8/25- Consultive Hematology (Pregnancy, Age Extremes) Flashcards

1
Q

What are some changes seen in BV/cell counts/EPO level in pregnancy?

A
  • Blood volume increases by 40-50%
  • Plasma volume increase mostly in 2nd trimester
  • Red cell mass increases mostly in late 2nd & 3rd TM
  • Erythropoietin increases throughout pregnancy & maxes at 150% at delivery
  • Platelet count change controversial
  • WBC count rises, leukocytosis during labor degree correlated with length of labor
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2
Q

What are some physiologic changes seen in pregnancy designed to prevent women from bleeding out at birth?

A

PLASMA PROTEINS:

  • ESR rises due to anemia and gestational age (result of increased levels of globulins, fibrinogen, so use as a marker of inflammation difficult)
  • vWF, fibrinogen, factors VII, VIII, X increase
  • Factors II, V, XII stable
  • Factors XI, XIII decrease
  • Protein C & Antithrombin stable
  • Protein S total & free decrease
  • Fibrinolysis impaired by PAI I and PAI II
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3
Q

Iron deficiency anemia in pregnancy:

  • Epidemiology
  • Hb levels
  • Requirements in pregnancy
  • Risks
  • Assessment
A

Iron def is the commonest cause of anemia in pregnancy worldwide

  • Up to 75% African pregnant women

Definition:

  • Hb under 11 in 1st and 3rd TMs
  • Hb under 10.5 in 2nd TM Require 1 gm of iron during pregnancy
  • Exceeds normal Fe storage (300 mg)
  • Fetal requirements are always met…

Risks: in first 2 TMs, iron deficiency associated with:

  • 2x increased risk of preterm delivery
  • 3x increased risk of low birth weight

Assess Fe storage with ferritin and transferrin saturation; Fe supplements as needed

Pica is more common in Fe def pregnant women than other Fe def populations

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4
Q

What is the 2nd most common nutritional deficiency in pregnant women?

A

Folate deficiency (first is iron)

  • Rare in the US
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5
Q

What are folate requirements in pregnancy?

When does anemia typically occur?

What complications may be seen?

A
  • Doubled requirements of folate in pregnancy: 400-800 ug/d
  • Anemia usually occurs in 3rd TM and responds in 1-3 days
  • Severe pancyotpenia and HELLP-like states have been reported
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6
Q

What happens to B12 levels in pregnancy?

Levels?

Measurement method?

A
  • B12 deficiency is rare in pregnancy, because it’s hard to get pregnant if B12 is deficient
  • B12 levels fall during pregnancy due to shift from serum to tissue stores (should not drop below 180 pmol/L)
  • MMA levels should be normal if not B12 deficient
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7
Q

What is a common bleeding disorder in pregnancy?

A

DIC

  • Most often from: placental abruption, retained dead fetus, amniotic fluid embolism (AFE)

—-DIC in abruption depends on degree of abruption (delivery and correction of maternal coag are key)

—-DIC due to fetal death may not be detectable for 3-4 wks after fetal demise

—-DIC in AFE results from procoagulant properties of vernix, fetal squamous cells in circulation followed by a fibrinolytic response

  • Clinically you will see oozing at IV sites, hematuria, hemoptysis, excessive uterine bleeding…
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8
Q

What does AFE (amniotic fluid embolism) look like?

A
  • Heralded by vascular collapse
  • Dyspnea
  • Arrhythmias
  • Then DIC
  • AFE mortality decreased the last few decades (now 30%)
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9
Q

What does Von Willebrand Disease look like in pregnancy?

  • Manifestations
  • Clotting factor levels/changes
  • Treatment/monitoring
A
  • Menorrhagia and post partum hemorrhage are common manifestations
  • In types I and II, factor VIIIc and vWF rise in pregnancy, especially 3rd TM (Factor concentrates often unnecessary at delivery)
  • Levels fall rapidly after delivery (high risk of hemorrhage)
  • Type I pts: monitor VIIIc levels late pregnancy and 1-2 wks post partum
  • Bleeding risk minimal if levels > 40 u/dL
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10
Q

What is seen in type 2B vWD in pregnancy? Treatment?

A
  • Platelets may fall significantly in late pregnancy
  • May need platelets or plasma derived vWF containing concentrates if they bleed Use of dDAVP is controversial due to risk of placental vasoconstriction and maternal hyponatremia
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11
Q

What treatment for type 3 vWD in pregnancy?

A
  • Need infusion of vWF concentrate at delivery (40-80 IU/KG)
  • Then 20-40 IU/kg daily for a week, then taper over a few weeks Use of dDAVP is controversial due to risk of placental vasoconstriction and maternal hyponatremia
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12
Q

What are the nuances for Hemophilia carriers in pregnancy?

A
  • Ideally carriers identified before delivery
  • Baseline factor levels measured at 1st visit & 3rd TM
  • Remember: FIX (9) levels do not rise in pregnancy
  • At a minimum the sex of the fetus should be known before delivery
  • C/S not routinely necessary
  • Factor VIII or IX level of 40 IU/dl safe for vaginal delivery

To protect potentially affected fetus (50% male offspring of female carrier)

  • No vacuum extraction, no forceps
  • No IM injections of newborn until status known
  • Testing should be done on cord blood (no blood draws)

Mother’s factor level should be followed for several days

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13
Q

What may cause thrombocytopenia in pregnancy?

A

Gestational and Immune

  • Gestational: late and asymptomatic (late b/c of increased plasma volume; dilutional)
  • Immunologic: early and more severe
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14
Q

What is the diagnosis for thrombocytopenia in pregnancy?

A

Same as non pregnant

  • Platelet count cutoff between the two = 70,000
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15
Q

When to treat thrombocytopenia in pregnancy?

Treatment methods?

What is the cutoff platelet level for vaginal delivery/C-section?

A

Treat when?

  • Platelets < 10K require treatment
  • Platelets >30-50K without bleeding: no treatment
  • Platelets 10-30K late in pregnancy or bleeding: treat
  • Maternal platelet counts >50,000 safe for vaginal delivery and C/S (but may not be approved for epidural)

Treatment:

  • IVIg & steroids are safe, but may have no effect on the fetus
  • Splenectomy, if necessary, best in 2nd TM
  • Less that 5% of babies born to mothers with ITP will have platelet counts less than 20K
  • No clear recommendations on mode of delivery
  • Newborns should be monitored for 5-7 days
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16
Q

What is HELLP?

A

Hemolysis Elevated, Liver Enzymes, Low Platelets

  • Clotting a bigger issue than bleeding
  • Can cause seizures in pregnant women
  • Hematologic manifestations usually resolve with delivery
  • Steroids do not help
  • If symptoms persist beyond postpartum day 3 – consider TTP and start plasma exchange
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17
Q

What can acute fatty liver of pregnancy cause?

A

Mild thrombocytopenia

18
Q

What is the risk of thromboembolic events in pregnancy?

Factors influencing it?

Where do they typically occur?

A

Risk of venous thromboembolism is 2-6x that of nonpregnant women

  • Obstruction of venous return
  • Venous atonia from hormonal change
  • Changes in clotting factor levels
  • Inherited predispositions (50%)

90% in the left iliofemoral system due to compression by right iliac/ovarian arteries (from big gravid uterus)

  • Post partum rates are probably higher (6-12 wks)
19
Q

Antiphospholipid Antibody (APLA) syndrome is implicated in what?

A

Fetal loss

  • 20% of women with recurrent fetal loss have APLA
20
Q

How are thromboembolic events diagnosed in pregnancy? Is D-dimer msmt helpful?

A
  • Symptoms often common to pregnancy
  • Compression U/S best test
  • V/Q scan can be done
  • MRI or MRV if available
  • D-dimer levels rise during normal pregnancy and in complications, so may not be useful
21
Q

What prophylactic treatment can be done for thromboembolic events in pregnancy?

A
  • NO warfarin due to teratogenesis
  • LMW heparin anticoagulant of choice
  • Postpartum anticoagulation should be continued for 6-8 weeks
22
Q

What is the treatment for thromboembolic events in pregnancy?

A
  • Full dose LMW heparin
  • Ideally elective induction of labor
  • Stop heparin 24 hrs before induction
  • If risk is very high, give IV heparin up to 4-6 hrs pre-delivery
  • No epidural!!
  • Heparin and warfarin are safe postpartum even if breast feeding (organs already formed)
23
Q

Describe the symptom and treatment nuances of lymphoma in pregnancy

A
  • Outcome is not worse
  • Staging can be difficult due to imaging limitations; can do CXR with shielding Chemotherapy
  • Risk to fetus is greatest in 1st TM (organogenesis); can give chemo after
  • No evidence that dosing should be changed
  • Time treatment to prevent cytopenias at delivery XRT (Radiation)
  • May be a higher risk of breast cancer after XRT to chest in pregnant or lactating women (2-6x increase)
  • Vigilance for 2nd malignancies and hypothyroidism (especially important in women of childbearing years- baby will become hypothyroid)
24
Q

Describe the symptom and treatment nuances of acute leukemia in pregnancy

A
  • 1 in 75,000 pregnancies
  • Cannot delay treatment to continue pregnancy
  • Risk of fetal loss or maternal death around 2% each based on meta analysis
  • Risk of congenital defects ~8%
  • ATRA probably safe after 1st TM

- NO BREAST FEEDING!

25
Q

Describe Essential Thrombocytosis in pregnancy

  • Complications
  • Treatment
A

- Thrombotic risk increases pregnancy risk: common 1st TM fetal loss

ASA may help

Interferon indicated if:

  • Platelet count > 1,000,000
  • Hx of major thrombosis or bleeding
  • Familial thrombophilia
  • Cardivoascular risk factors Avoid hydroxyurea
26
Q

Sickle syndromes in pregnancy

  • Nutritional requirements
  • Management
  • High risks
A

Nutritional requirements:

  • Need folate (1 mg/d)
  • No Fe unless iron deficiency is documented (typically iron overload)

Management:

  • Stop hydrea 3 months before pregnancy

Increased risk for:

  • IUGR (Intrauterine Growth Retardation)
  • Low birth weight
  • Prematurity, preterm labor

No evidence that prophylactic transfusions improve outcome

Most experts recommend avoiding induction of labor, but epidurals are safe

27
Q

B thalassemia in pregnancy

  • Nutritional requirements
  • Management
  • Treatment
A

Pts with B thal minor typically have no problems

Nutritional requirements:

  • Higher doses of folic acid recommended before conception and in 1st trimester (4 mg)

Management:

  • Transfusion recommended to keep Hb~ 10 g/dL
  • Iron chelator hiatus during pregnancy
28
Q

a thalassemia in pregnancy

  • What happens to the anemia
  • HbH sensitivities
A
  • Anemia often worsens during pregnancy
  • Pts with HbH disease are sensitive to oxidizing compounds and medicines
29
Q

What does hematopoiesis look like in the neonate?

A
  • Begins in yolk sac (probably “seeds” the liver, but longer term SCs migrate to liver from AGM [aorto-gonad-mesonephros] region)
  • Marrow hematopoiesis begins ~ 10 wks, but liver is predominant until about 6 mo
  • Lymphopoiesis begins in thymus and lymph plexus at about 9 wks
30
Q

When do HbF levels really drop off?

A

By about 6 mo after delivery

31
Q

What are hemoglobin levels/allotypes in fetus/neonate?

A
  • HbF (a2y2) is major Hb of fetal life
  • At birth, HbF is about 60% of total Hb
  • At 6 mo, it’s under 3%
  • B thalassemia and sickle cell dz (involving faulty B chains) do not manifest until about 3-6 mo old (a thalassemia is the major globin at birth; manifests early)
32
Q

What is the fetal Hb at delivery? What is the sequence of events after delivery?

A
  • Hb level at birth ~ 17 g/dL
  • Hb level subject to asphyxia and time the cord is clamped
  • Hb level falls for about 2 mo to a level of 11 then EPO levels increase
  • This is “physiologic anemia” of the newborn
33
Q

How do fetal RBCs in neonates differ from adult?

A
  • Red cell antigens of neonates differ slightly

—-Express i antigen (adults express the more complicated I antigen)

—-A and B antigens are weakly expressed

  • Red cell lifespan is shorter (60-80 days)
  • Serum ferritin levels are high at birth, rise for a month or so and then fall to about 30 mg/dl at 1 year
  • Neonatal RBCs may be more sensitive to oxidative stress
34
Q

What do the WBCs in neonates look like?

Total count?

Antibodies?

A
  • Neutrophil count rises from about 8,000/ml at birth to 12,000/ml at 24 hrs, then back to 4,000/ml at 3 days
  • Neutrophils predominate in the first 4 days, then lymphocytes rise and predominate for first 4 years of life
  • Newborns are particularly susceptible to bacterial infection largely due to diminished opsonization of particular organisms, especially in preemies
  • Phagocytosis usually normal
  • CD4/CD8 ratio higher in infants and children
  • Most cellular immunity is present in newborn (Ag recognition/binding, ADCC, graft vs host reactivity), but decreased
  • Fetal lymphocytes synthesize little IgG
  • Neonate IgG levels similar to maternal due to transplacental passage of IgG
  • Breastfeeding provides IgA, lysozyme, lactoferrin
  • Newborn splenic function is limited
35
Q

Characterize coagulation in the neonate?

A
  • Platelet counts are normal at birth
  • Bleeding times of neonates are generally shorter than adults or children
  • One platelet antigen to be aware of is the human platelet antigen (HPA)-1a
  • If the mother is (HPA)-1a negative (2% of Europeans) and father is (HPA)-1a positive, mother can develop antibodies in 1st pregnancy that destroy platelets in 2nd and subsequent pregnancies.

Neonates will be severely thrombocytopenic – neonatal alloimmune thrombocytopenia (NAIT)

  • Factor VIII and vWF levels similar to adults
  • Factors II, IX, X, XI, XII levels are reduced
  • Factors II, VII, IX, X require vitamin K for synthesis and levels fall for first 3-4 days
  • Vitamin deficiency common in the newborn due to an immature liver, low vitamin K content of breast milk, a sterile gut, and poor placental transfer of vitamin K.

- IM Vitamin K given at birth to prevent hemorrhagic disease of the newborn (HDN)

  • Although not well understood – hypoxia during birth seems to lead to clotting disorders – usually prolonged PT/PTT
  • Clotting disorders – arterial and venous are common and usually related to catheters
36
Q

Hempohilia in the neonate

  • Incidence of Hemophilia A/B?
  • Genetics
  • De novo mutations
  • Manifestations
A

Incidence:

  • Hemophilia A: 1/5,000
  • Hemophilia B: 1/25,000

Both A and B are X-linked

30% of mutations are de novo

Manifestations

  • Hemophiliac babies have different manifestations than older children
  • Recognized by rabbis in 2nd century when circumsizing babies
  • Most bleeds in infants are iatrogenic (not in the muscles or joints)
  • Factor VIII levels are within the normal adult range at birth, whereas Factor IX is low (making diagnosis a bit more difficult).
  • Neonates with unexplained bleeding symptoms should be investigated for inherited hemostatic disorders.
37
Q

What causes a dramatic increase in hematologic malignancies after the age of 50?

A

Age related effects on cellular DNA

38
Q

What hematologic complications arise in the elderly population?

A
  • Increased hematologic malignancies
  • Decrease in immune function (impact on vaccines and resistance to infection)
39
Q

Aging and hematopoeisis

  • What happens?
  • Marrow depletion
  • Marrow cellularity
A
  • Normal diploid cells reach a state of replication senescence (?telomere shortening) – may not be true in hematopoietic stem cells
  • NO evidence for exhaustion of marrow stem cells with aging
  • Marrow cellularity decreases with aging from (30% by age 75)
40
Q

How do cell counts change with age?

A
  • In men, Hb level falls by under 1 g/dl by age 80, may not fall in women
  • Never ignore anemia in the older patient (evaluate for Iron, B12, folate and Heme malignancy)
  • The leukocyte count and the proportion of neutrophils rise much less in response to bacterial infection in individuals > 70
  • Platelet count does not change with age
41
Q

How does immune response change with age?

A

Thymic atrophy occurs by middle age. T lymphocyte development disappears. Older individuals dependent on existing T lymphocyte pool to mediate T cell–dependent immune responses.

  • Naive T cells numbers decrease with age and memory T cells are the predominant type
  • B lymphocyte function depends on T cell accessory roles, thus the decreased ability to generate antibody responses, especially to primary antigens.