Pulmonary hemorrhage, in a broader sense, is a life-threating condition described by the bleeding or oozing of blood from the total respiratory tract including the lung mainly due to the disruption of the basement membrane of alveolar-capillary. Pulmonary hemorrhage is a complete ominous condition with a very high mortality rate in newborns. The actual cause of the disease is still under research and the disease is characterized by the pattern of clinic-radiologic features like anemia, hemoptysis or imaging shows airspace opacities. In this review article, we mainly focus on better understanding of the disease: its symptoms, causes, epidemiology, pathophysiology, associated risk factors, prognosis, diagnosis, treatment and preventive measures.
What is Pulmonary Hemorrhage?
Pulmonary hemorrhage is a catastrophic acute discharge of blood or continuous bleeding from the lung, upper respiratory tract, endotracheal tube or alveoli. The onset of the disease is usually characterized by the overflowing of blood during coughing, i.e., hemoptysis or deficiency of oxygenation resulting in cyanosis. In severe cases, pulmonary hemorrhage involves very high neonatal mortality rate associated with bleeding from other sites. In this case, an immediate treatment is required including positive pressure ventilation, tracheal suction, oxygenation, or detection and correction of underlying abnormalities. Blood transfusion is also sometimes required.
Pulmonary hemorrhage is commonly subdivided into two broad categories or types.
- Diffuse Alveolar Hemorrhage or DAH and Diffuse Pulmonary Hemorrhage or DPH
- Localized Pulmonary Hemorrhage
Symptoms of Pulmonary Hemorrhage
Both in children or adult, the signs of pulmonary hemorrhage or alveolar hemorrhage are almost same. The common symptoms include:
- Diffused alveolar bleeding either alone or together with eye lesions, rashes, hepatosplenomegaly, purpura, etc.
- Coughing associated with blood discharge, dyspnea, and fever.
- Sub-acute or acute condition results in a complete respiratory failure which may require mechanical ventilation otherwise can be fatal.
- Hemoptysis is a common symptom but not observed in one-third of the patients because of increase in alveolar volume.
- Continuous bleeding with decreased hematocrit (HCT) level resulting in anemia.
- Recurrent episodes of this disease lead to diffusion of alveolar infiltrate, collagen deposition in insignificant airways, organizing pneumonia, and fibrosis.
Epidemiology of Pulmonary Hemorrhage
The occurrence of pulmonary hemorrhage is very rare and affects only 1 in every 1,000 live born babies. Pulmonary hemorrhage usually attack 7 out of 10% of autopsies in newborns in which about 80% autopsies have been seen very much in preterm infants. In an extreme condition, pulmonary hemorrhage is found to be combined with bleeding from different sites of the body which involves about one-third of the lung and this condition is highly mortal.
Prognosis of Pulmonary Hemorrhage
Pulmonary hemorrhage usually varies with the progression of the underlying source of the disease. In the case of repeated occurrence, pulmonary hemorrhage can result in massive fibrosis or sometimes leads to pulmonary hemosiderosis. Both of these conditions are featured by the development of ferritin aggregates in the alveoli which may cause a very toxic effect. Patients often need mechanical ventilation and sometimes can die due to hemorrhage-related respiratory failure. Depending on the cause of this disease, survival rate is near about 2 years which can vary between 20% and 90%. In some patients, COPD or chronic obstructive pulmonary disease can also happen in combination with persistent DAH or in severe cases of microscopic polyarteritis.
Causes of Pulmonary Hemorrhage
In the case of newborn, the major cause of pulmonary hemorrhage is infant prematurity. Other factors manifesting this disease symptom include maternal cocaine addiction, bleeding disorder or perinatal asphyxia, toxemia of pregnancy, breech delivery, IRDS or Infant Respiratory Distress Syndrome, hypothermia, erythroblastosis fetalis, ECMO or Extracorporeal Membrane Oxygenation, any sorts of infection, usage of exogenous surfactants etc.
Other factors that are responsible for causing pulmonary hemorrhage in adults as well as children are the following:
- Wegener granulomatosis (granulomatosis combined with polyangiitis);
- Isolated pauci-immune pulmonary capillaritis;
- Microscopic polyangiitis;
- IgA nephropathy;
- Immune complex-linked glomerulonephritis;
- Hypocomplementemic urticariavasculitis syndrome;
- Anti-phospholipid antibody syndrome;
- Behçet's disease or syndrome;
- Cryoglobulinemia, i.e. presence of huge amount of cryoglobulins in blood;
- HSP or IgA vasculitis;
- Spontaneous thrombocytopenic purpura and coagulative thrombocytopenic purpura;
- Acute lung-graft rejection;
- Mitral regurgitation and mitral stenosis;
- Pauci-immune glomerulonephritis;
- Anticoagulants, thrombolytics or antiplatelet agents; disseminated intravascular coagulation;
- Pulmonary veno-occlusive disease;
- Drugs like Methotrexate, Propylthiouracil, Amiodarone, Diphenylhydantoin, D-penicillamine, Mitomycin, Sirolimus, Nitrofurantoin, Haloperidol, Bleomycin (with increased concentration of oxygen), all-trans-retinoic acid, Montelukast, Infliximab, Zafirlukast, and Gold;
- Malignant disorders (Kaposi Sarcoma, Pulmonary Angiosarcoma, Acute Promyelocytic Leukemia, Multiple Myeloma, Lymphangioleiomyomatosis, etc.);
- Tuberous sclerosis;
- Toxins like Isocyanates, Trimellitic anhydride, pesticides, crack cocaine, and detergents;
- Infections for eg., cytomegalovirus infection, invasive aspergillosis, herpes simplex virus infection, legionellosis, hantavirus infection, leptospirosis, HIV, mycoplasmosis, infective endocarditis and other bacterial pneumonia;
- Solid organ or bone marrow transplantation;
- Diffuse alveolar damage;
- Isolated pauci-immune pulmonary capillaritis;
- Pulmonary embolism;
- Barotrauma or high-altitude pulmonary edema;
- Pulmonary capillary hemangiomatosis;
- Autoimmune disorders (e.g., Connective tissue disorders, Goodpasture syndrome, Systemic Vasculitides, and Anti-phospholipid Antibody Syndrome);
- Idiopathic Pulmonary Hemosiderosis;
Pathophysiology of Pulmonary Hemorrhage
The actual pathophysiology of the disease is still unclear. However, it is assumed that pulmonary hemorrhage could be caused by hemorrhagic pulmonary edema since HCT is usually less in blood, whereas concentration of different small proteins is higher in plasma. It is also assumed that infants generally suffer from asphyxia threat together with myocardial failure which thereby increases the pulmonary microvascular pressure leading to pulmonary hemorrhage. Consequently, mild bleeding is also seen from pulmonary interstitial spaces and alveoli. Other factors that contribute to the increase of filtration from pulmonary capillaries are increased alveolar surface tension, hypervolemia, reduced concentration of plasma proteins, and lung damage.
DAH can also occur due to severe damage of pulmonary blood vessels resulting in accumulation of blood into the alveoli and therefore leads to disruption in gaseous exchange. The precise pathophysiology although differs with the cause of the disease but this ailment has been seen to attack people of ages between 18 and 35 years.
Risk Factors of Pulmonary Hemorrhage
The common risk factors that increase the chance of pulmonary hemorrhage include:
- Gender. Males are affected more often.
- Premature baby
- Intrauterine growth restriction or IUGR, i.e., the growth of the baby is not normal within the uterus.
- PDA or Patent Ductus Arteriosus, the condition when the babies are born with the defective closer of ductus arteriosus.
- RDS or Respiratory Distress Syndrome in newborn.
Complications of Pulmonary Hemorrhage
Repeated incidence of pulmonary hemorrhage can lead to the following conditions:
- Organizing pneumonia
- Deposition of collagen proteins inside the minute airways
- Pulmonary fibrosis
Diagnosis of Pulmonary Hemorrhage
The common method of identifying the disease symptoms as well as the progression includes the following:
- Common Laboratory Investigations: These include:
- Platelets count
- Bronchoalveolar lavage
- Complete Blood Count or CBC
- Coagulation studies
- Serologic tests (antinuclear antibody, anti-glomerular basement membrane or anti-GBM antibodies, anti-double-stranded DNA or anti-dsDNA, anti-phospholipid antibody, and anti-neutrophil cytoplasmic antibodies or ANCA).
- Bronchoscopy including BAL, if alveolar hemorrhage is present with frank blood, or presence of >5% haemosiderin-laden macrophages), excluding infection and airway source.
- Pulmonary function tests including elevated DLCO, usually restrictive is greater than an obstructive pattern with the low exhalation of Nitric Oxide.
- Chronic or acute anemia.
- UEC and urinalysis for pulmonary-renal syndromeslike HSP, Wegener's, or Goodpasture syndrome.
- Increased CRP and ESR
- Autoimmune screening
- Biopsies of kidney and lung (e.g., PR3-ANCA positive or MPO-ANCA positive).
- Radiographic Imaging: The radiographic diagnosis includes –
- CXR for detecting patchy alveolar opacification (may be normal sometimes)
- Chest X-ray
- CT chest for detecting spreading of the disease in normal areas
- HRCT pattern varies with the beginning of the hemorrhage.
Serologic tests are performed to find out the exact underlying disorders. Echocardiography may also require if there is mitral stenosis. Lung or renal biopsy is often done when a cause is undetectable or if the progression of the disease is very fast. Specimens usually show blood along with numerous siderophages and erythrocytes; lavage fluid characteristically remains hemorrhagic or becomes highly hemorrhagic just after consecutive sampling.
Treatment of Pulmonary Hemorrhage
Treatment for pulmonary hemorrhage involves the correction of the cause responsible for the occurrence of the disease. Corticosteroids and mainly cyclophosphamide are used for the treatment of connective tissue disorders, Goodpasture syndrome, and vasculitides. However, the affectivity of Rituximab in the treatment of DAH has not been observed. Sometimes plasma exchange is done for the treatment of Goodpasture syndrome. Various studies have exposed that the highly active recombinant Human Factor VII is successfully used for treating various unresponsive pulmonary hemorrhage, but this kind of therapy is a little controversial as it shows other multiple thrombotic complications in patients.
Other probable treatments for pulmonary hemorrhage include bronchodilators, tracheal suction, supplemental oxygen, mechanical ventilation, protective strategies by decreased involvement of lung, positive pressure ventilation, intubation with bronchial tamponade, and reversal of coagulopathy.
Prevention of Pulmonary Hemorrhage
Tremendously low birth weight neonates with severe pulmonary hemorrhage have a high risk of having very reduced long-term recovery. Prophylactic indomethacin lessens the risk of early-stage severe pulmonary hemorrhage mainly by correcting the effect of symptomatic PDA. However, even after the proper management of the usage of antenatal steroids, gestational age, and gender, prophylactic indomethacin reduced the risk of extreme pulmonary hemorrhage by only 26% and cannot prevent the occurrence of the diseases after the first week of birth.
The management of pulmonary hemorrhage also requires the following things:
- Airway Breathing Condition or ABCs.
- Proper thorough treatment of the underlying cause.
- Stoppage of suspected causative medications.
- Frequently treated with corticosteroids like IV methylprednisolone 500mg for continuous 5 days followed by oral courses.
- Immunosuppressants can also be used as a second line of treatment.
- If Ig-mediated then consider plasmapheresis.
- Factor VII needs further assessment.
Lifestyle and Coping with Pulmonary Hemorrhage
The coping with pulmonary hemorrhage condition takes time. One must take a good care post this condition. Avoiding heavy and exhausting work is recommended. One must look for relapse of symptoms to take immediate action.
The outcome of serious pulmonary hemorrhage basically depends on the actual underlying cause of the disease. In order to reduce the effect of the disease preliminary airway pressure is needed to be increased relatively either by high-frequency ventilation or by increasing positive end-expiratory pressure or PEEP, i.e., 6-10 cm H2O. The proper detection and correction of the underlying abnormalities should be done specially, in the case of coagulation disorders. If the blood discharge is more then quick blood transfusion is necessary to maintain proper circulating blood volume. Usually, in the case of severe pulmonary hemorrhage, the mortality rate ranges from 30% to 40%.