Postpartum hemolytic uremic syndrome with multiple organ involvement in a severe case
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Here we report for the first time a severe case of PHUS complicated by pancreatic necrosis, bilateral visual loss due to central retinal artery occlusion (CRAO) and disseminated intravascular coagulation (DIC). </p><p class="elsevierStylePara">A 20-year-old primigravid was admitted for edema and headache when she was 34 weeks pregnant. On presentation her blood pressure (BP) was 180/115 mmHg and moderate edema on face was noted. Initial investigations showed 3+ proteinuria and normal serum creatinine (Scr) concentration. The diagnosis of preeclampsia was established and a cesarean section was performed in the 35th week of gestation.</p><p class="elsevierStylePara">Nine days later, the patient complained of oliguria, nausea with BP of 175/105 mmHg. Laboratory tests revealed hemolytic anemia, with hemoglobin of 81 g/L, serum haptoglobin <0.2 g/L, and schistocytes shown in peripheral blood smear. Platelets (Plt) were markedly reduced at 41×10<span class="elsevierStyleSup">9</span>/L and an acute rise of Scr to 463.2 μmol/L showed acute renal failure. The immunologic studies revealed negative anti nuclear antibody and Coomb’s tests. Under suspicion of PHUS, antihypertensives, aspirin and furosemide were commenced on the 1st day of presentation and renal biopsy was performed on day 2.</p><p class="elsevierStylePara">The patient complained of left-upper abdominal pain after renal biopsy and developed a sudden bilateral painless visual loss. The subcutaneous bleeding over her upper arms was noted and she rapidly developed anuria, dyspnea, confusion, hypotension with BP of 70/50 mmHg. The ultrasound scan excluded the existence of perinephric / subcapsular hematoma caused by renal biopsy. The fundus exam revealed bilateral CRAO. Laboratory tests on day 3 showed elevated serum amylase, lipase and Scr up to 625μmol/L, Plt down to 12.2×10<span class="elsevierStyleSup">9</span>/L. The level of fibrinogen decreased to 3.82μmol/L with delaying activated partial thromboplastin time and positive D-dimer. Computed tomography scan confirmed pancreatic necrosis. Renal pathology showed thickened glomerular capillary walls with subendothelial edematous expansion that forming double contouring and renal arteriolar intimal expansion with fibrin exudation on the arteriolar wall (Figure 1). Based on these findings, the diagnosis of PHUS complicated by pancreatic necrosis, CRAO and DIC was established.</p><p class="elsevierStylePara">She was treated with pulse methylprednisolone 500mg/d and intravenous immunoglobulin (IVIG) 20g/d for 3 days. Meanwhile, plasma exchange (PE) with fresh frozen plasma (FFP) infusion and CRRT were initiated. Anticoagulant therapy for DIC and CRAO were also carried out. On day 15, she was improved significantly and the urinary output increased whereas the bilateral vision improved only slightly and hyperglycemia became noted. On review after 6 months of onset, she remained bilateral visual loss, elevated blood glucose and Scr when hemodialysis and subcutaneous injection of insulin were suspended. These showed the irreversible visual impairment, secondary diabetes mellitus dependent on insulin and the progression to CRF.</p><p class="elsevierStylePara">HUS and thrombotic thrombocytopenic purpura (TTP), collectively referred to as TMAs, occur with increased frequency during pregnancy or the postpartum period. These two disorders are considered by many to be manifestations of the same disease process; however, others consider HUS and TTP to be distinct entities.<span class="elsevierStyleSup">3</span> Since TTP and HUS share many overlapping features, distinguishing the two disorders may be difficult.<span class="elsevierStyleSup">4</span> As in the case we showed, the patient developed TMA with disturbance of consciousness that seemed to suggest TTP; however, the prominent renal insufficiency and the lack of diffused thrombi in renal tissue might support PHUS rather than TTP. Another differential diagnosis should be included in this case is hemolysis, elevated liver enzymes, and low platelets syndrome (HELLP syndrome). HELLP, usually associated with preeclampsia is more common in multiparous women and approximately 70% of HELLP occur prior to term, with the remainder usually occurring within 48 hours after delivery.<span class="elsevierStyleSup">5</span> Patients with HELLP frequently present with severe right upper quadrant pain. Based on these characteristics of HELLP, we prefer to diagnose our case as PHUS.</p><p class="elsevierStylePara">Although the pathogenesis of PHUS is unknown, the previous cases reported<span class="elsevierStyleSup">2,6,7</span> and the case presented here demonstrated preeclampsia could possibly trigger PHUS by causing platelet aggregation, deposition of microthrombi and occlusions in the microvasculature of the kidney, resulting in acute renal failure. The deficiency of ADAMTS-13, a metalloprotease that cleaves ultra-large von Willebrand factor (VWF) multimers observed in PHUS<span class="elsevierStyleSup">8</span> which suggest PHUS may be also associated with ADAMTS-13 deficiency. Recent studies revealed alternative complement 3 convertase dysregulation were detected in most PHUS patients suggesting PHUS was probably associated with complement gene mutation.<span class="elsevierStyleSup">9</span></p><p class="elsevierStylePara">Multiple organ involvement such as pancreas and ocular structures were reported in non-pregnancy-related HSP,<span class="elsevierStyleSup">10,11</span> whereas PHUS involving extrarenal vascular beds has been less reported so far except central nervous system and liver damage.<span class="elsevierStyleSup">12,13</span> Does this mean PHUS have a better prognosis than non-pregnancy HUS? The case we described here developed multiple organ damage such as pancreatic necrosis, CRAO, DIC and progressed to secondary diabetes mellitus, bilateral visual loss and CRF eventually. The severe complications of pancreatic necrosis and CRAO might be the manifestations of TMA in PHUS, but might be more likely induced by DIC in this patient. Anyway, this case suggests PHUS could also involve multiple organ dysfunctions and result in bad outcomes even if the appropriate treatments have been given without delay.</p><p class="elsevierStylePara">The renal pathology in HUS is characterized by glomerular capillary subendothelial expansion, arteriolar fibrinoid necrosis, arterial edematous intimal expansion and vascular thrombosis. The preceding etiologic conditions of HUS and the histological findings appeared not to be related to each other.<span class="elsevierStyleSup">14</span> Our case showed typical subendothelial edematous expansion and renal arteriolar intimal expansion with fibrin exudation which supported renal microangiopathy, but without diffused thrombi and fibrinoid necrosis in renal tissue which seemed to be inconsistent with the following development of multiple organ complications and the progression to CRF. This was considered to be due to the early performance of renal biopsy after the attack and the early pathological findings in PHUS presented here may be difficult to predict the disease development and poor prognosis.</p><p class="elsevierStylePara">In conclusion, pancreatic necrosis, CRAO and DIC were observed in PHUS. Although renal replacement therapy and PE with FFP infusion have improved the survival of PHUS significantly, multiple organ complications such as pancreatic necrosis, CRAO and DIC may cause severe sequelae and lead to a poor prognosis of PHUS.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflict of interest</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara">The authors declare that there is no conflict of interest associated with this manuscript.</p><p class="elsevierStylePara"><a href="grande/11334_108_25509_en_11334_f1.jpg" class="elsevierStyleCrossRefs"><img src="11334_108_25509_en_11334_f1.jpg" alt="Renal biopsy findings in postpartum hemolytic uremic syndrome"></img></a></p><p class="elsevierStylePara">Figure 1. Renal biopsy findings in postpartum hemolytic uremic syndrome</p>" "pdfFichero" => "P1-E536-S3514-A11334-EN.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig1" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "11334_108_25509_en_11334_f1.jpg" "Alto" => 259 "Ancho" => 600 "Tamanyo" => 236748 ] ] "descripcion" => array:1 [ "en" => "Renal biopsy findings in postpartum hemolytic uremic syndrome" ] ] ] "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:14 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Weiner CP. Thrombotic microangiopathy in pregnancy and the postpartum period. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 24 | 11 | 35 |
| 2024 October | 110 | 37 | 147 |
| 2024 September | 131 | 26 | 157 |
| 2024 August | 170 | 76 | 246 |
| 2024 July | 147 | 36 | 183 |
| 2024 June | 138 | 57 | 195 |
| 2024 May | 154 | 31 | 185 |
| 2024 April | 117 | 34 | 151 |
| 2024 March | 134 | 44 | 178 |
| 2024 February | 111 | 61 | 172 |
| 2024 January | 155 | 44 | 199 |
| 2023 December | 140 | 31 | 171 |
| 2023 November | 156 | 50 | 206 |
| 2023 October | 142 | 34 | 176 |
| 2023 September | 200 | 38 | 238 |
| 2023 August | 145 | 19 | 164 |
| 2023 July | 180 | 38 | 218 |
| 2023 June | 221 | 22 | 243 |
| 2023 May | 199 | 35 | 234 |
| 2023 April | 101 | 37 | 138 |
| 2023 March | 84 | 19 | 103 |
| 2023 February | 102 | 24 | 126 |
| 2023 January | 85 | 30 | 115 |
| 2022 December | 104 | 31 | 135 |
| 2022 November | 118 | 22 | 140 |
| 2022 October | 118 | 42 | 160 |
| 2022 September | 98 | 29 | 127 |
| 2022 August | 100 | 42 | 142 |
| 2022 July | 91 | 42 | 133 |
| 2022 June | 99 | 48 | 147 |
| 2022 May | 99 | 29 | 128 |
| 2022 April | 99 | 51 | 150 |
| 2022 March | 84 | 48 | 132 |
| 2022 February | 108 | 33 | 141 |
| 2022 January | 60 | 35 | 95 |
| 2021 December | 77 | 50 | 127 |
| 2021 November | 79 | 39 | 118 |
| 2021 October | 121 | 39 | 160 |
| 2021 September | 92 | 39 | 131 |
| 2021 August | 94 | 38 | 132 |
| 2021 July | 59 | 34 | 93 |
| 2021 June | 48 | 18 | 66 |
| 2021 May | 64 | 34 | 98 |
| 2021 April | 120 | 61 | 181 |
| 2021 March | 115 | 38 | 153 |
| 2021 February | 41 | 24 | 65 |
| 2021 January | 74 | 22 | 96 |
| 2020 December | 49 | 18 | 67 |
| 2020 November | 28 | 12 | 40 |
| 2020 October | 29 | 18 | 47 |
| 2020 September | 36 | 8 | 44 |
| 2020 August | 38 | 13 | 51 |
| 2020 July | 31 | 7 | 38 |
| 2020 June | 24 | 10 | 34 |
| 2020 May | 47 | 11 | 58 |
| 2020 April | 30 | 19 | 49 |
| 2020 March | 29 | 6 | 35 |
| 2020 February | 33 | 16 | 49 |
| 2020 January | 42 | 20 | 62 |
| 2019 December | 51 | 18 | 69 |
| 2019 November | 47 | 21 | 68 |
| 2019 October | 23 | 12 | 35 |
| 2019 September | 25 | 28 | 53 |
| 2019 August | 13 | 8 | 21 |
| 2019 July | 17 | 19 | 36 |
| 2019 June | 28 | 18 | 46 |
| 2019 May | 17 | 18 | 35 |
| 2019 April | 42 | 35 | 77 |
| 2019 March | 21 | 21 | 42 |
| 2019 February | 18 | 17 | 35 |
| 2019 January | 26 | 17 | 43 |
| 2018 December | 74 | 36 | 110 |
| 2018 November | 102 | 16 | 118 |
| 2018 October | 83 | 14 | 97 |
| 2018 September | 53 | 14 | 67 |
| 2018 August | 47 | 17 | 64 |
| 2018 July | 44 | 21 | 65 |
| 2018 June | 48 | 12 | 60 |
| 2018 May | 42 | 10 | 52 |
| 2018 April | 60 | 8 | 68 |
| 2018 March | 58 | 8 | 66 |
| 2018 February | 48 | 6 | 54 |
| 2018 January | 63 | 8 | 71 |
| 2017 December | 58 | 6 | 64 |
| 2017 November | 57 | 12 | 69 |
| 2017 October | 50 | 11 | 61 |
| 2017 September | 47 | 5 | 52 |
| 2017 August | 53 | 19 | 72 |
| 2017 July | 43 | 20 | 63 |
| 2017 June | 32 | 9 | 41 |
| 2017 May | 55 | 12 | 67 |
| 2017 April | 28 | 8 | 36 |
| 2017 March | 32 | 12 | 44 |
| 2017 February | 26 | 8 | 34 |
| 2017 January | 22 | 10 | 32 |
| 2016 December | 44 | 8 | 52 |
| 2016 November | 67 | 21 | 88 |
| 2016 October | 106 | 19 | 125 |
| 2016 September | 122 | 7 | 129 |
| 2016 August | 185 | 3 | 188 |
| 2016 July | 171 | 13 | 184 |
| 2016 June | 106 | 0 | 106 |
| 2016 May | 137 | 0 | 137 |
| 2016 April | 90 | 0 | 90 |
| 2016 March | 84 | 0 | 84 |
| 2016 February | 118 | 0 | 118 |
| 2016 January | 117 | 0 | 117 |
| 2015 December | 122 | 0 | 122 |
| 2015 November | 114 | 0 | 114 |
| 2015 October | 95 | 0 | 95 |
| 2015 September | 66 | 0 | 66 |
| 2015 August | 58 | 0 | 58 |
| 2015 July | 65 | 0 | 65 |
| 2015 June | 45 | 0 | 45 |
| 2015 May | 39 | 0 | 39 |
| 2015 April | 5 | 0 | 5 |
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