Hematologic Complications of Pregnancy. Joseph Breuner, MD October 10, 2006. outline. Anemia Thrombophilias Thrombocytopenia. Case #1. Anemia, pro’s and cons of treating. Anemia. Which patients will benefit from iron treatment? What hematocrit at 28 wks should generate attention? .
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Hematologic Complications of Pregnancy Joseph Breuner, MD October 10, 2006
outline • Anemia • Thrombophilias • Thrombocytopenia
Case #1 • Anemia, pro’s and cons of treating
Anemia Which patients will benefit from iron treatment? What hematocrit at 28 wks should generate attention?
Anemia • Dilutional or physiologic • Iron Deficiency Anemia • Thalassemias
Physiologic Anemia of Pregnancy • Pregnancy-induced hypervolemia has several important functions:1. To meet the demands of the enlarged uterus with its greatly hypertrophied vascular system.2. To protect the mother, and in turn the fetus, against the deleterious effects of impaired venous return in the supine and erect positions.3. To safeguard the mother against the adverse effects of blood loss associated with parturition. Williams 2006
Physiologic Anemia of Pregnancy • Normal hemoglobin by gest age in pregnant women taking iron supp • 12 wks 12.2 [11.0-13.4] • 24wks 11.6 [10.6-12.8] • 40 wks 12.6 [11.2-13.6]
Iron stores • The amount of iron absorbed from diet, together with that mobilized from stores, is usually insufficient to meet the maternal demands imposed by pregnancy Williams 2006
Iron stores Figure 5-6. Indices of iron turnover during pregnancy in women without overt anemia but who were not given iron supplementation. (From Kaneshige, 1981, with permission.)
Prenatal vitamins • At DFM contain 27 mg of elemental iron as ferrous fumarate • Measured this way because different iron salts are absorbed differently
Anemia-who to treat • CDC: if Hgb is < 11 in 1st or 3rd tri, or <10.5 in 2nd tri • Obtain ferritin, cbc, smear, iron level • If ferritin < 15 mcg/dl, confirms Fe def • If ferritin <30 mcg/dl, 85% PPV and 90%NPV
Anemia-who to treat • ACOG-no specific recommendation • Hemoglobinopathy bulletin recommends • If MCV<80, obtain hgb electrophoresis • Check ferritin. • If ferritin >15, excludes iron-deficiency • B-thal will have elevated Hgb A2 or F • If both negative, send DNA thal screen for alpha-thal. Costs $35-50 at Dynacare, results take 3 wks
Anemia-who to treat • Up to date: uses CDC definition 11/10.5 • Follow with dx of cause of anemia: ferritin level, cbc for hemolysis and mcv, electrophoresis if mcv low.
Anemia-who to treat • The USPSTF recommends routine screening for iron deficiency anemia in asymptomatic pregnant women. B recommendation. • B. The USPSTF recommends that clinicians provide [the service] to eligible patients. The USPSTF found at least fair evidence that [the service] improves important health outcomes and concludes that benefits outweigh harms. • http://www.aafp.org/afp/20060801/us.html
Anemia-who to treat • Cochrane 2006 on routine iron supplementation • The data suggest that daily antenatal iron supplementation: • increases haemoglobin levels in maternal blood both antenatally and postnatally. • increase difficult to quantify due to significant heterogeneity between the studies. • Women who receive daily antenatal iron supplementation are less likely to have iron deficiency and iron-deficiency anaemia at term as defined by current cut-off values
Anemia-who to treat • Cochrane 2001, 5 studies • Oral iron treatment in pregnancy was assessed in one small trial (n=125), where it was compared with placebo. • This showed a reduction in the number of women with haemoglobins under 11g/dl (odds ratio (OR) 0.12, 95% confidence interval (CI) 0.06 to 0.24) • greater mean haemoglobin level 11.3g/dl compared to 10.5 g/dl (weighted mean difference 0.80, 95% CI 0.62 to 0.98). • no data on clinically relevant outcomes.
Anemia-who to treat • Where’s the outcomes data? • Observational studies published to date in iron-supplemented populations show association between • High hematocrits >40% at 30-34 wks and IUGR, preterm delivery and stillbirth • Low hematocrits<30% associated with no bad outcomes OBSTETRICS AND GYNECOLOGY 1991
Anemia-who to treat • How to explain this? • Plasma volume expansion is important for fetal growth and well being • High hematocrits likely represent failure of plasma volume expansion • Results persist even when controlled for HTN and preeclampsia
My recommendations • Use Hgb 11 in 1st and 3rd and 10.5 in 2nd tri to define anemia • Ferritin, cbc • Ferritin<15=iron deficiency. • Mcv<80=hgb electrophoresis • If neither explains anemia, consider DNA testing for alpha thal
My recommendations • If iron-deficient, treat with iron until • Hgb in normal range (over 11/10.5) • Use ferrous sulfate 325 bid-tid • Or IV iron dextran if not tolerated
My recommendations • If not iron deficient, rule out thalassemias • No need to treat if ferritin ok
My recommendations • Note that real outcome data are lacking • Nutritional history and 3rd world experience dictate practice
Thrombophilias • Complex and overlapping sets of recommendations • Key is in history taking
Thrombophilias • Ask your patient • Have you or a family member had • Blood clot, in the leg or elsewhere? • Stroke? • Temporary blindness or bleeding in the eye?
Thrombophilias • Understand in terms of clot :relative risk • OCP’s: 4x • personal hx of venous thromboembolism:20x • pregnancy and the puerperium:5x • obesity • surgery • air travel • familial coagulation disorders:1.2-8x ACOG 2006
Thrombophilias • Also understand: • up to half of women who have thrombotic events during pregnancy possess an underlying congenital or acquired thrombophilia ACOG 2001
Thrombophilias: who to screen • Tests for inherited thrombophilias • Factor V leiden • Prothrombin G20210A • Antithrombin III antigen • Fasting homocystine levels (or MTHFR mutation) • Protein C Ag • Protein S Ag ACOG 2001
Thrombophilias: who to screen • Inherited tests for antiphospholipid ab syndrome: • Lupus anticoagulant • Anticardiolipin ab ACOG 2001
Thrombophilias: who to screen • Screen inherited and acquired for • Personal or FH<50 of thrombosis • Unexplained IUFD >14 wks • Preeclampsia <34 wks • Abruption ACOG 2001
Thrombophilias: who to screen • Screen acquired only for • 1 SAB 10-14 wks • 3 or more SAB’s <10 wks ACOG 2001
Thrombophilias: who to treat • BID low molecular wt heparin or TID heparin to APTT 1.5x control, and • Postpartum warfarin x 6 wks • For: ACOG 2001
Thrombophilias: who to treat • Hx of life-threatening thrombosis • Recent thrombosis (?6 mos) • Recurrent thrombosis • On chronic anticoagulation • Personal hx thrombosis and • AT-III deficient • FVL or Prothrombin G20210A homozygote • Heterozygous for FVL and G20210A ACOG 2001
Thrombophilias: who to treat • Offer prophylactic dosing heparin-5000 units SQ BID or enoxaparin prophy dose • 6 wks postpartum warfarin • For: ACOG 2001
Thrombophilias: who to treat • Hx of idiopathic thrombosis • Thrombosis due to pregnancy or OCP use • Thrombosis accompanied by any thrombophilia not on previous list • No hx of thrombosis but an underlying thrombophilia and a strong FH (<age 50) of thrombosis ACOG 2001
Thrombophilias: who to treat • Offer prophylaxis or not, and pp warfarin, to • Pregnant pts c hx of isolated venous thrombosis due to transient highly thrombogenic event (orthopedic trauma, complicated surgery) in whom thrombophilia is excluded. ACOG 2001
Thrombocytopenia • Physiologic • ITP vs gestational thrombocytopenia • Preeclampsia/HELLP
Physiologic Thrombocytopenia • The lower limit of normal platelet counts in pregnancy has been reported to be 106,000 to 120,000 platelets/microL. Up to date April 2006
Gestational Thrombocytopenia • Mild and asymptomatic thrombocytopenia • No past history of thrombocytopenia (except possibly during a previous pregnancy) • Occurrence during late gestation • No association with fetal thrombocytopenia • Spontaneous resolution after delivery
Gestational Thrombocytopenia • Plt counts >70,000, with two thirds between 130 and 150,000 • Frequency is 5% • No neonatal thrombocytopenia • Therefore, considered benign and pregnancy care is unchanged
ITP • Idiopathic thrombocytopenic purpura • Immune mediated • Platelet destruction
ITP • presumptive diagnosis: • history (eg, lack of ingestion of a drug that can cause thrombocytopenia) • physical examination • complete blood count • peripheral blood smear. • HIV testing • Blood pressure, proteinuria, liver transaminases • Antiplatelet antibody testing not routinely recommended
Preeclampsia/HELLP • Can present with thrombocytopenia • Should develop within 7-10 days • Elevated blood pressure • Proteinuria • Elevated liver transaminases
My recommendations • Platelet counts not standard screen • If count below 100,000, evaluate for ITP • Discuss with consultant • Evaluate for preeclampsia/hellp • Follow q 4 wks through pregnancy
References • Genetic Thrombophilias and Preeclampsia, Lin and August 105 (1): 182. (2005)