Lab work in pregnancy. Now what?

Gail Hart, mana, boston 2002

Im going to start with a quick discussion of the "usual" blood labs, and the way they may change in pregnancy. Then move on to some specific conditions we might discover in pregnancy (anemias, pre-eclampsia, thrombocytopenias, and abnormal blood sugars).

Blood abnormalities are difficult to diagnose in pregnancy because pregnancy is an altered state. It is "natural," but not "normal", and pregnancy affects the entire physiology. The circulatory system NORMALLY changes in pregnancy. -- which throws off the "normal range" printed on your lab slips.

Theres an increase of total cell volume of 18% and a plasma volume increase of 40% to 50%. Hemoglobin itself the packed cell volume --- doesnt change, but plasma rises, and the increase in plasma causes a "hemodilution", which creates "artificial anemia" or "the physiologic anemia of pregnancy. (Think of adding an extra cup of water to a pitcher of juice mix. There would still be the same amount of solids in the pitcher, but the juice will be "thinner", weaker. Your kids may blame you for not adding enough juice mix to the pitcher!)

To make it even more confusing, the plasma levels fluctuate during pregnancy, dropping the hematocrit as much as 4 points at the time of maximum dilution (32 weeks) before hemoconcentration occurs near term. Ironically, that 32-week point is when many routine blood tests are repeated. We treat many pregnant women for anemia based on their "diluted" blood condition when they arent anemic at all. Worse, we use iron supplements to treat mild anemia in pregnancy even though data shows no benefit and does show potential harm!

A LOW HGB/HCT does not automatically indicate anemia -- especially if the blood is drawn before 36 weeks. After 32 weeks a "hemoconcentration" occurs and will cause a rise in hgb of as much as 2 points until term. This rise occurs without supplements of any kind. (We will often be thrilled with how effective our treatments appear, when women begin taking herbs or supplements during that time period!)

Non-pregnant range pregnant range

Hgb 12.0 to 16 11.0 to 14

Hct - - 35 to 47 32 to 36

RBC 3.8 to 5.20 3.5 to 4.75

WBC 3.5 to 11.0 10.5 to 20

Platelets 140 to 440 (1000) 187 to 300

What do you do when results are outside these ranges?

In general, relax. Pregnant blood values vary so widely and the normal range varies widely in individuals, and lab errors are common. Something as simple as a delay from the time of blood draw to testing, can affect the numbers you see on your report! EVERY ABNORMAL RESULT DEMANDS A RETEST BEFORE YOU BEGIN ANY "TREATMENT"! Pregnant women are easily stressed. Lets make sure an unusual lab result is worth worrying about, before alarming the mom!

Hemoglobin -- low hgb.

We used to think the non-pregnant range of 12.0 to 16 would drop to 11.5 to 14, but new research shows this number may be several points lower. The NORMAL range of pregnant hgb values may be as low as 10.5 to 12.0! (Stay tuned for new recommendations on treatment of anemia in pregnancy). Almost every pregnant woman will show a drop of about 2 points in hgb during pregnancy and yet be just under her beginning number at 40 weeks. We can sometimes prevent this drop by giving iron supplements, (even though we really should give iron ONLY to women with PROVEN anemia). A low hct in the beginning of pregnancy probably IS a sign of anemia. After 12 weeks it will be difficult to get an accurate reading.

Stable hemoglobin -- failure of the hemoglobin to drop is an early warning sign of pre-eclampsia.

High hemoglobin generally worrisome, especially in middle trimester. A hgb of above 14 at term is highly suspicious for pre-eclampsia

Hematocrit think of this as just another way to measure hemoglobin. Everything I said about hgb applies to hct as well. The hct may fluctuate as much as 4 to 6 points during the course of pregnancy; the hemoglobin is relatively stable in comparison. High hct is a marker to watch. And old rule of thumb says to expect the hct to drop 4 points from the beginning of pregnancy and to come back up 3 points by 40 weeks.

RBC falls from 4.5 (per cubic mill) to 3.8. Use to help show "real" versus "physiologic anemia. If RBC is tested after the first trimester, and is within the normal range, the woman is probably not anemic even if hct/hgb are low (31/10.5).

WBC normally elevated during pregnancy. May run as high as 14,000 or even reach 20,000. (Called "leukocytosis of pregnancy).

Platelets show wide range of normal, and wide range even within the same woman and pregnancy! Can be unusually high in lupus type conditions, and abnormally low in ITP, or HELLP. (Discuss during pre-eclampsia labs).

Anemias: Iron deficiency anemia. Most common anemia. Lab work shows Low hct, low hgb, decreased MCV (as if the cells themselves are "smaller and lighter". A peripheral smear may show "microcytic or hypochromic cells" cells smaller and paler than average. The body cannot make hemoglobin without iron! Symptoms = raised pulse, fatigue, rough nails, "rough tongue", pale conjunctiva. Elevated erythrocytes (baby red blood cells) may show the body is trying hard to build new blood cells this can be a good sign of iron therapy success or it may rarely mean that red cells are being rapidly destroyed as in some form of hemolytic anemia. Treatment = Iron supplements, plus vitamin C and perhaps vit B12.

Thalassemias anemia caused by a variant hemoglobin which throws all of our tests off! A racial variant, common in Mediterranean and northern African countries. There is Alpha-thalassemia, beta-thalassemia and hemoglobin E. The condition may be minor, causing a mild chronic microcytic anemia with hct in the low thirties. Can occasionally be severe. Some states test for this with the PKU forms.

Sickle cell --- ditto thalassemia re symptoms and genetic distribution.

Acquired anemias lead poisoning, chronic exposure to some solvents. Lead exposure shows symptoms of anemia with small "stippled" malformed cells. HIV, tumors etc

Macrocytic anemias elevated MCV (cells are large but have low mass). Megaloblastic anemia usually caused by folic acid deficiency needs folate and b12. (A risk for vegetarians). Can also be caused by alcoholism or liver disease, or exposure to some toxins. Folate need is increased in pregnancy; some people have a high enough intake, but dont absorb it well. (Folates found in leafy greens, B12 in meat products)

Hemoconcentration high or rising hct and hgb is usually the first sign. One "panel" if suspicious of pre-eclampsia includes -- hct/hgb, peripheral blood smear, BUN, Uric acid, protein, and SGOT.

Plasma proteins albumin: may fall. But sign not totally reliable.

Uric acid and urea nitrogen (BUN), rise

creatinine may rise (sign not as reliable)

Liver panel shows changes rising SGOT (above 72)

Urine test for protein catch is unreliable vaginal debris gives a false protein reading. If very concerned, do a 24 hour clean catch or catheter. Albumin levels vary too greatly to be significant as predictors of pre-eclampsia, but repeated catches may show a progression of the process.

Note: labs vary in their printed "normal ranges" and in their testing methods. You may see numbers slightly different from these. These tests tell little by alone, and need to be put in context of the womans symptoms and other bloodwork and need to be repeated to show a trend".

Ranges of normal female:

Albumin 3.2 to 4.1

Uric acid 3 to 5 (avg 4.1)

BUN 9 to 17 (lower in pregnancy. Even as low as 5 may still be normal)

Creatinine 0.6 to 1.3

SGOT 3 to 40

In one of the severe pre-eclampsia/eclampsia syndromes, liver functions deteriorate and hemolysis occurs. The red blood cells become rapidly microcytic and deformed, hgb/hct drops, fibrinogen decreases, platelet destruction may occur, billirubin may rise, and DIC may develop. HELPP is the acronym to remember and to seek! Hemolysis, Elevated Livers, Low Platelet. Or a regional variation of the acronym: High BP, Elevated Liver, Low Platelet. Remember this condition can develop without alarmingly high BP!

Confusing bits: The normal range of platelets is quite large. A low number may mean nothing or it could mean mother has gestational thrombocytopenia a poorly understood condition of little consequence. Or it could mean mom is terribly sick. Its important to retest to see if the platelet levels or hct/hgb numbers are steady or if they are falling.

BUN and liver panels are most accurate in the fasting state so blood draw should occur first thing in the morning. Also we no little about the range of normal in pregnancy, numbers can range throughout the day and vary with diet. Its hard to "diagnose" anything on one test repeat tests will show you a trend. I doubt if anyone has sufficiently established the normal range in pregnancy for some of the oddball tests like phosphorous and alkaline phosphate etc

Thrombocytopenia a drop in platelets. May be part of HELLP syndrome, but may be a normal variation of pregnancy.

gestational thrombocytopenia (old term "ideopathic thrombocytopenia"). Affects about 4% of pregnancies at levels around 130,000 to 150,000. Controversy over lower limit of normal, but GT generally stays above 100,000. Levels can rarely drop to 75,000 without likely risk to baby or mom. Bleeding rarely occurs at this level. Tests should be repeated to see if levels are dropping or are stable, and pre-eclampsia panels should be done.

Immune Thrombocytopenia Purpura rare. 1/1000 to 3/1000. May be an auto-immune disorder. May show evidence of unusual bruising or petechia. May be linked to Lupus, HIV, sepsis, DIC. Spontaneous bleeding usually doesnt occur if levels are above 20,000. Treatment is a doctors problem not a midwifes!

ANTIPHOSPHOLIPID ANTIBODY SYNDROM This is a hyper-coagulable syndrome which may include thrombocytopenia and may be associated with repeated early miscarriages. May be associated with Lupus and have similar symptoms and risks. The test may be called a "lupus panel" or Lupus screen. Some doctors recommend aspirin therapy or heparin for women with APLA and a history of miscarriage.

There is little international consensus on normal glucose levels in pregnancy and little agreement on which tests should be done to discover the occasional hidden diabetic. There is even less agreement on the concept of "gestational diabetes" as separate from diabetes mellitus -- and whether or how this should be diagnosed, tested for, or treated. The numbers used to "diagnose" change constantly and different groups use very different numbers. I personally lean to the conclusions of the Cochrane Database that gestational diabetes is poorly researched and there is no evidence that mildly elevated glucose levels are detrimental in pregnancy, or that treatment is effective at controlling macrosomia, or that there is any risk to the baby other than macrosomia (which we cant affect with diet restriction). You will have to use your own judgment about whether and how to screen for "gestational diabetes" taking into consideration the standard of care in your community. I personally think a reasonable approach is to screen women at high risk, and women with any s/s of diabetes and that post-prandial blood sugars are a reasonable test for DM.

I will list a few common tests and cut-off levels:

It probably is irrelevant whether or not moms "carbo-load" for several days before the test. The test itself is poorly reproducible. A mom who fails today may easily pass tomorrow. I think the whole concept of gestational diabetes is a deeply confused "tempest in a teapot", which will brew for a few more years and then disappear just like 24 hour urinary estriol assays did 20 years ago. We will eventually find an accurate and reproducible test for hidden diabetes and we will better understand the effects of normal renal intolerance in pregnancy.

URINE TESTS

Glucose spilled so commonly in pregnancy as to be almost irrelevant as a screen for diabetes

Protein trace to one plus is common almost expected. Difficult to get a clean catch. The albuminuria associated with PIH is usually a very late symptom may not occur until the woman is very sick.

Ketones product of "starvation". Illness, fever, lack of food, dehydration, diabetes (a woman with Diabetes Miletus, may spill both Glucose and ketones in the same sample)

Leukocytes commonly due to a contaminate. If high may indicate a urinary tract infection especially if

blood is also found. Vaginal, cervical, or rectal blood is a frequent contaminant.

Ph one of the pretty much irrelevant things we do.

(Routine dipsticks arent particularly helpful and I predict that in twenty years people will have forgotten all about them!)

VERY WEIRD THINGS!

Uremia: may be a result of severe platelet loss.

A sign of von Willebrand (the disease of the month! Another poorly understood and overly diagnosed syndrome which has caught the public eye.

DIC disseminated intravascular coagulation We are unlikely to discover this in bloodwork. Mother will probably be in hospital long before. Platelets will usually be decreased (50 to 75), and serum fibrinogen may be decreased. Thrombin time will be increased.

A GOOD SCREEN FOR SUSPECTED BLEEDING DISORDERS -- hematocrit, platelet count, PT/aPTT, fibrinogen, D-Dimer and euglobulin clot lysis time.

AN OLD STANDBY CENTURIES-OLD TEST FOR BLEEDING DISORDERS Poke moms finger with a sterile needle, pin or lancet. Put several drops of blood onto a microscope slide or the flat bottom of a drinking glass. Wait 1 minute. Draw your pin/needle/lancet through the blood drop. Repeat every 30 seconds. Note time when blood firms up and clots on both sides of the "trail" made by your needle. Normal blood will clot in less than 5 minutes and many pregnant women will clot within two!

REFERENCES

George JN, Woolf SH, Raskob GE, Wasser JS, Aledort LM, Ballem PJ, Blanchette VS, Bussel JB, Cines, DB, Kelton JG, Lichtin AE, McMillan R, Okerbloom JA, Regan DH, Warrier I: Diagnosis and treatment of idiopathic thrombocytopenic purpura: Recommendations of the American Society of Hematology. Ann Intern Med 1997;126:319-326.

George JN, Shattil SJ. The clinical importance of acquired abnormalities of platelet function. New Engld J Med. 1991;324:27-39

Thomas G. DeLoughery OHSU hematology website.

Obstetrics; normal and problem pregnancies gabbe, niebyl, simpson (3^rd edition, 1999)

Bensons Handbook of Obstetrics and Gynecology

An introduction to the Principles of Disease Walter

A Textbook of Clinical Pathology -- Miller

Oxygen -- is it the best thing for newborn resucitation?

(gail hart, Midwife Updates Conference Aug 2002)

Things we know about oxygen:

• Necessary for life
• Available in air at 21%
• All normal humans are designed to function in 21% O2
• Humans suffer harm if blood oxygen drops below normal
• Humans suffer harm at O2 levels in excess of room air
• Toxic if given at levels higher than needed.

Things we dont know about oxygen:

• How delicate is neonatal balance?
• How easily harmed are neonates, even during short term O2 exposure?
• Is pure O2 the best way the most efficient way -- to get oxygen into a baby?

A question we are just beginning to ask and researchers to answer:

• Is room air superior to oxygen for resuscitation of asphyxiated newborns?

Neonatal physiology: What makes a baby draw breath?

• Reflex (in utero breathing)
• Oxygen deprivation with resulting rise in CO2. (meconium aspiration syndrome)
• Birth (above reflexes plus deprivation of placenta, plus pressure, temperature, air, etc)

Three physiologic states in ballance during birth of fetus/newborn;

• Fetus blood levels =slightly more CO2 than O2, little stimulus to respiration
• Birth moments blood levels= CO2 rises, O2 drops, strong stimulus to breathe
• Asphyxia high levels of CO2, low O2 = overcomes cerebral-centered breathing reflex = apnea

O2 relatively new.

• the first resuscitation gas was Co2 found to stimulate deep and rapid breathing in mildly asphyxiated infants less effective in severe aspxia.
• Mixtures of CO2 and O2 were proposed and used until at least the 1970s.

• Oxygen was felt to be superior to CO2 was adopted with little question, in spite of the example of retrolental-fibroplasia.
• O2 only recently studied against room air (early reports fuel spate of research)

Common observation: the asphyxiated baby seems to responds well to O2 resuscitation shows color and tone improvement, but "will not breathe" or seems slow to begin spontaneous breaths. Real life cure: wean the oxygen. Unknown: was spontaneous respiration delayed by O2? Were there harmful effects?

Copywrite gail hart, midwiferyeducation.org

More things we now know about O2

• saturation with oxygen reduces breathing efforts in ALL airbreathing creatures, and newborns are more susceptible than adults
• resuscitation with O2 shows marked delay in respiration compared to resuscitation with room air.
• newborns exposed to O2 FOR EVEN SHORT DURATION (minutes) show changes in eye development (rods extremely susceptible)
• chemical receptors markers for stress show -- for weeks, maybe longer

research points now known after a decade of study of room air vrs O2 for resucitation;

• There are no apparent clinical disadvantages in using room air for ventilation of asphyxiated neonates rather than 100% oxygen.
• Room Air Resuscitated (RAR) infants recover more quickly
• higher Apgar scores at 1, 5, and 10 minutes in RAR infants

• time to first cry, and sustained pattern of respiration less in RAR infants

(Pediatrics 2001 Apr; 107(4):642-7 Resuscitation with room air instead of 100% oxygen prevents oxidative stress in moderately asphyxiated term neonates.

• Three clinical studies have established that normal ventilation is delayed after oxygen resuscitation.
• Oxidative stress is augmented for several weeks in infants exposed to oxygen at birth -- the long-term implications of these observations remain unclear. (Semin Neonatol 2001 Jun;6(3):233-9) Resuscitation of newborn infants with room air or oxygen. Saugstad OD.

• No significant differences in the effectiveness of either gas sources or in the final outcome have been found.
• RAR required a shorter time of positive pressure ventilation to attain a spontaneous pattern of respiration.
• The OxR group showed hyperoxaemia during resuscitation, which was positively correlated with increased GSSG concentrations.
• Significant oxidative stress was found in the OxR group at 28 days of postnatal life when compared with normal control infants and the RAR group (Biol Neonate 2001;79(3-4):261-7 Six years of experience with the use of room air for the resuscitation of asphyxiated newly born term infants.

• To reduce oxidative stress, reoxygenation with low oxygen concentrations, even room air, might be beneficial.
• Increased oxidative stress might have long-term effects on brain growth and development
• there is evidence indicating that exposure to 100% oxygen after birth for only a few minutes might have long-term effects. (Biol Neonate 2001;79(3-4):258-60 Resuscitation of the asphyxic newborn infant: new insight leads to new therapeutic possibilities. Saugstad OD

Copyright gail hart, midwiferyeducation.org

citations

: Biol Neonate 2001;79(3-4):258-60

Six years of experience with the use of room air for the resuscitation of asphyxiated newly born term infants.

Vento M, Asensi M, Sastre J, Garcia-Sala F, Vina J.