Thrombotic microangiopathy (TMA) is a group of highly heterogeneous, acute and severe clinicopathological syndromes, characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia and ischemic injury of end organs. TMA has the characteristics of dangerous condition, multiple organ involvement and high mortality. Patients with severe TMA need to be admitted to intensive care unit (ICU) for organ function support therapy. Early and rapid evaluation, differential diagnosis, and timely and effective treatment are the key to improve the prognosis of TMA patients. Here, we review the pathophysiological changes, diagnosis differential diagnosis, and treatment of the severe TMA in adult.
Adult ; Humans ; Thrombotic Microangiopathies/therapy* ; Purpura, Thrombotic Thrombocytopenic/therapy* ; Anemia, Hemolytic/therapy* ; Treatment Outcome ; Diagnosis, Differential

INTRODUCTION: ADAMTS13 (a disintegrin-like and metalloproteinase with a thrombospondin Type 1 motif, member 13) plays a fundamental role in the regulation of haemostasis and thrombosis. Its deficiency leads to an accumulation of ultra-large von Willebrand multimers, inducing spontaneous platelet aggregation, thrombosis in the microvasculature, and thrombotic thrombocytopenic purpura (TTP), a condition with 90% mortality when left untreated. Prompt quantification of ADAMTS13 antigen, activity and autoantibody plays a crucial role in the diagnosis and management of TTP and can help differentiate it from other thrombotic microangiopathies (TMAs). Reference ranges for ADAMTS13 are generally derived from Caucasian patients. Given that polymorphism in the ADAMTS13 gene can be associated with variable ADAMTS13 levels, we aimed to establish the first reference range in Singapore and provide a crucial laboratory test for institutions here and elsewhere. METHODS: 150 healthy voluntary donors (75 men, 75 women) aged 21-60 years, with an ethnic mix mirroring Singapore's population profile, were recruited. ADAMTS13 antigen, activity and autoantibody levels were measured using the fluorescence resonance energy transfer-vWF73 and enzyme-linked immunosorbent assay methodologies. RESULTS: Levels (activity 0.65-1.79 IU/mL, antigen 0.36-1.17 IU/mL, autoantibody 1.4-12.5 U/mL) were not statistically different between the genders and various age groups. CONCLUSION TTP and TMAs are encountered in a wide range of specialties. The availability of new assays in Singapore will aid clinicians in the timely management of these conditions. Standardising reference ranges established for Singapore against World Health Organization standards allows harmonisation of measurements between laboratories and for future research collaborations.
ADAMTS13 Protein/analysis* ; Adult ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Purpura, Thrombotic Thrombocytopenic/diagnosis* ; Reference Values ; Singapore

Diagnosis of thrombotic microangiopathy (TMA) is challenging due to its close association with other forms of microangiopathic hemolytic anemia, such as malignant hypertension and disseminated intravascular coagulation, and because other manifestations including cytopenia and acute kidney injury are manifestations of other medical comorbidities. Further challenges for accurate diagnosis include distinguishing between primary and secondary TMA, as well as between hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). TTP is typically differentiated from HUS by the presence of more severe thrombocytopenia, along with a higher frequency of altered mental status with relatively preserved renal function. However, the clinical course can vary among patients, requiring polymerase chain reaction testing of patient stools for enterohemorrhagic Escherichia coli and a disintegrin and metalloproteinase with thrombospondin type 1 motif 13 (ADAMTS13) assay. To reduce the mortality rate, prompt initiation of plasmapheresis is important in cases where TPP cannot be excluded. Future advances enabling more rapid testing for ADAMTS13 levels will reduce the need for unnecessary plasmapheresis, so that treatment strategy can be more optimized.
Acute Kidney Injury ; Anemia, Hemolytic ; Comorbidity ; Diagnosis ; Diagnosis, Differential ; Disseminated Intravascular Coagulation ; Enterohemorrhagic Escherichia coli ; Hemolytic-Uremic Syndrome ; Humans ; Hypertension, Malignant ; Mortality ; Plasma Exchange ; Plasmapheresis ; Polymerase Chain Reaction ; Purpura, Thrombotic Thrombocytopenic ; Thrombocytopenia ; Thrombospondins ; Thrombotic Microangiopathies

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder that affects multiple organs and is fatal in some cases. Thrombotic thrombocytopenic purpura (TTP), another rare disease, is characterized by multiple organ failure and microangiopathic hemolytic anemia. TTP is an extremely rare complication of AOSD. We report a 59-year-old woman who presented with TTP that manifested after she was diagnosed with AOSD. Initially, her clinical manifestations improved with glucocorticoid therapy. However, her disease worsened and was accompanied by acute kidney injury, thrombocytopenia, hemolytic anemia, petechiae, and impaired consciousness. These clinical findings led to a diagnosis of TTP. This is the first report of AOSD complicated by TTP in Korea. Awareness of the possible development of TTP as a complication of AOSD is important for early diagnosis and treatment.
Acute Kidney Injury ; Anemia, Hemolytic ; Consciousness ; Diagnosis ; Early Diagnosis ; Female ; Glycogen Storage Disease Type VI ; Humans ; Korea ; Middle Aged ; Multiple Organ Failure ; Purpura ; Purpura, Thrombotic Thrombocytopenic* ; Rare Diseases ; Still's Disease, Adult-Onset* ; Thrombocytopenia

Hemolytic anemia and thrombocytopenia are rare clinical manifestations of acute glomerulonephritis. Initially, in all such cases, a diagnosis of hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, systemic lupus erythematosus, and amyloidosis should be ruled out. The presence of hemolytic anemia and thrombocytopenia is rare, but possible, in a case of acute poststreptococcal glomerulonephritis, and may result in delayed diagnosis or misdiagnosis. Correct and timely diagnosis would ensure adequate treatment in such patients. We report of a 22-month-old boy with acute glomerulonephritis coexistent with hemolytic anemia and idiopathic thrombocytopenia.
Amyloidosis ; Anemia, Hemolytic* ; Delayed Diagnosis ; Diagnosis ; Diagnostic Errors ; Glomerulonephritis* ; Hemolytic-Uremic Syndrome ; Humans ; Infant* ; Lupus Erythematosus, Systemic ; Male ; Purpura, Thrombotic Thrombocytopenic ; Thrombocytopenia*

Hemolytic anemia and thrombocytopenia are rare clinical manifestations of acute glomerulonephritis. Initially, in all such cases, a diagnosis of hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, systemic lupus erythematosus, and amyloidosis should be ruled out. The presence of hemolytic anemia and thrombocytopenia is rare, but possible, in a case of acute poststreptococcal glomerulonephritis, and may result in delayed diagnosis or misdiagnosis. Correct and timely diagnosis would ensure adequate treatment in such patients. We report of a 22-month-old boy with acute glomerulonephritis coexistent with hemolytic anemia and idiopathic thrombocytopenia.
Amyloidosis ; Anemia, Hemolytic* ; Delayed Diagnosis ; Diagnosis ; Diagnostic Errors ; Glomerulonephritis* ; Hemolytic-Uremic Syndrome ; Humans ; Infant* ; Lupus Erythematosus, Systemic ; Male ; Purpura, Thrombotic Thrombocytopenic ; Thrombocytopenia*

ADAMTS13, a plasma metalloprotease, specifically cleaves von Willebrand factor (vWF). Severe deficiency of plasma ADAMTS13 activity results in thrombotic thrombocytopenic purpura (TTP). In this review, the structure and function of ADAMTS13 protease and its relationship with TTP are summarized.
ADAM Proteins ; metabolism ; ADAMTS13 Protein ; Humans ; Purpura, Thrombotic Thrombocytopenic ; diagnosis ; pathology ; therapy

OBJECTIVETo comprehensively analyze the clinical characteristics, treatment strategies and outcome of patients with thrombotic thrombocytopenic purpura (TTP).

METHODSA retrospective survey of 51 TTP patients confirmed in our database. Relevant statistical analyzes were performed by GraphPad Prism 5 software.

RESULTS51 cases of patients with acquired TTP were identified as idiopathic TTP. In our study, only 18 cases (35.29%) had typical pentalogy of TTP, where thrombocytopenia (100.00%), microangiopathic hemolytic anemia (92.16%) and neurologic abnormalities (88.24%) were more common than fever (72.55%) and renal abnormalities (70.59%). Plasma ADAMTS13 activity was detected in 37 patients with TTP with ADAMTS13 deficiency confirmed in 31 patients (83.78%). Plasma exchange with response of 72.3% was still the preferred strategy in TTP with individuation. Among 36 survival TTP patients, 8 patients (22.22%) relapsed. 15 patients (29.41%) died in our study. The mean ages of responders and deaths were of (37.5±14.5) and (50.1±18.9) respectively; whereas total bilirubin level of responders and deaths were of (43.3±23.5)μmol/L and (63.7±39.7) μmol/L respectively, the differences were statistically significant. Conversely, body temperature, WBC, HGB, PLT, serum creatinine and LDH showed no significant differences (P>0.05).

CONCLUSIONThe diagnosis of TTP was based on comprehensive analysis of clinical manifestations. Plasma ADAMTS13 activity test had a higher clinical practical value. The therapeutic alliance with corticosteroids, immunosuppressive agents and Rituximab significantly improved its outcome. The age and high total bilirubin level at onset were associated with less sensitive to plasmapheresis and poor prognosis.

ADAM Proteins ; blood ; ADAMTS13 Protein ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Plasma Exchange ; Purpura, Thrombotic Thrombocytopenic ; diagnosis ; therapy ; Retrospective Studies ; Young Adult

Thrombotic thrombocytopenic purpura (TTP), a fatal disease, is mostly idiopathic but can occur secondary to cancer, infection, transplantation, pregnancy, surgery, or drugs. The mechanism of TTP is still unknown, however, and detection is difficult because of unclear diagnosis criteria. Colonic stent insertion is commonly used in management of malignant colon obstruction. This is a very safe procedure with a low procedure-related mortality rate, but serious complications can develop. The authors first experienced a patient with TTP when the phenomenon occurred after stent insertion for palliation of obstructive colon cancer and therefore would like to report the case.
Colon ; Colonic Neoplasms* ; Diagnosis ; Humans ; Mortality ; Pregnancy ; Purpura, Thrombotic Thrombocytopenic* ; Stents*

In order to enhance the understanding of thrombotic thrombocytopenic purpura (TTP), the clinical features, laboratory characteristics, treatment and outcome of 14 patients with TTP were retrospectively analyzed and investigated. The results showed that 7 out of 14 patients with TTP had predisposing factors, such as pregnancy in 4 cases, infection in 3 cases, systemic lupus erythematosus (SLE) in 1 case and hematopoietic stem cell transplantation (HSCT) in 1 case. Fourteen patients all had neuropsychological symptoms, hemolytic anemia with negative-Coombs test, and decreased platelet counts. Eight patients had irregular fever with different degree. There were 8 patients with kidney damage including proteinuria in 8 cases and renal function abnormalities in 4 cases. The von Willebrand factor-cleaving protease (VWF-CP, ADAMTS13) activity of 13 cases out of 14 patients significantly decreased (less than 10%). At same time, plasma ADAMTS13 inhibitors were detected in 12 cases out of these 13 patients with decreased ADAMTS13 activity. After treatment with plasma exchange, glucocorticoid and rituximab so on, 12 cases achieved complete remission, in which 8 cases relapsed in two years. Two patients died at last, in which one case was secondary to HSCT. It is concluded that TTP is a kind of thrombotic microangiopathy due to platelet microthrombosis involved in multiple systems and multiple organs dysfunction with dangerous clinical process. The mortality of TTP patients is very high. Early diagnosis and early treatment with plasma exchange as the main means can greatly improve the prognosis of patients with TTP.
ADAM Proteins ; blood ; ADAMTS13 Protein ; Adolescent ; Adult ; Female ; Humans ; Male ; Middle Aged ; Plasma Exchange ; Pregnancy ; Prognosis ; Purpura, Thrombotic Thrombocytopenic ; diagnosis ; therapy ; Retrospective Studies ; Young Adult