1. Define anemia in pregnancy.

2. Recognize common types of anemia in pregnancy.

3. Prescribe appropriate therapy for pregnant patients with iron deficiency anemia.

4. Classify blood loss from postpartum hemorrhage based on clinical signs.

5. Manage patients with postpartum hemorrhage requiring fluid resuscitation and blood products.

Anemia Complicating Pregnancy
Robert G. Bonebrake, MD, Associate Clinical Professor, Maternal Fetal Medicine, Creighton University School of Medicine, and Partner, Perinatal Associates at Methodist Perinatal Center, Nebraska Methodist Hospital, Omaha

General considerations: definition of anemia—hemoglobin (Hb) value below lower limits of normal and not explained by state of hydration; 14 +/- 2.0 g/dL normal Hb for women; Centers for Disease Control and Prevention (CDC) defines anemia in pregnancy as Hb and hematocrit (Hct) <11 g/dL and <33% in first and third trimesters and <10.5 g/dL and <32% in second trimester; CDC recommends cutoff for diagnosis in black women be lowered by 2% for Hct and 0.8 g/dL for Hb; clinical presentation—fatigue, lightheadedness, weakness, exertional dyspnea, palpitations, and tachycardia; associated clinical conditions—multiple pregnancy, trophoblastic disease, chronic renal disease, arthritis, chronic liver disease, and chronic infection; in obstetrics, anemia most commonly discovered by complete blood cell count (CBC), not symptoms; anemia is sign, not diagnosis; define mechanism or disease process by determining morphology, reticulocyte count, underlying disease, and appropriate treatment; laboratory studies—CBC; serum ferritin level; transferrin saturation; plasma iron level; plasma total iron-binding capacity; free erythrocyte protoporphyrin level; folate level (most laboratories using RBC folate level rather than serum folate); serum vitamin B12 ; bone marrow aspiration if needed

Blood volume changes in pregnancy: increases by ≈34% to 40%; plasma volume increases by ≈1000 mL or 50%; RBC expansion ≈300 mL or 10% to 25%; hemodilution throughout pregnancy lowers Hb, Hct, and RBC count; no change in mean corpuscular volume (MCV) or mean corpuscular Hb concentration (MCHC); useful in differentiating between dilutional and true anemia

Iron, folate, and vitamin B12: iron—most women enter pregnancy with marginal stores; ≈0.5 mg iron lost for every mL of blood, and 25 to 30 mL lost during menses; pregnancy requires additional iron to support increased plasma volume and RBC expansion; average diet contains 6 mg of iron per 1000 kilocalories; only 10% of dietary iron absorbed, so iron balance precarious at best; folate—folic acid water soluble vitamin; folate requirements increase from 50 µg/day to 300 to 500 µg/day in pregnancy; antiseizure medications, alcohol, and sulfonamides decrease absorption; vitamin B12 —abundantly available in diet, except in strict vegetarian diet; bound to animal protein; intrinsic factor essential for absorption; pernicious anemia result of absence of intrinsic factor; no risk with high-dose folate unless patient has pernicious anemia

Classification of anemia and effects on pregnancy: 3 major groups based on size and Hb content of RBCs; microcytic—MCV <80; abnormal Hb synthesis with normal RBC production; macrocytic—MCV >100; either increased rate of RBC production and release of immature RBCs or disorders of impaired DNA synthesis; normocytic—in between; anemia in pregnancy—limited data to support suboptimal fetal outcome; increased risk for prematurity, low birth weight, and perinatal mortality; nonreassuring fetal heart tracing associated with severe anemia; margin of safety appears large; conditions consistent with polycythemia may be associated with small-for- gestational-age infants and intrauterine fetal death

Iron deficiency anemia: risk factors—diets poor in iron-rich foods; diet rich in foods that diminish iron absorption (eg, alcohol, coffee, tea), or diet poor in foods that aid in absorption of iron (eg, acidic juices, broccoli); gastrointestinal (GI) disease affecting iron absorption; heavy menses; short interpregnancy interval (<12 mo); blood loss at delivery exceeding that of uncomplicated vaginal delivery; symptoms—fatigue, lethargy, headache; pica; pallor; glossitis; cheilitis (pitting or fissures at angle of lip); findings—depletion of stored iron; decreased serum iron and saturation; iron binding capacity rises; microcytic hypochromic RBC; Hb and Hct eventually fall; diagnosis—empiric iron therapy; CBC; Hb, Hct; RBC indices; may want to assess iron stores (serum ferritin and transferrin saturation); discontinue iron supplementation ≈48 hr before obtaining iron study to ensure reliability; peripheral blood smear; sickle cell preparation if ethnicity warrants; serum iron, ferritin or both; treatment with oral iron—ferrous salts absorbed better than ferric salts; all ferrous salts absorbed equally; all have side effects; some absorption prevented with enteric-coated preparations; best absorbed on empty stomach; ferrous aspartoglycinate and polysaccharide iron (Niferex) appear better tolerated than iron salts; 325 mg orally tid recommended (based on expert opinion only); research shows bid dosing likely as good as tid; should be taken ≈30 min before meals for maximum absorption; vitamin C shown to increase absorption; decrease or avoid antacids when taking iron supplement (interfere with absorption); nausea, vomiting, abdominal cramps, diarrhea, and constipation side effects; ferrous sulfate syrup can be used to titrate dose to patient’s tolerance; 2- to 3-times-weekly dosing provides response in patients who cannot tolerate daily dosing; parenteral iron—iron dextran and iron polysaccharide; indicated for malabsorption syndrome or significant anemia; response to iron therapy—reticulocytosis occurs in ≈1 wk; Hb can rise by as much as 1g in ≈1 wk in severely anemic patient; increasese in Hb usually seen in ≈2 to 3 wk; parenteral route faster in first 2 wk, but no significant difference in response to oral vs parenteral therapies at ≈30 to 40 days; subcutaneous epoetin alfa— used with or without iron therapy; studies show benefit in antenatal and postpartum patients; response in ≈70% to 75% of antepartum patients within 2 wk; some reports of associated hypertension; iron prophylaxis—safe with few side effects; 60 mg of elemental iron in one 325-mg tablet of ferrous sulfate (10% absorbed); iron absorption increases in pregnancy; provides 1.3 to 2.6 mg of elemental iron in well nourished patients; prevention and supplementation recommended for all patients after first trimester

Anemia of chronic disease: chronic renal failure; cancer and or chemotherapy; HIV; inflammatory bowel disease; autoimmune conditions; chronic inflammation and infection; microcytic and hypochromic anemia; decreased serum iron and increased serum ferritin; intensified in pregnancy (due to plasma volume expansion); recombinant erythropoietin shown effective

Acute blood loss: second most common cause of anemia in pregnancy after iron deficiency; in early pregnancy due to ectopic, abortion (elective or spontaneous), and hydatidiform mole; more commonly encountered in postpartum patient; residual anemia treated with iron for ≈6 mo to build up stores, especially if patient breast-feeding

New Concepts in Obstetric Hemorrhage
Karrie E. Francois, MD, Clinical Assistant Professor, Department of Obstetrics and Gynecology, University of Arizona College of Medicine, Phoenix; Perinatal Medical Director, Scottsdale Healthcare, Scottsdale, AZ

Estimating blood loss: ≈500 mL normal blood loss for vaginal delivery, ≈1000 mL for cesarean delivery; blood loss generally underestimated in obstetrics; obtain baseline laboratory assessment, but do not wait for results before deciding whether patient needs blood products; absence of clots clue to possibility patient in disseminated intravascular coagulation (DIC); draw blood sample into nonheparinized tube; if no clots after 5 to 6 min, fibrinogen likely <200 mg/dL; class 1 blood loss—1 L or ≈15% of blood volume; dizziness, palpitations, minimal blood pressure (BP) changes; class 2—1500 mL or 20% to 25% of blood volume; tachycardia, tachypnea, sweating, weakness; narrowing of pulse pressure (systolic BP minus diastolic BP) represents body’s attempt to compensate and maintain BP by vasoconstriction; loss of >20% of blood volume indication for dramatic attempts at resuscitation with intravenous (IV) fluids, and blood products required; class 3—2000 mL or 30% of blood volume; significant tachycardia, restlessness, pallor, and significant hypotension; class 4—>2500 mL; cardiogenic shock, airway hunger, and oliguria

Causes postpartum hemorrhage (PPH): uterine atony; genital tract lacerations, invasive placentation, uterine rupture, uterine inversion, and coagulopathy; coagulation cascade affected as bleeding progresses; plasma bradykinin (released with depletion of clotting factors) relaxes smooth muscle (eg, uterus) and contributes to worsening uterine atony

Fluid resuscitation and blood products: warmed crystalloids in 3:1 ratio to blood loss traditionally used; military data support early use of 1 U of fresh frozen plasma (FFP) per every unit of packed RBCs; type and cross- match; packed RBCs—1 U provides 250 to 300 mL of volume and increases Hb by 1g/dL, hematocrit by 3%; platelets—6-pack of platelets provides 300 mL of volume; increases platelet count by ≥40,000/mm3 ; FFP and cryoprecipitate—difference is volume; FFP associated with volume; cryoprecipitate condensed version of fibrinogen; 1 U of FFP increases fibrinogen by 10 mg/dL; same for cryoprecipitate; generally, patient receives both

Uterotonic drugs: oxytocin (eg, Pitocin)—20 to 40 U/L typical dose; data show less blood loss in women receiving 80 U/L than in women receiving 10 U/L; higher dose for short duration in acute episode of hemorrhage recommended; methylergonovine (Methergine)—dosing frequency every 2 to 4 hr; switch to another drug if ineffective; carboprost tromethamine (Hemabate)—effective; short-acting; dosing frequency every 15 to 30 min; intrauterine administration highly effective (also true for methylergonovine and oxytocin); prostaglandin E2 (Dinoprostone); misoprostol (Cytotec)—some consider second-line agent after oxytocin; typically administered rectally (1000-µg suppository available), but can also give sublingually

Intraoperative management: bimanual massage (compress uterus); uterine artery ligation; hypogastric artery ligation; compression sutures (B-Lynch; Hayman vertical; Pereira transverse and vertical; multiple square knot); compression sutures and fluid resuscitation before performing hysterectomy; retroperitoneal packing; SOS Bakri Tamponade Balloon Catheter—maximum inflation volume 500 mL; intrauterine placement; can be used with Foley bag for monitoring of bleeding; hysterectomy—double clamps and ligatures; supracervical approach; involve other specialties and departments (eg, interventional radiology, pharmacy, intensive care unit [ICU]); selective arterial embolization—data show 95% success rate; fever common; intense pain reported after procedure

Other pharmacologic agents: recombinant activated factor V11—IV bolus of 60 to 100 µg/kg; clotting starts within 15 to 20 min; temporary measure; case reports of thrombosis, pulmonary embolism, and stroke in older patients; reserve for most extreme cases of PPH; fibrin sealants (eg, Tisseal)—combination of fibrinogen, factor XIII thrombin, and calcium; administered by spraying; hemostatic matrix (eg, Floseal)—shown to stop bleeding within 2 min; combination containing thrombin; Gelfoam—highly effective packing; calcium—needed for smooth muscle contraction and clot formation; vitamin K—necessary element in clotting cascade; complications—consider ICU admission during recovery phase; hypoperfusion injuries (eg, kidneys, brain), pituitary necrosis, infection, acute lung injury, and persistent anemia; transfuse patient to safe level only, not normal level; avoid placing patient in supine position, since massive amounts of fluids patient has received can cause patient to mimic signs of pulmonary edema; IV iron (Venofer) increases iron counts quicker than oral iron and allows patient to replace own Hb and Hct quickly