolar Hemorrhage

Lee Gazourian, Maryl Kreider and Gerald L. Weinhouse

Diffuse alveolar hemorrhage (DAH) is characterized by the clinical triad of (1) blood in the terminal airspaces, (2) anemia, and (3) infiltrates on chest radiographs. In DAH, bleeding occurs at the level of the alveolar capillaries, arterioles, or venules. Hemoptysis may not occur, as the bleeding is located in these most distal portions of the lung and may be absorbed before expectoration. However, bronchoalveolar lavage (BAL) will still yield erythrocytes and hemosiderin-laden macrophages. Patients with lethal DAH die of refractory hypoxemia and not exsanguination or airway obstruction.

This chapter reviews the clinical presentation of DAH, describes an approach to its diagnosis, and briefly summarizes the management approach to the most common causes of DAH.

Clinical Presentation

Patients typically present with acute to subacute symptoms of dyspnea, cough, and hemoptysis. Any fever at presentation is usually related to the underlying etiology. Absent hemoptysis, these very nonspecific presentation findings require a high degree of clinical suspicion to confirm the diagnosis. Untreated DAH is often life threatening and is associated with a poor prognosis. Consequently, the clinician must maintain a high index of suspicion and work quickly to diagnose DAH, identify the likely etiology, and select an appropriate therapy.

Physical Examination

The physical examination is nonspecific but may provide clues to an underling systemic vasculitis, collagen vascular disorder, or cardiac etiology. Physical findings may be indistinguishable from those found in other alveolar filling processes (i.e., pulmonary edema), which may help explain why the diagnosis is initially unexpected in the majority of cases.

Radiology

The chest radiograph (CXR) in DAH is usually abnormal but nonspecific. Alveolar infiltrates are usually present and diffuse, but they may rarely be focal or asymmetric. The diffuse infiltrates are often indistinguishable from those of pulmonary edema. The computed tomographic (CT) scan of the lung is characterized by a nonspecific alveolar-filling pattern, which may demonstrate areas of consolidation interspersed with areas of ground-glass attenuation and other normal areas. A CT scan may be useful diagnostically in detecting ground-glass opacities when DAH is suspected in the presence of a normal CXR. However, once DAH is suspected with an abnormal CXR, CT rarely offers additional benefit.

Laboratory Evaluation

Initial screening tests should include a complete blood count including platelet count, prothrombin and partial thromboplastin times, blood urea nitrogen and creatinine determinations, and urinalysis including the urine sediment. An admission electrocardiogram may reveal occult cardiac disease and provide a baseline in the event that hemodynamic compromise with cardiac injury ensues. Finally, sputum, if available, should be sent for Gram stain and culture.

Serologic studies are an important diagnostic tool in DAH. However, their results often are unavailable for several days, so they often do not contribute to the acute management of the patient. Antinuclear antibody (ANA) and anti–double-stranded DNA support the diagnosis of systemic lupus erythematosus (SLE). However, a small percentage of patients with SLE are seronegative. If a pulmonary-renal syndrome is suspected, titers of both antiglomerular basement membrane antibody (anti-GBM) and antineutrophil cytoplasmic antibody (ANCA) should be sent. A high titer of anti-GBM supports the diagnosis of Goodpasture syndrome. ANCA titers are reported as either cytoplasmic (C-ANCA) or perinuclear (P-ANCA). A high C-ANCA titer with a positive enzyme-linked immunosorbent assay (ELISA) for antibody to proteinase 3 (PR3) is highly specific and sensitive for granulomatosis with polyangiitis (GWP, historically known as Wegener’s granulomatosis). A high P-ANCA titer with a positive ELISA for antibody to myeloperoxidase (MPO) is associated with several small-vessel vasculitides, including microscopic angiitis (which can cause DAH) as well as Churg-Strauss syndrome and, rarely, some drug reactions. Many other disorders, including infections, can result in positive C-ANCA or P-ANCA, emphasizing the need to test for antibody to PR3 or MPO by ELISA.

Significant obstruction or restriction from pulmonary function testing could suggest an underlying lung disease that may be leading to the hemorrhage. The diffusing capacity (DLco) is frequently touted as a way to diagnose pulmonary hemorrhage. The red blood cells in the air spaces absorb the carbon monoxide administered during the test, leading to an elevation in the DLco. However, patients with DAH in the ICU are rarely stable enough for pulmonary function testing to be practical.

Bronchoscopy

Bronchoscopy with bronchoalveolar lavage (BAL) should confirm DAH by documenting an increasing red blood cell count in serial aliquots from the same location. In addition, bronchoscopy aids in the exclusion of an associated infectious process and specimens of the BAL should be sent for bacterial, fungal, and viral cultures, as well as Pneumocystis jiroveci (carinii) when clinically indicated.

It has been suggested that ≥ 20% hemosiderin-laden macrophages in BAL is diagnostic of DAH. However, these findings vary according to the timing of the bronchoscopy in relation to the onset of bleeding. Increasingly bloody BAL returns are most sensitive and specific in the first 48 hours of bleeding before spillage can occur, and it takes 48 hours for macrophages to become hemosiderin laden. In addition, hemosiderin-laden macrophages can be found in patients with biopsy-proven diffuse alveolar damage, without DAH.

Surgical Lung Biopsy

Surgical biopsy may be warranted when serologic workup fails to provide a diagnosis. Likewise, if a patient is deteriorating and the serology is pending, biopsy should also be considered. Empiric therapy often begins before establishing a diagnosis in patients admitted to the ICU because of DAH; however, the diagnosis of the underlying etiology (and exclusion of unsuspected other diagnoses) will ultimately be necessary to determine the duration and intensity of immunosuppression.

Open lung biopsy or the less invasive video-assisted thoracoscopic surgery (VATS) is the preferred means of biopsy. The yield of transbronchial biopsies is limited by sampling error and the small amount of tissue obtained by this procedure. Lastly, if a pulmonary-renal syndrome, such as Goodpasture syndrome, is suspected, one should consider renal biopsy to establish the diagnosis.

Secondary (Integrated) Diagnostic Workup (Figure 78.1)

Once the diagnosis of DAH has been established with BAL and concomitant infection ruled out, a more detailed medical and exposure history should be taken to look for evidence of collagen vascular disease, vasculitis, and toxin/drug exposure. A urinary sediment should be examined for evidence of renal involvement. If there is renal involvement, appropriate serologies including ANA, anti-GBM, and ANCA should be sent. If there are symptoms or evidence of sinus disease in addition to evidence of renal involvement so that there is a high suspicion for GWP, a sinus biopsy should be considered; otherwise, a kidney biopsy is typically preferred to confirm the diagnosis. For the critically ill patient with a clinical story compelling for any of the pulmonary renal syndromes, treatment with high-dose steroids can begin while awaiting the tests results, as most of these syndromes are treated similarly (discussed later).

Figure 78.1 Evaluation of diffuse alveolar hemorrhage.

Absent evidence of kidney involvement by urinalysis and serum creatinine, then the same serologies should still be sent. In addition, one should send the patient’s blood for an antiphospholipid antibody, cryoglobulins, and hepatitis B serologies. If all of these are unrevealing, surgical lung biopsy may be necessary, although some patients may be too ill or unstable for biopsy. The major advantage of a biopsy is a more confident diagnosis in the future when considering ongoing cytotoxic therapy.

One exception to this evaluation is a patient who has had a stem cell transplant. If BAL confirms DAH and excludes infection, consider empiric therapy without additional testing.

Differential Diagnosis of DAH

The causes of DAH may be categorized into three groups based on histologic findings: (1) those with vasculitis or capillaritis present, (2) those with no associated vasculitis or capillaritis (“bland hemorrhage”), and (3) those associated with another process or condition. Typical changes seen in capillaritis include fibrin thrombi occluding the capillaries of the alveolar septae, fibrinoid necrosis of the capillary walls, and perivascular and interstitial accumulation of fragmented neutrophils with an associated extravasation of red blood cells into the alveoli and interstitium. In bland hemorrhage there is extravasation of the red blood cells without any accompanying inflammation or destruction of the capillaries, venules, or arterioles. Finally, the extravasation can occur in the setting of another lung pathology such as diffuse alveolar damage, metastatic tumor, lymphangioleiomyomatosis, sarcoidosis, or other disorders.

Table 78.1 illustrates the multiple etiologies that should be considered when evaluating a patient with DAH.

TABLE 78.1

Etiologies of Diffuse Alveolar Hemorrhage Categorized by Histologic Appearance

Capillaritis	Bland	Secondary
*ANCA Associated* GWP Microscopic polyangiitis Churg-Strauss syndrome Essential mixed cryoglobulinemia Behçet’s syndrome Henoch-Schönlein purpura IgA nephropathy *Immunologic* Goodpasture syndrome Connective tissue disorder Acute lung rejection Antiphospholipid antibody syndrome Cryoglobulinemia *Isolated Pauci–Immune* Pulmonary capillaritis Drug induced Propylthiouracil All-trans retinoic acid Diphenylhydantoin *Thrombocytopenias* Idiopathic thrombocytopenic purpura Thrombotic thrombocytopenic purpura	Drugs —Anticoagulants —Phenytoin —Penicillamine —Mitomycin —Nitrofurantoin —Cocaine —Amiodarone —Pesticides Mitral stenosis and mitral regurgitation Pulmonary veno-occlusive disease Infection HIV, endocarditis Toxins Isocyanates, trimellitic anhydride, pesticides, detergents Idiopathic pulmonary hemosiderosis Coagulation disorders	Diffuse alveolar damage Pulmonary embolus Sarcoidosis High altitude pulmonary edema Barotrauma Infection Invasive aspergillosis, CMV, legionella, hantavirus, leptospirosis Post-BMT Malignancies in the lung Lymphangioleiomyomatosis Pulmonary capillary hemangiomatosis

ANCA, Anti-neutrophil cytoplasmic autoantibody; GWP, granulomas with polyangiitis.

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Tags: Intensive Care Unit Manual Expert

Jul 7, 2016 | Posted by admin in CRITICAL CARE | Comments Off

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