Decreased risk of underdosing with continuous infusion versus intermittent administration of cefotaxime in patients with sickle cell disease and acute chest syndrome.

OBJECTIVE: Underdosing of antibiotics is common in patients with sickle cell disease (SCD). We hypothesized that in critically-ill patients with SCD receiving cefotaxime during acute chest syndrome, the continuous infusion may outperform the intermittent administration in achieving pharmacokinetic/pharmacodynamic targets. DESIGN: Prospective before-after study. SETTINGS: Intensive-care unit of a French teaching hospital and sickle cell disease referral center. PATIENTS: Sixty consecutive episodes of severe acute chest syndrome in 58 adult patients with sickle cell disease. INTERVENTIONS: Patients were treated with intermittent administration during the first period (April 2016 -April 2018) and with continuous infusion during the second period (May 2018 -August 2019). MEASUREMENTS AND MAIN RESULTS: We included 60 episodes of acute chest syndrome in 58 patients (29 [25-34] years, 37/58 (64%) males). Daily dose of cefotaxime was similar between groups (59 [48-88] vs. 61 [57-64] mg/kg/day, p = 0.84). Most patients (>75%) presented a glomerular hyperfiltration with no difference between groups (p = 0.25). More patients had a cefotaxime trough level ≥2 mg/L with continuous infusion than intermittent administration: 28 (93%) vs. 5 (16%), p<0.001. The median residual concentration was higher in the continuous infusion than intermittent administration group: 10.5 [7.4-13.3] vs. 0 [0-0] mg/L, p<0.001. No infection relapse was observed in the entire cohort. Hospital length of stay was similar between groups. CONCLUSION: As compared to intermittent administration, continuous infusion of cefotaxime maximizes the pharmacokinetic/pharmacodynamic parameters in patients with SCD. The clinical outcome did not differ between the two administration methods; however, the study was underpowered to detect such a difference.

Kidney Increase Natriuresis but Not Glomerular Filtration Under Veno-venous ECMO, a Retrospective Study.

PURPOSE: Acute kidney injury is a frequent complication of acute respiratory distress syndrome (ARDS). We aim to study the evolution of kidney function in patients presenting severe ARDS and requiring veno-venous extracorporeal membrane oxygenation (VV ECMO). METHODS: We conducted a multicenter retrospective study, including adult patients requiring VV ECMO for ARDS. The primary outcome was the evolution of the serum creatinine level after VV ECMO initiation. Secondary outcomes were change in urine output, and urine biochemical parameters after VV ECMO initiation. RESULTS: One hundred and two patients were included. VV ECMO was initiated after a median of 6 days of mechanical ventilation, mainly for ARDS caused by COVID-19 (73%). Serum creatinine level did not significantly differ after VV ECMO initiation (P = .20). VV ECMO was associated with a significant increase in daily urine output (+6.6 mL/kg/day, [3.8;9.3] P < .001), even after adjustment for potential confounding factors; with an increase in natriuresis. The increase in urine output under VV ECMO was associated with a reduced risk of receiving kidney replacement therapy (OR 0.4 [0.2;0.8], P = .026). CONCLUSIONS: VV ECMO initiation in severe ARDS is associated with an increase in daily urine output and natriuresis, without change in glomerular filtration rate.

Chest Computed Tomography Characteristics of Critically Ill COVID-19 Patients with Auto-antibodies Against Type I Interferons.

PURPOSE: Patients with auto-antibodies neutralizing type I interferons (anti-IFN auto-Abs) are at risk of severe forms of coronavirus disease 19 (COVID-19). The chest computed tomography (CT) scan characteristics of critically ill COVID-19 patients harboring these auto-Abs have never been reported. METHODS: Bicentric ancillary study of the ANTICOV study (observational prospective cohort of severe COVID-19 patients admitted to the intensive care unit (ICU) for hypoxemic acute respiratory failure between March 2020 and May 2021) on chest CT scan characteristics (severity score, parenchymal, pleural, vascular patterns). Anti-IFN auto-Abs were detected using a luciferase neutralization reporting assay. Imaging data were collected through independent blinded reading of two thoracic radiologists of chest CT studies performed at ICU admission (± 72 h). The primary outcome measure was the evaluation of severity by the total severity score (TSS) and the CT severity score (CTSS) according to the presence or absence of anti-IFN auto-Abs. RESULTS: Two hundred thirty-one critically ill COVID-19 patients were included in the study (mean age 59.5 ± 12.7 years; males 74.6%). Day 90 mortality was 29.5% (n = 72/244). There was a trend towards more severe radiological lesions in patients with anti-IFN auto-Abs than in others, not reaching statistical significance (median CTSS 27.5 (21.0-34.8) versus 24.0 (19.0-30.0), p = 0.052; median TSS 14.5 (10.2-17.0) versus 12.0 (9.0-15.0), p = 0.070). The extra-parenchymal evaluation found no difference in the proportion of patients with pleural effusion, mediastinal lymphadenopathy, or thymal abnormalities in the two populations. The prevalence of pulmonary embolism was not significantly different between groups (8.7% versus 5.3%, p = 0.623, n = 175). CONCLUSION: There was no significant difference in disease severity as evaluated by chest CT in severe COVID-19 patients admitted to the ICU for hypoxemic acute respiratory failure with or without anti-IFN auto-Abs.

Chest computed tomography characteristics of critically ill COVID-19 patients with auto-antibodies against type I interferons.

Purpose: patients with auto-antibodies neutralizing type I interferons (anti-IFN auto-Abs) are at risk of severe forms of coronavirus disease 19 (COVID-19). The chest computed tomography (CT) scan characteristics of critically ill COVID-19 patients harboring these auto-Abs have never been reported. Methods: Bicentric ancillary study of the ANTICOV study (observational prospective cohort of severe COVID-19 patients admitted to the intensive care unit (ICU) for hypoxemic acute respiratory failure) on chest CT scan characteristics (severity score, parenchymal, pleural, vascular patterns). Anti-IFN auto-Abs were detected using a luciferase neutralization reporting assay. Imaging data were collected through independent blinded reading of two thoracic radiologists of chest CT studies performed at ICU admission (±72h). The primary outcome measure was the evaluation of severity by the total severity score (TSS) and the CT severity score (CTSS) according to the presence or absence of anti-IFN auto-Abs. Results: 231 critically ill COVID-19 patients were included in the study (mean age 59.5±12.7 years; males 74.6%). Day 90 mortality was 29.5% (n=72/244). There was a trend towards more severe radiological lesions in patients with auto-IFN anti-Abs than in others, not reaching statistical significance (median CTSS 27.5 (21.0-34.8] versus 24.0 (19.0-30.0), p=0.052; median TSS 14.5 (10.2-17.0) versus 12.0 (9.0-15.0), p=0.070). The extra-parenchymal evaluation found no difference in the proportion of patients with pleural effusion, mediastinal lymphadenopathy or thymal abnormalities in the two populations. The prevalence of pulmonary embolism was not significantly different between groups (8.7% versus 5.3%, p=0.623, n=175). Conclusion: There was no significant difference in disease severity as evaluated by chest CT in severe COVID-19 patients admitted to the ICU for hypoxemic acute respiratory failure with or without anti-IFN auto-Abs.

High-Dose Steroids for Nonresolving Acute Respiratory Distress Syndrome in Critically Ill COVID-19 Patients Treated With Dexamethasone: A Multicenter Cohort Study.

OBJECTIVES: To determine the impact of high doses of corticosteroids (HDCT) in critically ill COVID-19 patients with nonresolving acute respiratory distress syndrome (ARDS) who had been previously treated with dexamethasone as a standard of care. DESIGN: Prospective observational cohort study. Eligible patients presented nonresolving ARDS related to severe acute respiratory syndrome coronavirus 2 infection and had received initial treatment with dexamethasone. We compared patients who had received or not HDCT during ICU stay, consisting of greater than or equal to 1 mg/kg of methylprednisolone or equivalent for treatment of nonresolving ARDS. The primary outcome was 90-day mortality. We assessed the impact of HDCT on 90-day mortality using univariable and multivariable Cox regression analysis. Further adjustment for confounding variables was performed using overlap weighting propensity score. The association between HDCT and the risk of ventilator-associated pneumonia was estimated using multivariable cause-specific Cox proportional hazard model adjusting for pre-specified confounders. SETTING: We included consecutive patients admitted in 11 ICUs of Great Paris area from September 2020 to February 2021. PATIENTS: Three hundred eighty-three patients were included (59 in the HDCT group, 324 in the no HDCT group). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At day 90, 30 of 59 patients (51%) in the HDCT group and 116 of 324 patients (35.8%) in the no HDCT group had died. HDCT was significantly associated with 90-day mortality in unadjusted (hazard ratio [HR], 1.60; 95% CI, 1.04-2.47; p = 0.033) and adjusted analysis with overlap weighting (adjusted HR, 1.65; 95% CI, 1.03-2.63; p = 0.036). HDCT was not associated with an increased risk of ventilator-associated pneumonia (adjusted cause-specific HR, 0.42; 95% CI, 0.15-1.16; p = 0.09). CONCLUSIONS: In critically ill COVID-19 patients with nonresolving ARDS, HDCT result in a higher 90-day mortality.

Necrotizing soft tissue infections in critically ill neutropenic patients: a French multicentre retrospective cohort study.

BACKGROUND: Necrotizing soft tissue infections (NSTIs) are rare life-threatening bacterial infections. Few data are available regarding neutropenic patients with NSTIs. Our objectives were to describe the characteristics and management of neutropenic patients with NSTIs in intensive care units (ICUs). We conducted a retrospective multicentre cohort study in 18 ICUs between 2011 and 2021. Patients admitted with NSTIs and concomitant neutropenia at diagnosis were included and compared to non-neutropenic patients with NSTIs. The relationship between therapeutic interventions and outcomes was assessed using Cox regression and propensity score matching. RESULTS: 76 neutropenic patients were included and compared to 165 non-neutropenic patients. Neutropenic patients were younger (54 ± 14 vs 60 ± 13 years, p = 0.002) and had less lower limb (44.7% vs 70.9%, p < 0.001) and more abdomino-perineal NSTIs (43.4% vs 18.8%, p < 0.001). Enterobacterales and non-fermenting gram-negative bacteria were the most frequently isolated microorganisms in neutropenic patients. In-hospital mortality was significantly higher in neutropenic than in non-neutropenic patients (57.9% vs 28.5%, p < 0.001). Granulocyte colony-stimulating factor (G-CSF) administration was associated with a lower risk of in-hospital mortality in univariable Cox (hazard ratio (HR) = 0.43 95% confidence interval (CI) [0.23-0.82], p = 0.010) and multivariable Cox (adjusted HR = 0.46 95% CI [0.22-0.94], p = 0.033) analyses and after overlap propensity score weighting (odds ratio = 0.25 95% CI [0.09; 0.68], p = 0.006). CONCLUSIONS: Critically ill neutropenic patients with NSTIs present different clinical and microbiological characteristics and are associated with a higher hospital mortality than non-neutropenic patients. G-CSF administration was associated with hospital survival.

SARS-CoV-2 variants and mutational patterns: relationship with risk of ventilator-associated pneumonia in critically ill COVID-19 patients in the era of dexamethasone.

We aimed to explore the relationships between specific viral mutations/mutational patterns and ventilator-associated pneumonia (VAP) occurrence in COVID-19 patients admitted in intensive care units between October 1, 2020, and May 30, 2021. Full-length SARS-CoV-2 genomes were sequenced by means of next-generation sequencing. In this prospective multicentre cohort study, 259 patients were included. 222 patients (47%) had been infected with pre-existing ancestral variants, 116 (45%) with variant α, and 21 (8%) with other variants. 153 patients (59%) developed at least one VAP. There was no significant relationship between VAP occurrence and a specific SARS CoV-2 lineage/sublineage or mutational pattern.

Adverse Events and Infectious Complications in the Critically Ill Treated by Plasma Exchange: A Five-Year Multicenter Cohort Study.

OBJECTIVES: The aim of this study was to determine, in critically ill patients treated with therapeutic plasma exchange (TPE), the incidence of adverse events as well as the incidence of secondary infections and its predictive factors. DESIGN: A multicenter retrospective cohort study of an intensive care population treated with TPE to collect adverse events and infectious complications. The characteristics of patients who developed an infection after plasma exchange were compared with those of patients who did not. SETTING: Four ICUs of French university hospitals. PATIENTS: All adults admitted between January 1, 2015, and December 31, 2019, who received at least one plasma exchange session were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 711 TPE sessions were performed on 124 patients. The most frequent TPE indications were thrombotic microangiopathies (n = 32, 26%), myasthenia gravis (n = 25, 20%), and acute polyradiculoneuropathy (n = 12, 10%). Among the 124 patients, 22 (21%) developed arterial hypotension, 12 (12%) fever, and 9 (9%) electrolyte disturbance during TPE. Moreover, 60 (48%) presented at least one infectious complication: ventilator-associated pneumonia 42, pneumonia 13, bacteremia 18 (of which 6 catheter-related infections) viral reactivation 14. Independent risk factors for ICU-acquired infection were the ICU length of stay (24 vs. 7 d; hazard ratio [HR]: 1.09 [1.04-1.15], p < 0.001) and invasive mechanical ventilation (92% vs. 35%; HR: 16.2 [5.0-53.0], p < 0.001). CONCLUSIONS: In critically ill patients treated with TPE, adverse events occurring during the procedure remain moderately frequent and are mostly not life-threatening. Infectious complications, mainly ventilation-associated pneumonia, are frequent in this population. The need of mechanical ventilation and longer ICU stay is associated with an increased risk of infection.

Auto-antibodies against type I IFNs in > 10% of critically ill COVID-19 patients: a prospective multicentre study.

BACKGROUND: Auto-antibodies (auto-Abs) neutralizing type I interferons (IFN) have been found in about 15% of critical cases COVID-19 pneumonia and less than 1% of mild or asymptomatic cases. Determining whether auto-Abs influence presentation and outcome of critically ill COVID-19 patients could lead to specific therapeutic interventions. Our objectives were to compare the severity at admission and the mortality of patients hospitalized for critical COVID-19 in ICU with versus without auto-Abs. RESULTS: We conducted a prospective multicentre cohort study including patients admitted in 11 intensive care units (ICUs) from Great Paris area hospitals with proven SARS-CoV-2 infection and acute respiratory failure. 925 critically ill COVID-19 patients were included. Auto-Abs neutralizing type I IFN-α2, ß and/or ω were found in 96 patients (10.3%). Demographics and comorbidities did not differ between patients with versus without auto-Abs. At ICU admission, Auto-Abs positive patients required a higher FiO2 (100% (70-100) vs. 90% (60-100), p = 0.01), but were not different in other characteristics. Mortality at day 28 was not different between patients with and without auto-Abs (18.7 vs. 23.7%, p = 0.279). In multivariable analysis, 28-day mortality was associated with age (adjusted odds ratio (aOR) = 1.06 [1.04-1.08], p < 0.001), SOFA score (aOR = 1.18 [1.12-1.23], p < 0.001) and immunosuppression (aOR = 1.82 [1.1-3.0], p = 0.02), but not with the presence of auto-Abs (aOR = 0.69 [0.38-1.26], p = 0.23). CONCLUSIONS: In ICU patients, auto-Abs against type I IFNs were found in at least 10% of patients with critical COVID-19 pneumonia. They were not associated with day 28 mortality.

SARS-CoV-2 Genomic Characteristics and Clinical Impact of SARS-CoV-2 Viral Diversity in Critically Ill COVID-19 Patients: A Prospective Multicenter Cohort Study.

The SARS-CoV-2 variant of concern, α, spread worldwide at the beginning of 2021. It was suggested that this variant was associated with a higher risk of mortality than other variants. We aimed to characterize the genetic diversity of SARS-CoV-2 variants isolated from patients with severe COVID-19 and unravel the relationships between specific viral mutations/mutational patterns and clinical outcomes. This is a prospective multicenter observational cohort study. Patients aged ≥18 years admitted to 11 intensive care units (ICUs) in hospitals in the Greater Paris area for SARS-CoV-2 infection and acute respiratory failure between 1 October 2020 and 30 May 2021 were included. The primary clinical endpoint was day-28 mortality. Full-length SARS-CoV-2 genomes were sequenced by means of next-generation sequencing (Illumina COVIDSeq). In total, 413 patients were included, 183 (44.3%) were infected with pre-existing variants, 197 (47.7%) were infected with variant α, and 33 (8.0%) were infected with other variants. The patients infected with pre-existing variants were significantly older (64.9 ± 11.9 vs. 60.5 ± 11.8 years; p = 0.0005) and had more frequent COPD (11.5% vs. 4.1%; p = 0.009) and higher SOFA scores (4 [3-8] vs. 3 [2-4]; 0.0002). The day-28 mortality was no different between the patients infected with pre-existing, α, or other variants (31.1% vs. 26.2% vs. 30.3%; p = 0.550). There was no association between day-28 mortality and specific variants or the presence of specific mutations. At ICU admission, the patients infected with pre-existing variants had a different clinical presentation from those infected with variant α, but mortality did not differ between these groups. There was no association between specific variants or SARS-CoV-2 genome mutational pattern and day-28 mortality.

Acute Kidney Injury in Critically-Ill COVID-19 Patients.

Purpose: Acute kidney injury (AKI) is common in patients with COVID-19, however, its mechanism is still controversial, particularly in ICU settings. Urinary proteinuria profile could be a non-invasive tool of interest to scrutinize the pathophysiological process underlying AKI in COVID-19 patients. Material and Methods: We conducted a retrospective study between March 2020 and April 2020. All patients with laboratory-confirmed COVID-19 and without end-stage kidney disease requiring renal replacement therapy before ICU admission were included. Our objectives were to assess the incidence and risk factors for AKI and to describe its clinical and biological characteristics, particularly its urinary protein profile. Results: Seventy patients were included; 87% needed mechanical ventilation and 61% needed vasopressor during their ICU stay; 64.3% of patients developed AKI and half of them needed dialysis. Total and tubular proteinuria on day 1 were higher in patients with AKI, whereas glomerular proteinuria was similar in both groups. The main risk factor for AKI was shock at admission (OR = 5.47 (1.74−17.2), p < 0.01). Mortality on day 28 was higher in AKI (23/45, 51.1%) than in no-AKI patients (1/25, 4%), p < 0.001. Risk factors for 28-days mortality were AKI with need for renal replacement therapy, non-renal SOFA score and history of congestive heart failure. Conclusions: AKI is common in COVID-19 patients hospitalized in ICU; it seems to be related to tubular lesions rather than glomerular injury and is related to shock at ICU admission.

Plasma Exchange to Rescue Patients with Autoantibodies Against Type I Interferons and Life-Threatening COVID-19 Pneumonia.

PURPOSE: To report four cases of life-threatening COVID-19 pneumonia in patients with high blood concentrations of neutralizing autoantibodies against type I interferons (IFNs), who were treated with plasma exchange (PE) as a rescue therapy. METHODS: Prospective case series, which included patients, diagnosed with RT-PCR-confirmed SARS-CoV-2 infection and positive autoantibodies against type I IFNs in two French intensive care units (ICUs) between October 8 and November 14, 2020. Six critically ill COVID-19 patients with no anti-IFN antibodies were used as controls. Anti-IFN autoantibodies and IFN concentrations, together with the levels of anti-SARS-CoV-2 antibodies, were measured sequentially in serum. Viral load was determined in the upper and lower respiratory tract. Patients were followed during hospital stay. RESULTS: Three men and one woman were included. Three of the patients had four PE sessions each, while another had three PE sessions. PE decreased the concentrations of autoantibodies against type I IFN in all four patients, whereas anti-SARS-CoV-2 antibody levels remained stable. Autoantibodies against type I IFN levels were high in tracheal aspirates of one patient and decreased after three PE sessions. By contrast, anti-IFN autoantibodies were not detected in tracheal aspirates from five control patients without detectable anti-IFN autoantibodies in serum. During PE, serum IFN-α levels slightly increased in three out of four patients, and upper respiratory tract viral load decreased in all patients. All patients were alive at day 28 of ICU admission. Two patients eventually died in the ICU, while the two survivors were discharged from the ICU at days 50 and 66. CONCLUSIONS: PE efficiently removes autoantibodies against type I IFNs, including those detected in tracheal aspirates, without affecting anti-SARS-CoV-2 antibody levels, in patients with life-threatening COVID-19 pneumonia. The clinical benefit of PE in patients with autoantibodies against type I IFNs should be tested in a larger study.

The spectrum of kidney biopsies in hospitalized patients with COVID-19, acute kidney injury, and/or proteinuria.

We report a multicentric retrospective case series of patients with COVID-19 who developed acute kidney injury and/or proteinuria and underwent a kidney biopsy in the Paris and its metropolitan area. Forty-seven patients (80.9% men) with COVID-19 who underwent a kidney biopsy between March 08 and May 19, 2020 were included. Median age was 63 years IQR [52-69]. Comorbidities included hypertension (66.0%), diabetes mellitus (27.7%), obesity (27.7%), history of chronic kidney (25.5%), cardiac (38.6%) and respiratory (27.3%) diseases. Initial symptoms were fever (85.1%), cough (63.8%), shortness of breath (55.3%), and diarrhea (23.4%). Almost all patients developed acute kidney injury (97.9%) and 63.8% required renal replacement therapy. Kidney biopsy showed two main histopathological patterns, including acute tubular injury in 20 (42.6%) patients, and glomerular injury consisting of collapsing glomerulopathy and focal segmental glomerulosclerosis in 17 (36.2%) patients. Two (4.3%) patients had acute vascular nephropathy, while eight (17%) had alternative diagnosis most likely unrelated to COVID-19. Acute tubular injury occurred almost invariably in the setting of severe forms of COVID-19, whereas patients with glomerular injury had various profiles of COVID-19 severity and collapsing glomerulopathy was only observed in patients harboring a combination of APOL1 risk variants. At last follow-up, 16 of the 30 patients who initially required dialysis were still on dialysis, and 9 died. The present study describes the spectrum of kidney lesions in patients with COVID-19. While acute tubular injury is correlated with COVID-19 severity, the pattern of glomerular injury is intimately associated with the expression of APOL1 risk variants.

Risks of ventilator-associated pneumonia and invasive pulmonary aspergillosis in patients with viral acute respiratory distress syndrome related or not to Coronavirus 19 disease.

BACKGROUND: Data on incidence of ventilator-associated pneumonia (VAP) and invasive pulmonary aspergillosis in patients with severe SARS-CoV-2 infection are limited. METHODS: We conducted a monocenter retrospective study comparing the incidence of VAP and invasive aspergillosis between patients with COVID-19-related acute respiratory distress syndrome (C-ARDS) and those with non-SARS-CoV-2 viral ARDS (NC-ARDS). RESULTS: We assessed 90 C-ARDS and 82 NC-ARDS patients, who were mechanically ventilated for more than 48 h. At ICU admission, there were significantly fewer bacterial coinfections documented in C-ARDS than in NC-ARDS: 14 (16%) vs 38 (48%), p < 0.01. Conversely, significantly more patients developed at least one VAP episode in C-ARDS as compared with NC-ARDS: 58 (64%) vs. 36 (44%), p = 0.007. The probability of VAP was significantly higher in C-ARDS after adjusting on death and ventilator weaning [sub-hazard ratio = 1.72 (1.14-2.52), p < 0.01]. The incidence of multi-drug-resistant bacteria (MDR)-related VAP was significantly higher in C-ARDS than in NC-ARDS: 21 (23%) vs. 9 (11%), p = 0.03. Carbapenem was more used in C-ARDS than in NC-ARDS: 48 (53%), vs 21 (26%), p < 0.01. According to AspICU algorithm, there were fewer cases of putative aspergillosis in C-ARDS than in NC-ARDS [2 (2%) vs. 12 (15%), p = 0.003], but there was no difference in Aspergillus colonization. CONCLUSIONS: In our experience, we evidenced a higher incidence of VAP and MDR-VAP in C-ARDS than in NC-ARDS and a lower risk for invasive aspergillosis in the former group.

Severe HELLP syndrome masquerading as thrombocytopenic thrombotic purpura: a case report.

BACKGROUND: Thrombotic microangiopathies (TMAs) occurring in the postpartum period may be difficult to manage. They present as the combination of mechanical hemolytic anemia and consumption thrombocytopenia due to endothelial dysfunction. The cause of this endothelial aggression can be multiple: thrombocytopenic thrombotic purpura (TTP), HELLP syndrome, antiphospholipid syndrome, atypical hemolytic and uremic syndrome or acute fatty liver of pregnancy. TTP results from a severe deficiency of ADAMTS13, which is a protease cleaving specifically von Willebrand factor chiefly produced by liver cells. There are two main causes, the production of anti-ADAMTS13 auto-antibodies and, more rarely, a genetic deficiency in ADAMTS13. First-line treatment is based on plasma exchange. HELLP syndrome occurs in the third trimester of pregnancy usually in association with preeclampsia and represents a form of TMA characterized by damage to the sinusoidal capillaries of the liver. Prompt delivery is the main treatment. We present a case illustrating the challenges in discriminating between different postpartum TMAs, with a focus on the distinction between TTP and HELLP syndrome. Specifically, we highlight how acute liver failure (ALF) stemming from HELLP may lead to TTP with a spectacular response to plasma exchanges. CASE: A 28-year-old, 33 + 4 weeks pregnant woman presented with severe preeclampsia complicated by ALF in the setting of partial liver necrosis, disseminated intravascular coagulation, microangiopathic hemolytic anemia and acute kidney injury. Greatly diminished levels of ADAMTS13 (< 5%) activity and neurological impairment suggested an initial diagnosis of thrombotic thrombocytopenic purpura (TTP). Therapeutic plasma exchange (TPE) was initiated and complete renal, neurological, hematological and hepatic recovery was observed. Secondary TTP induced by ALF due to HELLP syndrome was the final diagnosis. CONCLUSION: Our case addresses the overlapping nature of postpartum TMAs and raises the possibility that HELLP-induced ALF may constitute an additional mechanism resulting in TTP, thereby opening a possible indication for TPE.