HEMATOLOGICAL DISORDERS

DOC TRASPORTO (September 1, 2009)

HEMATOLOGICAL CHANGES IN NORMAL PREGNANCY Iron stores

Increase in plasma volume o Male: 1000 mg
Lesser increase in red cell mass o Female: 300 mg
Additional gram of iron needed during pregnancy
HEMOSTATIC CHANGES DURING PREGNANCY o 300 mg for the fetus
Increased synthesis of some coagulation factors o 500 mg for the expanded maternal red cell
o Factor VIII volume
o von Willebrand Factor (vWF) o 200 mg lost due to excretion
o Fibrinogen Obtained by:
Decreased level of Protein S o Taking 150-200 mg of element iron in three
Increased production of plasminogen activator or four divided doses daily one hour before
inhibitor-1 (PAI-1) meals

NORMAL PLASMA AND RED CELL VOLUME CHANGES NORMAL PLATELET COUNT DURING AN
DURING PREGNANCY UNCOMPLICATED PREGNANCY
Increased intravascular or plasma volume from Platelet count falls about 10% during an
2.5 to 3.8 liters over 40 weeks AOG uncomplicated pregnancy
o Begins about 15 weeks of gestation Platelet count decline is greatest at 30-34 weeks of
o Continues linearly through 35 weeks of gestation
gestation Incidental thrombocytopenia of pregnancy
o Constant over the last 5 weeks of gestation o Sever drop in platelet count that leads to
o Modified by the position taken by the moderate but aymptomatic
subject thrombocytopenia that develops just before
Smaller in the supine than in the left delivery
lateral position MILD thrombocytopenia
Uterine pressure on the o Physiological variant
IVC with pooling of blood o Requires no intervention or specific therapy
in the lower extremities
o Increases in healthier pregnancies and with Frequency of Thrombocytopenia During Pregnancy
the number of fetuses Thrombocytopenia
o One of the most common hematological
Increased red cell volume or mass abnormalities seen in pregnant women
o The rate of increase is less than that of the o Platelet count <150,000/ul
plasma volume o 6.6%
o Fall in the venous hematocrit from 0.40-0.35 o Most common cause
Physiologic Anemia 74% incidental thrombocytopenia of
o Hemoglobin falls from 13-11 g/dl pregnancy
o RBC count falls from 4.5-3.9 million/mm 21% thrombocytopenia associated
with hypertensive disorder of
IRON DEFICIENCY ANEMIA DURING PREGNANCY pregnancy
85% to 100% 3.8% thrombocytopenia associated
900 mg of iron are lost during pregnancy with an immunologic disorder,
o Diversion of iron to the fetus for typically idiopathic
erythropoiesis thrombocytopenic purpura (ITP) or
o Blood loss at delivery (150-200 mg of iron) systemic lupus erythematosus
o Lactation (SLE)
Equivalent to a loss of over 2 liters of blood Others:
Iron supplementation Aplastic anemia
o Increased in the hemoglobin from 11 to 12.4 Leukemia
g/dl Thrombotic
Suggests that all pregnant women thrombocytopenic purpura
should receive prophylactic oral iron (TTP)
therapy
Body iron content Incidental Thrombocytopenia of Pregnancy
o Approximately 4 grams in the adult male Most common cause of mild thrombocytopenia during
o 2 grams in the adult female pregnancy
6-7% of well pregnant women
 74% of all cases of thrombocytopenia Idiopathic Thrombocytopenic Pupura Complicating
Detected over the last few weeks of pregnancy and Pregnancy
around the time of delivery Low platelet count in early pregnancy
Platelet count may drop as low as 70,000/ul but can Hallmarks of ITP:
sustain >80,000/ul o Isolated thrombocytopenia
Platelet count returns to normal by 3-5 days after o Large and well-granulated platelets
delivery o Normal homeostasis inspite of a significant
o Gestational thrombocytopenia reduced platelet count
o Unremarkable RBC and WBC morphology
Diagnosis o Normal to increased number of
o Not specific megakaryocytes in the bone marrow
o Platelet count was normal either prior to 15-65% neonatal thrombocytopenia (<150,000/ul)
pregnancy or early in the pregnancy 60-70% risk of severe fetal thrombocytopenia
(<50,00/ul)
Treatment
o Watchful observation without further Management
investigations o >50,000/ul platelet count
o Proceed with NSVD Twice a month monitoring of the
o Epidural anesthesia clinical status
Requires CBC
Thrombocytopenia Complicating Hypertensive Disorders Vaginal delivery should be allowed
of Pregnancy
20% of all cases of thrombocytopenia during o <50,000/ul platelet count
pregnancy Increased risk of bleeding at
1-2% of all pregnancies delivery
25% with preeclampsia Reaise platelet count to >50,000/ul
o Usually mild (<100,000/ul) for delivery
o Moderate to severe can occur 1mg/kg/day
CS
Laboratory abnormalities
o HELLP Syndrome o Earlier pregnancy (<20,000/ul)
(H) Microangiopathic hemolytic Corticosteroids
anemia High dose IVIg
(EL) Elevated liver enzymes
(LP) Low platelet count Maternal side-effects
20% preeclampsia o Hypertension
Fairly rapid rise in liver function o Hyperglycemia
abnormalities, peak at 24-48 hours o Weight gain
post-delivery, with corresponding o Acne
fall in the platelet count o Psychosis
72-96 hours post-delivery
Transaminases fall back to American Society of Hematology Practice
normal Guidelines
Platelet count has usually o Indication for treatment
reached 100,000/ul Platelet counts <10,000/ul
Hematocrit may continue to fall over Platelet counts <10,000 to 30,000/ul
ensuing days who are in the second or third
Reaching a nadir at 3-5 trimester
days postpartum o IVIg
5-6 days following delivery Platelet counts of 10,000/u lint he
rd
Syndrome resolves 3 trimester
Platelet counts of 10,000 to
Platelet count rises to
30,000/ul who are bleeding
greater than 100,000 to
o Splenectomy
150,000/ul
Failed glucocorticoid and IVIg
Treatment
therapy
Aggressive obstetrical
Platelet counts <10,000/ul who are
management
bleeding
 Should not be performed in
asymptomatic pregnant women with
platelet counts >10,000/ul
HEMOSTASIS DURING NORMAL GESTATION
Hypercoagulable state
o Increased incidence of thromboembolic
disease that occurs in women with
congenital deficiencies of antithrombin III or
Protein C or activated Protein C resistance
during pregnancy
o Levels of several coagulation factors
increase markedly
Incidence of thromboembolic disease in women
Risk Factors for Thrombosis During Pregnancy
Hemostatic alterations during pregnancy, combined
with the increased stasis that occurs in the lower
extremities from a gravid uterus
Women without recognized inherited or acquired
disorders of hemostasis
o 0.09% during pregnancy
o 0.2-0.4% in the puerperium
Untreated women with congenital AT III deficiency,
Protein C deficiency or Protein S deficiency
o 18%, 7%, 0% respectively during pregnancy
o 33%, 19%, 17% respectively during the
puerperium
Family history of venous thromboembolism
Diagnosis and Management of Inherited Deficiencies of AT
III, Protein C, Protein S
Prophylaxis against thrombosis
o Should be given throughout pregnancy to
women with AT III deficiency
Heparin
o Anticoagulant of choice
o SubQ q 12H
Osteoporosis
o May occur if heparin is given for more than 6
months at a daily dose 15,000-20,000 units
Two indications for use of AT III concentrates
o During delivery when heparin dose may be
reduced or held
o If heparin resistance develops during
treatment for venous thromboembolism
15-68 years old
st
o Occurrence of the 1 manifestation of
Protein S deficiency, which is inherited in an
autosomal dominant fashion
38 years old
st
o Mean age of the 1 thrombotic episode
Antiphospholipid Antibody Syndrome
5-15% of women with recurrent pregnancy loss
Two groups
o Infectious Antibodies
APA that arises as a response to
infections by lipid coated
microorganisms like syphilis or HCV
o Autoantibodies
APA that bend to several proteins
tahat are attracted to phospholipids
Two general types of assays used to identify APA
o Lupus Anticoagulant (LA)
Detected by using coagulation tests
o ELISAs
Detection of APAs against specific
proteins
Involves testing for anticardiolipin
antibody (ACA) and B2-GP1
Criteria to prove the presence of LA
o Prolongation of phospholipids-dependent
screening test
PT
PTT
o Lack of correlation with added normal
plasma
o Shortening of the clotting time with added
phospholipid
o Exclusion of a specific factor inhibitor
Antibodies to factor VIII or factor V
Guidelines:
o High tests ACA (>40 GPL) are more
predictive of the disease than low titer
antibodies
o Anti-B2-GPI antibody tests are more specific
than ACA, in part because infectious APA
are not reactive
o LA are more highly correlated with
thromboses than ACA
o No single assay achieves maximal sensitivity
and specificity. Multiple assays must still be
used to reliably identify patients at risk for
vascular disease
Low dose heparin plus low dose aspirin in high-risk
patients significantly increases the likelihood of a live
birth
Inherited Bleeding Disorders During Pregnancy
von Willebrand Disease (vWD)
o most common
o 1 in 100 persons
o Autosomal dominant
o Diagnosis
Positive personal and family history
Decreased in ristocetin cofactor and
von Willebrand antigen
o Platelet adherence
Major function of vWF
Damage vessels
Serve as a carrier for Factor VIII
o Management
IV infusion of desmopressin
 Alternative Abruption placenta
Factor VII concentrate o Placental enzymes or tissues including
Cryoprecipitate thromboplastin-like material may be released
o 100 units of vWF into the uterine and next the systemic
o 10 bags before maternal circulation and lead to activation of
parturition + 10 the coagulation system
bags every 8-12
st
hours for the 1 Retained fetus syndrome
48 hours in o 50% with retained fetus greater than 5
patients with months
severe vWD o Low-grade compensated DIC
Factor IX Deficiency o Progress into a more fulminant hemorrhagic-
o Autosomal recessive thrombotic form
o Mild bleeding disorder
o Treatment Eclampsia
Plasma infusion to raise the Factor o DIC often remains low-grade and organ-
IX levels to at least >30% specific
o Localized to the renal and placental micro-
Acquired Bleeding Disorders During Pregnancy: DIC circulation
Associated obstetric conditions
o Abruption placenta Treatment
o Amniotic fluid embolism o Aggressive but reasonable therapeutic
o Septic or hypertonic abortion approach
o Intrauterine infections o Anticoagulant therapy with heparin
o Retained dead fetus
o Acute fatty liver Only components considered safe in patients with
active, uncontrolled DIC
Pathogenesis o Washed PRBC
o Thromboplastin-like material released from o Platelet concentrates
the necrotic placental tissues or dead fetus o AT III concentrates
o Thrombin activation o Volume expanders
o Consequences: Plasma protein fraction
Thrombosis with deposition of fibrin Albumin
monomer and polymerized fibrin in Hydroxyethyl starch
the microcirculation and
occasionally, large vessels LYMPHOMA AND LEUKEMIA
Lymphoma
Responsible for the hemorrhage seen in DIC o Reported to invade the placenta
o Plamin Acute leukemia
o Plasmin-induced lysis of coagulation o Transplanted from mother to child
factors V, VIII, IX, and XI presumably through the placenta
Most lymphoma and leukemias dont seem to behave
A process associated with both hemorrhage and differently during pregnancy
thrombosis o Except Burkitts lymphoma
Accompanied by decreased fibrinogen levels, platelet Diagnosis
counts, AT III levels and increased fibrin degradation o Bone marrow biopsy
products o Lymph node biopsy
o Assessed by D-dimer test o UTZ
Treatment
Amniotic fluid embolism o Delaying treatment later treatment
st
o Most catastrophic and common of the life- o Chemotherapy on the 1 trimester
threatening obstetric accidents Fetal Risks
o Manifest by the acute onset of respiratory Can lead to an infant being born
failure, circulatory collapse, shock and DIC with myelosupression