Hematologic Complications of Pregnancy (PowerPoint)

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					Hematologic Complications of
      Joseph Breuner, MD
       October 10, 2006
• Anemia
• Thrombophilias
• Thrombocytopenia
                Case #1
• Anemia, pro’s and cons of treating
Which patients will benefit from iron
What hematocrit at 28 wks should generate
• Dilutional or physiologic
• Iron Deficiency Anemia
• Thalassemias
Physiologic Anemia of Pregnancy
 Physiologic Anemia of Pregnancy
• Pregnancy-induced hypervolemia has several important

  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
 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

                     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
         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.
          Anemia-who to treat
• Cochrane 2006 on routine iron supplementation
• The data suggest that daily antenatal iron
  – 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

        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
• Complex and overlapping sets of
• Key is in history taking
• 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?
• 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
• Also understand:
  – up to half of women who have thrombotic
    events during pregnancy possess an
    underlying congenital or acquired

                     ACOG 2001
 Thrombophilias: who to screen
• Tests for inherited thrombophilias
  – Factor V leiden
  – Prothrombin G20210A
  – Antithrombin III antigen
  – Fasting homocystine levels (or MTHFR
  – Protein C Ag
  – Protein S Ag
                          ACOG 2001
 Thrombophilias: who to screen
• Inherited tests for antiphospholipid ab
  – 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,
  – 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
• 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
• Occurrence during late gestation
• No association with fetal
• 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
• Idiopathic thrombocytopenic purpura
  – Immune mediated
  – Platelet destruction
• presumptive diagnosis:
   – history (eg, lack of ingestion of a drug that can cause
   – physical examination
   – complete blood count
   – peripheral blood smear.
   – HIV testing
   – Blood pressure, proteinuria, liver transaminases
• Antiplatelet antibody testing not routinely
• 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
• Genetic Thrombophilias and
  Preeclampsia, Lin and August 105 (1):
  182. (2005)