What do blood tests test for and what do they tell us?
General information when looking at blood test results:
- All measurements done on a blood sample have a normal reference range and not a single absolute value
- Usually, 95% of normal values fall within the given reference range, which means that a value may fall outside the reference range and still be normal but the further from that range the more likely it is to suggest something is amiss
- Assays (the methods used to measure a substance in the blood) can vary from laboratory to laboratory and so the reference ranges can be different between laboratories, which means it is important to compare the test result to that laboratory’s specific reference range.
- Some tests have different normal ranges depending upon the age of the patient.
- For some tests, the different assays may quote results in different units, so comparison of test results done in different laboratories can be challenging.
Lab work discussed includes:
- Liver Function Tests (LFTs)
- Thyroid Function Tests (TFTs)
- Fat-soluble Vitamins
- Alpha Fetoprotein (AFP)
- Serum Amino Acids (**Metabolic diseases only)
- Complete Blood Count (CBC)
- Coagulation Labs
- Iron Studies (Fe-)
1. Liver Function Tests (LFTs) - This panel of tests usually includes bilirubin levels, transaminases, alkaline phosphatase, and albumin, and may include GGT
Bilirubin is produced from the breakdown of hemoglobin. Once the iron has been removed from the hemoglobin molecule and recycled by the body, the remaining complex molecule is carried by the blood to the liver. At this stage, the bilirubin is not soluble in water and is known as unconjugated bilirubin. In the liver the bilirubin is joined to another chemical, glucuronic acid, in a process known as conjugation. This makes the conjugated bilirubin water-soluble, and this allows it to be excreted from the body in the bile.
Some laboratories use specific assays for conjugated and unconjugated bilirubin, but many laboratories still report direct and indirect bilirubin levels. Although not exactly the same the direct bilirubin generally equates to the conjugated bilirubin and the indirect to the unconjugated bilirubin levels.
Total bilirubin: This is the sum of the conjugated, the unconjugated and the delta bilirubin or the sum of the direct and indirect bilirubin.
Conjugated or Direct bilirubin: Conjugated bilirubin rises in many diseases of the liver cells or obstruction of the bile ducts, and this is the form of elevated bilirubin that concerns us in the transplanted liver.
Unconjugated or Indirect bilirubin: Unconjugated bilirubin levels rise if there is excessive bilirubin production due to red blood cell breakdown in conditions such a hemolytic anemia, trauma and to a minor extent after blood transfusion, or if the liver is unable to conjugate in an exceedingly rare inherited condition, Crigler-Najjar syndrome, or is just slow to conjugate, a much more common condition known as Gilbert syndrome
Delta bilirubin: Delta bilirubin is mostly bilirubin bound to proteins in the blood and is not useful in determining the cause of elevated bilirubin but tends to be elevated with longer term elevation of the conjugated bilirubin
- Aspartate aminotransferase (AST) (aka serum glutamic oxaloacetic transaminase (SGOT))
- Alanine aminotransferase (ALT) (aka serum glutamic pyruvic transaminase (SGPT))
When the liver cells are distressed or injured, in liver transplant recipients this may be due to rejection, infection or bile duct problems, these proteins escape into the bloodstream. Their concentrations in the blood rise in rough proportion to the severity of liver cell damage.
The AST tends to be most sensitive in that it rises fast with injury and falls quickly with resolution, but is not as specific to liver damage as the ALT in that the AST will also rise with injury to other organs especially heart and muscle
This protein also rises with liver injury and more specifically with biliary obstruction. However, in growing children, there is a higher background level of alkaline phosphatase, which comes from bone metabolism and not from the liver, limiting the value of this test for assessing liver disease. Alkaline phosphatase can be helpful in understanding vitamin D deficiency and metabolic bone disease which is common in liver disease and liver transplant patients. Normal levels for alkaline phosphatase change with age.
Gamma glutamyl transferase (GGT) (aka gamma glutamyl transpeptidase (GGTP))
GGT is another liver protein that is monitored for signs of liver injury and is more specific to biliary injury, like alkaline phosphatase, but is not elevated in bone disease so is particularly useful in growing children and adolescents. Interpreting GGT levels can be difficult in that the level of GGT can rise with both injury and recovery from injury, but when recovery is complete the GGT eventually returns to normal.
Albumin is the major protein component of blood plasma. The liver makes all the albumin in the blood and so levels may fall as the severity of liver disease increases. Low levels are also seen in conditions where there is excessive loss of albumin usually from the kidneys or the intestines.
2. Thyroid Function Tests (TFTs)
Thyroid function is rarely affected in liver transplant patients but often tested. Thyroid hormones affect many processes in the body including growth and development, metabolism, body temperature and heart rate.
Thyroid stimulating hormone (TSH)
TSH is a hormone made in the pituitary gland that tells the thyroid how much T4 and T3 to make.
A high TSH level often means an underactive thyroid (hypothyroidism) meaning that the thyroid is not making enough hormone. A low TSH level usually means hyperthyroidism, or an overactive thyroid. Meaning the thyroid is making too much hormone. If the TSH test results are not normal, at least one other test is needed to help find the cause of the problem.
A high blood level of T4 may mean hyperthyroidism. A low level of T4 may mean hypothyroidism. In some cases, high or low T4 levels may not mean you have thyroid problems. Pregnancy, medications and other significant health issues can affect the T4 levels. These conditions and medicines change the amount of proteins in your blood that “bind,” or attach to T4. Bound T4 is kept in reserve in the blood until it is needed. “Free” T4 is not bound to these proteins and is available to enter body tissues. Because changes in binding protein levels do not affect free T4 levels, many healthcare professionals prefer to measure free T4.
Sometime a T3 level is also measured. This hormone is more potent than T4 but only makes up a lesser proportion of circulating thyroid hormones.
3. Fat-soluble Vitamins
Vitamins are nutrients required in small amounts for essential metabolic functions. Four vitamins, A, D, E and K, will not dissolve in water so the mechanisms that are needed for digesting and absorbing fats in the gut need to be intact to be able to absorb these vitamins. A crucial part of this ability to absorb fats is the presence of bile in the gut, so patients with poor bile flow, due to bile duct obstruction or liver cell damage, are at risk for deficiencies.
Vitamin A: is important for vision and immune function. The tests measure retinol and sometime a precursor to the active vitamin, beta-carotene. [Caution: many centers measure retinol-binding protein levels but this is a measure of overall nutritional sufficiency and not of vitamin A.]
Vitamin D: is essential for bone health and a deficiency leads to thin bones, more liable to fracture. The most important level measured is 25-hydroxycholecalciferol (25OH vitamin D3). Optimal level is >30mcg/dL but above 20 may be adequate to prevent osteopenia.
Vitamin E: is a group of eight fat soluble compounds; the main component and the one we usually measure is alpha tocopherol. Vitamin E is an important antioxidant which helps protect cell membranes. Deficiency of vitamin E can cause nerve problems that are irreversible, so prevention of deficiency is critical.
Vitamin K: is an essential component of blood clotting and vitamin K deficiency puts the patient at risk of bleeding. Although vitamin K levels can be measured, it rarely is. Most centers will use a test of blood clotting, either the Prothrombin time or INR (International Normalized Ratio). A normal result indicates vitamin K sufficiency.
4. Alpha Fetoprotein (AFP)
This protein is the most important blood protein in babies before they are born and after birth this changes to the production of albumin and the level of AFP drops rapidly over the first few months of life. However, if there is injury to the liver and especially if there is a cancer of the liver the level may increase, and the level can be used as a “tumor marker” which can be followed to assess growth of the tumor (levels continue to rise) and response to treatment (levels fall with treatment). If a child gets a liver transplant for hepatoblastoma or hepatocellular carcinoma, the levels of AFP can be followed to monitor for tumor recurrence.
5. Serum Amino Acids
**This test is for children transplanted for metabolic diseases only**
When related to monitoring after liver transplantation in a child, they are only required in children transplanted for metabolic diseases.
Amino acids are a group of organic compounds that are the primary building block for proteins, and they participate in a vast array of metabolic processes. There are 20 “common” amino acids, which are measured in all labs but often the test has 30 or even 40 compounds measured. Therefore, there are many reasons for measuring serum amino acids, and an even larger number of interpretations of the results from this test the majority of which are beyond the scope of this discussion.
- In MSUD (Maple Syrup Urine Disease), MMA (methylmalonic acidemia) and PA (Propionic Acidemia) the branch-chain amino acids leucine, isoleucine and valine are monitored to ensure levels do not rise when there is an illness or an episode of rejection.
- In urea cycle disorders [CPS (carbamyl phosphate synthetase deficiency), OTC (ornithine transcarbamylase deficiency), citrullinemia, etc.], arginine levels are followed to ensure it does not drop too low. Such patients are commonly supplemented with arginine or citrulline (which is converted into arginine in the body)
They are in your body managing the flow of nutrients and waste of your cells.
Sodium (Na): found in your body and related to the flow of water. You can have lower sodium levels if you are having a fever/sweating, vomiting, or diarrhea. When the levels are higher or lower you may have a headache or dizziness. Treatment of a high or lower sodium levels needs done by your doctor.
Potassium (K): found in your body and important to help your heartbeat correctly. Sometimes tacrolimus can cause your potassium level to go higher than normal values. There are many foods, such as bananas, that are high in potassium.
Carbon Dioxide (CO2): found in your body and is waste the body gets rid of by your lungs and kidneys. These two organs create a careful balance for the health of your body. Dehydration, infection, or illnesses of your lungs and kidney can affect this level.
Chloride (Cl-): found in your body and is related to sodium and water. If you have a high fever with sweating, vomiting, or diarrhea you can lose chloride as you do with sodium mentioned previously. Fever, vomiting, and diarrhea are reasons to call your doctor.
BUN (blood urea nitrogen): found in your body and happens when protein is broken down by your liver. If travels in your blood to your kidneys. Your kidneys filter the urea from your blood into your urine. Tacrolimus can cause elevation of your BUN as well as dehydration. This test refers to your kidney function.
Creatinine (Cr): found in your body and is waste from daily muscle breakdown. Your kidneys filter the creatinine into your urine. Tacrolimus can cause elevation of your Cr as well as dehydration. This test refers to your kidney function.
Glucose (Glu): is found in your body and can have high or low levels. You can feel dizzy, have increased thirst, or urinate more than usual. It is related to the type of food you eat and timing of food you eat. Sometimes medication is needed to help keep levels normal. The pancreas and the liver are the main organs involved.
Calcium (Ca): Calcium is found in your body and stored in your bones. Normal calcium levels with strong bones are needed to grow in height, not break, and not develop bone thinning later in life. Some medication, such as steroids, can affect your bone health.
Phosphorus (P): found in your body and closely works with calcium for strong bones and teeth. Your kidneys keep a balance of phosphorus in your body.
Magnesium (Mg): found in your body and important for the stability of your nerves and nervous system. Tacrolimus can cause lower magnesium levels. Low magnesium levels can play a role in seizures.
7. Complete Blood Count (CBC)
Normal ranges change based on age and other factors. Please check the reference range provided by your center.
WBC (White blood cell count): total number of white blood cells per a volume. This reflects all the different white blood cells combined. This level may be high when taking medications, such as steroids. This level may be high or low when there is an infection.
RBC (Red blood cell count): measures the number of red blood cells in the body. Typically, Hgb is trended.
Hgb (Hemoglobin): the amount of oxygen-carrying cells within each red blood cell. This level is usually trended to determine if any bleeding is occurring and need for blood transfusion.
Hct (Hematocrit): the calculated volume percentage of red blood cells in the body.
MCV (Mean corpuscular volume): measures the average size of your blood cells. If they are smaller than normal, this may reflect low iron stores or chronic disease. If they are larger than normal, this may reflect a vitamin B12 deficiency. Blood disorders may also impact this size, such as thalassemia.
MCH (Mean corpuscular hemoglobin): This reflects the average amount of hemoglobin in a red blood cell. Typically, other markers are used to track your blood counts.
MCHC (Mean corpuscular hemoglobin concentration): This reflects the average volume of your red blood cells. Typically, other markers are used to track your blood counts.
RDW (Red cell distribution width): reviews the range of the size of your red blood cells
MPV (Mean platelet volume): reviews the average size of your platelets. This may be abnormal when taking medications that impact platelet. Typically, other markers are used to track your platelets.
Platelets: Platelets are the first line for clotting in the body. Platelets may be high or low during an infection or may be low due to portal hypertension or another process. Medications can also impact the platelet count.
The remainder of the CBC reviews the different components of the WBCs and shows the values in two separate ways: a percentage and the total amount (ABS) that are noted by the machine per volume:
- Neutrophils/ ABS Neutrophils: Neutrophils are the most common white blood cell type in your body. These cells typically respond first to infections. The levels may be low or high during an infection, particularly a bacterial infection, depending on the clinical course.
- Lymphs/ABS Lymphs (lymphocyte): Lymphocytes are the second most common white blood cell type, compromising T cells, B cells, and NK cells. This cell line can be low during viral infections or after medications are given, such as thymoglobulin or basiliximab.
- Monocytes /ABS monocytes: type of white blood cell that becomes macrophages
- Basophils/ABS basophils: type of white blood cell, the least common type in the body.
- Eosinophils/ABS eosinophils: type of white blood cell, may be elevated during a parasite infection or allergic reaction.
8. Coagulation Labs
Three labs that evaluate various aspects of the coagulation cascade. These labs may reflect that you are taking a blood thinner, or at higher risk for clotting.
- PT (Prothrombin time): measures how long it takes for a sample to clot (the extrinsic pathway), specifically the function of factors 1, 2, 5, 7, and 10. May be prolonged when vitamin K is not absorbed in liver disease.
- PTT (Partial thromboplastin time): measures how long it takes to clot after other reagents are added (the intrinsic pathway) specifically the function of factors 2, 5, 8, 10, 9, 11, and 12. Heparin prolongs the PTT.
- INR (International normalized ratio): measures PT ratio to normalized. This lab may be elevated when vitamin K is not absorbed in chronic liver disease, or a medication is given to prolong the PT, such as coumadin or warfarin.
9. Iron Studies
Iron level (Fe): Iron is needed to make hemoglobin. This calculates how much iron is in the blood. If low, an iron supplement may be started. Some diseases impact iron levels, including hemochromatosis or porphyria. Additionally, if you have recently had a blood transfusion, the iron level may be higher than normal.
Total iron binding capacity (TIBC): measures the blood availability to bind iron. This indirectly measures a molecule produced by the liver, transferrin. This level may be abnormal in liver synthetic dysfunction but can also reflect other processes. If the TIBC is low, it may reflect an anemia of chronic disease. If the TIBC is high, there may not be enough iron circulating to optimize red blood cell production.
Ferritin: Reflects how much iron is stored in the body. Used with iron level and TIBC to determine if an iron supplement is needed or not.
This information should not replace medical advice from your doctors or medical team. We encourage our readers to follow their transplant team's medical advice and reach out to their doctors and medical team for further recommendations.