Case Report: Microangiopathic Hemolytic Anemia With Normal ADAMTS13 Activity (original) (raw)
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Thrombotic Microangiopathic Hemolytic Anemia With Reduction of ADAMTS13 Activity
American Journal of Clinical Pathology, 2011
Upon completion of this activity you will be able to: • describe overlapping clinical features of noncongenital thrombotic thrombocytopenic purpura, systemic lupus erythematosus (SLE), and the catastrophic variant of the antiphospholipid syndrome (APS). • define clinical, laboratory, and histopathologic diagnostic features of SLE and APS.
2014
Thrombotic microangiopathies (TMAs) include several diseases, most prominently are thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS). TMAs are characterized by profound thrombocytopenia, microangiopathic hemolytic anemia and organ ischemia. In most cases TTP results from deficiency of ADAMTS13, the von Willebrand factor-cleaving protease leading to increase of ultra-large von Willebrand factor (ULVWF) multimers. Congenital TTP is due to mutations in the gene of ADAMTS13 whereas acquired TTP is due to production of autoantibodies against ADAMTS13. In both cases severe deficiency of ADAMTS13 exists. However, the presence of ADAMTS13 activity does not rule out TTP. Diagnostic criteria of TTP are based on clinical features of neurologic and renal disfunction along with anemia and thrombocytopenia, low ADAMTS13 activity, and the presence of ULVWF. The standard treatment of TTP includes plasma exchange, protein A immunoabsobtion, immunosuppressive drugs, CD20 antibodies against B cells, and splenectomy. HUS is commonly caused by infection with Shiga-toxin produced by Escherichia coli. HUS is characterized by thrombocytopenia, anemia, renal impairment and diarrhea. Rarely, atypical HUS appears as a consequence of mutations related to the alternative pathway for the compliment system. Plasmapheresis in HUS is not efficient. Alternatively, plasma therapy and in some cases dialysis are used. TMA diseases may be associated with other infections, bone marrow transplantation, pregnancy, systemic vasculitis, and certain drugs.
Thrombotic Thrombocytopenic Purpura and Other Thrombotic Microangiopathic Hemolytic Anemias
Diagnostic Criteria in Autoimmune Diseases, 2008
TMAs) include several diseases, most prominently are thrombotic thrombocyto-23 penic purpura (TTP) and hemolytic-uremic syndrome (HUS). TMAs are characterized by profound thrombocyto-24 penia, microangiopathic hemolytic anemia and organ ischemia. In most cases TTP results from deficiency of 25 ADAMTS13, the von Willebrand factor-cleaving protease leading to increase of ultra-large von Willebrand factor 26 (ULVWF) multimers. Congenital TTP is due to mutations in the gene of ADAMTS13 whereas acquired TTP is due to 27 production of autoantibodies against ADAMTS13. In both cases severe deficiency of ADAMTS13 exists. However, 28 the presence of ADAMTS13 activity does not rule out TTP. Diagnostic criteria of TTP are based on clinical features 29 of neurologic and renal disfunction along with anemia and thrombocytopenia, low ADAMTS13 activity, and the 30 presence of ULVWF. The standard treatment of TTP includes plasma exchange, protein A immunoabsorption, 31 immunosuppressive drugs, CD20 antibodies against B cells, and splenectomy. HUS is commonly caused by infection 32 with Shiga-toxin produced by Escherichia coli. HUS is characterized by thrombocytopenia, anemia, renal impair-33 ment and diarrhea. Rarely, atypical HUS appears as a consequence of mutations related to the alternative pathway 34 for the compliment system. Plasmapheresis in HUS is not efficient. Alternatively, plasma therapy and in some cases 35 dialysis are used. TMA diseases may be associated with other infections, bone marrow transplantation, pregnancy, 36 systemic vasculitis, and certain drugs. 37
A Case of Atypical Thrombotic Microangiopathy
Journal of the Korean Society of Pediatric Nephrology, 2013
We report the case of a 14-year-old girl, diagnosed with atypical thrombotic microangiopathy (TMA). The patient presented with persistent fever, nausea, and newly developed peripheral edema. Her laboratory findings indicated chronic anemia with no evidence of hemolysis, thrombocytopenia, or elevated serum creatinine level. A few days after hospitalization, acute renal failure and fever worsened, and proteinuria developed. On day 40 of hospitalization, she experienced a generalized tonic seizure for 5 min, accompanied by renal hypertension. Brain magnetic resonance imaging revealed posterior reversible leukoencephalopathy syndrome. After steroid pulse therapy, a renal biopsy was performed because of delayed recovery from thrombocytopenia. The biopsy findings showed features of thrombotic microangiopathic hemolysis with fibrinoid change restricted. Current diagnostic criteria for TMA have focused on thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, and diagnosis is based on the clinical presentation and etiology, with the consequence that idiopathic and atypical forms of TMA can be overlooked. Developing effective tools to diagnose TMA, such as studying levels of ADAMTS13 or testing for abnormalities in the complement system, will be the first step to improving patient outcomes.
The thrombotic microangiopathies
Pediatric Nephrology (Berlin, Germany), 2008
The term thrombotic microangiopathy (TMA) encompasses a group of conditions that are defined by, or result from, a similar histopathological lesion. Hemolytic uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP), and several other conditions are associated with TMA. Distinguishing HUS from TTP is not always possible unless there are specific causes, such as Shiga toxin, Streptococcus pneumoniae, or a specific molecular defect such as factor H or ADAMTS13 deficiency. This review describes the forms of HUS/TTP that are not related to Shiga toxin, pneumococcal infection, genetic causes, or ADAMTS13 deficiency. Conditions include HUS/TTP associated with autoimmune disorders, human immunodeficiency virus (HIV) infection, transplantation, malignancy, and medications.
Case Reports in Internal Medicine, 2015
The first approach to a patient with thrombotic microangiopathy (TMA) involves differentiating thrombotic thrombocytopenic purpura (TTP) from hemolytic uremic syndrome (HUS), since both pathogenesis and treatment differ. Case-by-case decision making based on all the clinical, laboratory and response-to-therapy criteria can result in an accurate diagnosis, leading to the most appropriate therapy and a better chance of improving clinical outcome while preserving organ function. We report the case of a 21-year-old female admitted for TMA characterized by severe renal involvement and no neurological symptoms. Clinical onset occurred after a three-day long episode of diarrhea. First analysis showed no evidence of shiga toxin-producing E. Coli (STEC) and revealed severely deficient ADAMTS13 activity, which is common in TTP. After an initial response to steroids and plasma exchange therapy (PEX), the patient became PEX-dependent. A complete remission and PEX-independence was achieved by a B cell depletion therapy with Rituximab. Results of the subsequent genetic analysis showed a new heterozygous variant p.Arg448Leu, as an isolated mutation, in the complement factor I gene.
Making the Correct Diagnosis in Thrombotic Microangiopathy: A Narrative Review
Canadian Journal of Kidney Health and Disease, 2021
Purpose of review: Thrombotic microangiopathy (TMA) is suspected in patients presenting with thrombocytopenia and evidence of a microangiopathic hemolytic anemia. Patients with TMA can be critically ill, so rapid and accurate identification of the underlying etiology is essential. Due to better insights into pathophysiology and causes of TMA, we can now categorize TMAs as thrombotic thrombocytopenic purpura, postinfectious (mainly Shiga toxin-producing Escherichia coli–induced) hemolytic uremic syndrome (HUS), TMA associated with a coexisting condition, or atypical HUS (aHUS). We recognized an unmet need in the medical community to guide the timely and accurate identification of TMA, the selection of tests to clarify its etiology, and the sequence of steps to initiate treatment. Sources of information: Key published studies relevant to the identification, classification, and treatment of TMAs in children or adults. These studies were obtained through literature searches conducted wi...
Cureus, 2021
Hemolytic anemia with thrombocytopenia and organ damage raises suspicion for thrombotic microangiopathy (TMA), a pathology that results in thrombosis within the small vessels secondary to endothelial injury. While usually attributed to atypical hemolytic uremic syndrome (aHUS) or thrombotic thrombocytopenic purpura (TTP), an increasingly recognized and treatable entity is pseudo-thrombotic microangiopathic anemia (pseudo-TMA) secondary to severe vitamin B-12 deficiency. While TMA often requires expensive diagnostic testing and can lead to invasive treatment options such as plasma exchange, immunosuppression, and/or complement cascade blocking, pseudo-TMA requires only vitamin supplementation. Therefore, the prompt and accurate diagnosis of this entity is important for the clinician to recognize in order to avoid unnecessary health costs and institute appropriate treatment. We present the case of a 51-year-old male without any past medical history, who presented with generalized weak...
Pathogenesis of thrombotic microangiopathies
2008
Profound thrombocytopenia and microangiopathic hemolytic anemia characterize thrombotic microangiopathy, which includes two major disorders: thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). TTP has at least three types: congenital or familial, idiopathic, and nonidiopathic. The congenital and idiopathic TTP syndromes are caused primarily by deficiency of ADAMTS13, owing to mutations in the ADAMTS13 gene or autoantibodies that inhibit ADAMTS13 activity. HUS is similar to TTP, but is associated with acute renal failure. Diarrhea-associated HUS accounts for more than 90% of cases and is usually caused by infection with Shiga-toxin-producing Escherichia coli (O157:H7). Diarrhea-negative HUS is associated with complement dysregulation in up to 50% of cases, caused by mutations in complement factor H, membrane cofactor protein, factor I or factor B, or by autoanti-bodies against factor H. The incomplete penetrance of mutations in either ADAMTS13 or complement regulatory genes suggests that precipitating events or triggers may be required to cause thrombotic microangiopathy in many patients. Keywords thrombotic thrombocytopenic purpura; hemolytic uremic syndrome; von Willebrand factor-cleaving metalloprotease; ADAMTS13; complement dysregulation DISCLOSURE STATEMENT The authors are not aware of any biases that might be perceived as affecting the objectivity of this review.