Hematologic Complications of Pregnancy

Joseph Breuner, MD October 10, 2006

outline
Anemia Thrombophilias Thrombocytopenia

Case #1
Anemia, pros 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

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

Physiologic Anemia of Pregnancy

Normal hemoglobin by gest age in pregnant women taking iron supp 12 wks 24wks 40 wks 12.2 [11.0-13.4] 11.6 [10.6-12.8] 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 alphathal. 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
Wheres 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
OCPs: 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 SABs <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)