17.1 Laboratory Diagnostics: Hematology, Coagulation, Chemistry, Hormone, Serologic & Screening Tests
Key Takeaways
Normal pregnancy lowers serum creatinine (to about 0.4–0.6 mg/dL), raises alkaline phosphatase (from the placenta) and fibrinogen, and causes a mild leukocytosis, so non-pregnant reference ranges can mislead.
Nontreponemal tests (RPR, VDRL) track disease activity with titers but have biologic false positives, while treponemal tests (TP-PA, FTA-ABS, EIA) usually stay positive for life.
A urine protein-to-creatinine ratio of 0.3 mg/mg or higher (or 300 mg or more in 24 hours) defines significant proteinuria in pregnancy.
Annual fecal immunochemical testing (FIT) needs no dietary restriction; a single stool sample collected during a digital rectal exam is not adequate colorectal cancer screening.
A negative rapid COVID-19 antigen test in a symptomatic person should be repeated after 48 hours, while a NAAT (PCR) is the most sensitive test.
Interpreting Labs in Context
Reference ranges come from nonpregnant adults. Pregnancy, the menstrual cycle, hormonal contraception, and lactation change many values, and the exam often tests whether you can tell a physiologic change from disease.
| Test | Nonpregnant Adult | Normal Pregnancy | Clinical Pearl |
|---|---|---|---|
| Hemoglobin | 12–16 g/dL | Lower (anemia: <11 in the 1st and 3rd trimesters, <10.5 in the 2nd) | Plasma volume rises more than red-cell mass |
| White blood cells | 4,500–11,000/mcL | Up to about 15,000 (higher in labor) | Leukocytosis alone does not prove infection |
| Platelets | 150,000–400,000/mcL | Mildly lower | Gestational thrombocytopenia is usually >100,000 |
| Creatinine | 0.6–1.1 mg/dL | About 0.4–0.6 | 0.8 or higher warrants evaluation for renal impairment; >1.1 is a severe feature of preeclampsia |
| Alkaline phosphatase | 30–120 U/L | 2–4 times higher (placental) | Not a liver marker in pregnancy |
| AST/ALT | Normal | Unchanged or slightly lower | Elevation is abnormal (HELLP, cholestasis, hepatitis, acute fatty liver) |
| Fibrinogen | 200–400 mg/dL | 400–600 mg/dL | Below 200 in hemorrhage predicts severe bleeding |
| TSH | 0.4–4.0 mIU/L | Lower in the first trimester (hCG effect) | Use trimester-specific ranges |
Hematology and Coagulation
- CBC and indices: MCV sorts anemia into microcytic, normocytic, and macrocytic types; RDW is high in iron deficiency and normal in thalassemia trait (see the anemia section).
- Blood type and antibody screen: Done at the first visit in every pregnancy (see the Rh alloimmunization section).
- Hemoglobin electrophoresis or HPLC: Sickle cell trait (HbAS, about 40% HbS), sickle cell disease (HbSS), HbC and HbE, and beta-thalassemia trait (HbA2 >3.5%). Alpha-thalassemia trait shows normal electrophoresis and needs DNA testing. If the patient is a carrier, test the reproductive partner.
- Coagulation studies:
- PT/INR reflects the extrinsic pathway and is used to monitor warfarin and assess liver synthetic function.
- aPTT reflects the intrinsic pathway and is used for unfractionated heparin monitoring; it is paradoxically prolonged by lupus anticoagulant, which causes clotting, not bleeding.
- Von Willebrand panel (vWF antigen, ristocetin cofactor activity, factor VIII) for heavy menstrual bleeding since menarche.
- D-dimer helps exclude VTE outside pregnancy but rises normally in pregnancy.
Chemistry, Diabetes, and Urine Studies
- Comprehensive metabolic panel: Electrolytes, renal function, glucose, liver enzymes, albumin (lower in pregnancy), and calcium.
- Lipid profile: Fasting is not required for most patients (see the dyslipidemia section).
- Diabetes tests: Fasting glucose (126 mg/dL or higher diagnostic), 2-hour 75-g OGTT (200 or higher), and A1C (6.5% or higher). A1C is unreliable in pregnancy, after transfusion or hemorrhage, with hemoglobinopathies, and with iron deficiency or anemia; pregnancy uses the 50-g challenge followed by a 100-g OGTT, or the one-step 75-g OGTT.
- Urinalysis: Leukocyte esterase and nitrites suggest UTI (nitrites need gram-negative organisms), protein, glucose (normal pregnancy can show mild glycosuria), ketones (fasting or hyperemesis), and blood.
- Urine culture: 100,000 CFU/mL or more of a single organism in a clean-catch sample; lower counts can be significant in a symptomatic patient.
- Proteinuria in pregnancy: A protein-to-creatinine ratio of 0.3 mg/mg or higher or 300 mg or more in 24 hours is significant; a dipstick of 2+ is used only when quantitative tests are unavailable.
Hormone Studies
| Test | Use | Interpretation |
|---|---|---|
| hCG (quantitative) | Pregnancy, ectopic, GTD | Rises at least 35% every 48 hours in a viable early pregnancy; markedly high in molar pregnancy |
| FSH and estradiol | POI, menopause, amenorrhea | FSH >25 IU/L with at least 4 months of oligomenorrhea suggests POI; routine FSH is not needed to diagnose menopause after 45 |
| Mid-luteal progesterone | Ovulation | >3 ng/mL confirms ovulation |
| Prolactin | Amenorrhea, galactorrhea | Repeat mild elevations fasting; check TSH and medications; very high levels suggest prolactinoma (pituitary MRI) |
| TSH and free T4 | Thyroid | Interpret with trimester-specific ranges in pregnancy |
| Total testosterone and DHEA-S | Hyperandrogenism | Testosterone >150–200 ng/dL or DHEA-S >700 mcg/dL raises concern for a tumor |
| 17-hydroxyprogesterone | Non-classic CAH | Early-morning follicular-phase value <200 ng/dL makes it unlikely |
| AMH | Ovarian reserve; PCOS | Low suggests diminished reserve; does not predict natural fertility |
Serologic Screening
- Syphilis: Nontreponemal tests (RPR, VDRL) give titers that track activity and fall after treatment (a fourfold drop shows response), but have biologic false positives (pregnancy, lupus, antiphospholipid syndrome, viral infections). Treponemal tests (TP-PA, FTA-ABS, EIA/CIA) confirm infection and usually stay positive for life. Many labs use the reverse algorithm (treponemal test first).
- HIV: Laboratory 4th-generation antigen/antibody test, then a differentiation assay; HIV RNA testing resolves discordant results or suspected acute infection.
- Hepatitis: HBsAg (current infection), anti-HBs (immunity), anti-HBc (past or current exposure; IgM for acute); HCV antibody followed by HCV RNA to confirm active infection.
- Immunity screening: Rubella IgG and varicella IgG.
- CMV and toxoplasmosis: IgM can persist or be falsely positive; IgG avidity testing separates recent from past infection. Routine screening is not recommended.
- HSV type-specific serology (glycoprotein G) identifies prior infection, but routine screening of the general population is not recommended, and low-positive HSV-2 results can be false positives that need confirmation.
Fecal, Vaginal, Throat, and Skin Tests
- Fecal occult blood testing: FIT detects human hemoglobin, needs no dietary restriction, and is done annually at home; guaiac FOBT needs dietary limits and three samples. A positive stool test requires colonoscopy. A single in-office stool sample from a digital rectal exam is not adequate screening.
- Vaginal microscopy and pH: Saline wet mount (clue cells, trichomonads, white blood cells), KOH (hyphae, whiff test), and pH; vaginitis NAAT panels improve accuracy.
- STI testing: NAAT on a vaginal swab (preferred for women, including self-collected), first-catch urine (preferred for men), and rectal or pharyngeal swabs based on exposure.
- Throat culture: Used as a backup after a negative rapid strep test in children, not adults; also for gonococcal pharyngitis (NAAT).
- Skin and wound cultures: For purulent infections, to identify MRSA and guide antibiotics; KOH or fungal culture for suspected tinea or onychomycosis.
COVID-19 Testing
NAAT (PCR) is the most sensitive test. Antigen tests are less sensitive, so the FDA advises repeating a negative antigen test after 48 hours in a symptomatic person (and testing three times, 48 hours apart, after an exposure without symptoms). Pregnant patients with COVID-19 are at higher risk of severe illness and are eligible for antiviral treatment; check drug interactions with ritonavir-boosted nirmatrelvir.
A 26-year-old at 30 weeks of gestation has routine labs showing alkaline phosphatase 260 U/L (reference 30–120), AST 22 U/L, ALT 18 U/L, and normal bilirubin. She has no symptoms. How should the alkaline phosphatase be interpreted?
It indicates intrahepatic cholestasis of pregnancy and requires ursodiol.
It suggests bone metastases and requires a bone scan.
It indicates HELLP syndrome and requires delivery.
It is a normal finding, because the placenta produces alkaline phosphatase.
A 23-year-old at her first prenatal visit has a reactive RPR at a titer of 1:2 and a nonreactive TP-PA. She has no symptoms and no history of syphilis. What is the most likely explanation?
Secondary syphilis requiring benzathine penicillin weekly for 3 weeks
A biologic false-positive nontreponemal test
Neurosyphilis requiring lumbar puncture
Previously treated syphilis with a serofast state
A 52-year-old woman at average risk for colorectal cancer chooses stool-based screening. Which statement about fecal immunochemical testing (FIT) is correct?
FIT is done annually at home without dietary restriction, and a positive result requires colonoscopy.
FIT requires avoiding red meat and vitamin C for 3 days before collection.
A single stool sample collected during her pelvic examination is an acceptable alternative to FIT.
A positive FIT should be repeated in 1 year before any further testing.
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