Lab work in pregnancy.   

©Gail Hart Gist of Midwifery (first presented at mana convention, boston 2002)

I’m 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).

 Abbreviations:

RBC red blood (cell) count

WBC white blood count

HgB-  Hemoglobin – The oxygen-carrying  pigment found in red blood cells. They contain iron.

Hct- Hematocrit- The percent by volume of packed red blood cells in a centrifuged sample of blood.

Platelets – minute bodies found in  blood plasma which function to promote blood clotting.

Mean Corpuscular Volume – A lab term: The volume of the average red blood cells in a given blood sample (found by multiplying the hematocrit by 10 and dividing by the estimated number of red blood cells)

Points for discussion:

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. – and this will throw off the “normal range” printed on your lab slips.

There’s an increase of total cell volume of 18% and a plasma volume increase of 40% to 50%.  Hemoglobin itself – the packed cell volume --- doesn’t change, but plasma rises. This 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, but you DO have the correct amount of juice!)

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 aren’t 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. From 32 weeks until term, a “hemoconcentration” occurs and  causes a rise in hemoglobin lab levels of as much as 2 points. 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!)

The non-pregnant norms are usually adjusted downward: I’m using shorthand numbers. I’m sure you all know these are exponents (IE RBC is actually 3.8x 10/12)

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 we do when results are outside these ranges?

In general, don't panic. 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  blood is drawn until it’s tested, can affect the numbers you see on your report. EVERY ABNORMAL RESULT DEMANDS A RETEST”! Pregnant women are easily stressed. Let’s 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 physiologically normal 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 after several large studies have confirmed that the best maternal and fetal outcome is in women with Hgb range of 9.5 to 11). Almost every pregnant woman will show a drop of about 2 points in hgb during pregnancy –and yet return to her beginning number at 40 weeks.

We can sometimes prevent this drop by giving iron supplements, but it’s unwise to give iron to women unless they have a proven iron-deficiency anemia. Iron supplements raise the risk of pre-eclampsia!) 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 during pregnancy is an early warning sign of pre-eclampsia. 

High hemoglobin – generally worrisome, especially in middle trimester. A hgb of above 14 near term should make you be suspect pre-eclampsia.

Hematocrit – think of this as just another way to measure hemoglobin. Everything I said about hgb applies to hct as well. The hematocrit 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. It can be used 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 though her hct/hgb may be low (31/10.5).

WBC – normally elevated during pregnancy. May run as high as 14,000 or even reach 20,000. (Elevated WBC is 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 (Immune Thrombocytopenia of Pregnancy), or HELLP. (Hemolyis, Elevated Liver enzymes, Low Platelets). We’ll discuss this more when we deal with -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”). PLUS low available iron (feritin test).

A peripheral smear may show “microcytic or hypochromic cells” – cells smaller and paler than average. The body is unable to  make hemoglobin without iron, so the red blood cells are fewer and lighter than usual.

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 – but in rare cases it means that red cells are being rapidly destroyed as in some form of hemolytic anemia. Treatment = diet changes; iron supplements; plus vitamin C B12. Consider brewers yeast, acidophilus (to improve digestive absorption).

(People often self-treat mild anemia through diet or OTC supplements, but they obviously must consult a doctor for severe anemia or blood disorders!) 

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 levels in the low thirties. Can occasionally be severe. Some states test newborns for this on the PKU forms.

Sickle cell --- similar to thalassemia, similar  symptoms and genetic distribution. Red blood cells are smaller and shaped differently (sickle-shaped, instead of spherical). These types of cells are an advantage in areas with malaria, but a disadvantage when too many of them are affected. 

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

Macrocytic anemias – elevated MCV (cells are large but have low mass) and Megaloblastic anemia –usually caused by folic acid deficiency. This is a real risk for vegetarians and vegans. It can also be caused by alcoholism or liver disease, or exposure to some toxins. Folate need increases in pregnancy. Some people have a high enough intake, but don’t absorb it well. Treatment is folate - folic acid -- and b12. (Folates are found in leafy greens, B12 in meat products).

Pre eclampsia Labwork

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

Plasma proteins – albumin: – may fall. But this sign isn’t 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 – a dipstick catch is unreliable because vaginal debris gives a false protein reading.  If very concerned, a doctor may ask for a 24 hour clean catch or a catheter specimen. Albumin levels vary too greatly to be significant as predictors of pre-eclampsia, but repeated catches may show a progressive increase as the pre-eclamptic process continues.(Also, protienuria often appears very late in the process. It's not a strong "predictive" sign).

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  alone, and need to be put in context of the woman’s symptoms and other bloodwork – and they 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 (this is lower in pregnancy. Even as low as 5 may still be normal)

Creatinine              0.6 to 1.3

SGOT                     3 to 40

Help! HELPP

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 (Disseminated Intra-vascular Coagulation) may develop. HELPP is the acronym to remember – and to seek! – Hemolysis, Elevated Livers, Low Platelets. Or a regional variation of the acronym: High BP, Elevated Liver, Low Platelet. Remember: this condition can develop without alarmingly high blood pressure readings! 

Confusing bits, Rare findings, and Hemotology puzzles.

Platelets:

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. It’s important to retest within a few days to see if the platelet levels, or hct/hgb numbers, are steady or if they are falling. (And ALWAYS consult a specialist!)

BUN and liver panels are most accurate in the fasting state – so the 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. It’s 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 doesn’t occur if levels are above 20,000. Treatment is a doctor’s problem – not a midwife’s!

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.

BLOOD SUGARS

There is little international consensus on normal glucose levels in pregnancy – and little agreement on which tests should be done to discover the  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” diabetes 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 can’t 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 I also think post-prandial (after meal) blood sugars are a reasonable test for DM.

I will list a few common tests and common 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 (a true risk in pregnancy)  – 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 – a trace to one plus is common – almost expected – because it’s difficult to get a clean catch. The albuminuria associated with PIH is usually a very late symptom – it 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, it may indicate a urinary tract infection especially if

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

Ph – one of the pretty much irrelevant things we do.

(Routine dipsticks aren’t particularly helpful – and I predict that in twenty years people will have forgotten all about doing routine dips!)

VERY WEIRD AND SERIOUS THINGS!

Uremia: may be a result of severe platelet loss.

A sign of von Willebrand (or Factor V Lieden) 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 by bloodwork because the 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 mom’s 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 the time when the 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  

  1926;26:388-393.WILLIAMS

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

The Gist of Midwifery -- Gail Hart