Thrombotic Microangiopathy: An Under-Recognized Cause of CKD Following Viper Envenomation.
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ABSTRACT:
SUBMITTER: Arora S
PROVIDER: S-EPMC9171703 | biostudies-literature | 2022 Jun
REPOSITORIES: biostudies-literature
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Thrombotic Microangiopathy: An Under-Recognized Cause of CKD Following Viper Envenomation.
Arora Sahil S Ramachandran N N Srinivas Bheemanathi Hanuman BH Rajesh Nachiappa Ganesh NG Parameswaran Sreejith S Priyamvada P S PS
Kidney international reports 20220425 6
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Project description:Methylmalonic aciduria and homocystinuria, cobalamin C (cblC) type, is the most common genetic type of functional cobalamin (vitamin B12) deficiency. This metabolic disease is characterized by marked heterogeneity of neurocognitive disease (microcephaly, seizures, developmental delay, ataxia, hypotonia) and variable extracentral nervous system involvement (failure to thrive, cardiovascular, renal, ocular) manifesting predominantly early in life, sometimes during gestation. To enhance awareness and understanding of renal disease associated with cblC defect, we studied biochemical, genetic, clinical, and histopathological data from 36 patients. Consistent clinical chemistry features of renal disease were intravascular hemolysis, hematuria, and proteinuria in all patients, with nephrotic-range proteinuria observed in three. Renal function ranged from normal to renal failure, with eight patients requiring (intermittent) dialysis. Two thirds were diagnosed with atypical (diarrhea-negative) hemolytic uremic syndrome (HUS). Renal histopathology analyses of biopsy samples from 16 patients revealed glomerular lesions typical of thrombotic microangiopathy (TMA). Treatment with hydroxycobalamin improved renal function in the majority, including three in whom dialysis could be withdrawn. Neurological sequelae were observed in 44 % and cardiopulmonary involvement in 39 % of patients, with half of the latter group demonstrating pulmonary hypertension. Mortality reached 100 % in untreated patients and 79 and 56 % in those with cardiopulmonary or neurological involvement, respectively. In all patients presenting with unclear intravascular hemolysis, hematuria, and proteinuria, cblC defect should be ruled out by determination of blood/plasma homocysteine levels and/or genetic testing, irrespective of actual renal function and neurological status, to ensure timely diagnosis and treatment.
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Project description:The Green Bush Viper, Atheris squamigera, is native to West and Central Africa and has few well reported envenomations. Bite victims experience dizziness, nausea, headache, regional lymphadenopathy, and localized edema. Most reports also detail severe effects including thrombocytopenia, coagulopathy, hemolysis, hemorrhage, or renal failure. Fatalities are reported, but poorly described. There is no specific antivenom for A. squamigera, but non-species specific antivenom has been reported helpful in several cases. We report the case of a 36-year-old woman who was bitten by a green bush viper and was treated with several non-species specific antivenoms. There were no complications to antivenom administration and the patient experienced a milder envenomation than detailed in previous reports. Graphical Abstract ga1 Highlights • The Green Bush Viper has no specific antivenom and envenomation is poorly reported.• Local and systemic effects can be seen. Multi-organ failure and severe bleeding reported.• Echis antivenoms are reported helpful, but early administration has not previously been reported.
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Project description:The syndrome of thrombotic microangiopathy (TMA) is a clinical-pathological entity characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end organ involvement. It comprises a spectrum of underlying etiologies that may differ in children and adults. In children, apart from ruling out shigatoxin-associated hemolytic uremic syndrome (HUS) and other infection-associated TMA like Streptococcus pneumoniae-HUS, rare inherited causes including complement-associated HUS, cobalamin defects, and mutations in diacylglycerol kinase epsilon gene must be investigated. TMA should also be considered in the setting of solid organ or hematopoietic stem cell transplantation. In this review, acquired and inherited causes of TMA are described with a focus on particularities of the main causes of TMA in children. A pragmatic approach that may help the clinician tailor evaluation and management is provided. The described approach will allow for early initiation of treatment while waiting for the definitive diagnosis of the underlying TMA.
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Project description:ObjectivesAcute kidney injury (AKI) following surgery involving the heart-lung-machine is associated with high mortality and morbidity. In addition to the known mechanisms, thrombotic microangiopathy (TMA) triggered by the dysregulation of complement activation was recently described as another pathophysiological pathway for AKI following aortic surgery. The aim of this retrospective study was to analyse incidence, predictors and outcome in these patients.MethodsBetween January 2018 and September 2019, consecutive patients undergoing aortic surgery requiring hypothermic circulatory arrest were retrospectively reviewed. If suspected, diagnostic algorithm was initiated to identify a TMA and its risk factors, and postoperative outcome parameters were comparably investigated.ResultsThe incidence of TMA in the analysed cohort (n = 247) was 4.5%. Multivariable logistic regression indicated female gender {odds ratio (OR) 4.905 [95% confidence interval (CI) 1.234-19.495], P = 0.024} and aortic valve replacement [OR 8.886 (95% CI 1.030-76.660), P = 0.047] as independent predictors of TMA, while cardiopulmonary bypass, X-clamp and hypothermic circulatory arrest times showed no statistically significance. TMA resulted in postoperative AKI (82%), neurological disorders (73%) and thrombocytopaenia [31 (interquartile range 25-42) G/l], corresponding to the diagnostic criteria. Operative mortality and morbidity were equal to patients without postoperative TMA, despite a higher incidence of re-exploration for bleeding (27 vs 6%; P = 0.027). After 6 months, survival, laboratory parameters and need for dialysis were comparable between the groups.ConclusionsTMA is a potential differential diagnosis for the cause of AKI following aortic surgery regardless of the hypothermic circulatory arrest time. Timely diagnosis and appropriate treatment resulted in a comparable outcome concerning mortality and renal function.
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