Pregnancy-associated Thrombotic Microangiopathy Research Articles

КЛИНИКО-ПАТОФИЗИОЛОГИЧЕСКИЕ АСПЕКТЫ МИКРОВЕЗИКУЛЯРНОГО СОСТАВА ПЕРИФЕРИЧЕСКОЙ КРОВИ У БЕРЕМЕННЫХ С ПРЕЭКЛАМПСИЕЙ

Abstract. Introduction. Preeclampsia is a pregnancy complication characterized by the development of arterial hypertension after 20 weeks of gestation, proteinuria, and/or oedemas. The pathogenesis of preeclampsia remains unclear to this day. Some studies have shown the importance of microvesicles in the pathogenesis of various pathological conditions. Involvement of microvesicles in the preeclampsia pathogenesis is a relevant issue. Taking into account all of the above, we have made an attempt to consider the pathogenesis of preeclampsia from the perspective of clinical and laboratory data. Aim. To establish the importance of microvesicles circulating in peripheral blood, their quantity and phenotype in the pathogenesis of preeclampsia. Materials and Methods. A one-stage cohort study was conducted, including 105 pregnant women: 30 pregnant women with severe preeclampsia (group 1), 35 pregnant women with mild preeclampsia (group 2), and 40 pregnant women without hypertensive syndrome (group 3), at 29–40 weeks of gestation. All patients were delivered surgically (Joel-Cohen laparotomy, cesarean section in the lower segment). All pregnant women underwent blood sampling to define the number and phenotypes of microvesicles (using flow cytometry) and laser scanning microscopy of the clot to confirm the presence of microvesicles of placental origin containing tissue factor, as well as the lipopolysaccharide of gram-negative microorganisms. Results and Discussion. In the group of patients with severe preeclampsia, a statistically significant increase was found in the number of placental, erythrocyte microvesicles, microvesicles with the tissue factor and lipopolysaccharide, compared to the group of patients with mild preeclampsia and pregnant women without hypertensive syndrome. In the group of patients with mild preeclampsia, a statistically significant increase was found in microvesicles with tissue factor and lipopolysaccharide, compared to pregnant women without hypertensive syndrome. The data obtained from the study confirm the fact that severe preeclampsia is a separate nosological entity, most likely pregnancy-associated thrombotic microangiopathy. Conclusions. The data obtained from the study indicate the need for further research to clarify the importance of microvesicles in the preeclampsia pathogenesis.

Features of Postpartum Hemorrhage-Associated Thrombotic Microangiopathy and Role of Short-Term Complement Inhibition

BackgroundIn pregnancy-related atypical hemolytic uremic syndrome (p-aHUS), transferring recommendations for treatment decisions from non-pregnant cohorts with thrombotic microangiopathy (TMA) is difficult. Although potential causes of p-aHUS may be unrelated to inherent complement defects, peripartal complications such as postpartum hemorrhage or (pre)-eclampsia/HELLP-syndrome may be unrecognized drivers of complement activation. MethodsTo evaluate diagnostic and therapeutic decisions in the practical real-life setting, we conducted an analysis of a cohort of 40 patients from three German academic hospitals with a diagnosis of p-aHUS, stratified by the presence (n= 25) or absence (n=15) of postpartum hemorrhage. ResultsHistological signs of TMA were seen in 84.2% of all patients (100% versus 72.7% in patients without or with postpartum hemorrhage). Patients without postpartum hemorrhage had a higher likelihood (20 % versus 0 %) of pathogenic genetic abnormalities in the complement system although notably less than in other published cohorts. Four out of five patients with seen renal cortical necrosis after postpartum hemorrhage received complement inhibition and partially recovered kidney function. Patients on complement inhibition with or without postpartum hemorrhage had an increased need for kidney replacement therapy and plasma exchange. Since renal recovery was comparable among all patients treated with complement inhibition, a potential beneficial effect in this group of pregnancy-associated thrombotic microangiopathies and p-aHUS is presumed. ConclusionsBased on our findings, we suggest a pragmatic approach towards limited and short-term anti-complement therapy for patients with the clinical diagnosis of p-aHUS, which should be stopped once causes of TMA other than genetic complement abnormalities emerge.

Management and follow-up of pregnancy-onset thrombotic thrombocytopenic purpura: the French experience

AbstractPregnancy-onset thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening disease of which diagnosis and management requires experienced multidisciplinary teams. The mechanisms responsible for a deficiency in the disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS13) leading to pregnancy-onset TTP may be congenital or acquired, and studying ADAMTS13 conformation could be of interest. The differential diagnosis between TTP and other pregnancy-associated thrombotic microangiopathies (TMA) is often challenging. Our retrospective multicenter study highlights the significance and the challenges associated with pregnancy-onset TTP and childbirth in terms of diagnosis, obstetric management, and follow-up aspects. Among 1174 pregnancy-onset TMA enrolled in the French Registry for TMA from 2000 to 2020, we identified 108 pregnancy-onset TTP: 52 immune-mediated TTP (iTTP, 48.1%), 27 acquired TTP of unidentified mechanism (uTTP, 25%), and 29 congenital TTP (cTTP, 26.9%). Data show that maternal outcome is good (survival rate: 95%) and fetal outcome is linked to the gestational age at the onset of the disease (survival rate: 75.5%). Three distinct entities with different natural histories emerged: pregnancy-onset iTTP appears similar to idiopathic iTTP, with an open ADAMTS13 conformation, and is marked by a relapse risk independent of subsequent pregnancies; pregnancy-onset uTTP appears to have a different pathophysiology with an unexpected open ADAMTS13 conformation and a very low relapse risk independent of subsequent pregnancies; finally, pregnancy-onset cTTP is characterized by the necessity of pregnancy as a systematic and specific trigger and a need for prophylactic plasmatherapy for subsequent pregnancies. This trial was registered at www.clinicaltrials.gov as #NCT00426686, and at the Health Authority and the French Ministry of Health (P051064/PHRC AOM05012).

#3885 KIDNEY TRANSPLANTATION IN EARLY PREGNANCY-ASSOCIATED ATYPICAL HEMOLYTIC UREMIC SYNDROME

Abstract Background and Aims Clinical differentiation of pregnancy-associated thrombotic microangiopathies is challenging and can occur in conjunction with or mimic conditions including hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome, pre-eclampsia (PET), thrombotic thrombocytopenia purpura (TTP) and atypical HUS (aHUS). aHUS that occurs during pregnancy classically presents in the third trimester. When kidney transplantation is performed in aHUS patients, disease recurrence is high and can be associated with transplant failure. Here, we report a unique case of aHUS that presented early during pregnancy where the patient subsequently underwent kidney transplantation. Method We present a case report. Ethics approval was obtained by the Queen's University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board. Results A 30 year old G2P0A1 diabetic African American woman presents at 9 weeks gestation with new hypertension. At 18 weeks, she developed acute kidney injury and proteinuria. Further investigations revealed hemoglobin 68 g/L, platelets 120 x 109/L, increased LDH 588 U/L, undetectable haptoglobin and schistocytes on blood smear. Creatinine was 88 umol/L, increased from a baseline of 50 umol/L, and proteinuria greater than 1 g/day. Pre-eclampsia was ruled out as her presentation began at 9 weeks gestation, prior to placental implantation. Placental growth factor levels at 24 and 28 weeks remained >100 pg/mL. HELLP syndrome was excluded given the timing in pregnancy and normal liver enzymes. TTP was excluded with a normal ADAMTS13. Complement Factor H autoantibody was negative. Complement studies revealed grossly elevated soluble C5b-9 level (sC5b-9) of 1.05 (normal <0.3 mg/L). aHUS was diagnosed and she began treatment with eculizumab (ECU). Ex-vivo serum C5b-9 deposition on human microvascular endothelial cells was assessed and was severely abnormal pre-treatment with ECU (activated 223%, normal <150%), and normalized with ECU therapy (activated 123%, normal <150%). Genetic testing eventually revealed a Complement Factor I mutation, NM_000204.3:c.550G/A, p. Vall84Met reported as likely pathogenic and confirming primary aHUS. Due to worsening renal function, she delivered a healthy boy at 30 weeks gestation by Caesarean section. A renal biopsy performed 3 weeks post-partum demonstrated features of TMA, mainly chronic (i.e. treated) and severe diabetic nephropathy with advanced glomerular sclerosis. Six months post-partum, she required dialysis. She remained on ECU and had an unrelated living kidney transplantation 1.5 years later. Her kidney transplantation included basiliximab and methylprednisolone induction. Calcineurin inhibitors were prescribed in standard fashion. Given severity of original multiorgan aHUS and CFI mutation, she was treated with eculizumab 1200 mg the day prior to surgery and another 1200 mg on post operative day 1. Subsequently she was given eculizumab 900 mg weekly for 4 weeks then 1200 mg every 2 weeks. Eculizumab drug level for adequacy of complement blockade was measured on day 4 post transplant and was 279 (therapeutic >100 mcg/mL) and sC5b-9 was 1504 (normal < 244). Repeated ECU level pre 900 mg dose was 189 and sC5b-9 was 392. 6 months post transplant she has excellent graft function without proteinuria (urine ACR 2.2 mg/mmol) or evidence of aHUS recurrence. Conclusion aHUS, although described to occur late in pregnancy or post-partum, presented here during the first trimester. Thus, TMA in pregnancy is not always PET or HELLP. aHUS is a treatable condition in pregnancy, and should be considered as a possibility particularly for presentations occurring prior to 20 weeks gestation. Complement function studies may aid in aHUS diagnosis. Despite extra ECU dosing and therapeutic ECU levels for this patient post kidney transplantation, she had evidence of massive C5 release (grossly elevated sC5b-9 level). sC5b-9 measurement post transplantation may be useful to guide ECU dosing.

Pregnancy-Associated Renal Cortical Necrosis and Nonenhanced Functional Magnetic Resonance Imaging: A Case Series

Pregnancy-associated renal cortical necrosis is a critical illness with a poor prognosis. We aimed to describe the clinical and magnetic resonance imaging (MRI) characteristics of a case series of patients with acute kidney injury in the setting of pregnancy-associated renal cortical necrosis. Case series. Seventeen patients from a single center diagnosed by nonenhanced functional MRI and/or kidney pathology. All patients presented with postpartum acute kidney injury stage 3. Of the 17 patients, 15 (88%) had pregnancy-associated atypical hemolytic uremic syndrome, 11 (65%) had postpartum hemorrhage, 7 (41%) had preeclampsia/hemolysis elevated liver enzymes low platelet count syndrome, and 4 (24%) had disseminated intravascular coagulation. On T2-weighted MRI, the diffuse phenotype showed outer cortex swelling in the early phase, with a dark signal rim involving the inner cortex and Bertin column, which became more apparent over time along with cortical thinning, substantially decreasing T2 signal intensity. The focal phenotype showed focally distributed hypointense signals in the cortex. After 8-101 (median: 60) months of follow-up, 4 individuals had estimated glomerular filtration rates≥60mL/min/1.73m2, 6 had estimated glomerular filtration rates of 15-60mL/min/1.73m2, and 7 had kidney failure requiring kidney replacement therapy. The diffuse phenotype was present in all of the individuals who remained kidney replacement therapy dependent. Retrospective study; small sample size. Different forms of pregnancy-associated thrombotic microangiopathy were the major causative diseases in our pregnancy-associated renal cortical necrosis case series. Nonenhanced functional MRI may provide valuable data for establishing diagnosis and kidney prognosis.

IMPACT OF PREGANCY RELATED ACUTE KIDNEY INJURY IN MATERNAL HEALTH IN CENTRAL INDIA- A CASE SERIES

Many pregnancies associated diseases are adding to the development of Pregnancy Related Acute Kidney Injury (PR-AKI) like Pre-Eclampsia/Eclampsia (PE/E), HELLP Syndrome, Antepartum/Postpartum Hemorrhage (APH/PPH) and Pregnancy Associated Thrombotic Microangiopathy (P-TMA) are common. Puerperal sepsis, septic abortion, Pre-Eclampsia/Eclampsia, HELLP Syndrome, Antepartum and Postpartum Hemorrhage are common risk factors for PR-AKI development. PR-AKI patients have adverse impact on the maternal health and may leads to development of CKD even death.

SY10-1. Differential diagnosis of pregnancy-associated thrombotic microangiopathies (TTP, aHUS, and HELLP syndrome)

Neuromyelitis Optica Spectrum Disorder (NMOSD) is an autoimmune relapsing disease involving the central nervous system with predominant inflammatory attack of optic nerves, spinal cord and area postrema, often leading to severe disability. Women with NMOSD typically experience adverse pregnancy outcomes and high relapse rates during pregnancy and the postpartum period.Herein we present a case of pregnancy in a young NMOSD woman treated with tocilizumab. The course of her pregnancy was clinically unremarkable and treatment whit Tocilizumab was well tolerated.This case raises the possibility that the modulation of immune system by inhibitors of the IL-6 pathway could a promising therapeutic option for pregnancy in NMOSD patient.

Thrombotic Microangiopathy Associated with Pregnancy: Various Outcomes in Different Disorders

Thrombotic microangiopathy (TMA) associated with pregnancy can be fulminant and fatal disorder. Pregnancy outcomes and survival of patients depend on the precise diagnose and appropriate treatment approaches. When a pregnant or postpartum woman presents with sudden and severe microangiopathic hemolytic anemia and thrombocytopenia, conditions that require urgent care must be considered: preeclampsia with severe features (PE/HELLP syndrome), thrombotic thrombocytopenic purpura (TTP), catastrophic antiphospholipid syndrome (CAPS), complement-mediated thrombotic microangiopathy (atypical hemolytic-uremic syndrome, aHUS). The distinction among these syndromes is often unclear because they share multiple clinical features. Overlap between PE/HELLP and TTP, CAPS and aHUS is also apparent from the fact that pregnancy can be a trigger for TMA before and after delivery. These disorders, especially PE imitators, are very important as the causes of maternal and fetal death.Since 2010 we observed 104 patients with pregnancy-associated TMA. Women's age at the time of pregnancy was 32,04±0,83 years old, delivery performed at 34,89±0,74 gestation weeks. The reasons of TMA defined as PE/HELLP in 71 (68,3%) women (main signs: blood pressure more than 160 mm systolic or 110 mm diastolic, platelet count <100 x 10⁹/l and/or abnormal liver function, renal insufficiency, pulmonary edema, cerebral symptoms, eclampsia - generalized seizures, peripartum cardiomyopathy), aHUS- 32 (30,8%), TTP-1 (0,9%) (ADAMTS13 level less than 10%). All of them required preterm operative delivery. Therapeutic plasma exchange (1-9 procedures) performed in 88 (84,6%). ADAMTS13 level assessed before plasma therapy (45-84%, excluding the TTP case), as well as lupus anticoagulant (LA) and antiphospholipid antibodies (APLA) (negative in all patients). In cases of aHUS we use eculizumab in 14/32 (43,75%), but a full course with subsequent successful discontinuation of the drug was received only by one patient. 13/14 patients received 1 to 6 injections of eculizumab.Overall mortality rate was 10 (9,6%), It is noteworthy that only patients with aHUS died- 10/32 (31,25%). Antenatal fetal death occured in 16 (15,4%), among them 12/32 (37,5%) were diagnosed with aHUS. The condition of patients with PE/HELLP improved on 1-3 days after delivery in all cases. In aHUS patients, life-threatening complications persisted and even progressed after delivery: massive uterine bleeding required hysterectomy occurred in 23,2%, acute kidney injury registered in 100% patients, neurological symptoms had 61%, respiratory distress syndrome- 55%, dilated cardiomyopathy- 16,7%. 61,3% required hemodialysis, 51,8%- respiratory care. All of patients who died had 2 “waves” of TMA: first wave has damaged 2-5 organs without any proved infections, but treated with antibacterial combination. Second TMA wave was fatal due to superimposed septic disorders, resistant to antibiotic therapy. Patients on eculizumab treatment had more severe disease at debut with shorter history of aHUS and responded well to eculizumab. Survival of aHUS patients on eculizumab treatment was 71,4%, without it - 64,7%.Therapeutic approaches in TMA associated with pregnancy are different and survival of patients depends on a timely diagnosis. Clinical vigilance requires for early detection of TMA. After that is necessary as soon as possible investigate the ADAMTS13 level to avoid TTP, and LA and APLA to avoid CAPS. Plasma exchange may be first urgent step of treatment in all cases of TMA, but after clarifying the diagnosis therapy should be adjusted. Timely diagnosis and effective approaches including early prescribed targeted therapy in aHUS patients can improve the survival rate and pregnancy outcomes. DisclosuresNo relevant conflicts of interest to declare.

Assessment of risk factors and pregnancy outcomes in women with thrombotic microangiopathy in Ain Shams University Maternity Hospital over a 5-year period

Thrombotic microangiopathy in pregnancy can lead to maternal and fetal life-threatening adverse events. Objective. To study the demographic characteristics (age, parity), risk factors, treatment modalities, and pregnancy outcomes in women with thrombotic microangiopathy in Ain Shams University Maternity Hospital over a 5-year period. Patients and methods. This study was retrospectively conducted at Ain Shams University Maternity Hospital and included 419 patients; the study population were pregnant women admitted to the hospital from January 2014 to December 2018, with pregnancy-associated thrombotic microangiopathy. The study was performed through revising the medical records in the archive and the ICU and contacting the patients to assess demographic data, risk factors, presentation of the patient, type of the syndrome, and the maternal and fetal outcome. Results. HELLP syndrome was the most common pregnancy complication. In most of cases, women delivered by cesarean section (72.1%). Complications included chronic hypertension (CHTN), acute kidney injury (AKI), chronic kidney injury (CKI). Maternal mortality was significantly more frequent in hemolytic uremic syndrome (HUS). Maternal mortality was 8.8 %, and neonatal mortality was 26.7%. Most of women were admitted to the ICU (87.1%). Conclusion. Thrombotic microangiopathy in pregnancy continues to pose a large challenge to obstetricians, immunologists, and nephrologists due to potential risks and complications. Pregnancy outcome is more optimistic when termination of pregnancy occurs early in the disease with the possible use of corticosteroids with or without plasma exchange transfusion under the control of a multidisciplinary approach team. Key words: risk factors, outcome, pregnant women, thrombotic microangiopathy

Diagnostic dilemma in postpartum associated hemolytic uremic syndrome in a 38th week pregnant 31-year-old Congolese: a case report

BackgroundThrombotic microangiopathy is associated with HELLP syndrome, thrombotic thrombocytopenic purpura, or atypical hemolytic uremic syndrome (aHUS) during pregnancy. Standard laboratory and physical examinations can help distinguish between these three diseases promptly and guide their management. This is critical because their managements and prognoses differ considerably. The ADAMTS13 test, complement tests, and biopsies can help ascertain the diagnosis; however, they take time, and are not widely available. In this case report, we present a case that highlights the diagnostic and therapeutic dilemmas associated with the aforementioned diseases.Case presentationA 31-year old P3G3 patient presented at 38 weeks with high blood pressure, bilateral pitting edema, and a low fetal heart rate. A cesarean section was performed to extract the fetus. On postoperative day 2, the suites were marked by anemia, low platelet count, acute kidney injury, declining liver function, and the presence of schistocytes on the peripheral thin smear. The patient was lucid, coherent, and presented no neurological deficits. The ADAMTS13 test and anti-complement therapy were not readily available, so the team made a presumptive diagnosis of aHUS based on the history, clinical presentation, and standard laboratory results. Due to a lack of anticomplement therapy, the patient was prescribed four sessions of hemodialysis. The renal function and platelet count gradually increased, and the patient was discharged on postoperative day 18. The patient was followed for over a year and did not present relapses of thrombocytopenia or microangiopathic hemolytic anemia.ConclusionsThe prompt diagnosis and management of aHUS lead to favorable outcomes. Healthcare providers should be able to rapidly differentiate between pregnancy-associated thrombotic microangiopathies and prescribe appropriate management. Here, we highlighted the challenges of diagnosing and managing postpartum associated aHUS in a low-resource setting.

Changing epidemiology of acute kidney injury in pregnancy: A journey of four decades from a developing country.

The incidence of acute kidney injury in pregnancy (P-AKI) has markedly decreased over the last three decades in India, particularly due to decreased incidence of postabortion AKI. However, P-AKI still accounts for 3%-5% of cases of total AKI. Postabortion sepsis has decreased to between 0.9% and 1.5% in 2014 from 9.4% in 1980-1990 in the new millennium. Currently, in India, majority of P-AKI (70%-90%) occurs in the postpartum period and in late 3rd trimester similar to the developed countries, but causes are different. We observed that preeclampsia/eclampsia is the most common cause of P-AKI in the late 3rd trimester and postpartum period followed by puerperal sepsis and postpartum hemorrhage (PPH). Both puerperal sepsis and PPH are treatable and preventable etiologies of P-AKI. Timely and aggressive management of antepartum hemorrhage (APH/PPH) and puerperal sepsis are required to reduce the burden of P-AKI in developing countries. Specific-pregnancy disorders such as P-aHUS/thrombotic thrombocytopenic purpura, pregnancy-associated thrombotic microangiopathy, and acute fatty liver of pregnancy are the uncommon/rare causes of P-AKI in India and possibly also because of the lack of awareness toward diagnosis. Despite decreasing incidence of P-AKI, fetal mortality remained high and unchanged. However, maternal mortality has decreased to 5% from initial high mortality of 20%-25%. The incidence and severity of renal cortical necrosis have significantly decreased at our center.

Microangiopathic Hemolytic Anemia in Pregnancy.

Thrombotic microangiopathies (TMAs) are associated with microangiopathic hemolytic anemia and thrombocytopenia, resulting in microvascular thrombosis and end-organ damage. In pregnancy, this may be the result of pregnancy-related TMAs such as preeclampsia; hemolysis, elevated liver enzymes, and low platelets; or pregnancy-associated TMAs, specifically thrombotic thrombocytopenic purpura (TTP) or complement-mediated hemolytic uremic syndrome (CM HUS). TTP and CM HUS are rare disorders, and their diagnosis may be missed, no less because features at presentation may be misdiagnosed as a pregnancy-related TMA, such as hypertension, proteinuria, fetal growth restriction, or in utero fetal death. The mainstay of treatment for pregnancy-associated TMAs is plasma exchange. Presentation is likely in the third trimester for TTP and postpartum for CM HUS. However, both conditions can present in any trimester, unlike pregnancy-related TMAs which rarely present before the second trimester, commonly in the third trimester. Delivery is the mainstay of treatment for pregnancy-related TMAs. More recently, it has become clear that pregnancy may be a trigger for late-onset congenital TTP, as well as immune-mediated TTP, diagnosed by ADAMTS13 analysis. Complement inhibitor therapy is the treatment of choice for CM HUS cases. However, their diagnosis is by exclusion, but complement inhibitor therapy reduces the risk of end-stage renal failure. Subsequent pregnancies can be supported for TTP and CM HUS.

Acute kidney injury in pregnancy with special reference to pregnancy-specific disorders: a hospital based study (2014-2016).

There are numerous reports in the literature describing acute kidney injury in pregnancy (P-AKI) due to various obstetric complications. However, there is a dearth of studies on AKI related to pregnancy-specific disorders from India. We aimed to analyze clinical features and outcome of P-AKI related to pregnancy-specific disorders compared to total pregnancy, in India. All pregnant women attending the department of Obstetrics and Gynecology from November 2014 to July 2016 were screened for AKI based on: (1) sudden elevation of serum creatinine ≥ 1mg/dl; (2) oligoanuria for > 12h; and (3) need for dialysis. The detailed clinical profile of AKI in patients with preeclampsia/eclampsia (PE/E), hemolysis/elevated liver enzymes/low platelet count (HELLP) syndrome, acute fatty liver of pregnancy (AFLP), and pregnancy-associated thrombotic microangiopathy (P-TMA) was analyzed. Laboratory investigations included: complete blood count, renal function tests, urinalysis, coagulation profile (platelet count, INR, prothrombin time and activated partial thromboplastin time), and immunological assay (C3, C4, ANA, anti-dsDNA antibody, antiphospholipid antibody). Contrast-enhanced CT scan of kidney ureter and bladder (KUB) and renal biopsy were performed in selected cases. Maternal and fetal outcome were analyzed individually. The patients were followed for 3 months or longer to determine the recovery of renal function or progression to chronic kidney disease (CKD). Overall, 4741 pregnant women (mean age 26.8 ± 4.8years) were evaluated for AKI. P-AKI was found in 132/4741 (2.78%) patients. In the majority (91.6%), AKI developed in the late 3rd trimester and post-partum period. P-AKI was related to obstetric complications (in 61.4%), pregnancy-specific disorders (in 57.5%) and miscellaneous factors (7.5%). Puerperal sepsis, ante-partum and post-partum hemorrhage were contributing factors for P-AKI in 34 (25.8%), 11 (8.3%) and 28 (21.2%) patients, respectively. P-AKI due to pregnancy-specific disorders developed in 76/4741 patients, i.e. in 1:62 pregnancies. PE/E was the cause of P-AKI in 62 patients (46.9%) followed by HELLP syndrome in 9 (6.8%) and AFLP in 05 (3.8%). P-TMA causing AKI was not observed. Complete recovery of renal function occurred in 89.4% of patients while 6 (4.6%) progressed to CKD (ESRD: 3 and CKD stage IV: 3). Maternal mortality was 6%. Puerperal sepsis was the sole cause of patchy cortical necrosis in 5 (3.7%) cases. Premature delivery occurred in 40.9% patients and full-term delivery in 35.6%. Perinatal mortality was 23.5%, mainly due to intrauterine death (17.5%) and prematurity (6%). PE/E was the commonest cause of P-AKI in our study, similar to the situation in developed countries. Post-partum hemorrhage was the second-most common (21.5%) cause. Puerperal sepsis contributed to AKI in one-fourth of pregnant women. P-TMA was not recorded in this study and AFLP was an uncommon cause of P-AKI in our country. Renal function returned to normal in all patients with P-AKI due to pregnancy-specific disorders. However, perinatal mortality was high despite the good prognosis of P-AKI.

Microangiopathies thrombotiques secondaires

Thrombotic microangiopathies (TMA) are termed secondary when associated to a specific context favouring their occurrence. They encompass mainly TMA associated with pregnancy, allogeneic hematopoietic stem cell transplantation, cancer, drugs, or HIV infection. Secondary TMA represent a heterogeneous group of diseases which clinical presentation largely depends on the associated context. It is therefore mandatory to recognize these conditions since they have a significant impact in TMA management and prognosis. A successful management still represents a challenge in secondary TMA. Significant progresses have been made in the understanding of pregnancy-associated TMA, allowing an improvement of prognosis; on the opposite, other forms of secondary TMA such as hematopoietic stem cell transplantation-associated TMA or TMA associated with chemotherapy remain of dismal prognosis. A better understanding of pathophysiology in these forms of TMA, in association with a more empirical approach through the use of new therapeutic agents that can also help in the understanding on new mechanisms a posteriori, should improve their prognosis. The preliminary encouraging results reported with complement blockers in this field could represent a convincing example.

Clinical dissection of thrombotic microangiopathy.

Differential treatment strategies are applied in thrombotic microangiopathy (TMA) according to the sub-classifications. Hence, it is worthwhile to overview clinical manifestations and outcomes of overall TMA patients according to sub-classifications. We analyzed TMA patients whose serum lactate dehydrogenase levels >250IU/L, with the presence of schistocytes in their peripheral blood smear, or with typical vascular pathologic abnormalities in their renal biopsy. We compared clinical manifestations including overall survival (OS) and renal survival according to TMA causes. A total of 117 TMA patients (57 primary and 60 secondary TMA) were analyzed. Renal symptom was the most common manifestation in whole patients, while renal function at diagnosis was worst in pregnancy-related TMA group. Primary TMA patients had more frequent CNS symptom and hematologic manifestation compared to secondary TMAs. Among secondary TMAs, pregnancy- and HSCT-related TMA patients showed prevalent hemolytic features. During 150.2months of follow-up, 5-year OS rate was 64.8%. Poor prognostic factors included older age, combined hematologic and solid organ malignancies, lower hemoglobin levels, and lower serum albumin levels. There was no significant difference in OS between primary and secondary TMAs. Seventy-eight percent of patients experienced AKI during TMA. Five-year death-censored renal survival rate was poor with only 69.2%. However, excellent renal outcome was observed in pregnancy-associated TMA. TMA showed various clinical manifestations according to their etiology. Notably, both OS and renal survival were poor regardless of their etiologies except pregnancy-associated TMA. Physicians should differentiate a variety of TMA categories and properly manage this complex disease entity.

P-096: Pregnancy-associated thrombotic microangiopathies (Pa-TMA): features of intrarenal blood flow (IBF) in severe preeclampsia (PE), HELLP syndrome and pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS)

P-096: Pregnancy-associated thrombotic microangiopathies (Pa-TMA): features of intrarenal blood flow (IBF) in severe preeclampsia (PE), HELLP syndrome and pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS)

Acute Kidney Injury in Pregnancy-specific Disorders.

The incidence of acute kidney injury in pregnancy (P-AKI) has declined significantly over the last three decades in developing countries. However, it is still associated with significant fetomaternal mortality and morbidity. The diagnosis of P-AKI is based on the serum creatinine increase. The usual formulas for estimating glomerular filtration rate (GFR) are not validated in this population. The incidence of P-AKI with respect to total AKI cases has decreased in the last three decades from 25% in 1980s to 9% in 2000s at our centre. During the first trimester of gestation, AKI develops most often due to septic abortion or hyperemesis gravidarum. Septic abortion related AKI with respect to total AKI decreased from 9% to 5% in our study. Prevention of unwanted pregnancy and avoidance of septic abortion are keys to eliminate abortion associated AKI in early pregnancy. However, we have not seen AKI on account of hyperemesis gravidarum over a period of 33 years at our center. In the third trimester, the differential diagnosis of AKI in association with pregnancy specific conditions namely preeclampsia/HELLP syndrome, acute fatty liver of pregnancy and thrombotic microangiopathies of pregnancy (P-TMA) is more challenging, because these 3 conditions share several clinical features of thrombotic microangiopathy which makes the diagnosis very difficult on clinical grounds. It is imperative to distinguish these conditions to make appropriate therapeutic decisions. Typically, AFLP and HELLP syndrome improve after delivery of the fetus, whereas plasma exchange is the first-line treatment for pregnancy associated thrombotic microangioathies (P-TMA). We observed that preclampsia/eclampsia is the most common cause of AKI in late third trimester and postpartum periods followed by puerperal sepsis and postpartum hemorrhage. Pregnancy-associated thrombotic microangiopathies (aHUS/TTP) and AFLP are rare causes of AKI during pregnancy in developing countries.

Имитаторы тяжелой преэклампсии и HELLP-синдрома: различные виды тромботической микроангиопатии, ассоциированной с беременностью

Имитаторы тяжелой преэклампсии и HELLP-синдрома: различные виды тромботической микроангиопатии, ассоциированной с беременностью

Clinical and renal biopsy findings predicting outcome in renal thrombotic microangiopathy: a large cohort study from a single institute in China.

Objective. The current study aimed to investigate the spectrum of etiologies and associated disorders of renal biopsy-proven thrombotic microangiopathy (TMA) patients. Methods. The clinical, laboratory, and renal histopathological data of patients with renal TMA from 2000 to 2012 in our institute were collected and reviewed. Results. One hundred and nine TMA patients were enrolled in this study. The mean age was 34.0 ± 11.1 years. Seventy patients (64.2%) were male and thirty-nine patients (35.8%) were female. There were eight patients (7.3%) with hemolytic uremic syndrome (HUS). Sixty-one patients (56.0%) were secondary to malignant hypertension. Fourteen patients (12.8%) were pregnancy-associated TMA. Other associated disorders included 17 patients with connective tissue disorders, 2 patients with hematopoietic stem cell transplantation, 4 patients with Castleman's disease, 1 patient with cryoglobulinemia, and 2 patients with glomerulopathy. During followup, 8 patients died due to severe infection, 17 patients had doubling of serum creatinine, and 44 had end-stage renal disease. In multivariate analysis, male, elevated serum creatinine, and decreased hemoglobin were independently associated with poor renal outcomes. Conclusions. Renal TMA changes consisted of different disorders with various etiologies. aHUS, pregnancy-associated TMA, and malignant hypertension accounted for the majority of patients in our cohort.