Immune‐related pancytopenia in pregnancy

Although pancytopenia is uncommon in pregnancy, common causes include nutritional deficiencies (e.g. vitamin B12, folate), infections, autoimmune diseases and bone marrow failure syndromes. ¹ Immune‐related pancytopenia (IRP) is a disorder in which autoantibodies target bone marrow haemopoietic cells, leading to a reduction in one or more peripheral blood cell lines, and is characterised morphologically by increased erythroblastic islands (EIs) and active macrophage phagocytosis. ² IRP in pregnancy has not been reported previously. We present a case of IRP in pregnancy and discuss its clinical features, diagnostic approach and treatment strategy.

A 38‐year‐old woman, G4P1, was admitted at 27 weeks of gestation due to progressive thrombocytopenia for over 4 months. Six months before pregnancy, her platelet count nadir was 111 × 10⁹/L, with normal white blood cell (WBC) and red blood cell counts. Regular follow‐up was conducted without specific intervention. At 8 weeks of gestation, the platelet count was 64 × 10⁹/L; at 11 weeks, 57 × 10⁹/L; and at 16 weeks, 30 × 10⁹/L. Subsequent monitoring showed platelet counts fluctuating between 32 and 34 × 10⁹/L, accompanied by progressive haemoglobin decline. At 27 weeks of gestation, her WBC count was 2.75 × 10⁹/L, with neutrophils 1.13 × 10⁹/L and lymphocytes 1.55 × 10⁹/L, haemoglobin was 74 g/L and platelet count was 28 × 10⁹/L. She had no bleeding signs and no lymphadenopathy or hepatosplenomegaly was noted. Liver and renal function tests, antinuclear antibody, extractable nuclear antigen profile, antiphospholipid antibodies, Coombs test, ferritin, vitamin B12 and folate levels were all normal. Bone marrow aspiration revealed markedly hypercellular marrow with a reduced myeloid‐to‐erythroid ratio and increased erythroid lineage, with no dysplastic changes. The number of megakaryocytes across the entire smear was normal, with a total of 13, all of which were of the granular type. Chromosomal analysis, flow cytometry and paroxysmal nocturnal haemoglobinuria tests were unremarkable.

She received intravenous immunoglobulin (0.4 g/kg/day for 5 days) and low‐dose prednisone (20 mg/day), along with platelet transfusion support. There was no improvement in her blood cell counts. At 29 weeks of gestation, caesarean section was performed due to chronic hypertension complicated by pre‐eclampsia. Post‐operatively, the prednisone dose was increased to 40 mg/day, and thrombopoietin and romiplostim were administered. One week after delivery, her platelet count began to rise, reaching 73 × 10⁹/L by post‐operative day 13, and haemoglobin levels gradually increased (Fig. 1). After discharge, the patient received two additional doses of romiplostim. When prednisone was tapered, her WBC count remained normal, her haemoglobin level fluctuated slightly around 120 g/L, and the platelet count declined again to 50–70 × 10⁹/L.

Figure 1.

Trends in blood cell counts and treatment interventions during this admission. HgB, haemoglobin (g/L); PLT, platelet (10⁹/L); WBC, white blood cell (10⁹/L).

The core pathogenesis of IRP involves autoimmune dysregulation, characterised by overactivation of B lymphocytes that produce autoantibodies (primarily IgG) against bone marrow haemopoietic cells. These autoantibodies induce peripheral blood cytopenia either by Fc receptor‐mediated phagocytosis via macrophages or by blocking haemopoietic growth factor receptors. ² , ³ A hallmark bone marrow morphological finding is an increased number of EIs, which are sites where macrophages surround and phagocytose erythroblasts, considered a distinctive feature of IRP. ³ The optimal confirmatory test for IRP is a positive bone marrow mononuclear cell Coombs (BMMNC‐Coombs) test. ²

The aetiology of pancytopenia during pregnancy is diverse. In regions with a high prevalence of nutritional deficiencies, vitamin B12 and folate deficiency are common causes, leading to megaloblastic anaemia and pancytopenia. ¹ , ⁴ Other causes include infections, autoimmune diseases (e.g. systemic lupus erythematosus) and inherited bone marrow failure syndromes (e.g. Fanconi anaemia). ⁵ To our knowledge, IRP complicating pregnancy has not been previously described, and its diagnosis requires exclusion of the aforementioned common aetiologies.

Several features in this case support the diagnosis of IRP. First, normal ferritin, vitamin B12 and folate levels ruled out nutritional anaemia. Hypercellular bone marrow excluded aplastic anaemia. Negative autoantibody panels ruled out connective tissue disease. Second, the remarkable response to full‐dose glucocorticoids combined with a thrombopoietin receptor agonist is highly consistent with the sensitivity of IRP to immunosuppressive therapy. ² This ‘therapeutic diagnosis’ provides strong indirect evidence for IRP. Third, the decline in platelet count upon glucocorticoid tapering indicates persistent disease activity. In addition, the patient had mild thrombocytopenia prior to pregnancy, which progressed to pancytopenia during gestation and showed significant postpartum recovery, suggesting that pregnancy played a major role in the haematological deterioration. Although BMMNC‐Coombs testing was not performed due to technical limitations, the clinical features strongly suggested IRP.

In summary, IRP is a rare but important cause of pancytopenia during pregnancy. When encountering unexplained cytopenia in pregnant women, IRP should be included in the differential diagnosis. A characteristic response to immunosuppressive therapy can provide strong diagnostic support.

Informed consent was obtained from the patient.

Data availability statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.