Mechanical Hemolytic Anemia Research Articles

Foot-strike Hemolysis: A Systematic Review of Long-Distance Runners

Foot-strike Hemolysis: A Systematic Review of Long-Distance Runners

#2183 Does thrombotic microangiopathy drive the occurrence and pattern of cerebrovascular disease in malignant hypertension?

Abstract Background and Aims Malignant hypertension (MHT) is characterized by diffuse microvascular damage caused by severe hypertension, often presenting with multiple organ involvement. Cerebrovascular injury, occurring in both acute and chronic forms, stands as a hallmark of the disease, being identified in up to half of patients. Thrombotic microangiopathy (TMA), defined as the association of mechanical hemolytic anemia with thrombocytopenia, also emerges as a frequent complication in MHT patients. However, the potential contribution of TMA to cerebrovascular disease remains unexplored. The secondary objective of this study was to provide a comprehensive description of the patterns of cerebrovascular injury occurring in MHT, with a focus on acute ischemic strokes (AIS). Method We retrospectively assessed the brain MRI of patients admitted to the kidney intensive care unit at Tenon hospital for malignant hypertension during the 2017-2023 period. Brain MRIs were performed on a systematic basis regardless of neurological symptoms and were independently reviewed by two trained specialists in a blinded fashion. Patterns of acute cerebrovascular disease, defined as AIS, intracerebral hematoma (ICH) or posterior reversible encephalopathy syndrome (PRES), were systematically assessed. Number of AIS lesions, their size and localization were recorded. Underlying chronic cerebral small vessel disease (CSVD) was defined as presence of lacunes, white matter hyperintensities, cerebral microbleeds or perivascular spaces. Severity of the chronic cerebrovascular disease was measured using a validated CSVD score. Results A total of 60 patients were admitted for malignant hypertension, with a mean age of 42.9 years. 40 patients (66.7%) presented with severe acute kidney injury. Cerebrovascular disease, either acute or chronic, was found in 42 patients (70.0%). Underlying chronic CSVD was present in 33 patients (55.0%). Acute patterns of injury occurred in 27 patients (45.0%). AIS was the most frequent (33.3%), followed by PRES (21.7%). Only one patient presented with ICH. Among patients with AIS, 14 (70%) presented with multiple simultaneous lesions. Of note, most patients with AIS exhibited diffuse encephalopathy syndrome (60.0%) rather than focal deficit (40.0%). Systemic TMA was present at admission in 34 patients (56.7%). In an exploratory data analysis, presence of AIS on brain MRI was associated with the presence of underlying CVSD (p = 0.013), but not with the presence of TMA at admission (p = 0.79). No association was found between TMA and PRES (p = 0.22). Conclusion Our study confirmed the high incidence of cerebrovascular disease during MHT. Most notably, 1 in 3 patients presented with AIS. TMA did not appear to increase the incidence nor to influence the pattern of brain injury.

Mechanical Hemolytic Anemia Associated With Mitral Valve Repair: A Case Report With Literature Review.

Hemolytic anemia could be caused by several conditions, depending on intrinsic or extrinsic defects of the erythrocyte. The latter group includes mechanical intravascular hemolysis, generally related to malfunctioning prosthetic heart valves or, rarely, heart valves repair. We describe a case of a child with Down syndrome, who developed hemolytic anemia after mitral valve repair. We observed that this condition is a rare complication in pediatrics, with only 7 cases reported in literature. Mechanical hemolysis should always be considered in the differential diagnosis of a new-onset hemolytic anemia, especially in patients with valvular heart disease, undergoing cardiac surgery.

Mechanical hemolytic anemia after mitral valve surgery: a case report

Mechanical hemolytic anemia after mitral valve surgery: a case report

Hemolytic anemia caused by kinked graft 6 months after aortic dissection repair

BackgroundClinically insignificant hemolytic anemia is occasionally a complication of prosthetic valve replacement. However, hemolysis related to kinked grafts is a very rare complication after central repair for acute aortic dissection.Case presentationA 42-year-old man had undergone replacement of the ascending aorta and a root repair for type A aortic dissection 6 months previously. Laboratory data showed mild hemolysis 5 months later, and he began to complain of fatigue on exertion. The serum hemoglobin level reduced to 8.6 g/dL, and lactate dehydrogenase levels increased to 3071 IU/L with gross change in urine color, indicating hemoglobinuria. We diagnosed mechanical hemolytic anemia caused by a kinked graft and planned a repeat operation. The kinked graft was resected and graft-graft anastomosis was performed. Postoperatively, the clinical course was uneventful, and the hemolytic anemia completely resolved.ConclusionWe herein report a case of hemolytic anemia caused by kinking of the graft 6 months after acute aortic dissection repair. The diagnosis was swiftly made, and the patient was successfully managed with redo surgery.

COVID-19 vaccination and Atypical hemolytic uremic syndrome.

COVID-19 vaccination has been associated with rare but severe complications characterized by thrombosis and thrombocytopenia. Here we present three patients who developed de novo or relapse atypical hemolytic uremic syndrome (aHUS) in native kidneys, a median of 3 days (range 2-15) after mRNA-based (Pfizer/BioNTech's, BNT162b2) or adenoviral (AstraZeneca, ChAdOx1 nCoV-19) COVID-19 vaccination. All three patients presented with evident hematological signs of TMA and AKI, and other aHUS triggering or explanatory events were absent. After eculizumab treatment, kidney function fully recovered in 2/3 patients. In addition, we describe two patients with dubious aHUS relapse after COVID-19 vaccination. To assess the risks of vaccination, we retrospectively evaluated 29 aHUS patients (n=8 with native kidneys) without complement-inhibitory treatment, who received a total of 73 COVID-19 vaccinations. None developed aHUS relapse after vaccination. In conclusion, aHUS should be included in the differential diagnosis of patients with vaccine-induced thrombocytopenia, especially if co-occuring with mechanical hemolytic anemia (MAHA) and acute kidney injury (AKI). Still, the overall risk is limited and we clearly advise continuation of COVID-19 vaccination in patients with a previous episode of aHUS, yet conditional upon clear patient instruction on how to recognize symptoms of recurrence. At last, we suggest monitoring serum creatinine (sCr), proteinuria, MAHA parameters, and blood pressure days after vaccination.

March hemoglobinuria progressed to acute kidney injury after kendo practice: a case report

BackgroundMarch hemoglobinuria is caused by a hemolytic mechanism due to transient hematuria after physical exercise which, although rare, may lead to acute kidney injury. We report a case of a patient with march hemoglobinuria induced by kendo, which was diagnosed by the presence of Berlin blue iron staining in the proximal tubules through renal biopsy.Case presentationA 15-year-old male complained of fever (37 °C), general malaise, and nausea after hard kendo sessions. Laboratory findings revealed indirect bilirubin dominant hyperbilirubinemia (total bilirubin 3.8 mg/dL), high lactate dehydrogenase (LDH), and acute kidney injury (serum creatinine: 3.11 mg/dL and estimated glomerular filtration rate: 26 mL/min/1.73m2). Urine test was positive for occult blood but without hematuria. Renal biopsy was performed to clarify the cause of renal injury, which showed minor glomerular abnormalities. Meanwhile, hemosiderin deposition was identified in the proximal tubules by Berlin blue iron staining, and lysosomes were observed to contain granular iron. In addition to clinical background of strenuous kendo exercise, renal biopsy led to a definitive diagnosis of march hemoglobinuria.ConclusionsMarch hemoglobinuria is a hemolytic disease that can occur after intense exercise, especially kendo. Considering its rarity due to the lack of critical symptoms, it is important to note that occult blood-positive findings may be indicative of march hemoglobinuria if the patient underwent strenuous exercise. Therefore, clinicians should be aware of this possibility to provide timely and appropriate treatment.

Prevalence of Iron Deficiency in Endurance Runners: A Cross-Sectional Study of the Detroit Free Press Marathon and Half-Marathon Athletes

Background Iron deficiency, with or without anemia, may be more prevalent in endurance athletes than the general population. Marathon and half-marathon runners, a subset of these endurance athletes, are at risk for iron deficiency via several mechanisms, such as increased demand, foot-strike hemolysis, sweat, and others. The prevalence of iron deficiency among marathon and half-marathon runners in the United States has not been studied. Methods We performed a cross-sectional study to identify the prevalence of iron deficiency in runners participating in the Detroit Free Press Marathon or Half-Marathon on October 17, 2021. Eligible participants were screened at the pre-race expo, at which time they filled out questionnaires and had blood samples taken. The questionnaires included items such as demographic information, exercise and dietary habits, bleeding history, and symptoms. The blood samples were tested the same day for hemoglobin, hematocrit, ferritin, serum iron, total iron binding capacity (TIBC) and iron saturation. Participants received their laboratory results and a $30 Amazon gift card via email for participating. For the purpose of our study, we defined severe iron deficiency as ferritin <15 ng/mL, or ferritin <35ng/mL and iron saturation <16%. This was likely consistent with absent iron storage and similar to previous definitions used in studies examining other endurance athletes. As clinicians, we agreed upon clinical iron deficiency as ferritin <30 ng/mL, or ferritin <100 ng/mL and iron saturation < 20%. This was likely consistent with low iron stores, at-risk iron stores, or iron deficiency in some populations. This definition is also likely to prompt treatment and/or investigation. Data were analyzed using chi-squared analysis, Student's t-test, ANOVA and logistic regression using SPSS v. 28.0. Results Of 277 participants, the mean age was 40.6 ± 13.6 years, and 38.6% (n=107) were male. Most of our participants identified as white (n=219, 79.1%). All participants were residents of the United States; 213 participants (80.1%) were from Michigan. The majority of our participants registered for the half marathon: 185 (66.8%) half marathon, 87 (31.4%) marathon, and three (1.1%) unknown. The prevalence of clinical iron deficiency was significantly higher in females than males, 47.6% versus 15%, respectively (p<0.001). The same trend was found for severe iron deficiency, 14.7% in females vs. 2.8% in males (p=0.001). These results were independent of anemia status. On univariable analysis, factors associated with iron deficiency (clinical and/or severe) included younger age, race entered, history of anemia, heavy menstrual bleeding, blood thinner use, ≥15 hours of exercise per week, restrictive dietary habits, and lightheadedness. For multivariable analysis, we ran separate models by sex (Table). Conclusion Iron deficiency is prevalent in marathon and half-marathon runners and is associated with several risk factors, which differ by sex. Patients who participate in endurance sports and/or training should be screened accordingly. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A Case of Mechanical Hemolytic Anemia due to Aortic Regurgitation Jet Collision with the Mitral Valve Stent-Post

A Case of Mechanical Hemolytic Anemia due to Aortic Regurgitation Jet Collision with the Mitral Valve Stent-Post

Comparative Genomics of Shiga Toxin-Producing Escherichia coli Strains Isolated from Pediatric Patients with and without Hemolytic Uremic Syndrome from 2000 to 2016 in Finland.

ABSTRACTShiga toxin-producing Escherichia coli (STEC) infection can cause mild to severe illness, such as nonbloody or bloody diarrhea, and the fatal hemolytic uremic syndrome (HUS). The molecular mechanism underlying the variable pathogenicity of STEC infection is not fully defined so far. Here, we performed a comparative genomics study on a large collection of clinical STEC strains collected from STEC-infected pediatric patients with and without HUS in Finland over a 16-year period, aiming to identify the bacterial genetic factors that can predict the risk to cause HUS and poor renal outcome. Of 240 STEC strains included in this study, 52 (21.7%) were from pediatric patients with HUS. Serotype O157:H7 was the main cause of HUS, and Shiga toxin gene subtype stx2a was significantly associated with HUS. Comparative genomics and pangenome-wide association studies identified a number of virulence and accessory genes overrepresented in HUS-associated STEC compared to non-HUS STEC strains, including genes encoding cytolethal distending toxins, type III secretion system effectors, adherence factors, etc. No virulence or accessory gene was significantly associated with risk factors for poor renal outcome among HUS patients assessed in this study, including need for and duration of dialysis, presence and duration of anuria, and leukocyte counts. Whole-genome phylogeny and multiple-correspondence analysis of pangenomes could not separate HUS STEC from non-HUS STEC strains, suggesting that STEC strains with diverse genetic backgrounds may independently acquire genetic elements that determine their varied pathogenicity. Our findings indicate that nonbacterial factors, i.e., characteristics of the host immunity, might affect STEC virulence and clinical outcomes.IMPORTANCE Shiga toxin-producing Escherichia coli (STEC) is a serious public health burden worldwide which causes outbreaks of gastrointestinal diseases and the fatal hemolytic uremic syndrome (HUS) characterized by the triad of mechanical hemolytic anemia, thrombocytopenia, and acute renal failure. Understanding the mechanism underlying the disease severity and patient outcome is of high importance. Using comparative genomics on a large collection of clinical STEC strains from STEC-infected patients with and without HUS, our study provides a reference of STEC genetic factors/variants that can be used as predictors of the development of HUS, which will aid risk assessment at the early stage of STEC infection. Additionally, our findings suggest that nonbacterial factors may play a primary role in the renal outcome in STEC-infected patients with HUS; further studies are needed to validate this.

Acute renal failure with severe loin pain and patchy renal vasoconstriction in a patient with march hemoglobinuria.

Acute renal failure (ARF) with severe loin pain and patchy renal vasoconstriction is a rare syndrome described as an anaerobic exercise-induced acute kidney injury (AKI) without rhabdomyolysis. The characteristic computed tomography (CT) finding is multiple patchy wedge-shaped delayed contrast enhancement in the kidney. The syndrome is named as a clinical syndrome of ARF with severe loin pain after anaerobic exercise (ALPE). A 16-year-old Japanese boy was admitted to our hospital for vomiting and severe loin pain after Japanese fencing. He had kidney dysfunction with slightly increased serum creatine phosphokinase and was eventually diagnosed with ALPE based on the characteristic finding on delayed renal CT scans. He had no predisposing factors for ALPE, such as renal hypouricemia or analgesic use prior to the exercise; however, he had pigmenturia at the onset, which is an unusual finding for ALPE. The pigmenturia proved to be hemoglobinuria due to intravascular hemolysis, indicated by increased serum levels of indirect bilirubin and lactate dehydrogenase, an undetectable level of serum haptoglobin, and absence of red blood cells and myoglobin in the urine. The hemolysis following strenuous steps on a hard floor suggested that the phenomenon was march hemoglobinuria. Our patient is the first reported example in which ALPE developed in the setting of hemoglobinuria due to mechanical intravascular hemolysis.

MO163FIFTY-NINE CASES OF CANCER-ASSOCIATED THROMBOTIC MICROANGIOPATHY: TYPICAL PRESENTATION AND TREATMENT

Abstract Background and Aims Thrombotic microangiopathy (TMA) are a heterogeneous group of diseases characterized by mechanical hemolytic anemia, peripheral thrombocytopenia, and organ failure of variable severity. In patients with cancer, TMAs are frequently induced by antineoplastic drugs but may be related to the malignant disease itself. Small series have reported poor prognosis. Only chemotherapy succeeded in lengthening life expectancy, even if few reports have described efficacy of therapeutic plasma exchange (TPE) or Eculizumab. Complement regulation was not studied in these publications, as the pathophysiology was rarely explored. In this study, we investigated retrospectively 59 cases of cancer-associated TMAs, to describe characteristics at diagnosis and efficacy of treatment. Method We conducted a retrospective multicentric observational study including all patients with a diagnosis of cancer-associated TMA, hospitalized in nephrological intensive care units (members of the French Intensive Care Network), between 2008 and 2019. We excluded patients receiving chemotherapy known to cause TMAs. We analyzed clinical and biological characteristics at diagnosis. We reported complement analysis when available. We defined four distinct treatment groups: No treatment (N), Plasmapheresis (P), Chemotherapy with or without chemotherapy (C+P), Eculizumab with or without Chemotherapy or Plasmapheresis (E+C+P). Renal remission and global survival were compared according to treatment group. Results We included 59 patients admitted to intensive care units for cancer-associated TMA. Twenty patients had a past history of cancer. Fifty percent was female, and mean age was 62.8 years. The primary cancer was breast (23.7%), lung (18.6%), stomach (10.2%), and prostate (10.2%). Adenocarcinoma was the most frequent histologic subtype (47.5%). The cancer was metastatic in almost cases (89.8%). At presentation, TMA manifestations were pulmonary (57.6%), neurologic (49.2%), bone pain (30.5%), and disseminated intravascular coagulopathy (DIVC) (55.9%). Forty-one patients had a bone marrow aspiration and/or biopsy. Among them, medullar metastases were found in 20 patients (48.7%). We observed low C3 in 14.7% of cases suggesting an activation of the alternative pathway. No genetic analysis was performed. Only one patient had an undetectable ADAMTS13 &amp;lt;5% without inhibitory ADAMTS13 antibodies. Renal failure was seen in 28 patients whom 63.7% had severe grade 3 acute kidney injury. Renal biopsy was performed in 6 patients with severe arteriolar TMA lesions. Seventeen patients had no treatment (N), fifteen patients were treated with TPE (P), twenty patients received chemotherapy with TPE (C+P), and seven patients received Eculizumab with TPE (E). Hematological and renal remission was not significantly different between treatment groups (p=0.74 and p=0.10 respectively). Mortality was high, 52.5% at one month, 90% after one year of follow-up. The median duration of survival was 27 days [8.5;95.5] in patients who received treatment. Survival was improved in (C+P) and (E+C+P) groups, significantly (p&amp;lt;0.0001). Conclusion We report the largest series of cancer-associated TMAS since the advent of Eculizumab for the treatment of HUS. Typical presentation included old age, bone pain, dyspnea, and DIVC. These symptoms, when associated with TMA, should therefore suggest a diagnosis of cancer. Bone marrow aspiration or biopsy led to diagnosis of cancer in half of cases, and should be systematically performed to rapidly confirm diagnosis. The overall prognosis remained dramatically poor, with a mortality rate of 90% in the first year. Chemotherapy is probably the most efficient therapy to delay the death. C3 serum level was decreased in only 7 patients, suggesting that the pathophysiology of cancer-associated TMA is not linked to complement activation. As a result, neither TPE nor Eculizumab improved survival rate.

Retrospective and Systematic Analysis of Causes and Outcomes of Thrombotic Microangiopathies in Routine Clinical Practice: An 11-Year Study.

Background: Thrombotic microangiopathies (TMAs) are highly suspected in patients showing mechanical hemolytic anemia, thrombocytopenia, and haptoglobin consumption. Primary [thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome] and secondary TMA are considered. Even if ADAMTS13 measurements and alternative complement pathway explorations have greatly improved the ability to identify primary TMA, their diagnosis remains difficult, and their frequency relative to that of secondary TMA is undetermined. The objectives of the present study were, therefore, to describe the etiologies, management, and the outcomes of patients presenting with TMA in real-life clinical practice.Methods: We conducted a retrospective study between 01/01/2008 and 31/12/2018 that included all consecutive patients presenting with biological TMA syndrome at admission or developing during hospitalization. Patients were identified from the laboratory databases, and their medical files were reviewed to confirm TMA diagnosis, to determine etiology, and to analyze their therapeutic management and outcomes.Results: During this period, 239 patients with a full TMA biological syndrome were identified, and the TMA diagnosis was finally confirmed in 216 (90.4%) after the cases were reviewed. Primary TMAs (thrombotic thrombocytopenic purpura or atypical hemolytic uremic syndrome) were diagnosed in 20 of 216 patients (9.3%). Typical HUS was diagnosed in eight patients (3.7%), and the most frequent secondary TMAs were HELLP syndrome (79/216, 36.6%) and active malignancies (30/219, 13.9%). ADAMTS13 measurements and alternative complement pathway analyses were performed in a minority of patients. Multiple factors identified as TMA triggers were present in most patients, in 55% of patients with primary TMA, vs. 44.7% of patients with secondary TMA (p = 0.377). Death occurred in 57 patients (23.4%) during follow-up, and dialysis was required in 51 patients (23.6%). Active malignancies [odds ratio (OR) 13.7], transplantation (OR 4.43), male sex (OR 2.89), and older age (OR 1.07) were significantly associated with death.Conclusion: Secondary TMAs represent many TMA causes in patients presenting a full TMA biological syndrome during routine clinical practice. Multiple factors favoring TMA are present in about half of primary or secondary TMA. ADAMTS13 and complement pathway were poorly explored in our cohort. The risk of death is particularly high in patients with malignancies as compared with patients with other TMA.

Thrombotic Microvascular Injury is not Mediated by Thrombotic Micro Angiopathy Despite Systemic Complement Activation in COVID-19 Patients

Hypoxemia and coagulopathy are common in severe symptomatic patients of coronavirus disease 2019 (COVID-19). Histological evidence shows implication of complement activation and lung injury. We prospectively research sign of complement activation and presence of thrombotic microangiopathy in 8 severe patients. Six of them presented moderate elevation of final pathway of complement –sC5b-9 (median value: 350 ng/mL [IQR: 300,5-514,95 ng/mL]). Two patients have been autopsied and presence of thrombotic microvascular injury has been found. Interestingly, none the 8 patients had signs of mechanical hemolytic anemia (median value of hemoglobin : 10,5 gr/dL[IQR : 8,1-11,9], median value of haptoglobuline 4,49 [IQR 3,55-4,66], none of the patients has schistocyte) and thrombocytopenia (median value: 348000/mL [IQR : 266 000-401 000). Finally, all 8 patients had elevated d-dimer (median value: 2226 μgr/l [IQR: 1493–2362]) and soluble fibrin monomer complex (median value: 8.5 mg/mL, IQR [<6–10.6]). In summary, this study show moderate activation of complement and coagulation with presence of thrombotic microvascular injury in patients with severe COVID-19 without evidence of systemic thrombotic microangiopathy.

Basic Nutrition for Sports Participation, Part 2: Vitamins and Minerals.

Basic Nutrition for Sports Participation, Part 2: Vitamins and Minerals.

Successful transcatheter aortic valve implantation in a patient after an apico-aortic conduit for severe aortic stenosis complicated by haemolytic anaemia: a case report.

BackgroundApico-aortic conduit (AAC) which connects the left ventricular (LV) apex directly to the descending aorta through a valved conduit, is an alternative to surgical aortic valve replacement (AVR) for patients with aortic stenosis (AS) who are inoperable or high risk for surgical AVR and are not suitable candidates for transcatheter aortic valve implantation (TAVI).Case summaryAn 84-year-old man with severe AS underwent an AAC combined with coronary artery bypass grafting 8 years earlier. A saphenous vein graft was anastomosed from the conduit to the left anterior descending artery. He had developed haemolytic anaemia requiring frequent blood transfusions. The stenosis at the anastomosis of the left ventricle and the conduit might be the cause of a turbulent flow and a shear stress which led to mechanical haemolysis. We expected that dilatation of native aortic valve would reduce the blood flow at the anastomosis site and thereby improve haemolytic anaemia. Since balloon aortic valvuloplasty improved haemolytic anaemia without exacerbation of myocardial ischaemia, transsubclavian TAVI was performed. After the TAVI, significant reductions in the pressure gradient between the left ventricle and the ascending aorta and that between the left ventricle and the conduit were achieved, and the patient remained clinically stable without the recurrence of haemolytic anaemia.DiscussionThis is the first report regarding mechanical haemolytic anaemia after AAC which might result from a turbulence and a shear stress by the stenosis of the anastomosis of the LV apex and the conduit. A careful monitoring for conduit dysfunction should be made after AAC.

P1654INCIDENCE AND RISK FACTORS OF THROMBOTIC MICROANGIOPATHY AFTER KIDNEY TRANSPLANTATION

Abstract Background and Aims Thrombotic microangiopathy (TMA) is characterized by mechanical hemolytic anemia, thrombocytopenia, and renal impairment. TMA that occurs in kidney transplant recipients has multiple etiologies and may be de novo or recurrent. Main causes of TMA among recipients are atypical hemolytic uremic syndrome (aHUS), immunosuppressive drugs, ischemia-reperfusion injury (IRI), viral infections, and antibody-mediated rejection (ABMR). Pathological findings of TMA with thrombosis in glomeruli and arterioles are not rare in graft biopsies, but the clinical signs vary widely by etiologies, and incidence and risk factors for each are uncertain. The purpose of this study is to clarify the current status of TMA after kidney transplantation. Method The subjects were 1,336 patients (5,425 biopsy specimens) who underwent kidney transplantation (851 ABO-compatible and 485 ABO-incompatible) at Japanese Red Cross Nagoya Daini Hospital and Masuko Memorial Hospital from January 1, 2000 to June 30, 2018. We investigated patient characteristics and graft survival in 69 patients with pathological findings of TMA (12 with symptomatic TMA and 57 with asymptomatic TMA) and 1,207 patients without findings of TMA. Sixty patients were excluded because of incomplete data or biopsy specimens. TMA patients with acute kidney injury (AKI) were defined as symptomatic TMA in this study. Results The incidence of post-transplant TMA was 5.2% (symptomatic TMA : 0.9%, asymptomatic TMA : 4.3%) in our cohort. Multivariate analysis revealed significant risk factors for TMA were presence of donor specific antibodies (DSA) and use of cyclosporine (odds ratio [OR] 3.52; 95% confidence interval [CI] 1.58-7.88; p=0.002 and OR 3.70; 95% CI 1.68-8.11; p=0.001, respectively). Causes of symptomatic TMA were ABMR : 66.7% (5 patients with ABO-incompatibility, 3 with preformed DSA), aHUS : 16.7%, cytomegalovirus and adenovirus infection : 8.3%, and causes of asymptomatic TMA were drug-induced: 40.4% (21 patients with calcineurin inhibitor, 2 with everolimus), ABMR: 31.6% (10 with ABO-incompatibility, 8 with de novo DSA), IRI : 14.0 %. Onset of post-transplant TMA was significantly associated with lower graft survival (Figure A), with a stronger correlation in symptomatic TMA than in asymptomatic TMA (Figure B and C). Conclusion TMA with AKI that occurred after kidney transplantation had a poor graft prognosis. Therefore, avoiding transplantation, changing donors or using tacrolimus instead of cyclosporine should be considered for patients with DSA or ABO-incompatibility.

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

BackgroundThrombotic 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.CaseA 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.ConclusionOur 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.

Intractable mechanical hemolytic anemia complicating mitral valve surgery: a case series study

BackgroundIntractable, mechanical hemolytic anemia (IMHA) is a rare catastrophic complication following mitral valve surgery. We analyzed patient characteristics and IMHA management by reoperations after mitral valve surgery.MethodsWe collected medical records from mitral valve patients requiring reoperation due to IMHA. Inclusion criteria: hemoglobin < 100 g/L; positive hemolysis tests and echocardiography results; and exclusion of other hemolysis causes.ResultsData from 25 IMHA cases included 10 (40%) early onset (1.3 (0.3,3.0) months) and 15 (60%) late onset (120 (24,204) months) cases. Early IMHA etiologies included surgical defects (6, 60%), uncontrolled infection (3, 30%) and Bechet’s disease (1, 10%). Late IMHA etiologies included degeneration (13, 87%), new infection (1, 7%) and trauma (1, 7%). There were more mechanical valves (15, 88%) than bio-valves (2, 12%); the main valvular dysfunction was paravalvular leak (16, 64%). IMHA manifestations included jaundice (18, 72%), dark urine (21, 84%), heart failure (16, 64%), acute kidney injury (11, 44%), hepatomegaly (15, 60%), splenomegaly (15, 60%) and pancreatitis (1, 4%). Laboratory results showed decreased hemoglobin (70 ± 14 g/L) and increased bilirubin (72 ± 57 μmol/L), lactate dehydrogenase (2607 ± 2142 IU/L) and creatinine (136 ± 101 μmol/L) levels. Creatinine level negatively correlated with hemoglobin level (B = -3.33, S.E. B = 1.31, Exp(B) = 368.15, P = 0.018). Preoperative medications included iron supplements (20, 80%), erythropoietin (16, 64%) and beta-blocker (22, 88%). Two patients died of cardiac causes before reoperation. The other 23 underwent reoperation with long surgical times (aortic cross clamp 124 ± 50 min, cardiopulmonary bypass 182 ± 69 min) and blood transfusions (red blood cells 6 (6, 8) units, plasma 600 (400,800) ml, platelet 1(0,2) units). Postoperative complications included cardiac dysfunction (5, 22%), arrhythmia (10, 43%), sepsis (6, 26%), pulmonary infection (5, 22%), gastrointestinal bleeding (3, 13%), cerebral hemorrhage (2, 9%), chronic renal dysfunction (1, 4%) and surgical hemorrhage (1, 4%). Five (33%) patients died after reoperation from cardiac dysfunction (3, 60%), septic shock (1, 20%) and self-discharge (1, 20%).ConclusionsIMHA induces severe multi-organ dysfunction, contributing to high mortality. Perioperative management should focus on etiological treatment, organ protection, and blood management.

Diagnosis in thrombotic microangiopathy

Thrombotic microangiopathies (TMA) are relatively rare multisystem diseases characterised by microvascular endothelial damage with platelet-rich thrombus formation, consumption thrombocytopenia, mechanical haemolytic anaemia with schistocytes and multiorgan failure of variable severity. Thrombotic thrombocytopenic purpura (TTP) and haemolytic uraemic syndrome (HUS) are the two major disorders; other clinical entities that can be associated with TMA, are the HELLP syndrome, (haemolysis, elevated liver enzymes, low platelet count), the catastrophic antiphospholipid syndrome (CAPS) and bone marrow transplant (BMT). On the peripheral blood smears, the detection of schistocytes, that are fragments of red blood cells produced by extrinsic mechanical damage within the circulation, still remains an important morphological clue for the diagnosis of TMA. The International Council for Standardization in Hematology (ICSH) has prepared specific recommendations to standardise schistocyte identification, enumeration, and reporting. Measurement of activity of ADAMTS13 (a zinc-containing metalloprotease enzyme which cleaves and degrades large multimers of von Willebrand factor) remains the most reliable test to distinguish HUS from TTP, presenting with detectable and undetectable ADAMTS13 activity, respectively. Main clues in HELLP are weight gain, arterial hypertension, massive proteinuria, DIC, marked elevation of AST/ALT/LDH and detectable ADAMTS13 activity, while patients with CAPS present with weight loss, recent polyuria–polydipsia, vomiting, hypoglycaemia, jaundice (conjugated bilirubin), prolonged prothrombin time, reduced factor V and antithrombin levels, DIC and renal failure.