Microangiopathic Hemolytic Anemia Research Articles

Clinical features and outcomes of four atypical hemolytic uremic syndrome cases at a single institution in Miyazaki Prefecture from 2015 to 2019

BackgroundAlthough atypical hemolytic uremic syndrome (aHUS) is a life-threatening clinical entity that was characterized by thrombotic microangiopathy (TMA) with the activation of the complement system and the efficient treatment of eculizumab, the clinical features of aHUS have been unclear because of the rare incidence.Case presentationWe retrospectively analyzed 4 aHUS cases at a single institution during 2015–2019. Here, we presented 4 aHUS cases with renal transplantation (one case), influenza/acute interstitial pneumonia/disseminated intravascular coagulation (two cases), and severe fever with thrombocytopenia syndrome (one case), respectively. Initial clinical symptoms were microangiopathic hemolytic anemia (four cases), renal dysfunction (four cases), thrombocytopenia (four cases), and pulmonary hemorrhage (three cases) consisted with TMA features. Subsequent further examinations ruled out thrombotic thrombocytopenic purpura, Shiga toxin-producing E.coli-induced hemolytic uremic syndrome, and secondary TMA. Taken these findings together, we made the clinical diagnosis of aHUS. Furthermore, all cases also presented the high levels of plasma soluble C5b-9 (871.1 ng/ml, 1144.3 ng/ml, 929.2 ng/ml, and 337.5 ng/ml), suggesting persistent activation of complementary system. Regarding the treatment, plasma exchange (PE) (four cases) and eculizumab (two cases) therapy were administered for aHUS cases. Consequently, case 2 and case 4 were still alive with 768 days and 235 days, respectively. The other two cases were dead at 34 days and 13 days, respectively. Finally, although the previous reported genetic pathogenetic mutations were not detected in our cases, multiple genetic variants of complement factors were detected as CFH (H402Y, E936D), and THBD (A473V) in case 1, CFH (V62I, H402Y, V837I) in case 2, and CFH (H402Y, E 936D) and THBD (A473V) in case 3, CFH (V62I, H402Y, E936D) and THBD (473V) in case 4, respectively.ConclusionsBecause of still high mortality in our study, an urgent diagnosis of aHUS and subsequent immediate treatment including PE and eculizumab should be essential in clinical practice. Furthermore, the multiple genetic variants and the triggers may be related to one of the pathogenesis of aHUS. Thus, we assume that such a case-oriented study would be highly useful to the physicians who directly care for aHUS cases in clinical practice.

HIV-associated thrombotic thrombocytopenic purpura (HIV-TTP): A practical guide and review of the literature.

Thrombotic thrombocytopenic purpura (TTP), a serious thrombotic microangiopathy (TMA), is prevalent in the South African HIV-infected population. The exact pathogenesis of HIV-associated TTP (HIV-TTP) is however still unclear with diagnostic and therapeutic inconsistancies. A systematic review of the published literature regarding HIV-TTP was performed. HIV-TTP is still associated with significant morbidity and mortality in Africa despite the availability of anti-retroviral therpy (ART). Diagnosis of HIV-TTP requires the presence of a micro-angiopathic haemolytic anaemia with significant red blood cell schistocytes and thrombocytopenia in the absence of another TMA but background activation of the coagulation system and inflammation in HIV infected people can result in diagnostic anbiguity. Plasma therapy in the form of infusion or exchange is successful but expensive, associated with side-effects and not widely available. Adjuvant immunosuppression therapy may of benefit in patients with HIV-TTP and ART must always be optimised. Endothelial dysfunction caused by chronic inflammation and complement activation most likely contributes to the development of HIV-TTP. The role of adjuvant immunomodulating therpy, the therapeutic targets and pathogenic contribution from endothelial dysfunction in HIV-TTP requires further investigation.

Slow It Down: A Case Report Of Microangiopathic Hemolytic Anemia In A Heartmate III Patient

<h3>Introduction</h3> Incidence of hemolysis in left ventricular assist devices (LVADs) is reported from 13-18%, but with HeartMate 3 (HM3) LVAD has been decreased to <1%. Typically, hemolysis is associated with LVAD thrombosis with subsequent decreased survival rate at 1 year (38.9% vs. 89.3%). We present a case of microangiopathic hemolytic anemia (MAHA), not related to pump thrombosis in a recent implanted HM3 LVAD patient which resolved by decreasing LVAD speed. <h3>Case Report</h3> A 44 year-old man with status post LVAD HM3 4 months prior complicated with right ventricular (RV) failure, pulmonary hypertension and CKD Stage III was admitted for mixed vasodilatory and cardiogenic shock. Patient required dual inotropes, vasopressors and temporary renal replacement therapy in an effort to stabilize him and continue his evaluation for heart and kidney transplant. Meanwhile, patient developed acute, severe thrombocytopenia (platelet count of 26K) and mild anemia. Disseminated intravascular coagulation was unlikely (normal fibrinogen level). Heparin-induced thrombosis (HIT) antibody testing was non-reactive. No active sepsis. There were no power spikes or suspected LVAD thrombosis (Table 1). Intrinsic bone marrow disease was thought to be unlikely. LDH was elevated and haptoglobin level undetectable (Table 2), blood smear showed schistocytes, raising suspicious for MAHA, therefore LVAD speed was decreased to 5100 RPM to diminish red blood cell (RBC) fragmentation and maintained in systemic unfractionated heparin infusion. This resulted in recovery of platelets and hemolysis parameters (Table 2). Ultimately, patient underwent dual organ transplantation without complications. <h3>Conclusions</h3> Per our knowledge, this is the first case reported of MAHA in a LVAD HM3 patient, not related to pump thrombosis that resolves with decrease in LVAD speed. MAHA is caused by mechanical injury of RBCs. The effective treatment in this scenario was to decrease the speed of the LVAD, hypothetically to decrease excessive shear in circulation. Further research should be done to delineate efficacy of reducing LVAD speed in these patients.

Hemolytic Uremic Syndrome in Egyptian Children: A Single Center Experience across 10 Years.

Hemolytic uremic syndrome (HUS) is a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI) and is the most common cause of AKI in children. We aimed to demonstrate the clinical patterns, laboratory findings, management, and outcomes of HUS in Egyptian children. This was a retrospective cohort study carried out in the Nephrology Unit of the Pediatric Department at Tanta University Hospitals. Hospital-based records of HUS cases between January 2009 and January 2019 were used to obtain the disease history, clinical manifestations, investigations, treatment, and outcomes. Sixty-eight children were included in the study: 63 (96.56%) with Shiga-toxin-producing Escherichia coli (STEC) HUS and five (7.53%) with atypical HUS. The boy-to-girl ratio was 1.19:1. The age at the onset of the disease ranged from 0.5 to 13 years, with a median of 2.25 years. The main presenting manifestations were pallor (80.88%), diarrhea (67.65%), oliguria (54.41%), and convulsions (19.21%). The survival rate was 85.29%, whereas the mortality rate was 14.71%. Thirty-seven patients (54.41%) recovered completely, 17 (25%) patients survived but with chronic kidney disease, and four patients (5.88%) progressed to end-stage renal disease and are currently maintained on dialysis. The risk factors for mortality were female gender, age <5 years, anuria, and an affected central nervous system (CNS). STEC-HUS had a higher incidence than atypical HUS with better outcomes. Early dialysis improved the outcome in terms of mortality in young patients, females, and those with an affected CNS.

Dual pathology: Everolimus-induced microangiopathic haemolytic anaemia in a patient with myelodysplastic syndrome.

Dual pathology: Everolimus-induced microangiopathic haemolytic anaemia in a patient with myelodysplastic syndrome.

The paradox of thrombotic thrombocytopenic purpura and the TACO challenge!

Thrombotic thrombocytopenic purpura (TTP) is a rare medical emergency characterized by the pentad of microangiopathic hemolytic anemia, thrombocytopenia, fever, renal failure, and neurological dysfunction. TTP is an infrequent condition and is a thrombotic microangiopathy. TTP is essentially a clinical diagnosis. As untreated TTP has a high mortality, diagnosis is usually presumptive and prompt treatment with plasma exchange is highly beneficial and reduces mortality significantly. Therapeutic plasma exchange with fresh frozen plasma is the standard treatment of choice for TTP. Transfusion-associated reactions may occur in some patients further complicating the disease picture and prolonging hospital stay and recovery. Transfusion-associated circulatory overload and transfusion-associated acute lung injury are the leading cause of transfusion-related mortality. We present here the diagnostic and therapeutic challenges that we faced with a young male patient who presented with fever, jaundice, and seizures.

Oxaliplatin-induced thrombotic microangiopathy: a case report

BackgroundOxaliplatin-based chemotherapy represents a standard of care in the treatment of metastatic colorectal cancer. We report a rare case of fulminant oxaliplatin-induced thrombotic microangiopathy, clinically suggestive of hemolytic–uremic syndrome, occurring in a female patient with a prolonged history of exposure to oxaliplatin for the treatment of metastatic colon cancer.Case presentationA 73-year-old Caucasian female with a treatment history including several lines of chemotherapy for the management of metastatic colon cancer was reinitiated on chemotherapy with oxaliplatin, fluorouracil, and leucovorin with bevacizumab for disease progression. She presented to the emergency department with malaise, headache, vomiting, and decreased urine output appearing a few hours after chemotherapy administration. Clinical symptoms and laboratory findings were suggestive of thrombotic microangiopathy, with a triad of microangiopathic hemolytic anemia, pronounced thrombocytopenia, and acute renal failure. The predominance of the severe renal failure was evocative of hemolytic–uremic syndrome. The rapid development of the thrombotic microangiopathy was linked to exposure to oxaliplatin. The patient was promptly managed with daily plasma exchange and high-dose corticosteroids, platelet, and red blood cell transfusions in conjunction with intermittent hemodialysis, and she recovered progressively.ConclusionOur case confirms the risk of hemolytic–uremic syndrome as a rare and life-threatening complication of oxaliplatin-based chemotherapy. A dose-dependent, drug-induced toxicity mechanism is suggested. Physicians need to maintain a high level of clinical suspicion to diagnose and treat this acute life-threatening disorder.

Cerebral Infarction due to Severe ADAMTS-13 Deficiency with Normal Hematological Parameters: A Cause of Cryptogenic Stroke

ObjectivesThrombotic thrombocytopenic purpura (TTP) is a microangiopathy resulting from an inherited or acquired severe deficiency in a disintegrin and metalloproteinase called ADAMTS-13. Acquired or immune TTP is classically described as a pentad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, fever, renal insufficiency and neurological symptoms. Thrombotic thrombocytopenic purpura has been linked to stroke with the presence of hematologic abnormalities but whether or not severe ADAMTS-13 deficiency can cause stroke without hematological abnormalities is unknown. Materials and MethodsAs part of routine clinical care, we identified four cases of recurrent stroke attributed to severe deficiency of ADAMTS-13. We also conducted a search of a centralized electronic health record database including all inpatients and outpatient charts at a single academic medical center over the last ten years in an attempt to identify additional cases. ResultsHere we present four cases of stroke and severe ADAMTS-13 deficiency where stroke episodes occurred without microangiopathic hemolytic anemia or severe thrombocytopenia. These cases show the need to consider severe ADAMTS-13 deficiency in the setting of recurrent cryptogenic stroke in young patients. Conclusions and RelevanceTTP directed therapies may be considered for patients with recurrent stroke who have extremely low ADAMTS-13 levels, even when platelet and hemoglobin values are normal.

A case of acquired thrombotic thrombocytopenic purpura (TTP) mimicking transient ischemic attack (TIA)

TTP is a rare multisystem disease among children due to dysfunction of ADAMTS 13 enzyme in plasma causing defective vWF cleavage, thus giving rise to platelet aggregation, micro thrombi formation, platelet consumption, capillary blockage and finally organ dysfunction leading to a severe life-threatening condition with mortality around 90% if untreated. It can be congenital (5%) or acquired (95%) and Plasmapheresis works wonder for both the subtypes.: Here we have described a case of acquired TTP masquerading TIA in an 8-year-old girl child who had attacks of sudden onset aphasia and upper limb weakness lasting for few hours with spontaneous recovery. On detailed examination we found pallor and few petechial spots on face and upper limbs with a peripheral blood picture suggestive of thrombocytopenia with microangiopathic hemolytic anemia but a normal renal function. We sent blood for ADAMTS 13 activity which reported a critically low level of ADAMTS 13 enzymatic activity with presence of inhibitors and absent genetic mutation. Immediate Plasmapheresis was started along with oral prednisolone therapy for a span of one month which resulted both clinical and hematological recovery. Platelet count acted as a good indicator of clinical remission. A high degree of clinical suspicion is required to make a prompt diagnosis of this life threatening disease (TTP) since this carries a very high mortality rate and can mimic a more common disease HUS.

A novel missense mutation in complement factor I predisposes patients to atypical hemolytic uremic syndrome: a case report

BackgroundAtypical hemolytic uremic syndrome, also called the nondiarrheal form of hemolytic uremic syndrome, is a rare disease characterized by the triad of thrombocytopenia, Coomb’s test-negative microangiopathic hemolytic anemia, and acute renal failure. Approximately 60% of cases of atypical hemolytic uremic syndrome are associated with deficiencies of the complement regulatory protein, including mutations in complement factor H, complement factor I, or the membrane co-factor protein.Case presentationWe report the case of a 26-year-old Asian man who presented with pulmonary infection, elevated blood pressure, microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Renal biopsy revealed diffuse capillary fibrin deposition, endothelial swelling, and arteriole narrowing like “onion skinning” consistent with thrombotic microangiopathy. Bidirectional sequencing of CFH, CFHR5, CFHR1, CFI, DGKE, CFB, and MCP confirmed that the patient was heterozygous for a novel missense mutation, p.Cys67Phe, in CFI. This patient had rapid evolution to end-stage renal disease and needed renal replacement therapy. Plasma exchange seemed inefficacious in this patient.ConclusionsThis report confirms the importance of screening patients with atypical hemolytic uremic syndrome for mutations in genes involved in complement system to clarify the diagnosis and demonstrates the challenges in the management of these patients.

Case Report: A Rare Case of Thrombotic Microangiopathy Induced by Remethylation Disorders

In this research, we described a very rare case of thrombotic microangiopathy induced by remethylation disorders. A 16-year-old boy presented to the emergency department with 5 months of weakness and fatigue. He was diagnosed with thrombotic microangiopathy based on clinical manifestation and laboratory information, which showed microangiopathic hemolytic anemia, renal impairment, and thrombocytopenia. After a complex diagnostic workup, the metabolite screening parameters and sequencing results guided us toward the diagnosis of remethylation disorders. The patient was diagnosed with thrombotic microangiopathy induced by remethylation disorders (cblC).

Microangiopathic hemolytic anemia in a female patient with systemic lupus erythematosus.

Microangiopathic hemolytic anemia in a female patient with systemic lupus erythematosus.

How I Treat Complement-Mediated TMA.

Thrombotic microangiopathies (TMAs) are a heterogenous group of multisystem disorders characterized by microvascular endothelial injury with intravascular thrombi, microangiopathic hemolytic anemia, and thrombocytopenia. TMAs are syndromes with broad etiologic basis and variable phenotypic

Thrombotic Microangiopathy Syndromes-Common Ground and Distinct Frontiers.

Thrombotic microangiopathies (TMAs) have in common a terminal phenotype of microangiopathic hemolytic anemia with end-organ dysfunction. Thrombotic thrombocytopenic purpura results from von Willebrand factor multimerization, Shiga toxin-mediated hemolytic uremic syndrome causes toxin-induced endothelial dysfunction, while atypical hemolytic uremic syndrome results from complement system dysregulation. Drug-induced TMA, rheumatological disease-induced TMA, and renal-limited TMA exist in an intermediate space that represents secondary complement activation and may overlap with atypical hemolytic uremic syndrome clinically. The existence of TMA without microangiopathic hemolytic features, renal-limited TMA, represents an undiscovered syndrome that responds incompletely and inconsistently to complement blockade. Hematopoietic stem cell transplant-TMA represents another more resistant form of TMA with different therapeutic needs and clinical course. It has become apparent that TMA syndromes are an emerging field in nephrology, rheumatology, and hematology. Much work remains in genetics, molecular biology, and therapeutics to unravel the puzzle of the relationships and distinctions apparent between the different subclasses of TMA syndromes.

Case Report: Tackling Complement Hyperactivation With Eculizumab in Atypical Hemolytic Uremic Syndrome Triggered by COVID-19

Hemolytic uremic syndrome (HUS) is a rare life-threatening disease of unrestrained complement system dysregulation, microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure in genetically predisposed individuals. In this report, we describe two cases of SARS-CoV-2–associated HUS treated with eculizumab, a C5-blocking monoclonal antibody reported to be remarkably effective in the treatment of HUS. Detailed biochemical and genetic complement system analysis is reported, and the prompt clinical response after C5 pharmacological blockade is documented. Our report provides the rationale and supports the use of terminal complement pathway inhibition for the treatment of SARS-CoV-2–associated HUS.

POS-512 COMPLEMENT-MEDIATED THROMBOTIC MICROANGIOPATHY IN NEPHROLOGY

Atypical hemolytic uremic syndrome (aHUS) is a rare disease in adults. It is a thrombotic microangiopathy (TMA) characterized by the presence of renal failure, microangiopathic hemolytic anemia and thrombocytopenia. It is the consequence of a defective complement regulation due to genetic mutations or autoantibodies of the activators or regulators of the complement alternative pathway. Renal involvement is the major prognostic factor. Evaluation of the complement pathway including estimation of blood levels of C3, factor H, I and anti-factor H antibodies is essential for the etiological diagnosis.

Three shades of black - secondary thrombotic microangiopathy.

Thrombotic microangiopathy is a group of disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia and organ damage. Wide age distribution and the heterogeneity in presentation demand a deeper understanding into the pathogenesis of TMA. Primary TMA is distinct from TMA associated with secondary causes and remains clinically occult till a precipitating factor aggravates it. The extent and severity of renal damage caused by each of them is also distinct. The first alerting signal could be the presence of schistiocytes on peripheral smear and arteriolar thrombi on light microscopy. Thus in secondary TMA, identification of the underlying disorder is indispensible for targeted management.

Purple Thrombocytopenic Thrombotic

Thrombotic thrombocytopenic purpura is a rare disease of immune origin, belonging to thrombotic microangiopathies. In most cases, it can present as microangiopathic hemolytic anemia accompanied by thrombocytopenia, neurological deficit and kidney abnormalities. The present clinical case belongs to a female patient with no significant personal or family history, who went to the doctor for a clinical picture of 2 days of evolution with hematuria, general malaise, asthenia and adynamia, on physical examination without alterations, with vital signs in ranges of normality. The diagnosis of thrombotic thrombocytopenic purpura was made due to hemolysis, elevated levels of lactate dehydrogenase and a reduction in serum haptoglobin accompanied by the presence of serum schistocytes&gt; 6% in the peripheral blood smear. Thrombocytopenic purpura is a diagnostic challenge because its clinical picture is often nonspecific, making it more difficult to start its treatment in a timely manner. Another drawback is the high costs for ADAMTS13 activity tests. Despite the fact that the treatments for this disease have low success rates, in our clinical case our patient responded favorably to the treatment instituted

Thrombotic microangiopathy in children.

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.

Snakebite Associated Thrombotic Microangiopathy and Recommendations for Clinical Practice.

Snakebite is a significant and under-resourced global public health issue. Snake venoms cause a variety of potentially fatal clinical toxin syndromes, including venom-induced consumption coagulopathy (VICC) which is associated with major haemorrhage. A subset of patients with VICC develop a thrombotic microangiopathy (TMA). This article reviews recent evidence regarding snakebite-associated TMA and its epidemiology, diagnosis, outcomes, and effectiveness of interventions including antivenom and therapeutic plasma-exchange. Snakebite-associated TMA presents with microangiopathic haemolytic anaemia (evidenced by schistocytes on the blood film), thrombocytopenia in almost all cases, and a spectrum of acute kidney injury (AKI). A proportion of patients require dialysis, most survive and achieve dialysis free survival. There is no evidence that antivenom prevents TMA specifically, but early antivenom remains the mainstay of treatment for snake envenoming. There is no evidence for therapeutic plasma-exchange being effective. We propose diagnostic criteria for snakebite-associated TMA as anaemia with >1.0% schistocytes on blood film examination, together with absolute thrombocytopenia (<150 × 109/L) or a relative decrease in platelet count of >25% from baseline. Patients are at risk of long-term chronic kidney disease and long term follow up is recommended.