Thrombocytopenia in pregnancy

White cells in pregnancy and labour

• The white count rises through pregnancy (up to about 15 × 10^9/L) and in labour reaches 20–30 × 10^9/L, almost all neutrophils. Cortisol and adrenaline demarginate neutrophils from vessel walls; it settles within a week. Judge infection clinically, not on the count alone.
• Corticosteroids (antenatal betamethasone): neutrophils rise; eosinophils, lymphocytes and monocytes fall.
• Neutrophil alkaline phosphatase is high in pregnancy and reactive leucocytosis but low in CML.
• Infection: band forms, toxic granulation and Döhle bodies (left shift). In chorioamnionitis, neutrophil matrix metalloproteinases and elastase digest amniotic collagen, causing preterm rupture of membranes.

How neutrophils reach infection

• Sequence: margination, rolling, firm adhesion, transmigration, then chemotaxis and phagocytosis.
• Rolling on P-selectin (from Weibel–Palade bodies) and E-selectin, induced early by TNF and IL-1; adhesion by beta-2 integrins (CD18) to ICAM-1; transmigration (diapedesis) between endothelial cells by PECAM-1 (CD31); chemotaxis towards IL-8, C5a and LTB4.
• Killing uses the respiratory burst: NADPH oxidase makes superoxide, and myeloperoxidase makes hypochlorite. Its absence is chronic granulomatous disease.
• CD18 defect (leucocyte adhesion deficiency): delayed cord separation, infection without pus, neutrophilia.

White cells in the newborn

• Day 1 count is 10–26 × 10^9/L; lymphocytes dominate by the end of week 1.
• Neonatal sepsis: an immature to total neutrophil (I:T) ratio above 0.2 suggests infection. The marrow storage pool is small, so severe sepsis causes neutropenia, a poor sign.
• Babies of mothers with severe pre-eclampsia and growth restriction have mild neutropenia and thrombocytopenia from reduced production caused by chronic fetal hypoxia (marrow favours red cell production via erythropoietin). Cultures are negative and the mother's count is normal; recovery takes about 10 days, but the neutropenia still raises infection risk.
• Alloimmune neonatal neutropenia: maternal IgG against paternal neutrophil (HNA) antigens.
• Transient abnormal myelopoiesis in Down syndrome newborns (GATA1) resolves by 3 months, with later AML risk.

Platelets in pregnancy

• The count falls slightly in normal pregnancy (haemodilution and faster clearance). Von Willebrand factor and fibrinogen rise, so mild von Willebrand disease may be masked at term but levels fall after delivery, causing secondary PPH.
• Always check the film: EDTA-dependent clumping gives a falsely low count with no bleeding.

Treating immune and microangiopathic thrombocytopenia

• ITP in pregnancy: treat if platelets are below about 20–30 × 10^9/L, there is bleeding, or delivery approaches (aim above 50 for delivery, about 80 for neuraxial anaesthesia). First line is prednisolone or IVIG. If bleeding continues despite steroids, give intravenous immunoglobulin: it saturates Fc receptors on splenic macrophages and FcRn, so coated platelets escape destruction and the count rises in 1–3 days. Platelet transfusion is futile except for life-threatening bleeding or surgery, because the antibody destroys transfused platelets too.
• TTP: daily plasma exchange removes the anti-ADAMTS13 inhibitor and the large vWF multimers, and the donor plasma replaces ADAMTS13. Platelets feed the microthrombi and can worsen thrombosis.

Alloimmune and drug-related thrombocytopenia

• Neonatal alloimmune thrombocytopenia: a well baby with severe thrombocytopenia and a mother with a normal count. The mother lacks HPA-1a, carried on glycoprotein IIIa; the fetus inherits it from the father. It often affects the first pregnancy. Platelets carry HLA class I, not class II, antigens.
• Heparin-induced thrombocytopenia: day 5–10 (for example 10 days after cardiac surgery), IgG against heparin–platelet factor 4, causing thrombosis rather than bleeding.
• Low-dose aspirin irreversibly acetylates COX-1. Platelets have no nucleus and cannot make new cyclo-oxygenase, so thromboxane A2 stays low for their 7–10 day life, while nucleated endothelium makes new enzyme and recovers prostacyclin within hours. Pre-eclampsia shows high thromboxane and low prostacyclin, hence aspirin from 12 weeks.
• Reactive thrombocytosis: after haemorrhage, surgery, delivery or splenectomy and with iron deficiency.

Inherited and marrow disorders

• Vitamin K deficiency (long antibiotics with parenteral nutrition) and warfarin prolong the PT with a normal platelet count; a brother who bled after circumcision suggests haemophilia (factor VIII or IX assay).

Remember Mild, late and well: gestational thrombocytopenia. Early, severe or with a history: think ITP.

Exam trap A normal maternal count with a severely thrombocytopenic newborn points to alloimmune thrombocytopenia, not maternal ITP.

Exam trap Normal clotting tests do not exclude HELLP or TTP; they only show that DIC has not set in.

How FCPS asks about this

• Fever, confusion, low platelets, schistocytes, normal PT and APTT: TTP; treat with plasma exchange.
• ITP at 32 weeks bleeding despite steroids: intravenous immunoglobulin, not platelets.
• Antigen in severe alloimmune thrombocytopenia: HPA-1a on GPIIIa.
• Why low-dose aspirin spares prostacyclin: platelets cannot make new COX.
• Sequence of neutrophil events in acute inflammation: margination, rolling, adhesion, transmigration.
• Young woman with menorrhagia and giant platelets: Bernard–Soulier syndrome.
• Eczema, small platelets, infections in a boy: Wiskott–Aldrich syndrome.