Microangiopathy In Patients Research Articles

The association between plasma lipidome and diabetic microangiopathy: a mendelian randomization study.

Current studies have identified severe lipid metabolism diseases in diabetic microangiopathy patients, especially in diabetic kidney disease (DKD), diabetic retinopathy (DR) and diabetic neuropathy (DN), with unclear causal relationships. We employed a large-scale dataset containing 179 lipid species as the exposure and large-scale public summary-level datasets of DKD, DR and DN as the outcome. We applied Mendelian randomization (MR) approach to explore causal associations between circulating liposomes and diabetic microangiopathy. A sequence of sensitivity tests was conducted to verify the stability of the MR analysis. We manifest that diacylglycerol (18:1_18:3) (OR = 0.716, 95%CI = 0.559-0.917, P = 0.008), triacylglycerol (OR:0.741-0.763, P < 0.05) and phosphatidylcholine (OR:0.620-1.247, P < 0.05) have a potential association with DKD. And there is a nominal causal effect of phosphatidylinositol (16:0_18:2) (OR = 0.617, 95%CI = 0.401-0.948, P = 0.028), phosphatidylcholine (OR:0.499-0.672, P < 0.05) and sphingomyelin (OR:0.652-1.850, P < 0.05) to DR. In addition, phosphatidylethanolamine (18:1_0:0) (OR = 0.616, 95%CI = 0.405-0.935, P = 0.023), diacylglycerol (16:0_18:1) (OR = 0.675, 95%CI = 0.463-0.984, P = 0.041) and phosphatidylcholine (OR = 0.720-1.619, P < 0.05) nominally associate with DN. It is noteworthy that plasma lipidome of different structures show different effects. We establish a possible causal connection between certain plasma lipidome and major diabetic microangiopathies. Implementing intervention strategies targeting different lipid molecules may provide novel approaches for preventing and treating diabetic microangiopathies.

Clinical characteristics and genetic profile of complement system in renal thrombotic microangiopathy in patients with severe forms of arterial hypertension

The spectrum of diseases characterized by the development of renal thrombotic microangiopathy (TMA) encompasses the malignant hypertension (MHT). TMA in MHT has conventionally been regarded as a variation of secondary TMA, the treatment of which is restricted to the stabilization of blood pressure levels, a measure that frequently fails to prevent the rapid progression to end-stage renal disease in patients. Nevertheless, there exists a rationale to suggest that, in certain instances, endothelial damage in MHT might be rooted in the dysregulation of the complement system (CS), thereby presenting potential opportunities for the implementation of complement-blocking therapy. To study clinical manifestations and genetic profile of CS in patients with morphologically confirmed renal TMA combined with severe AH. 28 patients with morphologically verified renal TMA and severe AH were enrolled to the study. Patients with signs of microangiopathic hemolysis and thrombocytopenia were not included in the study due to possible compliance with the criteria for atypical hemolytic uremic syndrome (aHUS). The prevalence of rare genetic defects (GD) of the CS was assessed by molecular genetic analysis (search for mutations in the clinically significant part of the human genome - exome) by next-generation sequencing technology (NGS). GD of CS were detected in a quarter of patients. Rare genetic variants classified as "likely pathogenic" including defects in CFI, C3, CD46, CFHR4, CFHR5 genes were detected in five cases. Two patients were found to have chromosomal deletions containing CFH-related proteins genes (CFHR1, CFHR3). Rare variants of CS genes linked to aHUS were found in 25% of patients with renal TMA, the genesis of which was originally thought to be secondary and attributed to MHT, with partial or complete absence of hematological manifestations of microangiopathic pathology. The key to confirming TMA associated with MHT, particularly in the absence of microangiopathic hemolysis and thrombocytopenia, elucidating its nature, and potentially effective complement-blocking therapy in patients with GD of CS, appears to be a genetic study of CS combined with a morphological study of a renal biopsy.

Early increase in HbA1c trajectory predicts development of severe microangiopathy in patients with type 1 diabetes: the VISS study

IntroductionTo study the HbA1c trajectory from the time of diagnosis to examine if patients at the greatest risk for severe microangiopathy can be identified early allowing clinicians to intervene as...

Endoscopic manifestation of intestinal transplant-associated microangiopathy after stem cell transplantation

BackgroundEndoscopic features of intestinal transplant-associated microangiopathy (iTAM) have not been comprehensively investigated. This study aimed to examine the endoscopic characteristics of patients diagnosed with iTAM.MethodsThis retrospective analysis included 14 patients pathologically diagnosed with iTAM after stem cell transplantation for hematolymphoid neoplasms (n = 13) or thalassemia (n = 1). The sex, age at diagnosis, endoscopic features, and prognosis of each patient were assessed. Serological markers for diagnosing transplant-associated thrombotic microangiopathy were also evaluated.ResultsThe mean age at the time of iTAM diagnosis was 40.2 years. Patients diagnosed based on the pathognomonic pathological changes of iTAM presented with diverse symptoms at the times of endoscopic examinations, including diarrhea (n = 10), abdominal pain (n = 5), nausea (n = 4), appetite loss (n = 2), bloody stools (n = 2), abdominal discomfort (n = 1), and vomiting (n = 1). At the final follow-up, six patients survived, while eight patients succumbed, with a median time of 100.5 days (range: 52–247) post-diagnosis. Endoscopic manifestations included erythematous mucosa (n = 14), erosions (n = 13), ulcers (n = 9), mucosal edema (n = 9), granular mucosa (n = 9), and villous atrophy (n = 4). Erosions and/or ulcers were primarily observed in the colon (10/14, 71%), followed by the ileum (9/13, 69%), stomach (4/10, 40%), cecum (5/14, 36%), duodenum (3/10, 30%), rectum (4/14, 29%), and esophagus (1/10, 10%). Cytomegalovirus infection (n = 4) and graft-versus-host disease (n = 2) coexisted within the gastrointestinal tract. Patients had de novo prolonged or progressive thrombocytopenia (6/14, 43%), decreased hemoglobin concentration (4/14, 29%), reduced serum haptoglobin level (3/14, 21%), and a sudden and persistent increase in lactate dehydrogenase level (2/14, 14%). Peripheral blood samples from 12 patients were evaluated for schistocytes, with none exceeding 4%.ConclusionsThis study provides a comprehensive exploration of the endoscopic characteristics of iTAM. Notably, all patients exhibited erythematous mucosa throughout the gastrointestinal tract, accompanied by prevalent manifestations, such as erosions (93%), ulcers (64%), mucosal edema (64%), granular mucosa (64%), and villous atrophy (29%). Because of the low positivity for serological markers of transplant-associated thrombotic microangiopathy in patients with iTAM, endoscopic evaluation and biopsy of these lesions are crucial, even in the absence of these serological features.

Hydroxychloroquine Use is Associated with Decreased Prevalence of Cerebral Microangiopathy in Patients with Systemic Lupus Erythematosus (S34.006)

Hydroxychloroquine Use is Associated with Decreased Prevalence of Cerebral Microangiopathy in Patients with Systemic Lupus Erythematosus (S34.006)

Сhemotherapy-provoked thrombotic microangiopathy in ovarian cancer patient with APS

The article analyzes a clinical case of the development of thrombotic microangiopathy in a patient with ovarian cancer during chemotherapy, which manifested in the form of renal failure. An analysis of laboratory and biochemical findings is given, which were initially incorrectly interpreted and only a kidney biopsy made it possible to make a correct diagnosis and begin pathogenetic treatment. Cancer patients are at increased risk for developing secondary TMA, which requires increased attention to symptoms uncharacteristic of the underlying disease.

Assessment of Retinal Microangiopathy in Patients with Balkan Endemic Nephropathy Using Optical Coherence Tomography Angiography-A Pilot Study.

Background and Objectives: It is well known that alterations in microvascular structure and function contribute to the development of ocular, renal, and cardiovascular diseases. Accordingly, the presence of fundus vascular changes in patients suffering from chronic kidney disease (CKD) and Balkan endemic nephropathy (BEN) may provide information of prognostic value regarding the progression of renal disease. This study aimed to examine the associations between clinical characteristics and retinal optical coherence tomography angiography (OCTA) parameters in patients with BEN and compare them with those in CKD. Materials and Methods: This pilot study, conducted from March 2021 to April 2022, included 63 patients who were divided into two groups: the first group consisted of 29 patients suffering from BEN, and the second was a control group of 34 patients with CKD. Demographic, laboratory, clinical, and medication data were noted for all the patients included in this study. Each eye underwent OCT angiography, and the results were interpreted in accordance with the practical guide for the interpretation of OCTA findings. Results: Statistically significantly higher levels of total serum protein and triglycerides were recorded in the BEN group than in the CKD group, while the level of HDL cholesterol was lower. Based on the performed urinalysis, statistically significantly higher values of total protein and creatinine were detected in patients with CKD compared to the BEN group. It was demonstrated that the OCTA vascular plexus density of certain parts of the retina was in significant association with systolic and diastolic blood pressure, creatinine clearance, urinary creatinine, total cholesterol, diabetes mellitus type 2, age, body mass index, total serum and urinary protein, sCRP, and diuretic and antihypertensive treatment. Conclusions: In comparison with CKD, BEN leads to more significant disturbances in retinal vasculature density.

Differential contributions of the C5b-9 and C5a/C5aR pathways to microvascular and macrovascular thrombosis in complement-mediated thrombotic microangiopathy patients

To clarify the role of the C5a/C5aR (C5a receptor) and C5b-9 pathways in macrovascular thrombosis (MAT) and renal microthrombosis (MIT), 73 renal biopsy-proven complement-mediated thrombotic microangiopathy (C-TMA) patients were enrolled; 9 patients with pure MAT and 13 patients with pure MIT were selected for further study. Twenty-five external C-TMA patients were selected as the validation cohort. Plasma C5a and sC5b-9 (soluble C5b-9) levels were significantly higher in patients with MAT than in those with MIT (P = 0.008, P = 0.041, respectively). The mean optical density of C5aR1 in the kidney was significantly higher in MAT patients than in those with MIT (P < 0.001). Both urinary sC5b-9 levels (MIT: P < 0.001, MAT: P = 0.004) and renal deposition of C5b-9 (MIT: P < 0.001, MAT: P = 0.001) were significantly higher in C-TMA patients compared to normal control, but were similar between MAT and MIT groups. In the correlation analysis within 22C-TMA patients, urinary sC5b-9 levels and renal deposition of C5b-9 were positively correlated to renal MIT formation (P = 0.009 and P = 0.031, respectively). Furthermore, the renal citrullinated histone H3 (CitH3)- and neutrophil elastase (NE)-positive area ratios were both significantly higher in the MAT group than in the MIT group (P = 0.006 and P = 0.020, respectively). Therefore, the local C5b-9 and C5a/C5aR1 pathways might have differential contributions to MIT and MAT formation in the disease.

Diagnostic Methods of Premature phenomena of Diabetic Microangiopathy in Patients with Diabetes Mellitus Type 2

Type 2 diabetes mellitus belongs to the risk factors for the development of cardiovascular diseases, which are currently the main cause of early disability and mortality in the workingage population. According to Panzram G., diabetes mellitus increases mortality 2-3 times, the risk of coronary heart disease and myocardial infarction - 2 times, kidney pathology - 17 times, gangrene of the lower extremities - 20 times, arterial hypertension - more than three times.

Assessment of early macular microangiopathy in subjects with prediabetes using optical coherence tomography angiography and fundus photography.

Early detection of retinal microangiopathy in patients with prediabetes may reduce diabetic retinopathy complications. The aim of this study was to assess early macular vascular changes in prediabetics before development of over diabetes using OCTA and fundus photography. In this cross-sectional study, 66 prediabetic individuals and 66 normal controls underwent clinical, laboratory, and fundus photography evaluation followed by OCTA macular imaging to examine for the foveal avascular zone, and area of capillary non-perfusion, thickness, disorganization of vessels, and vessel density perfusion percentage of superficial capillary plexus and deep capillary plexus. Retinal microangiopathy was detected in 36.4% of prediabetics by OCTA and only in 10.6% by fundus photography. None of clinical or laboratory parameters had significant association with DR. Area of capillary non-perfusion and disorganization of SCP were detected in 53.8% and 56.8%, respectively, in prediabetics. VDP of SCP and DCP of whole image, parafoveal, and perifoveal areas was significantly lower in prediabetes group compared to normal control. VDP of DCP of perifoveal area (β coefficient: - 0.10, OR: 0.91, 95% CI: 0.86-0.96, P < 0.001) and disorganization of DCP (β coefficient: 1.93, OR: 6.89, 95% CI: 2.5-18.8, P < 0.001) were significant predictors of DR in prediabetics. There was no difference in FAZ in prediabetics with and without retinopathy. OCTA could detect early retinal vascular changes during the prediabetic state before developing diabetes. VDP was significantly reduced in prediabetic patients. Furthermore, VDP of DCP of perifoveal area and disorganization of DCP were the most important predictors of retinopathy in prediabetic patients.

Clinical and Translational Imaging and Sensing of Diabetic Microangiopathy: A Narrative Review.

Microvascular changes in diabetes affect the function of several critical organs, such as the kidneys, heart, brain, eye, and skin, among others. The possibility of detecting such changes early enough in order to take appropriate actions renders the development of appropriate tools and techniques an imperative need. To this end, several sensing and imaging techniques have been developed or employed in the assessment of microangiopathy in patients with diabetes. Herein, we present such techniques; we provide insights into their principles of operation while discussing the characteristics that make them appropriate for such use. Finally, apart from already established techniques, we present novel ones with great translational potential, such as optoacoustic technologies, which are expected to enter clinical practice in the foreseeable future.

13 Differential contributions of C5b-9 and C5a/C5aR pathways to microvascular and macrovascular thrombosis in complement-mediated thrombotic microangiopathy patients

13 Differential contributions of C5b-9 and C5a/C5aR pathways to microvascular and macrovascular thrombosis in complement-mediated thrombotic microangiopathy patients

Mechanistic Implications of Cortical Superficial Siderosis in Patients With Mixed Location Intracerebral Hemorrhage and Cerebral Microbleeds.

Hypertensive cerebral small vessel disease (HTN-cSVD) is the predominant microangiopathy in patients with a combination of lobar and deep cerebral microbleeds (CMBs) and intracerebral hemorrhage (mixed ICH). We tested the hypothesis that cerebral amyloid angiopathy (CAA) is also a contributing microangiopathy in patients with mixed ICH with cortical superficial siderosis (cSS), a marker strongly associated with CAA. Brain MRIs from a prospective database of consecutive patients with nontraumatic ICH admitted to a referral center were reviewed for the presence of CMBs, cSS, and nonhemorrhagic CAA markers (lobar lacunes, centrum semiovale enlarged perivascular spaces [CSO-EPVS], and multispot white matter hyperintensity [WMH] pattern). The frequencies of CAA markers and left ventricular hypertrophy (LVH), a marker for hypertensive end-organ damage, were compared between patients with mixed ICH with cSS (mixed ICH/cSS[+]) and without cSS (mixed ICH/cSS[-]) in univariate and multivariable models. Of 1,791 patients with ICH, 40 had mixed ICH/cSS(+) and 256 had mixed ICH/cSS(-). LVH was less common in patients with mixed ICH/cSS(+) compared with those with mixed ICH/cSS(-) (34% vs 59%, p = 0.01). The frequencies of CAA imaging markers, namely multispot pattern (18% vs 4%, p < 0.01) and severe CSO-EPVS (33% vs 11%, p < 0.01), were higher in patients with mixed ICH/cSS(+) compared with those with mixed ICH/cSS(-). In a logistic regression model, older age (adjusted odds ratio [aOR] 1.04 per year, 95% CI 1.00-1.07, p = 0.04), lack of LVH (aOR 0.41, 95% CI 0.19-0.89, p = 0.02), multispot WMH pattern (aOR 5.25, 95% CI 1.63-16.94, p = 0.01), and severe CSO-EPVS (aOR 4.24, 95% CI 1.78-10.13, p < 0.01) were independently associated with mixed ICH/cSS(+) after further adjustment for hypertension and coronary artery disease. Among ICH survivors, the adjusted hazard ratio of ICH recurrence in patients with mixed ICH/cSS(+) was 4.65 (95% CI 1.38-11.38, p < 0.01) compared with that in patients with mixed ICH/cSS(-). The underlying microangiopathy of mixed ICH/cSS(+) likely includes both HTN-cSVD and CAA, whereas mixed ICH/cSS(-) is likely driven by HTN-cSVD. These imaging-based classifications can be important to stratify ICH risk but warrant confirmation in studies incorporating advanced imaging/pathology.

Correlation Between Coronary and Retinal Microangiopathy in Patients With STEMI.

To investigate the morphological and functional correlation between microvascular retinal changes in optical coherence tomography angiography (OCTA) and the microvascular coronary circulation in patients with ST elevation myocardial infarction (STEMI) coronary heart disease (CHD). A total of 330 eyes from 165 participants (88 cases and 77 controls) were enrolled and imaged. Superficial capillary plexus (SCP) and deep capillary plexus (DCP) vascular density was measured in the central (1 mm) and perifoveal (1-3 mm) areas and in the superficial foveal avascular zone (FAZ) and choriocapillaris (3 mm). These parameters were then correlated to the left ventricular ejection fraction (LVEF), and the number of affected coronary arteries. Decreased vessel densities in the SCP and DCP and choriocapillaris were positively correlated to the LVEF values (P = 0.006, P = 0.026, and P = 0.002, respectively). No statistically significant correlation between the SCP and DCP central area or FAZ area was found. Regarding the number of affected vessels, significant negative correlations were revealed for the SCP and DCP central vessel densities (P < 0.001 and P < 0.001, respectively) and the SCP perifoveal vascular density (P = 0.009). OCTA vascular indices are significantly correlated with morphological and functional parameters in patients with STEMI CHD. SCP vascular density especially seems to be a promising biomarker for the extent of both macrovascular damage (number of affected coronary arteries) and microvascular damage, as mirrored in the decreased LVEF at admission. OCTA vascular indices offer a valuable insight into the microvascular status of coronary circulation.

Genetic, clinical, and pathological study of patients with severe hypertension-associated renal microangiopathy.

Severe hypertension may be a prominent manifestation of complement-mediated thrombotic microangiopathy. Furthermore, patients with severe hypertension-associated thrombotic microangiopathy may present with concurrent hematologic abnormalities that mimic complement-mediated thrombotic microangiopathy. Whether or not severe hypertension-associated thrombotic microangiopathy is associated with genetic susceptibility in complement- and/or coagulation-pathway genes remains unclear, and there is thus a need to identify clinicopathological clues to distinguish between these entities. Forty-five patients with concomitant severe hypertension and thrombotic microangiopathy on kidney biopsy were identified retrospectively. Whole-exome sequencing was performed to identify rare variants in 29 complement- and coagulation-cascade genes. Clinicopathological features were compared between patients with severe hypertension-associated thrombotic microangiopathy and complement-mediated thrombotic microangiopathy with severe hypertension. Three patients with pathogenic variants diagnostic of complement-mediated thrombotic microangiopathy and two with anti-factor H antibody positivity were diagnosed with complement-mediated thrombotic microangiopathy with severe hypertension. Among the 40 patients with severe hypertension-associated thrombotic microangiopathy, 53 rare variants of uncertain significance were found in the analyzed genes in 34 (34/40, 85%) patients, of whom 12 patients harbored two or more variants. Compared with complement-mediated thrombotic microangiopathy patients with severe hypertension, patients with severe hypertension-associated thrombotic microangiopathy were more likely to have left ventricular wall thickening (p < 0.001), less-severe acute glomerular thrombotic microangiopathy lesions including mesangiolysis and subendothelial space widening (both p < 0.001), and less arteriolar thrombosis formation (p < 0.001). Rare genetic variants involving complement and coagulation pathways can be found in patients with severe hypertension-associated thrombotic microangiopathy; their role needs further investigation. Cardiac remodeling and acute glomerular TMA lesions may help to differentiate between severe hypertension-associated thrombotic microangiopathy and complement-mediated thrombotic microangiopathy with severe hypertension.

Influence of Cortical Superficial Siderosis in Patients with Mixed Location Cerebral Microbleeds and Intracerebral Hemorrhage (S36.006)

Influence of Cortical Superficial Siderosis in Patients with Mixed Location Cerebral Microbleeds and Intracerebral Hemorrhage (S36.006)

Abstract WP118: Mechanistic Implications Of Cortical Superficial Siderosis In Patients With Mixed Location Intracerebral Hemorrhage And Cerebral Microbleeds

Introduction: Hypertensive cerebral small vessel disease (HTN-cSVD) is the predominant microangiopathy in patients with a combination of lobar and deep cerebral microbleeds (CMBs) and intracerebral hemorrhage (mixed ICH/CMB). We tested the hypothesis that cerebral amyloid angiopathy (CAA) is also a contributing microangiopathy in mixed ICH/CMB patients with cortical superficial siderosis (cSS), a marker that is strongly associated with CAA. Methods: Brain MRIs from a prospective database of consecutive non-traumatic ICH patients admitted to a single referral center (2003 to 2019) were reviewed for the presence of CMBs, cSS, and non-hemorrhagic CAA markers (lobar lacunes, centrum semiovale enlarged perivascular spaces (CSO-EPVS), and multispot pattern of leukoaraiosis). The frequency of CAA markers and left ventricular hypertrophy (LVH), a marker for hypertensive end-organ damage, were compared between mixed ICH/CMB patients with cSS (mixed +cSS ) and without cSS (mixed -cSS ) in univariate and multivariate models. Results: Of the 1824 ICH patients, 40 had mixed +cSS and 256 had mixed -cSS . LVH was less common in patients with mixed +cSS compared to those with mixed -cSS (34% vs. 59%, p = 0.01). The frequency of multispot pattern (18% vs. 4%, p &lt; 0.01) and severe CSO-EPVS (33% vs. 11%, p &lt; 0.01) were higher in patients with mixed +cSS compared to mixed -cSS , whereas lobar lacune frequency was similar (23% vs. 20%, p = 0.67). In a logistic regression model, older age (aOR 1.04 per year, 95% CI [1.01-1.08], p = 0.01), presence of multispot pattern (aOR 5.82, 95% CI [1.82-18.60], p &lt; 0.03), severe CSO-EPVS (aOR 4.08, 95% CI [1.73-9.61], p &lt; 0.01), and LVH (aOR 0.43, 95% CI [0.20-0.94], p = 0.03) were independently associated with mixed +cSS after further adjustment for sex and hypertension (Table). Conclusions: CAA and HTN-cSVD appear to confer injury in patients with mixed ICH/CMB and cSS, a finding that warrants confirmation in studies incorporating advanced imaging/pathology.

Capillaroscopic diagnostics of diabetic microangiopathy using artificial neural networks in patients with diabetes mellitus

Background. The widespread prevalence of diabetes and the progressive deterioration of health against the background of this disease substantiate the need for the use of new methods for the early diagnosis of diabetic microangiopathies. The combined use of digital capillaroscopy and deep learning technologies will significantly improve the quality and speed of microvascular disorders diagnostics.&#x0D; Aim. Development of a system for assessing capillary images based on artificial neural networks, as well as its testing for the early diagnosis of microangiopathy in patients with diabetes mellitus.&#x0D; Material and methods. 136 patients (59 females and 77 males) with type 1 diabetes mellitus aged 25.826.05 years were examined and divided into two groups: the first group included 65 (47.8%) patients who had no symptoms of diabetic microangiopathies, the second group 71 (52.2%) patients who were diagnosed with one or more diabetic microangiopathies. The control group consisted of 30 practically healthy volunteers. All patients with diabetes melitus, as well as individuals from the control group, underwent сapillaroscopic examination. The resulting images were analyzed using the developed evaluation system based on artificial neural networks. Statistical data processing was performed using the Student and MannWhitney tests (U-test), logistic regression analysis, and ROC analysis.&#x0D; Results. In patients with diabetes mellitus, there was a decrease in the capillary network density in both groups and the diameter of the arterial sections in the second group. Capillaroscopy using the developed system showed a sufficient level of significance (2=21, p=0.000), high sensitivity (71.43%) and specificity (85.71%). This method can be used in the diagnosis of microangiopathy in diabetic patients.&#x0D; Conclusion. The combined use of capillaroscopy and neural networks allows to increase the speed and quality of the examination, as well as simplify the interpretation of the resulting images.

Thrombotic microangiopathy in patients with malignant hypertension.

Thrombotic microangiopathy (TMA) is a complication of malignant hypertension (mHTN) attributed to high blood pressure (BP). However, no studies have investigated in patients with mHTN of different aetiologies whether the presence of TMA is associated with specific causes of mHTN. We investigated the presence of TMA (microangiopathic haemolytic anaemia and thrombocytopenia) in a large and well-characterized cohort of 199 patients with mHTN of different aetiologies [primary HTN 44%, glomerular diseases 16.6%, primary atypical haemolytic uraemic syndrome (aHUS) 13.1%, renovascular HTN 9.5%, drug-related HTN 7%, systemic diseases 5.5%, endocrine diseases 4.5%]. Outcomes of the study were kidney recovery and kidney failure. Patients with TMA [40 cases (20.1%)] were younger, were more likely female and had lower BP levels and worse kidney function at presentation. Their underlying diseases were primary aHUS (60%), drug-related mHTN (15%), glomerular diseases [all of them immunoglobulin A nephropathy (IgAN); 10%], systemic diseases (10%) and primary HTN (5%). The presence of TMA was 92.3% in primary aHUS, 42.9% in drug-related HTN, 36.4% in systemic diseases, 12.1% in glomerular diseases and 2.3% in primary HTN. No patient with renovascular HTN or mHTN caused by endocrine diseases developed TMA, despite BP levels as high as patients with TMA. A higher proportion of TMA patients developed kidney failure as compared with patients without TMA (56.4% versus 38.9%, respectively). The presence of TMA in patients with mHTN should guide the diagnosis towards primary aHUS, drug-related mHTN, some systemic diseases and IgAN, while it is exceptional in other causes of mHTN.

Mild forms of thrombotic microangiopathy in patients with advanced pancreatic cancer receiving gemcitabine and nab-paclitaxel.

Thrombotic microangiopathy (TMA) is an uncommon complication that may occur in cancer patients usually as an expression of cancer-associated coagulopathy or due to drug-related toxicity. The clinical spectrum of TMA may vary from an incidental laboratory finding in cancer outpatients to potentially severe life-threatening clinical forms with organ involvement requiring prompt recognition and multidisciplinary evaluation. We present the clinical characteristics and outcomes of four patients with advanced pancreatic cancer with acute non-immune intravascular haemolysis compatible with microangiopathic acute haemolytic anaemia associated with mild thrombocytopenia during long-term gemcitabine and nab-paclitaxel treatment. Abnormal blood parameters (all four cases) and renal involvement (one case) were reversed with a conservative approach and chemotherapy discontinuation. One patient required a short hospitalization while the other three were managed as outpatients. The rapid reversibility of the blood abnormalities supported gemcitabine dose-related toxicity as the most likely aetiologic mechanism and demonstrates the current challenges in daily long-term cancer survivor care. Clinicians must take into account TMA in the differential diagnosis of acute anaemia with or without thrombocytopenia and organ damage, since adequate recognition and early treatment discontinuation allow effective outpatient management and favourable patient outcomes.