Introduction
During the initial evaluation of a patient suspected of pulmonary hypertension (PH), there are numerous laboratory tests which may help raise suspicion of PH or suggest possible PH- associated conditions. One goal of laboratory testing is to identify any treatable parameters that may be impacting pulmonary hypertension. Once diagnosed with PH, a patient will be on medications that can affect the liver and thus basic liver laboratory testing is necessarily performed to establish a baseline level of liver functioning.
Hematology
Complete Blood Count (CBC)
Individual tests include:
- White Blood Cell Count (WBC)–elevations suggest infection or use of steroids; some immunosuppressants can depress WBC
- Red Blood Cell Count (RBC)–in the evaluation of PAH, this can help identify anemia which may impact a patient’s level of dyspnea.
- Hematocrit–if elevated may provide a clue that patient may be hypoxic at times.
- Platelet Count–levels are directly related to blood coagulability. Also, platelet count is assessed before
- and during treatment with certain PAH medications that can impact or cause thrombocytopenia, such as with some prostacyclins.
Blood Coagulation Parameters
- Prothrombin Time (PT)–measures the amount of time for blood to clot after addition of tissue factor.
- The usual reference range for PT is 12-13 seconds.
- International Normalized Ratio (INR)–the ratio of the Test PT to the Normal PT, or INR = (PTtest/PTNormal) ISI, where ISI refers to the specific performance of a batch of tissue factor compared to an international reference tissue factor (usually with a value of 1.0–2.0).
- Partial Thromboplastin Time (PTT)–normal range is between 30 and 50 seconds. Shortening of the PTT
- may suggest an increased risk of thromboembolism.
Chemistries
Control of blood pressure and renal function are linked together, and the function of the kidney directly impacts levels of blood electrolytes. Aside from the well-known renin-angiotensin-aldosterone-system (RAAS) which ties sodium metabolism, production of vasoconstrictors (angiotensin), and water metabolism to blood pressure control, the kidney is sensitive to changes in blood pressure and blood oxygenation.
There are several commonly assessed parameters of renal function, including:
- Electrolytes–including sodium (Na+), potassium (K+), and chloride (Cl-)
- Creatinine–a breakdown product of skeletal muscle which is normally removed by the kidneys.
- Normal values for urinary creatinine:
- 14 to 26 mg per kg of body mass per day for men
- 11 to 20 mg per kg of body mass per day for women
- Normal values for serum creatinine:
- 0.7 to 1.3 mg/dL for men
- 0.6 to 1.1 mg/dL for women
- Albumin–reduction in serum albumin may suggest renal failure (i.e. nephrotic syndrome)
- Blood Urea Nitrogen (BUN)–urea is a product of protein metabolism that is normally excreted by the kidneys. Elevation of BUN can indicate renal failure, congestive heart failure, hypovolemia, or a number of other conditions. Several commonly used drugs can elevate a patient’s BUN. Normal BUN values range from 6–20 mg/dL, however values can vary by laboratory.
Liver Function Tests (LFTs)
Liver function tests are tests which are used to screen for liver inflammation and damage. In patients with PH, the increased pressure in the pulmonary arteries contributes to right heart failure, resulting in a backup of blood in the venous circuits leading to the right heart. This also includes the hepatic vessels, and the resulting hepatic congestion can lead to liver damage. In patients already diagnosed with PH on therapy with bosentan, it is necessary to check liver function on a monthly basis.
Liver function tests examine a number of important measures of hepatic function, including serum and urinary bilirubin, alanine transaminase (ALT), and aspartate aminotransferase (AST). Labs often are obtained to look for evidence of prior or current infection with Hepatitis B or C, which can lead to liver disease which can sometimes cause portopulmonary hypertension.
- Alanine transaminase (ALT)–an enzyme found in highest concentrations in the liver. It is released into the blood upon hepatic injury, and its’ normal blood range is 10-40 international units per liter (IU/L).
- Aspartate aminotransferase (AST)–an enzyme found predominantly in liver and cardiac/skeletal muscle that is released into the blood upon liver or myocardial damage, ischemia, or disease. Normal serum range is 10 to 34 IU/L.
- Bilirubin–a protein released into serum upon breakdown of red blood cells by the liver; it is also found in bile. Normally, the liver helps break down bilirubin so it can be removed from the body via the feces. Large amounts of bilirubin in the blood can lead to jaundice, which is a yellowish color of the skin, mucus membranes, or eyes. Normal serum values are: total bilirubin-0.3 to 1.9 mg/dL, direct bilirubin (also called conjugated bilirubin)-0 to 0.3 mg/dL.
Immunological Tests
Within many of the WHO classes of pulmonary hypertension, underlying disease contributes to the development of the pulmonary hypertension. A number of these diseases, such as connective tissue diseases (i.e. scleroderma, lupus, or mixed connective tissue disease), can be detected by use of specific serum markers in the form of antibodies.
- Antinuclear Antibody (ANA)–ANA can be produced in patients with lung diseases, such as primary pulmonary fibrosis or pulmonary hypertension, or can be positive in patients with connective tissue disease. ANAs on laboratory cellular staining exhibit different “patterns”, which are not specifically associated with any particular disease. However, a “speckled” pattern is more commonly observed in patients with scleroderma, which is associated with WHO Group 1 PAH as well as Group 3 PH in patients with interstitial lung disease associated with connective tissue disease.
- Human Immunodeficiency Virus (HIV)–all patients suspected of having pulmonary hypertension should be tested for the presence of HIV. PAH is an uncommon complication of HIV. However, PAH occurs more frequently in the HIV-positive population than in the HIV-negative population. To date, there are no data to suggest that having HIV leads to more severe PAH. The relationship between the potential interaction of these two disease etiologies is not clear.
Biomarkers
- Brain Natriuretic Peptide (BNP)–although the function of the heart is primarily to pump blood, it also has some endocrine functions. In response to excessive stretching due to the afterload induced by PH-associated pulmonary artery constriction, the ventricles produce a small peptide called brain natriuretic peptide. The principal functions of BNP are to reduce systemic vascular resistance as well as central venous pressure. BNP has been shown to be a marker of pulmonary hypertension and elevations in serum BNP are correlated with increases in PH-associated mortality. High levels of BNP are associated with poor outcomes in PAH.
Summary
Laboratory testing is essential to evaluate underlying causes which may be impacting or leading to the development of PAH.
References
1. Konkle BA. Bleeding and Thrombosis, in Harrison’s Principles of Internal Medicine, 17th Ed., Fauci AS et al eds., 2008, pp.363-369.
2. Dugdale DC, Medline Plus–Creatinine urine. (http://www.nlm.nih.gov/medlineplus/ency/article/003610.htm). August 21, 2011.
3. Dugdale DC, Medline Plus–Creatinine blood (http://www.nlm.nih.gov/medlineplus/ency/article/003475.htm). August 20, 2011. Dugdale DC, Medline Plus-ALT.(http://www.nlm.nih.gov/medlineplus/ency/article/003473.htm). February 13, 2013.
4. Dugdale DC, Medline Plus-AST. (http://www.nlm.nih.gov/medlineplus/ency/article/003472.htm). January 21, 2013.
5. Dugdale DC, Medline Plus-Bilirubin-blood, (http://www.nlm.nih.gov/medlineplus/ency/article/003479.htm). February 13, 2013.
6. McLaughlin VV, Archer SL, Badesch DB, et al, ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension, JACC, 2009; 53(17):1573-1619.
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