The conundrum of postpartum thrombotic Microangiopathy: case report and considerations for management
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Microangiopathic hemolytic anemias and thrombocytopenias in pregnant or postpartum women constitute an interdisciplinary diagnostic and therapeutic challenge in the evaluation of thrombotic microangiopathies (TMA), where urgent care must be considered.
We here report the case of a 21-year-old Somali woman, who was delivered by emergency caesarean section at 35 weeks of gestational age with acute dyspnea, placental abruption and gross edema due to severe preeclampsia/HELLP syndrome. After delivery, she developed acute kidney failure and thrombotic microangiopathy as revealed by kidney biopsy. The lack of early response to plasma exchange prompted extensive laboratory workup. Ultimately, the patient completely recovered with negative fluid balance and control of severe hypertension.
This case report emphasizes the importance to differentiate between primary TMA syndromes and microangiopathic hemolytic anemias due to systemic disorders. Delayed recovery from preeclampsia/HELLP syndrome and malignant hypertension can clinically mimic primary TMA syndromes in the postpartum period.
KeywordsThrombotic microangiopathy Preeclampsia HELLP syndrome Plasma exchange Eculizumab
Plasma exchange therapy
Thrombotic thrombocytopenic purpura
Microangiopathic hemolytic anemias and thrombocytopenias in pregnant or postpartum women constitute an interdisciplinary diagnostic and therapeutic challenge in the evaluation of thrombotic microangiopathies (TMA), where urgent care must be considered for immediate treatment particularly of preeclampsia/HELLP (PE/HELLP) syndrome, thrombotic thrombocytopenic purpura (TTP), and complement-mediated thrombotic microangiopathy [1, 2, 3].
The patient had given birth to a daughter who had an Apgar score of 8/9/10, a body weight of 2260 g (26th percentile), and a length of 46 cm. The daughter did not have increased perinatal morbidity.
Methods for cell culture and complement deposition assay
Ea.hy 926 cells (human endothelial cell line) were cultured in DMEM low Glucose medium (Gibco, Thermo Fisher Scientific, Waltham, MA, USA) containing 10% fetal bovine serum, Antibiotic-Antimycotic (Gibco, Thermo Fisher Scientific), and HAT Supplement (Gibco, Thermo Fisher Scientific) on cell chamber slides and used when confluent. C3c and C5b-9 complement deposition assays were performed as described previously. Briefly, cells were incubated with patient serum (1:2 dilution) or control serum for 4 hours. Cells were then stained with FITC-conjugated polyclonal rabbit anti-human C3c complement antibody (F0201, DAKO, Glosturp, Denmark) and monoclonal mouse anti-human C5b-9 antibody (ab66768, Abcam, Cambridge, MA, USA), followed by secondary antibody incubation with Rhodamine (TRITC)-conjugated goat anti-mouse (115–025-146, Jackson Immuno Research Laboratories, West Grove, PA, USA). Rb IgG Isotype Control FITC (PA5–23092, Thermo Scientific) and Mouse IgG2a Isotype Control (MCA929, Bio-Rad, Hercules, CA, USA) were used as appropriate isotype control antibodies. Stained cells were mounted with ProLong Gold Antifade Mountant with DAPI (Thermo Scientific). Evaluation of C3 and C5b-9 complement deposition on human endothelial cells was performed on a LSM 510 confocal microscope (Zeiss, Oberkochen, Germany).
Discussion and conclusions
Taken together, this case report emphasizes the importance to differentiate between primary TMA syndromes and microangiopathic hemolytic anemias due to systemic disorders [3, 4, 5]. Delayed recovery from PE/HELLP syndrome and severe hypertension can clinically mimic primary TMA syndromes in the postpartum period. Since the diagnostic approach is costly in terms of time, it is nevertheless important to start standard therapy including PEX and revisit the first tentative diagnosis with the incoming diagnostic results as well as the clinical course of disease.
K. Artinger was enrolled in the PhD program in Molecular Medicine at the Medical University of Graz. P. Eller and K. Eller received grant support by the Austrian Science Funds (FWF) (P27537-B26). The funding body did not have any role in the design of the study, and collection, analysis and interpretation of data and in writing the manuscript.
Availability of data and materials
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
ECW performed the Caesarean section, KE performed the kidney biopsy, MJP performed the histopathological stainings, KA performed cell culture and complement deposition assay, CM performed the genetic analyses for mutations of atypical hemolytic uremic syndrome-related genes. GS, GH, FE, and PE treated the patient on ICU. PE and KE analysed the data and wrote the manuscript. ECW, MJP, KA, CM, GS, GH and FE critically revised the manuscript for important intellectual content. All authors approved the final version of the manuscript and agreed to be accountable for all aspects related to accuracy and integrity of the work.
Ethics approval and consent to participate
The Institutional Review Board of the Medical University of Graz approved this clinical study (EK-Nr.: 29–471 ex 16/17).
Consent for publication
Written informed consent was obtained from the patient for publication of this case report.
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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