Download Haematology Essentials - International Society of Obstetric Medicine

Hematologic Disease in
Pregnancy
Raymond Powrie, MD, FRCP(C) FACP
Professor of Medicine and Obstetrics and Gynecology
Alpert Medical School at Brown University
Interim Chief of Medicine
Women and Infants Hospital of Rhode Island
Chief Medical Quality Officer
Care New England Healthcare System
Incidence of
Common Hematologic Problems in Pregnancy
Iron Deficiency Anemia ~10%
B12 Deficiency
5%
Folate Deficiency
5%
Hemoglobinopathies and thalassemias 5%
Sickle Cell
4%
Alpha thalassemia 0.8-5%
Beta thalassemia
0.25-10%
Thrombocytopenia
<150
<100
Von Willebrand’s
Hemophilia
6.6%
1.2% %
1%
Anemia
Anemia
• Defined <10.5 g/dL
• Hgb < 6 g/dL has clear fetal
consequences
Anemia
MCV
Possible Etiologies
Initial Investigation
Low
Iron deficiency
Thalassemia
Hgb-opathies
Serum Ferritin
Low: Iron deficiency
Normal: Hgb electrophoresis
Normal
Anemia of chronic disease
Acute blood loss
Hemolysis
Reticulocyte count
Normal: Medical history ferritin,
TSH, Creatinine
High: Smear, LDH, Bili, haptoglobin
High
B12/Folate deficiencies
Alcohol/Liver Disease
Reticulocytosis
Reticulocyte count
Normal: B12, serum and RBC folate
levels, AST check alcohol and
medication history (AED, AZT)
High: Smear, LDH, Bili, haptoglobin
Iron Deficiency Anemia
• Evaluate for GI blood loss
• Ferrous sulfate 325 mg two to three times a day
– Supplement with vitamin C or red meat to increase
absorption
– Do not take with calcium, tea, coffee or wine
• Expect a 0.8 g/dL/week with iron supplementation
after a few weeks
• Rarely a need for parenteral iron
Thalassemia
Hemoglobinopathies
• 5% of the world’s population
• Mediterranean, Africa, Indian
Subcontinent, SE Asia, the Pacific
• Thalassemias
• Hemoglobinapathies
• Hemoglobin chains
NOT made so there
is anemia
• Hemoglobin chains
made with flaws so
there is anemia
Thalassemia
Thalassemia/Hgb-opathy
Hemoglobin Structure
• Two Alpha globin chains from 4 genes
• Two Beta globin chains from 2 genes
• Thalassemia classified by
– Phenotype: Clinical severity
– Genotype: number of gene abnormalities
• Fetuses have alternatives to Beta chains
but not to alpha chain deletions
Alpha thalassemia
Number of
absent/ineffective
Alpha genes
Variant Hemoglobin
Clinical
manifestation
1 gene mutation
None
Clinically silent mild
red cell microcytosis
2 gene deletions
None
Thalassemia trait:
Normal or Mild
microcytic anemia
3 gene deletions
Hgb H 8-10%
Hb A2 1-2%
Hb F 1-3%
Chronic anemia
Hb 7-10 g/dL
MCV 50-65 fL
MCH 15-20 pg
4 gene deletions
Hgb Barts
Hydrops fetalis
Lethal
Beta Thalassemia
Gene
mutation/deletion
Variant hemoglobin
Clinical Manifestation
One of the two beta
genes
Hgb A2>3.5%
“trait” : mild
microcytic, hypochromic
anemia
Both of the two beta
genes
Hb A2 and F
“major”: severe anemia
Hb3-7 MCV 50-50 and
NCH 12-18 pg
Sickle Cell Disease
Sickle Cell Trait/Disease
• Increased pregnancy complications
–
–
–
Miscarriage: 36% versus 10%
IUFD: 6% versus 1%
Preeclampsia: 15-20% versus 5%
Sickle Cell Disease
• Prevention of Crises
– Continuous good hydration
– Folate 1 mg daily
– No role for prophylactic blood transfusions
Sickle Disease
• Treatment of Crises
– Aggressive pain control with narcotics
– Hydration
– Oxygen
– Continued folate
– Careful search for and treatment of any infection
– Transfusion to achieve at least 50% normal
hemoglobin if severe
Chest crises have a significant mortality associated
with them and should be taken very seriously
Combinations
• Hb E 20-60% of
Southeast Asians
carry this gene
• Hb C 3% of Africans
• Hb S 12% of Africans
• Hb Lepore
• Significant when
combined with
thalassemia traits or
found in
homozygous states
Thrombocytopenia
Thrombocytopenia
• <150 X 109 /L
abnormal
• < 80-100 X 109 /L
epidural precluded
• <50 X 109 /L
Increased risk of
surgical bleeding
• <10-20 X 109 /L
increased risk of
spontaneous
bleeding
Etiology
Etiology
Diseases
Decrease
production
•
Tests
After viral infection (Rubella, mumps,
varicella, parvovirus, Hip and EBV)
Chemotherapy or radiation therapy
VitB12 and Folic acid deficiency
•
ITP
SLE
DIC, TTP,
APL syndrome, HELLP
Drugs: Heparin, Quinine, Valproic acid
HIV cause direct destruction of
megakaryocytes
•
•
HIV
Other tests based on
history and physical
Sequestration •
Hypersplenism
•
Examine for
splenomegaly
Factitious
Platelet clumping or thrombosis
•
Collect CBC with
citrated tube
•
•
Increased
destruction
•
•
•
•
•
•
•
•
Complete blood count
with MCV
Other tests based on
history and physical
Gestational
Thrombocytopenia
• The frequency in the largest series of consecutive women
admitted for delivery is 5% (Burrows RF, Kelton JG, N Engl J med
1993; 329:1263)
• Defined by the following five criteria:
– Mild and asymptomatic thrombocytopenia, More than 70.000
– No past history of thrombocytopenia (except previous
pregnancy)
– Occurrence during late gestation
– No association with fetal thrombocytopenia
– Spontaneous resolution after delivery
Immune (Idiopathic)
Thrombocytopenia
• Common acquired bleeding disorder
• Two criteria required for the diagnosis:
– 1. Isolated thrombocytopenia with other wise normal
CBC
– 2. Absence of clinically associated conditions ( e.g. SLE,
APL, CLL)
• Incidence is 50-60/million/year
• Women of childbearing age accounts for the
majority of the cases
• It is not uncommon therefore for a woman to enter
pregnancy with a known diagnosis of ITP or to
develop de novo ITP during pregnancy itself
Clinical
Manifestations
• Marked variability in the clinical presentation
• Onset usually insidious but can be acute and
abrupt
• Usually asymptomatic
• Bleeding usually muco-cutaneous
–
–
–
–
Petichiae, purpura, and easy bruising (Expected))
Epistaxis, gingival bleeding , and menorrhagia Common)
GI bleeding and gross hematuria( Rare)
Intracranial hemorrhage ( Fatal, Very rare)
Diagnosis
• Diagnostic approach to ITP in a is the same as in nonpregnant patients.
– No “gold standard” test to diagnose ITP.
– Diagnosis is reached after exclusion of other causes using
clinical history and exam, CBC and peripheral blood smear.
– Additional lab tests to consider include testing for
autoimmune disorders, and exclusion of HIV Antiplatelet
– Antibody testing is not recommended by American Society of
Hematology
Effect Of Pregnancy On ITP
• ITP accounts for 3-4% of the cases of
thrombocytopenia detected in pregnancy
• Pregnancy does not per se alter the
natural course of ITP or increase the risk
of relapse in women with previously
diagnosed ITP
Effect Of ITP
On Pregnancy
• Thrombocytopenia in the infant can occur due to passive
diffusion of autoimmune antibodies across the placenta
• In one review of 10 studies of 600 pregnancies in 469
women with known ITP reported neonatal
thrombocytopenia:
– < 150.000 in 28%
– < 50.000 in 11%
– ICH in 1.2%
• Maternal platelet count at delivery is not predictive of
neonatal platelet
• The risk of spontaneous bleeding in pregnant women is low
Treatment of ITP
• The goal for treatment of ITP is to provide a safe
platelet count to prevent major bleeding, rather
than returning the platelet count to normal
• Treatment is considered if the platelet count is
<30-50,000.
•
Some will treat for platelet counts <80,000 to allow regional anesthesia
Treatment in pregnancy
Prednisone is First line
• 1 mg/kg/day for 7-10 days and then gradually taper
taper to keep platelet above the desired threshold
• The lowest possible dose should be aimed for < 10
mg daily, most likely throughout the pregnancy
• Can increase the risk of GDM, HTN, maternal
infection and preterm delivery but no fetal effect
Treatment
(Continued)
IVIG (gamma globulin)
• May be considered first line in third trimester
– 1 g/kg ( pre pregnancy wt) daily for 2 days
Provides effective ( 80% )but temporary
improvement in platelet count (usually last for 2-4
weeks)
• Indicated in women with moderate or severe
bleeding symptoms or whose platelet < 10,000
• Can be repeated but expensive and time
consuming to administer
• No effect on fetal platelet count
•
Treatment
(Continued)
• Azathioprine
• Is a steroid-sparing agent
• used in pregnancy in conjunction with
corticosteroids in women with refractory ITP
Splenectomy
• Laparoscopic splenectomy has been safely
carried out mainly in second trimester
Treatment
(Continued)
• High doses Methylpredisone 1 gm IV
• Dexamethasone 40 g daily for 4 days
– can cross the placenta with fetal effect
• Rituximab Monoclonal antibody therapy
– used with caution in pregnancy as it crosses the
placenta and can cause temporary suppression of
fetal B lymphocytes and unclear long term effect
on development of fetal immune system
• Platelet transfusion
– for severe, symptomatic thrombocytopenia
Delivery
• Vaginal delivery preferable but mode of delivery
should be determined by obstetric indications
• Neuroaxial anesthesia:
– Although the precise platelet count needed to safely perform
neuroaxial analgesia is unknown, a platelet count variously
given as >50.000 or > 80.000 is considered safe for
epidural/spinal anesthesia/analgesia if coagulation is
otherwise normal.
von Willebrand’s Disease
VWD
• Most common inherited bleeding
disorder: 1% of population
• Quantitative or qualitative deficiency in
von Willebrand factor (VWF)
• VWF has two roles
– Helps platelets stick to each other, to damaged
tissue and to fibrinogen
– Carrier protein for FACTOR VIII that keeps FACTOR
VIII from being broken down prematurely
VWD
VWD type
Type 1
Not enough VWF made
Type 2
Faulty VWF made
Type 3
No VWF made
Type 2B has VWF that
works BETTER than the
other kind and can
cause thrombosis
Bleeding Disorders
Lab
•
•
•
•
History
Easy bruising
especially without
injury
Bleeding following
dental work or
surgery
Gingival bleeding
Menorrhagia
•
•
•
•
CBC
aPTT, INR
PFA-100
Bleeding time
Von Willebrand’s Disease
Testing for VWD
VWF antigen
How much VWF is there?
Factor VIII antigen
Does the VWF do its job at
protecting Factor VIII?
VWF ristocetin cofactor activity
(VWF:RCoA)
Does the VWF do its job at bringing
platelets together to do their work?
Pregnancy
• VWF and factor VIII levels go up in
pregnancy
• Patients generally fine if Ristocetin
cofactor activity levels >50 IU/dL
• Patients with type 2 VWD may have
worsened thrombocytopenia in
pregnancy
Treatment in Pregnancy
Review prior tests and confirm diagnosis
VWD testing at booking and at 34 weeks
•If >50 IU/L:
– no treatment
•If <50 IU/L
– If Type 1 or 2A
• PRN DDAVP 0.3 mcg/kg IV/SQ postpartum for vaginal
delivery
• Preventive DDAVP 0.3 mcg/kg IV/SQ prior to CS
– If Type 2B 2N 2 M or type 3… give intermediate
purity FVIII concentrate 20-40 IU/kg
Treatment in Pregnancy
• Inherited illness but generally high
levels of FVIII and VWF in newborn
Hemophilia
Hemophilia Treatment
Disease and
Inheritance
Deficiency
Pregnancy
Effects
Treatment
Hemophilia A
XLR
Factor VIII
Increase in
F VIII
DDAVP or FVIII concentrate to get
levels >50 IU/dL for any
procedure
• Hemophilia A
Male fetuses should not get
vacuum extraction or IM
injections prior to testing
Hemophilia B
XLR
Factor IX
No change in
F IX
Recombinant F IX to get levels >
50 IU/dL for any procedure
Male fetuses should not get
vacuum extraction or IM
injections prior to testing
Hemophilias
Deficiency and
Inheritance
Pregnancy concerns
Treatment
Factor XI
AR
Bleeding usually only
FFP or Factor XI concentrate
with trauma or surgery to maintain F IX levels > 50
IU/dL prior to procedure and
for 4/7 days after a vaginal
delivery / CS
Factor VII
AR
Levels increase in
pregnancy
FFP or F VII concentrates to
achieve ? goal
Factor XIII
AR
High risk of
Intracranial
hemorrhage
High miscarriage and
PPH rate
FFP or F XIII concentrates to
achieve ? goal