Pocket Obstetrics and Gynecology

HEMATOLOGY

HEMATOLOGIC CHANGES OF PREGNANCY

Plasma Volume

• ↑ by 40–50% of baseline plasma vol

• Plasma vol ↑ begins at ∼6 w gest & continues until 30–34 w

RBC Mass

• 20–30% ↑ in RBC mass during Preg beginning at ∼10 w gest

• 1000 mg iron req for Preg (RBCs – 500 mg, fetus – 300 mg, bleeding – 200 mg)

• Most common cause of anemia in Preg is iron deficiency

Leukocytes

• Plasma levels variable throughout Preg, WBC = 5000–12000/μL

• Physiologic leukocytosis in labor & puerperium, WBC = 14000–16000/μL

Coagulation System

• 5-fold increased risk of thromboembolic dz; absolute risk 1/1500 pregnancies

• ↑ risk from venous stasis (uterine mass effect), vessel wall injury, hypercoagulable state (↑ procoagulants; ↓ prot S; decreased fibrinolysis due to ↓ tPa)

• Coagulation factors normalize 2 w postpartum

Blood Loss with Delivery

• Avg EBL: Vaginal deliv = 500 mL; cesarean deliv = 1000 mL

• Cesarean hysterectomy = 1500 mL (nonurgent) & 2500 mL (emergent)

• Majority of bld loss w/i 1st hour after deliv → ∼80 mL lochia over next 72 h

ANEMIA

Definition

• Gravid: Hb ≤11 g/dL in 1st trimester; ≤10.5 g/dL in 2nd trimester; ≤11 g/dL in 3rd trimester

• Nongravid woman: ≤12 g/dL

• IOM recommends decreasing cutoff for anemia by 0.8 g/dL for AAs

• Risks: Non-Hispanic Black, malabsorption (eg, celiac sprue), gastric bypass, iron-poor diet, menorrhagia, teenage, minority, low socioeconomic status, short Preg interval

Clinical Manifestations

• Fatigue, IUGR, preterm deliv, perinatal mortality, pica, restless leg syn

• Hb <6 g/dL a/w NRFHT, oligohydramnios, fetal death, CHF (Hb <4 g/dL)

• Signs: Pallor (conjunctiva), tachy, orthostatic HoTN, jaundice (hemolysis), splenomegaly (thal, sickle cell, spherocytosis), petechiae (TTP, HUS, DIC)

Diagnostic Evaluation

• CBC w/ indices at 1st OB visit & 24–28 w gest; note MCV, RDW, retic count

• Periph smear, iron, iron sat, ferritin, TIBC, folate, B12, Hb electrophoresis

• Additional labs: LFTs, BUN/Cr, TFTs, hemolysis labs (↑ indirect bili, ↑ LDH, ↓ haptoglobin)

• Bone marrow aspirate/bx

• RI = [retic count × (pt’s Hct/nml Hct)]/maturation factor

Figure 16.1 Initial approach to anemia

Maturation factor dependent on Hct; Hct ≤15% = 2.5, >16% = 2, >26% = 1.5, >36% = 1 (Nml is 1–2% for healthy . >2–3% = adequate retic for anemia. <2% = inadeq.)

Microcytic Anemia (MCV <80 fL)

• Eval: Serum Fe, TIBC (transferrin), ferritin, transferrin sat

• 30 mg/d of elemental iron req during Preg for prevention of anemia

• Rx: Fe rich foods (cream of wheat, red meat, spinach, dried beans; take w/ Vit C rich foods for ↑ Absorp), Fe supplements, IV iron (intolerance to PO), xfusion (for symptomatic anemia or Hb <6), erythropoietin

Normocytic Anemia (MCV 80–100 fL)

• DDx includes acute bld loss, early Fe deficiency, bone marrow suppression (marrow invasion, RBC aplasia, aplastic anemia), chronic renal insufficiency, hypothyroidism, pancytopenia, anemia of chronic dz, sideroblastic anemia

Macrocytic Anemia (MCV > 100 fL)

• Megaloblastic anemia: Hypersegmented neutrophils on periph smear is pathognomonic

Folate deficiency: Age, malnut (alcoholism), malabsorption (celiac sprue), meds (trimethoprim, methotrexate), ↑ requirement (Preg, malig, dialysis)

B12 deficiency: May cause neurologic sx; causes – pernicious anemia, gastritis, bariatric Surg, malabsorption (Crohn’s, ileal resxn, tapeworm), meds (metformin, PPIs)

• Nonmegaloblastic anemia: Causes include liver dz, alcoholism, reticulocytosis, hypothyroidism, myelodysplastic syn, medication (AZT, acyclovir, azathioprine)

• Eval: Serum B12/folate, periph bld smear, homocysteine, methylmalonic acid

↑ homocysteine in B12 & folate deficiency, ↓ methylmalonic acid in B12 deficiency only

Schilling test, anti-IF antibodies → positive in pernicious anemia

• Rx: Folate deficiency – 1–5 mg PO QD → will treat anemia but, not neuro sx; B12 deficiency – 1 mg IM QD × q7d then weekly × 4 w then monthly as needed

Hemolytic Anemia

• Eval: ↑ retic count (RI >2%), ↑ LDH, ↓ haptoglobin, ↑ indirect bilirubin

• Direct Coombs test, periph smear, Hb electrophoresis, osmotic fragility test

HEMOGLOBINOPATHIES

Pathophysiology

• Adult Hb structure = 2 α-chains + 2 β-chains (HbA) or 2 δ-chains (HbA2)

• Fetal Hb = 2 α-chains + 2 γ-chains (HbF) (12–24 w gest)

Thalassemias (Lancet 2012; 379:373)

• Abn or ↓ synthesis of α- or β-chains → microcytic anemia; classified by absent chain

• a-thal: 4 α-chains (αα/αα) from 2 genes on chromo 16

Absence of ≥1 of 4 genes → abn Hb assembly → hemolysis & ↓ production

• b-thal: Nml state = 2 β-chains from 1 gene on chromo 11

At risk: Mediterranean, Asian, Middle Eastern, Hispanic, & West Indian

1 β-chain mut → β-thal minor → mild anemia

2 β-chain mutations → β-thal major (Cooley’s anemia) → sev anemia

β-thal intermedia = 2 β-chain mutations w/ milder sx

• Dx: CBC (MCV < 70), ferritin (exclude Fe deficiency anemia), Hb electrophoresis, periph smear → basophilic stippling

• Screening in Preg: Pts in high-risk groups → CBC & Fe indices → ↓ MCV & no iron deficiency → Hb electrophoresis; If Southeast Asian, DNA testing for α-thal

• Prenatal testing for α- & β-thal if mut/deletions in both parents via CVS, amnio, or PGD

• Preg in β-thal major recommended only if nml cardiac fxn & prolonged hypertransfusion → Hb >10 & w/ iron chelation

• Rx: xfusion for anemia + iron chelation; splenectomy; hematopoietic xplant

Sickle Cell Anemia (Lancet 2010;376:2018; Obstet Gynecol 2007;109(1):229)

• Autosomal recessive β-chain mut (valine replaces glutamic acid at 6th amino acid) resulting in abn Hb structure (HbS replaces HbA)

• HbS (heterozygote) = sickle cell trait (carrier); HbSS (homozygote) = sickle cell anemia

• HgbSS: ↓ oxygen tension → RBC sickles → hemolysis & microvascular occlusion

• 1 in 12 AAs w/ trait, 1 in 500 w/ dz; ↑ risk African, Mediterranean, Arab-Indian

• Signs/sx:

Anemia hemolysis, splenic sequestration, aplastic (parvovirus B19)

Infarction: Painful crises, acute chest syn, CVA, multiorgan failure: Functional asplenia, kidneys (renal papillary necrosis), heart, & brain (CVA)

Infxn encapsulated organisms (Hib, S. pneumoniae, Meningococcus), osteomyelitis

• Acute chest syn = new pulm infiltrate + a pulm symptom (chest pain, T > 38.5, resp sx, hypoxemia) from infxn/vaso-occlusion of pulm vessels; 3% mortality

• Dx: bld smear w/ sickle-shaped RBCs & Howell Jolly bodies; Hb electrophoresis

• Rx: hydroxyurea → ↑ HbF → ↓ frequency of painful episodes, acute chest syn & need for bld xfusion; bld xfusion → simple vs. exchange xfusion (indications: Preop, acute/chronic organ failure, acute anemia, acute pain); iron chelation; hematopoietic stem cell xplant (selected pts w/ sev dz)

Acute pain crisis → Opioids are mainstay, O2 for oximetry <95%, IV hydration

Infxn → vaccination against Hib, S. pneumoniae, N. meningitidis, influenza, & HBV

Acute chest syn/CVA → simple vs. exchange xfusion (ACS = respiratory symptoms, chest pain, or fever and a new pulmonary infiltrate on XR)

• Sickle cell variants: HbC not a/w dz, HbSC same as HbSS but ↓ frequency; HbS + thal a/w varying severity of dz

• Preg: HbSS a/w ↑ mat risk acute pain crises, acute chest syn, PROM, preeclampsia, pyelo, bld xfusion, alloimmunization, & infxn; ↑ fetal/neonat risk SAB (30%), IUFD (OR = 2), IUGR, PTD (25%), ↓ birth weight (20–40%). Prenatal diagnosis available

Mgmt: Stop hydroxyurea (teratogenic), start 1–4 mg folate daily, avoid cold, physical exertion, dehyd, & stress to avoid painful crises. If xfusion → monit serial Hb & % HbS, goal: Hb ∼10 g/dL & ≤40% HbS (Obstet Gynecol2007;109(1):229)

Serial growth USs & antenatal testing at 32 w for fetal monitoring

HbSS & HbS (trait) w/ ↑ risk of pyelo w/ asymptomatic bacteriuria. Consider daily UTI ppx & monthly urine cx.

THROMBOCYTOPENIA (PLT <150000/μL)

• Plt 50000–100000 – no increased surgical risk; ↑ risk for bleeding w/ major trauma

• Plt 20000–50000 – ↑ risk w/ minor trauma or Surg

• Plt <20000 – risk spont bleeding (<10000 ↑ risk of life-threatening bleeding)

Etiology

• Gestational thrombocytopenia → 8% of pregnancies; most common cause of ↓ Plt in Preg (66%); Plt typically >70000/μL; resolves 2–12 w postpartum

• ITP → IgG-mediated; persistent Plt <100000/μL; dx of exclusion (nml bld smear, no systemic dz); 15% of neonates have Plt <50000/μL if MoM has ITP (trans placental IgG).

• HIT → see Section below

• TTP–HUS → thrombocytopenia + microangiopathic hemolytic anemia ± renal failure ± fever ± Δ mental status; etiology: Meds (quinine, chemo, cyclosporine), Preg, Shiga toxin-producing E. coli, SLE, sev ADAMTS13 deficiency

• DIC → etiology: Sepsis, Preg (abruption, HELLP, PPH, IUFD, septic AB, preeclampsia), Surg, hepatic failure, xfusion rxn

NAIT → mech similar to RhD dz; 1st Preg can be affected;∼0.1% live births; risk of IVH, petechiae, bleeding; ∼100% recurrence for future pregnancies if fetus has same Plt Ag

• HELLP syn → see Chap. 15.

Evaluation

• H&P: PMHx, meds, infxns, splenomegaly, LAD, petechiae, mucosal bleeding

• Labs: CBC ± periph smear; retic count, LDH, haptoglobin, bilirubin, PT/aPTT, fibrinogen, D-dimer, Coombs, ANA, enzyme-immunoassay for HIT, HIV, HCV, Parvovirus, CMV, antiphospholipid antibodies, bone marrow bx

Figure 16.2 Initial approach to thrombocytopenia

Heparin-induced Thrombocytopenia (HIT)

• Type 1 (Nonimmune), occurs w/i 2 d of heparin; clinically inconsequential

• Type 2 (Ab-mediated resp to heparin-PF4 complex), w/i 4–10 d; Plt 30–70 K; risk thrombosis – venous (DVT, PE) & arterial (MI, CVA)

• Pts w/ >1% risk of HIT → CBC every 2–3 d from day 4–14.

• Dx: Pts w/ intermediate or high pretest probability require confirmatory testing

Ag assays (Anti-heparin/PF4 ELISA) vs. functional assays (serotonin release assay (gold std), heparin-induced Plt aggregation)

• Rx: Acute HIT – stop heparins & start argatroban or danaparoid; use danaparoid (1st line) or fondaparinux (2nd line) for pregnant pts; avoid warfarin alone, LMWH or prophylactic Plt xfusion (if pt NOT actively bleeding); may use warfarin alone in nonpregnant pts when INR therapeutic (after bridging w/ nonheparin) AND Plt >150 K

VENOUS THROMBOEMBOLIC DISEASE

Definition

• DVT & PE most common presentations

• DVT: Most commonly in legs; Calf-vein thrombosis → 80% resolve spontaneously

Prox vein thrombosis (popliteal/femoral/iliac veins) → ↑ risk embolism

• PE: Thrombus from venous system mobilizes to pulm arterial circulation

• VTE: Up to 600000 pts affected annually causing up to 100000 VTE-related deaths

• DVT & Preg: 50–66% occurs antepartum, left leg = 80% of thrombi

Pathology

• Virchow’s triad:

1. Endothelial injury – Surg, tobacco use, trauma, atherosclerosis, age

2. Hypercoagulable state – thrombophilia, hyperestrogenic state, malig

3. Alterations to nml bld flow – prolonged immobilization, cardiac dz, sickle cell

Clinical Manifestations

• DVT: Most asymptomatic, some have unilateral ext pain, swelling, erythema. Exam: >2 cm midleg diameter asymmetry, Homan’s sign (pain in calf w/ ankle dorsiflexion)

• PE: Dyspnea, pleuritic chest pain, cough, syncope. Exam: Tachy, tachypnea, low pulse oximetry, crackles, fever

Physical Exam

• DVT: Lower ext edema (3+ cm > unaffected leg), erythema, calor, tenderness, palpable cord, (+) Homan’s sign (calf pain on dorsiflexion in <5% of pts)

• PE: Crackles, Homan’s sign, cyanosis, pleural rub, loud P2massive: ↑ JVP, R-sided S3

Diagnostic Evaluation (DVT)

• Studies: Mod/high sens D-dimer <500 ng/mL → NPV = 94% for absence of DVT, (Not reliable in postop state or in Preg or if high pretest probability), CUS (PPV = 94%), contrast venography, MRI

Figure 16.3 Evaluation for DVT based on pretest probability

Figure 16.4 Suspected DVT in pregnancy

Diagnostic Evaluation (PE)

• D-dimer: <500 ng/mL may exclude DVT/PE; may be difficult to interpret in Preg

• ABG: Hypoxemia, hypocapnia, respiratory acidosis, ↑ A-a gradient; not routine for PE screen

• ECG: Most common: Sinus tachy, also S1Q3T3 or RBBB (Am J Cardiol 1991;68(17):1723)

• CXR: Atelectasis, effusion, ↑ hemidiaphragm, Hampton hump, Westermark sign; 1st study for PE workup in pregnant pts if no leg sx; not routine in nongravid pts for PE eval

• Echocardiography: ↑ RV size, ↓ RV fxn, tricuspid regurgitation, RV thrombus signs more likely w/ large PE; use in critically ill pts w/ high probability of PE

• Compression US: Suff to rule in PE; 2% false (+) (Ann Intern Med 1997;126(10):775)

• CTA: Most common 1st-line test; sens 83% & spec 96% w/ MDCT & institutional experience; contraindications include renal dz, contrast allergy, or prior rxn

• V/Q: Use for pts w/ contraindications to CTA, centers not experienced w/ CTA, or pregnant women w/ nml CXR & w/o leg sx. Abn CXR obscures findings.

• MRA/MRV: Sens 78% & spec 96% if technically adequate; 52% of studies inadeq; sens 100%, 84%, & 40% for lobar, segmental, & subsegmental PE

• Pulm angiography: Reserved for pts w/ consideration for endovascular rx of PE

Figure 16.5 Evaluation for suspected PE by pretest probability

Figure 16.6 Evaluation for PE in pregnancy

Treatment

• If high clinical suspicion treat immediately, do not wait for diagnostic testing. If hemodynamically unstable, consider thrombolysis.

• Initial rx: ≥5 d of UFH, LMWH, fondaparinux + warfarin, or thrombolysis/embolectomy

• Long-term rx: ≥3 mo warfarin w/ INR target 2–3

Pregnancy Considerations (Obstet Gynecol 2011;118(3):717)

• Preg w/ 4–5-fold risk VTE; 0.5–2/1000 pregnancies, 80% = DVT, 20% = PE; increased risk across all trimesters, but 3rd trimester highest risk

• Thrombophilia present in 20–50% of women w/ VTE during Preg

• D-dimer: Levels ↑ during Preg & w/ preeclampsia, not for use as independent screen

• Warfarin contraindicated in Preg (except in setting of mechanical heart valve); crosses placenta, greatest risk of teratogenicity @ 6–12 WGA; safe during lactation

• May use UFH or LMWH during Preg & lactation, use UFH after 36 w gest

• Stop anticoagulation @ onset of labor. Delay neuraxial anesthesia for 10–12 h after prophylactic dose LMWH & 24 after therapeutic dose LMWH.

• Resume UFH & LMWH usually 6–12 h after vaginal deliv or 12–24 h after C/S

PERIOPERATIVE VTE PREVENTION

THROMBOPHILIA EVALUATION

• Coagulopathy: Alteration in the ability of the bld to coagulate (either ↑ risk to bleed or to clot)

• Thrombophilia: Dz state that ↑ risk of thrombosis (Acq or hereditary)

Indications for Testing

• Personal h/o VTE a/w nonrecurrent risk factor

• 1st-degree relative w/ h/o high-risk thrombophilia, or VTE at <50 yo in absence of other risk factors (Obstet Gynecol 2011;118(3):717)

• See antiphospholipid Ab syn for Acq thromboembolic d/o

Diagnostic Evaluation

• FVL: Activated prot C resistance assay, if abn → DNA analysis

• G20210A: PCR DNA analysis

• AT-III: Antithrombin activity assay

• Prot C & prot S deficiencies functional assays for prot C & prot S

Clinical Considerations

• No clear association btw inherited thrombophilias & fetal loss, preeclampsia, IUGR, or abruption → screening not routinely recommended in these scenarios

• Avoid estrogen-containing contraceptives in pts w/ inherited thrombophilias

• Low-risk thrombophilias: Factor V Leiden heterozygous; prothrombin G20210A heterozygous; prot C or prot S deficiency

• High-risk thrombophilias: Antithrombin deficiency; double heterozygous for prothrombin G20210A mut & factor V Leiden; factor V Leiden homozygous or prothrombin G20210A mut homozygous

Figure 16.7 Thromboprophylaxis for pregnancy complicated by inherited thrombophilia

Monitoring Treatment

• Preg causes ↑ renal clearance which may ↑ heparin clearance & require ↑ dose

• UFH → check aPTT 6 h after injection (midinterval), goal 1.5–2.5 × nml range, long-term rx check aPTT every 1–2 w; monit for thrombocytopenia (see section on “HIT”)

• LMWH → reliable dose-dependent resp; may monit rx w/ antifactor Xa level

• Monitoring req IF pregnant or CrCl <30 mL/min or obese pts

• Check antifactor Xa levels 4 h after injection of LMWH, target 0.5–1 IU/mL

COAGULOPATHIES

Signs/Symptoms

• Mucocutaneous bleeds (ie, epistaxis, gingival bleeding), menorrhagia, bleeding w/ dental extraction, petechiae, ecchymoses, postop bleeding, PPH, hemoarthrosis

Disseminated Intravascular Coagulation (DIC)

• Pathogenesis: Systemic activation of coagulation → thrombosis of small–mid-size vessels → depletion of coagulation factors → hemorrhage, thrombosis, multiorgan failure

• Etiology: Sepsis, trauma, shock, cancer, obstetric (abruption, amniotic fluid embolus, IUFD)

• Dx: ↑ PT/aPTT, ↓ Plt (<100 K), ↓ fibrinogen, ↑ fibrin-related marker (ie, D-dimer, fibrin degradation products), ↓ haptoglobin, schistocytes on periph smear

• Rx: Manage underlying condition; for bleeding or high risk of bleed, give platelet or FFP xfusion (Plt <20 K or Plt <50 K & bleeding; goal fibrinogen >100 mg/dL)

Von Willebrand’s Disease (vWD) (Am J Obstet Gynecol 2010;203(3):194)

• Most common bleeding d/o

• Pathogenesis: vWF forms bridge btw Plts/Plts & subendothelial surfaces; carrier of FVIII; deficiency → bleeding predisposition

• Inherited: Quantitative vs. qualitative deficiency

Type 1: ∼80% of cases; partial quantitative deficiency; autosomal dominant

Type 2: Qualitative deficiency (4 subtypes); autosomal dominant

Type 3: Rare, autosomal recessive; sev quantitative deficiency; high risk of bleeding

• Acq: ↑ clearance/inhibition of vWF (autoimmune dz), ↑ destruction of vWF (VSD, AS, pulm HTN), or medication (ie, ciprofloxacin, valproate)

• Dx: aPTT ↑ or nml; if ↑ aPTT get mixing study to eval for FVIII inhib; ↓ vWF:Ag (vWF assay), ↓ vWF activity (ristocetin cofactor assay), ↓ factor VIII activity

• Rx: Trial of desmopressin (IV or intranasal) w/ Types 1 & 2 can ↑ vWF & FVIII → recheck vWF & FVIII levels for resp; risk for HoNa

vWF replacement: For acute bleeding, risk bleeding, or planned Surg; FVIII concentrates (also contains vWF), cryoprecipitate, recombinant vWF

Menorrhagia: OCP, levonorgestrel-IUS, endometrial ablation, tranexamic acid

• Preg: vWF/FVIII levels ↑ during Preg & fall postpartum, ↑ risk delayed PPH; check FVIII levels q trimester; maintain >50 IU/dL prior to procedures, intrapartum & 2 w postpartum; avoid operative vaginal deliveries; offer genetic counseling antepartum

Hemophilias (Lancet 2012;379:1447)

• X-linked recessive deficiency of factors VIII (hemophilia A) or IX (hemophilia B); wide phenotypic variation in heterozygous carriers → variable propensity to bleed in carriers

• Mild: (5–25% nml factor activity), mod (1–5%), sev (<1%)

• Dx: ↑ aPTT that resolves w/ mixing study, nml PT & vWF, ↓ factor VIII or IX

• Mixing study for ↑ PT or aPTT, mix pt’s plasma 1:1 w/ nml plasma & retest PT/aPTT

PT/aPTT normalizes w/ mixing → factor deficiency; remains elevated → factor inhib

• Rx: Recombinant or A-purified factor replacement (factor VIII or IX); desmopressin (↑ FVIII for mild hemophilia A); antifibrinolytics, cryoprecipitate (FVIII only)

Coagulation Factor Inhibitors

• Alloimmune antibodies directed against coagulation factors (FVIII inhib most common)

• Etiology: Repeated factor replacement in pts w/ hemophilia, autoimmune dz (ie, SLE), postpartum, malig

• Dx: ↑ aPTT (remains prolonged after mixing study; Bethesda coagulation assay titer)

• Rx: Acute bleed – FVIII concentrates for low titer; recombinant FVIIa or activated prothrombin complex for high titer; eliminating inhib – prednisone, rituximab, cyclophosphamide, plasma exchange

ANTIPHOSPHOLIPID ANTIBODY SYNDROME (APS)

Epidemiology

• 40% of SLE pts have APLA. Of these, 40% w/ h/o thrombosis

• Antiphospholipid Abs present in 10–15% of pts w/ RPL

Pathophysiology

• Clinical manifestations likely result from interference w/ phospholipid-dependent steps of the coagulation pathway

Clinical Manifestations

• Arterial/venous thrombosis, thrombocytopenia (40–50%), nephropathy, hemolytic anemia, skin (livedo reticularis/ulcers), stroke/TIA/multi-infarct dementia, cardiac valvular dz

• Pregnancy-specific: ↑ risk thrombosis (up to 25% w/o rx), IUGR (15–30%), IUFD, sev preeclampsia/eclampsia, recurrent Preg loss, preterm deliv

• Catastrophic APS: Requires (1) involvement of ≥3 organs, (2) dev in <1 w, (3) histopathology of small vessel occlusion, (4) presence of aPa; up to 50% mortality

Screening/Diagnosis

• Indications: Prior unexplained or pregnancy-associated arterial/venous thromboembolism, h/o 1 fetal loss, or ≥3 (ACOG) or ≥2 (ASRM) consecutive embryonic losses, unexplained prolonged aPTT (see “Recurrent pregnancy loss workup”)

• Detection not poss if pt on UFH, & difficult w/ LMHW or Coumadin

• Preg c/b APS → consider serial US assessment in 3rd trimester

ALLOIMMUNIZATION

Definition, Etiology, Epidemiology

• Mat antibodies to any fetal bld group factor inherited from father

• RhD Ag most commonly implicated; minor antigens include C, c, E, e, Kell

• Mat exposure to paternal Ag on fetal RBC → Ab formation → IgG crosses placenta & directs immune-mediated destruction of fetal RBCs

• 0.1 mL fetal bld may result in mat Ab formation; 2nd exposure → anamnestic immune resp

• 6.8/1000 live births affected by alloimmunization; 10% prior to routine testing/prevention

• Minor antigens present in ∼2% of pregnancies

Clinical Manifestations

• Positive Ab screen on bld typing

• Fetal anemia → hydrops fetalis (≥2 of the following: Ascites, pleural effusion, pericardial effusion, skin edema, polyhydramnios)

• Fetal complications (death, hemolytic dz of newborn)

Screening/Diagnosis (see also Chap. 11)

• 1st OB visit: Mat bld type & Ab screen; consider rpt @ 28 w if RhD neg

• If mat RhD neg & paternity known → obtain paternal bld type

• Anti-RhD Ab (+) → indirect Coombs; Critical titer typically 1:8–1:32 (lab dependent)

• Prior affected Preg: ↑ risk fetal anemia; Ab titers do not correlate w/ severity

• FMH testing: Rosette – qualitative, K-B – quantitative. If rosette + → K-B used to determine dose of anti-RhD Ig.

• cfDNA: Fetal DNA in mat bld used to determine fetal RhD status

• RhD genotyping: Determines if RhD Ag gene present on 1 (heterozygote) or both (homozygote) chromosomes

• MCA Dopplers: Records PSV of MCA; PSV >1.5 MoMs for GA predictive of mod–sev fetal anemia

Prophylaxis/Treatment

Figure 16.8 Management of alloimmunization in pregnancy

• Anti-RhD Ig → 300 mcg neutralizes 30 mL whole bld (15 mL fetal RBCs) after FMH

• 50 mcg if <12 w gest; human serum-derived product; effect up to 12 w; max dose 1500 mcg/24 h; give w/i 72 h of indication for prevention of alloimmunization

• Weak RhD pos (Du) → treat as RhD pos, ppx not indicated

• Rx → deliv; intrauterine bld xfusion if remote from term

Minor Antigens (Ag) (Obstet Gynecol 2006;108(2):457)

• Minor antigens present in ∼2% of pregnancies

• Many may case RBC destruction; no prophylactic rx available; mgmt of sensitization is Ab dependent, but typically mirrors RhD

• Lewis & I most common → do not cause erythroblastosis fetalis

• Anti-Kell Ab → may cause sev anemia, follow w/ MCA Dopplers, titers unreliable

• Anti-RhD Ig indicated in RhD neg pts w/ minor antigens but no RhD antibodies

BLOOD PRODUCTS FOR HEMORRHAGE AND CRITICAL CARE

Massive Transfusion (Transfusion 2007;47(9):1564; Clin Obstet Gynecol 2010;53(1):196)

• Red top tube test: 5 mL bld in nonheparinized tube; nml = clot in 8–10 min; lack of clot or partial dissolution in 8–10 min is a/w fibrinogen <150 mg/dL

• Recombinant FVIIa → reserve for bleeding refrac to intervention (ie, after 10–12 U RBC, 6–12 U FFP, & 2–3 U Plts); ↑ risk thrombosis; FDA approved rx for hemophilia A & B

• Core temp <30°C → ventricular arrhythmias, use bld warmer if ≥3 U pRBCs or cold RBCs/plasma infused @ >100 mL/min for 30 min to prevent hypothermia

• Periodic eval for ↓ Ca++ & ↑ K+; risk citrate tox (↓ cardiac output/↓ SVR, met alkalosis) See also Chap. 11 for OB PPH.

Figure 16.9 Massive transfusion protocol