Pregnancy and hematology

Physiologic changes in pregnancy

• Anemia: dilutional (plasma volume expands more than RBC mass); physiologic Hb may be 10.5 to 11. Iron deficiency very common.
• Thrombocytopenia: gestational, ~10% of pregnancies (mild, late, no fetal effect).
• Hypercoagulable state: estrogen-driven ↑ factors VII, VIII, X, vWF, fibrinogen; ↓ protein S; ↑ PAI-1. VTE risk 5× baseline; postpartum highest.
• Mild physiologic hyponatremia (osmostat reset) and ↑ alkaline phosphatase (placental).

Anemia in pregnancy

• Iron deficiency anemia: most common. Treat with PO iron (first-line); IV iron in the 2nd to 3rd trimester if intolerant or severe (Hb <9). Avoid IV iron in the 1st trimester (limited safety data).
• Folate: 0.4 mg/d preconception and throughout pregnancy; 4 mg/d if prior NTD or on anti-epileptics.
• B12 deficiency: vegan diet, gastric bypass; replace.

Thrombocytopenia in pregnancy: DDx

• Gestational thrombocytopenia (~75% of cases): most common; mild (plt >70K usually), late 2nd to 3rd trimester, no bleeding, no fetal effect, resolves postpartum.
• ITP (~3%): pre-existing or new-onset; the most common cause of thrombocytopenia in the 1st trimester. Incidence ~1 in 1,000 to 1 in 10,000 pregnancies; ~31% require intervention. Treatment is based on maternal hemorrhage risk; therapy to the mother does not change the fetal platelet count.
  • Treatment indications (1st/2nd trimester): symptomatic, platelet count <20 to 30K, or upcoming procedures. Monitor more closely in the 3rd trimester due to procedure needs.
  • First-line: corticosteroids, IVIG, or combination.
  • Refractory: anti-D immunoglobulin (WinRho), splenectomy (rarely done, best in 2nd trimester), azathioprine, high-dose methylprednisolone plus IVIG.
  • Avoid/contraindicated: cytotoxic/teratogenic agents (cyclophosphamide, mycophenolate), vinca alkaloids, danazol. Generally avoided but can be considered in severe refractory ITP: rituximab and TPO receptor agonists (esp. late pregnancy; limited safety data).
  • Epidural anesthesia: platelet ≥70K generally acceptable (SOAP 2021 consensus) in the absence of other risk factors.
  • Neonatal thrombocytopenia in ~10 to 20% (transplacental IgG); no correlation between maternal and neonatal counts, can occur even if the mother is in remission. Nadir at ~3 to 4 days of age (may be undetectable at birth); treat clinical bleeding with IVIG 1 g/kg for 1 to 2 doses; nadir is typically a few days after birth; counts may take weeks to recover because maternal IgG can persist ~6 weeks, so follow counts until recovery.
• Pre-eclampsia (PE) / HELLP syndrome: pregnancy-specific endothelial disease; HTN, proteinuria, organ dysfunction. HELLP = Hemolysis + Elevated LFTs + Low Platelets. Delivery is curative.
• TTP: ADAMTS13 <10%; can be triggered by pregnancy. Delivery does NOT improve it. Immune TTP in pregnancy: urgent PEX + corticosteroids are the backbone; caplacizumab and rituximab need individualized specialist use (limited pregnancy safety data). Congenital TTP (can present in pregnancy) is treated with plasma or ADAMTS13 infusion, not immunosuppression.
• aHUS: complement-mediated; postpartum trigger common. Eculizumab/ravulizumab.
• Acute fatty liver of pregnancy (AFLP): rare; LFTs ↑, hypoglycemia, coagulopathy, neonatal LCHAD deficiency association.
• DIC: placental abruption, amniotic fluid embolism, severe sepsis, intrauterine fetal demise.
• Other: lupus, antiphospholipid, drug-induced, viral (HIV/HCV).
• Distinguishing PE/HELLP vs TTP: PE/HELLP improves with delivery; TTP does NOT improve and has ADAMTS13 <10%. PLASMIC score helpful.
• Neonatal alloimmune thrombocytopenia (NAIT): maternal Ab to fetal HPA-1a (or other platelet antigens); severe neonatal thrombocytopenia even in the 1st pregnancy. Antenatal maternal IVIG +/- prednisone; HPA-1a-negative platelets at delivery.

VTE in pregnancy

• Risk: 5× baseline during pregnancy; ~20× postpartum (especially first 6 weeks).
• Diagnosis: D-dimer should not be used alone, but is useful within a validated pregnancy strategy: pregnancy-adapted YEARS rules out PE if D-dimer <1000 ng/mL with no YEARS criteria, or <500 ng/mL with ≥1 criterion. Compression US for DVT; CTPA or V/Q scan for PE (V/Q preferred to avoid breast radiation in young women).
• Treatment: LMWH (enoxaparin BID, anti-Xa monitored if needed) preferred. UFH for delivery. AVOID warfarin (1st trimester teratogenic, warfarin embryopathy: nasal hypoplasia, stippled epiphyses; for VTE, avoid warfarin throughout, not only the 1st trimester (mechanical valves and selected AF are exceptions, see below), given 2nd and 3rd trimester fetal CNS and bleeding risk; warfarin is acceptable postpartum during breastfeeding). DOACs CONTRAINDICATED.
• Duration: through pregnancy + 6 weeks postpartum (minimum).

Anticoagulation in pregnancy: by indication

• Mechanical heart valves: most challenging. Options: dose-adjusted LMWH (anti-Xa monitored, BID); UFH; or warfarin during the 2nd and 3rd trimesters (switch to heparin before delivery); 1st-trimester warfarin is also reasonable if the dose is ≤5 mg/day after shared decision-making. Shared decision with cardiology.
• VTE during pregnancy: therapeutic LMWH throughout pregnancy + 6 weeks postpartum (minimum 3 months total).
• Prior VTE + thrombophilia: prophylactic LMWH antepartum + 6 weeks postpartum.
• Prior unprovoked VTE without thrombophilia: prophylactic LMWH antepartum AND postpartum × 6 weeks (ASH 2018; also for prior hormone-associated VTE; antepartum not advised if prior VTE had a resolved non-hormonal provoking factor).
• APS with prior thrombosis: therapeutic LMWH + low-dose ASA throughout pregnancy + 6 weeks postpartum.
• APS with recurrent pregnancy loss only (no thrombosis): prophylactic LMWH + low-dose ASA throughout pregnancy, then prophylactic LMWH for 6 weeks postpartum (ACOG).
• High-risk inherited thrombophilia (AT deficiency with family hx VTE; homozygous FVL or combined regardless of family hx): prophylactic (or intermediate) LMWH antepartum + 6 weeks postpartum; AT deficiency without family hx: no routine prophylaxis (ASH 2018).
• Heterozygous FVL or PT G20210A alone + family hx VTE: ASH 2018 suggests against routine antepartum or postpartum prophylaxis; individualize (ACOG permits postpartum prophylaxis).
• Atrial fibrillation: LMWH or warfarin (2nd trimester); DOACs CONTRAINDICATED.
• Peripartum management: hold LMWH 24 hr before scheduled delivery; UFH OK closer to delivery. Resume prophylactic LMWH 12 h after vaginal delivery (24 h after C-section) once hemostasis is confirmed; therapeutic LMWH requires ≥24 h after neuraxial placement and ≥4 h after catheter removal, with adequate hemostasis.
• Neuraxial anesthesia: hold prophylactic LMWH ≥12 hr and therapeutic LMWH ≥24 hr before the procedure (normal renal function).

Hemoglobinopathies and pregnancy

• Sickle cell pregnancy: high-risk: ↑ VOCs, ACS, pre-eclampsia, IUGR, preterm delivery.
• Discontinue hydroxyurea preconception when feasible, but individualize: selected severe SCD may continue or restart after the first trimester under specialist care (shared decision-making).
• Consider chronic prophylactic transfusion (HbS <30%) for high-risk patients.
• VTE prophylaxis postpartum.

Postpartum hemorrhage (PPH)

• Definition (ACOG): cumulative blood loss ≥1000 mL, or blood loss with signs/symptoms of hypovolemia, within 24 hr regardless of route; >500 mL after vaginal delivery is still abnormal.
• Causes (4 Ts): Tone (atony, most common), Trauma (lacerations), Tissue (retained products), Thrombin (coagulopathy).
• Treatment: uterotonics (oxytocin, methergine, hemabate, misoprostol), uterine massage, balloon tamponade, surgical (B-Lynch, hysterectomy).
• TXA in PPH: WOMAN trial, give within 3 hours; reduces death from bleeding ~19% overall (RR 0.81) and ~31% when given within 3 hours (RR 0.69); no benefit after 3 hours.
• Massive transfusion: 1:1:1 ratio if MTP activated.

Other pregnancy considerations

• OCPs / HRT and FH of VTE: avoid combined OCPs in known severe thrombophilia (especially AT deficiency, double-het); progestin-only acceptable.
• Inherited thrombophilia in pregnancy: risk varies. ASH 2018 (no prior VTE): antepartum + postpartum prophylaxis suggested for homozygous FVL and combined defects regardless of family history, and for AT deficiency only with a family history of VTE (without it, AT deficiency gets no prophylaxis). Heterozygous FVL or PT G20210A alone → ASH suggests against prophylaxis even with a family history; individualize, some (ACOG) give prophylactic LMWH postpartum only.

High yield (pregnancy)

• Iron deficiency anemia is the most common cause of anemia in pregnancy.
• Folate 0.4 mg/d preconception (4 mg if prior NTD).
• Gestational thrombocytopenia (most common): late, mild, no fetal effect, resolves postpartum.
• ITP is the most common cause of thrombocytopenia in the 1st trimester; treat if platelet <20 to 30K, symptomatic, or before procedures.
• PE/HELLP improves with delivery; TTP does NOT.
• LMWH preferred for anticoagulation in pregnancy; warfarin teratogenic 1st trimester; DOACs CONTRAINDICATED throughout.
• TXA in PPH (WOMAN): within 3 hours.
• Sickle pregnancy: stop HU when feasible (individualize in severe disease); consider chronic transfusion.
• Postpartum prophylaxis per validated risk assessment: 6-wk LMWH for high-risk situations (prior VTE, selected thrombophilias); cesarean alone generally warrants mechanical prophylaxis, pharmacologic use/duration depend on added risks.
• Postpartum acquired hemophilia A: autoantibody to FVIII; bypassing agents + immunosuppression.
• NAIT: different from neonatal ITP: maternal anti-HPA-1a; severe even in the 1st pregnancy.