Hematologic diseases
Hematologic diseases, including sickle cell disease, gammopathies, and malignancies, can cause dyspnea primarily by decreasing the body’s ability to transport oxygen. This usually is due to anemia, but it also can be caused by increased viscosity or sickling. Suspect a hematologic cause of dyspnea when a patient repeatedly returns to your office complaining of progressive dyspnea on exertion and possible Raynaud’s-like symptoms.
Sickle cell disease
Sickle cell disease is a heterogeneous genetic disease with varied physical manifestations. The sickling phenomenon occurs in patients who inherit the homozygous hemoglobin S trait or heterozygous hemoglobin S and C (hemoglobin SC) disease. Sickle cell patients develop dyspnea due to comorbid anemia, infectious processes, or cardiopulmonary disease.
Cardiac disease is common and an often unrecognized comorbidity. It is the leading cause of mortality in adults with sickle cell disease, resulting in 26% of deaths (usually from pulseless electrical activity, pulmonary emboli, multiorgan failure, or stroke).17 Nonfatal cardiac complications may also develop, including chronic heart disease from prolonged increased cardiac output (leading to ventricular hypertrophy), heart failure, or arrhythmias; non-atherosclerotic MI;18 and hemosiderosis-induced cardiomyopathy from repeat blood transfusions.
Pulmonary-related complications may be chronic or acute and may include restrictive lung disease, chronic hypoxemia, pulmonary hypertension, and interstitial fibrosis. Acute chest syndrome and cor pulmonale cause sudden pulmonary disease. Acute chest syndrome is often caused by pneumonia, in situ thrombosis infarction of the lung, or embolic infarction from fat or bone marrow. It is a medical emergency that should be considered in any patient with pulmonary symptoms, fever, chest pain, or cough and an infiltrate on chest x-ray.
Treatment for acute chest syndrome consists of oxygen, aggressive analgesia, antibiotics (if infection is suspected), and transfusions. Research has shown that steroids provide improvement, but result in more hospital readmissions.19
Multiple myeloma and other hematologic malignancies
Multiple myeloma and Waldenstrom macroglobulinemia (discussed here), as well as leukemia, and other hematologic malignancies, can cause dyspnea or dyspnea on exertion through anemia, increasing blood viscosity, or direct lung involvement.
Multiple myeloma, a plasma cell neoplasm, is associated with anemia in 73% of patients at time of diagnosis.20 This is because of bone marrow destruction. Anemia prevalence increases in patients treated with chemotherapy because of the agent's adverse effects. The decision to treat with irradiated, leukoreduced red cell transfusion is based on anemia severity, the presence of symptoms, and whether the patient is currently undergoing chemotherapy.
Waldenstrom macroglobulinemia is an IgM-specific monoclonal gammopathy associated with a lymphoplasmacytic lymphoma in the bone marrow. Dyspnea results from hyperviscosity syndrome, hemolytic or other anemias, and/or direct lung involvement including pleural effusion, pulmonary infiltrates, or a mass.
Hyperviscosity syndrome usually results in neurologic symptoms such as vision changes, headaches, vertigo, dizziness, dementia, or other changes in consciousness. Heart failure, which is often associated with comorbid anemia, can develop in severe cases.
Patients are generally asymptomatic if serum viscosity is <3 centipoises (cP). Symptoms increase in frequency and severity with increasing serum viscosity so that about two-thirds (67%) of patients have symptoms when viscosity is >4 cP and 75% have symptoms when viscosity is >5 cP.21