The hemolytic uremic syndrome. Renal cortical thrombotic microangiopathy

1970 ◽  
Vol 126 (5) ◽  
pp. 816-822 ◽  
Author(s):  
D. Hammond
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Thrombotic Microangiopathy ◽  
Uremic Syndrome

Increased Tissue Factor Bearing Microparticles in Hemolytic Uremic Syndrome.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1006-1006 ◽  
Author(s):  
Morayma Reyes ◽  
Wayne Leslie Chandler ◽  
Sandra Watkins ◽  
Jody Mooney ◽  
Phillip Tarr
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Tissue Factor ◽  
Thrombotic Microangiopathy ◽  
Annexin V ◽  
Control Group ◽  
Healthy Children ◽  
Color Flow ◽  
E Coli ◽  
Uremic Syndrome ◽  
Time Of Presentation

Abstract Microparticles (MP) are circulating cellular fragments that are increased in thrombotic conditions including TTP, antiphospholipid syndrome, and HIT. Tissue factor (TF)-bearing MP are thought to be procoagulant in these conditions. Hemolytic Uremic Syndrome (HUS) is a thrombotic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia and renal failure secondary to glomerular thrombotic microangiopathy. In children, HUS most often occurs after infection with E. coli O157H7. It is hypothesized that E. coli verotoxin injures renal and other endothelium leading to activation of hemostasis, thrombotic microangiopathy and HUS. We studied 56 children at the time of presentation with bloody diarrhea associated with E. coli O157H7 infection (typically day 4 of illness) prior to developing HUS, and 5 healthy children as controls. Subsequently 14 children (Pre-HUS) went on to develop HUS while 42 (Uncomplicated) resolved their illness without developing HUS. We also studied 15 children that presented with already developed HUS (HUS group). We analyzed the total number of MPs, percent of TF-bearing microparticles and their cellular derivation using a 5-color flow cytometry assay. Endothelial-derived MP are identified as positive for CD144 (Ve-Cad)-PE, monocyte-derived MP are positive for CD14-PE-Cy7, and platelet derived MP are positive for CD41a-PerCP. MPs were collected from plasma by ultracentrifugation (100,000g). MPs were defined based on size (0.5–1 um) and strong annexin V binding. The MP distribution in the control group was similar to reports by others: 204 ±98 ×103 MPs/mL of plasma (55% platelet-, 5% endothelial- and 15% monocyte-derived), only 2.6% of MP express TF. The MP distribution in Uncomplicated was 996 ±766 ×103 MPs/mL (36% plat-, 11% endo- and 15% mono-derived) and 5.4% express TF; while pre-HUS showed 1197±1108 ×103 MPs/mL (21% plat-, 12% endo- and 11% mono-derived) and 8.2% express TF. The MP distribution in the HUS group was 1183±949 ×103 MPs/mL (45% plat-, 15% endo- and 19% mono-derived) and 10.9% express TF. Compared to controls, children infected with E. coli O157H7 showed a higher number of total MPs (p<0.02, Mann Whitney) and a higher number of tissue factor bearing MP (p<0.004). Compared to the Uncomplicated group, the pre-HUS group showed fewer platelet MPs (p<0.04). Progression from Pre-HUS to HUS is characterized by increased number of TF-bearing MP distributed in all cellular populations (p<0.01). In a prior study the pre-HUS group showed increased hemostatic activation as indicated by higher levels of F1.2 and D-dimer. We conclude that E. coli 0157:H7 infection results in increased microparticle production versus controls, and increased tissue factor positive microparticles. Development of HUS is associated with further increases in tissue factor positive microparticles, which correlates with the increased hemostatic activation observed in previous studies, suggesting a pathologic role for the release TF-bearing MP in HUS. Interestingly, Pre-HUS patients show reduced numbers of platelet derived microparticles versus uncomplicated patients that resolve without developing HUS, but when HUS develops the number of TF-bearing MP increases. Whether this reduction of platelet-derived microparticles preceding HUS development results from increased binding of MP to endothelium or reduced production of MP in pre-HUS are ongoing studies that may shed some light into the pathogenesis of HUS.

scholarly journals A Challenging Case of Atypical Hemolytic Uremic Syndrome in a Young African American Patient

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4225-4225
Author(s):  
Urwat Til Vusqa ◽  
Palash Asawa ◽  
Yazan Samhouri ◽  
Rama Bhagavatula ◽  
Robert B. Kaplan
Keyword(s):  
Blood Pressure ◽  
African American ◽  
Hemolytic Uremic Syndrome ◽  
Thrombotic Microangiopathy ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Malignant Hypertension ◽  
Coagulation Cascade ◽  
Complement Factors ◽  
Uremic Syndrome ◽  
Terminal Complement

Abstract Background It is known that malignant hypertension (mHTN) and thrombotic microangiopathy (TMA) commonly coexist. Deciding which phenomenon preceded the other remains a clinical dilemma, specifically in African American patients. However, making that determination is of utmost importance because the management will be different, and that can have dramatic effects on prognosis and outcomes. Herein, we report a case of atypical hemolytic uremic syndrome (aHUS) presenting as mHTN. Case Presentation A 35-year-old African American male with known history of hypertension, presented with nausea, vomiting, and diarrhea for four days. He also reported fatigue and exertional shortness of breath. Upon presentation, his blood pressure was 260/160 mmHg, otherwise physical exam was unremarkable. Initial work up showed hemoglobin of 8.8 g/dL (baseline 13.5), platelet count of 21,000/mL (baseline 250,000), serum creatinine of 16.99 mg/dL (baseline 0.99), MCV (84 fl), increased reticulocyte production index (3.58), increased LDH (1709 U/L), undetectable haptoglobin, and numerous schistocytes on peripheral blood smear. He was admitted as a case of hypertensive emergency and TMA. IV labetalol and hemodialysis were started. Given his gastrointestinal symptoms; stool for Shigella and E.Coli O157:H7 were checked and they were negative. Given the severity of his hematologic derangements and difficult to control blood pressure, we decided to proceed with renal biopsy to rule out primary aHUS which showed thrombotic microangiopathy, global glomerulosclerosis, moderate interstitial fibrosis and tubular atrophy suggestive of aHUS or rheumatologic disorders like systemic sclerosis and arguing against malignant HTN as the sole player. ANA and anti-Scl-70 antibodies were negative. Final impression was aHUS by exclusion, and patient received meningococcal vaccines (Menactra and Bexsero) in preparation to start eculizumab. aHUS genetic panel was sent which came back equivocal as it showed mutations of unknown significance (homozygous missense mutation in the MASP2 gene and 2 heterozygous mutations in the C2 gene). He was started on eculizumab 900 mg weekly for 4 weeks then 1200 mg biweekly starting week 5. He was seen in the office 2 months after initial presentation and receiving 5 doses of Eculizumab. His kidney function showed improvement with > 2 liters of urine output daily, blood pressure was better controlled. A decision by nephrology was made to give him a break from dialysis and remains dialysis-free a year later. Discussion aHUS is a rare disorder with an estimated prevalence of seven per one million children in Europe. It causes uninhibited activation of complement factors that leads to renal endothelial damage and activation of coagulation cascade leading to TMA. The diagnosis of aHUS requires the fulfillment of the classical triad (microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure) with a positive gene mutation or antibodies to complement factors. However, absence of these mutations or antibodies, as in the presented case, do not exclude the diagnosis. The early diagnosis of aHUS is necessary for treatment with eculizumab, a monoclonal antibody against C5 to block the terminal complement cascade. Kidney biopsy can be helpful in equivocal cases especially if it shows only the typical changes of malignant hypertension which essentially rules out aHUS. Hypertension with concurrent TMA is treated with strict BP control which is often enough to resolve TMA features and restores renal function, at least partially. On the contrary, aHUS causing severe HTN needs more sophisticated testing and blockade of the terminal complement component to improve outcome; that's why the distinction of which one is the primary process is of utmost importance. Our case emphasizes the importance of having low threshold for testing for aHUS in patients with mHTN and TMA, especially in African American patients where malignant HTN is known to happen more commonly, and to notice the subtle hints that may help in this distinction, such as profound hemolysis or thrombocytopenia out of proportion to what one would expect from mHTN alone. Early recognition of aHUS may save a patient's kidney. Disclosures No relevant conflicts of interest to declare.

scholarly journals Thrombotic Microangiopathy with Complement Factor H Gene Mutations Unassociated with Atypical Hemolytic Uremic Syndrome

2015 ◽  
Vol 32 (3) ◽  
pp. 275-276
Author(s):  
Yesim Oymak ◽  
Tuba Hilkay Karapınar ◽  
Yılmaz Ay ◽  
Esin Özcan ◽  
Neryal Müminoğlu ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Thrombotic Microangiopathy ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Gene Mutations ◽  
Factor H ◽  
Complement Factor H ◽  
Complement Factor ◽  
H Gene ◽  
Uremic Syndrome

scholarly journals Atypical Hemolytic Uremic Syndrome Presenting as Acute Heart Failure—A Rare Presentation: Diagnosis Supported by Skin Biopsy

2019 ◽  
Vol 7 ◽  
pp. 232470961984290
Author(s):  
Asim Kichloo ◽  
Savneek Singh Chugh ◽  
Sanjeev Gupta ◽  
Jay Pandav ◽  
Praveen Chander
Keyword(s):  
Heart Failure ◽  
Skin Biopsy ◽  
Hemolytic Uremic Syndrome ◽  
Thrombotic Microangiopathy ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Systolic Heart Failure ◽  
Kidney Injury ◽  
Rare Presentation ◽  
History Of ◽  
Uremic Syndrome

Atypical hemolytic uremic syndrome (aHUS) is a rare disorder of uncontrolled complement activation that manifests classically as anemia, thrombocytopenia, and renal failure, although extrarenal manifestations are observed in 20% of the patient most of which involving central nervous system, with relatively rare involvement of the heart. In this article, we report the case of a 24-year-old male with no history of heart disease presenting with acute systolic heart failure along with microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Given his presentation of thrombotic microangiopathy (TMA), along with laboratory results significant for low haptoglobin, platelets, hemoglobin, C3, C4, CH50, and normal ADAMTS13 levels, with no diarrhea and negative STEC polymerase chain reaction in stool, aHUS diagnosis was established with strong clinical suspicion, and immediate initiation of treatment was advised. Kidney biopsy to confirm diagnosis of aHUS was inadvisable because of thrombocytopenia, so the skin biopsy of a rash on his arm was done, which came to be consistent with thrombotic microangiopathy. Our case highlights a relatively rare association between aHUS and cardiac involvement, and the use of skin biopsy to support diagnosis of aHUS in patients who cannot undergo renal biopsy because of thrombocytopenia.

Atypical hemolytic uremic syndrome and pre-eclampsia: cause or effect?

2021 ◽  
Vol 20 (4) ◽  
pp. 55-63
Author(s):  
Yu.V. Korotchaeva ◽  
◽  
N.L. Kozlovskaya ◽  
E.M. Shifman ◽  
V.M. Guryeva ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Thrombotic Microangiopathy ◽  
Comparison Group ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Complete Recovery ◽  
Multiple Organ ◽  
Control Group ◽  
Early Postpartum ◽  
Organ Failures ◽  
Uremic Syndrome

Objective. To study the risk factors for transformation of pre-eclampsia (PE) into atypical hemolytic uremic syndrome (aHUS). Patients and methods. The study included 102 patients with PE, who were divided into two groups. The main group consisted of 59 women with PE and aHUS in the early postpartum period. In the comparison group, there were 43 patients who previously had severe PE, which was not complicated by the development of aHUS. Results. The complications associated with severe PE such as hemorrhage (76.3% vs 48.8%, p = 0.004), placental abruption (33.9% vs 6.9%, p = 0.001), and intrauterine fetal demise (32.2% vs 6.9%, p = 0.002) were significantly more frequent in patients with aHUS compared with the control group. Most of these complications occurred in patients in whom PE lasted more than one week. Also, patients with aHUS had significantly more severe microangiopathic hemolytic anemia (hemoglobin 61.0 [52.5; 73.5] g/L vs 88.0 [73.0; 104.0] g/L, p < 0.001, lactate dehydrogenase 2846.0 [1340.5; 5037.5] IU/L vs 801.0 [497.0; 1269.0] IU/L, p < 0.001), thrombocytopenia (49.5 [31.0; 71.5] K/μL vs 67.0 [43.0; 108.0] K/μL, p = 0.002), hypercreatininemia (424.5 [281.0; 605.0] μmol/L vs 99.0 [86.0; 134.0] μmol/L, p < 0.001) and more severe multiple organ dysfunction syndrome (average number of organ failures – 3.58 vs 1.88, p < 0.001). Among patients with aHUS, complete recovery of renal function was achieved in 42 (71.2%) of 59 women, 9 (15.2%) of 59 women remained on hemodialysis, 8 (13.6%) of 59 women died. In the comparison group, all women showed positive dynamics within 72 hours after childbirth with normalization of all clinical and laboratory parameters. Conclusion. PE itself is a risk factor for the development of aHUS, and patients with severe PE should be considered at high risk for thrombotic microangiopathy. Prolongation of pregnancy in patients with PE increases the risk of developing aHUS by 5 times. Key words: pre-eclampsia, pregnancy-associated atypical hemolytic uremic syndrome, pregnancy, thrombotic microangiopathy, eculizumab

The HLA-DRB1*11 Antigen Is Preferentially Expressed in Hairy Cell Leukemia, Particularly in Patients Who Had Hemolytic Uremic Syndrome with Recombinant Immunotoxin BL22.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2488-2488
Author(s):  
Evgeny Arons ◽  
Laura Roth ◽  
Sharon Adams ◽  
Jeffery Sapolsky ◽  
Ira Pastan ◽  
...  
Keyword(s):  
B Cell ◽  
Hemolytic Uremic Syndrome ◽  
Thrombotic Microangiopathy ◽  
Hairy Cell Leukemia ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Potential Marker ◽  
Recombinant Immunotoxin ◽  
Uremic Syndrome ◽  
Grade 3

Abstract Abstract 2488 Hairy cell leukemia (HCL) is a B-cell malignancy which is thought to originate in most patients after the B-cell contacts antigen. To determine whether certain HLA types are preferentially expressed in HCL, HLA class I and class II allele frequencies at low resolution were collected from 247 HCL patients including 233 Caucasian, 5 Black, 5 Hispanic, 2 Asian and 2 Hawaiian/Pacific Islanders. Out of 494 total alleles from the 247 patients, the most frequent were HLA-A*02 (145, 29%), HLA-B*07 (58, 12%), HLA-C*07 (141, 29%), and HLA-DRB1*11 (76, 15%). In comparison with normal donors, only HLA-DRB1*11 was preferentially expressed in HCL, with a population frequency among the 233 Caucasians of 70 (30%), compared to 17% of a database of USA Caucasians (n=61655, p<0.0001) and 12–21% in 8 other smaller USA Caucasian databases (n=194–8525, p=0.01, 0.005, p<0.0001 for 6 others). Because it was recently reported that HLA-DRB1*11 is a strong risk factor for acquired ADAMTS13 deficiency-related thrombotic microangiopathy, HCL patients who had hemolytic uremic syndrome (HUS) after anti-CD22 recombinant immunotoxin BL22 were examined for HLA expression at the DRB1 locus. BL22 was previously reported to be associated in HCL with a 12% risk of completely reversible grade 3–4 HUS mainly during the 2nd or 3rd retreatment cycle. We found that of 49 HCL patients treated with at least 2 cycles of BL22, most (71%) of 7 HCL patients with HUS expressed HLA-DRB1*11, compared to only 21% of 42 without HUS (p=0.015). Even when considering all 66 evaluable HCL patients who received BL22, including the 17 who received just 1 cycle, expression of HLA-DRB1*11 was more frequent in those with compared to without HUS (63% of 8 vs 24% of 58 patients, p=0.038). In the poor-prognosis variant of HCL, termed HCLv, we found that the most common HLA-DRB1 gene expressed was HLA-DRB1*04, found in 19 (56%) of 34 patients, compared to 30% of the normal USA Caucasian database (n=61655, p=0.002) and 27–37% in the 8 smaller databases mentioned above (p values 0.016 and 0.001–0.01). HLA-DRB1*04 expression was recently reported to be significantly reduced in patients with idiopathic thrombotic microangiopathy. In BL22-associated HUS in HCL, DRB1*04 expression was not increased and none had HCLv. Moxetumomab pasudotox, an affinity-matured version of BL22, binds with 14-fold higher affinity to CD22 due to mutations in the CDR3 domain of the heavy chain, and was recently reported in 28 HCL patients to be associated with only 2 cases of transient grade 2 HUS, defined as grade 1 creatinine and platelet abnormalities. No HUS was observed in 20 additional HCL patients treated. Despite the similarity in the population incidences of HLA-DRB1*11 in those receiving moxetumomab pasudotox and BL22 (35% vs 29%), the grade 3–4 HUS risk was significantly lower with moxetumomab pasudotox than with BL22 (p=0.02). We conclude that 1) HLA-DRB1*11 is preferentially expressed in HCL, 2) HLA-DRB1*04 is preferentially expressed in HCLv, and 3) HLA-DRB1*11 constitutes a potential marker in HCL for susceptibility to HUS from BL22, but not from moxetumomab pasudotox, possibly because the latter molecule binds more specifically to CD22 and avoids HUS. Disclosures: Off Label Use: BL22 and Moxetumomab Pasudotox are experimental agents for CD22+ malignancies. Pastan:NIH: Coinventor on NIH patents for BL22 and Moxetumomab, Coinventor on NIH patents for BL22 and Moxetumomab Patents & Royalties. Kreitman:NIH: Coinventor on NIH patents for BL22 and Moxetumomab, Coinventor on NIH patents for BL22 and Moxetumomab Patents & Royalties.

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